Future Growth of Cosmetic Skin Care Market by New Business Developments, Top Companies and Forecast to 2026 – Bulletin Line
By daniellenierenberg
Cosmetic Skin CareMarketBusiness Insights and Updates:
The latest Marketreport by a Data Bridge Market Researchwith the title[Global Cosmetic Skin CareMarket Industry Trends and Forecast to 2026].The new report on the worldwide Cosmetic Skin CareMarketis committed to fulfilling the necessities of the clients by giving them thorough insights into the Market. The various providers involved in the value chain of the product include manufacturers, suppliers, distributors, intermediaries, and customers.The reports provide Insightful information to the clients enhancing their basic leadership capacity identified.Exclusive information offered in this report is collected by analysis and trade consultants.
Global cosmetic skin care market is set to witness a substantial CAGR of 5.5% in the forecast period of 2019- 2026.
Cosmetic skin care is a variety of products which are used to improve the skins appearance and alleviate skin conditions. It consists different products such as anti- aging cosmetic products, sensitive skin care products, anti- scar solution products, warts removal products, infant skin care products and other. They contain various ingredients which are beneficial for the skin such as phytochemicals, vitamins, essential oils, and other. Their main function is to make the skin healthy and repair the skin damages.Get PDF Samplecopy(including TOC, Tables, and Figures) @https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-cosmetic-skin-care-market
Thestudy considers the Cosmetic Skin CareMarketvalue and volume generated from the sales of the following segments:Major Marketmanufacturerscovered in the Cosmetic Skin CareMarketare:LOral, Unilever, New Avon Company, Este Lauder Companies, Espa, Kao Corporation, Johnson & Johnson Services, Inc., Procter & Gamble, Beiersdorf, THE BODY SHOP INTERNATIONAL LIMITED, Shiseido Co.,Ltd., Coty Inc., Bo International, A One Cosmetics Products, Lancme, Clinique Laboratories, llc., Galderma Laboratories, L.P., AVON Beauty Products India Pvt Ltd, Nutriglow Cosmetics Pvt. Ltd, Shree Cosmetics Ltd
Segmentation:Global Cosmetic Skin Care Market
By Product
By Application
By Gender
By Distribution Channel
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Based on regions, the Cosmetic Skin CareMarketis classified into North America, Europe, Asia- Pacific, Middle East & Africa, and Latin AmericaMiddle East and Africa (GCC Countries and Egypt)North America (United States, Mexico, and Canada)South America(Brazil, Argentina etc.)Europe(Turkey, Germany, Russia UK, Italy, France, etc.)Asia-Pacific(Vietnam, China, Malaysia, Japan, Philippines, Korea, Thailand, India, Indonesia, and Australia)
Market Drivers:
Market Restraints:
Key Developments in the Market:
Key Benefits for Cosmetic Skin CareMarket:
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About Us:Data Bridge Marketresearch endeavors to provide appropriate solutions to the complex business challenges and initiates an effortless decision-making process Data Bridge set forth itself as an unconventional and neoteric Marketresearch and consulting firm with unparalleled level of resilience and integrated approaches. We are determined to unearth the best Marketopportunities and foster efficient information for your business to thrive in the Market.We ponder into the heterogeneous Markets in accord with our clients needs and scoop out the best possible solutions and detailed information about the Markettrends. Data Bridge delves into the Markets across Asia, North America, South America, Africa to name few.
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Sick bees social distance, but only within their own colony – Massive Science
By daniellenierenberg
Our relationship to Neanderthals has been a point of contention for over a century. It all began with an inaccurate reconstruction of the first Neanderthal ever found, which portrayed them as brutish, stooped-over cavemen (turns out, that Neanderthal was an injured old man with arthritis).
But within the last half century, scientists have noticed the many biological and behavioral similarities that show just how close our species are. While these similarities are clear from hard objects like bones and tools, perishable objects, which comprise the majority of material culture items in humans, have been lacking.
Now, scientists have discovered a Neanderthal feat that hammers another nail in the coffin of supposed Neanderthal inferiority. Last month, an international team of researchers found a small section of a twisted cord attached to a stone flake in Neanderthal site in southeastern France, dated to over 40,000 years old. This constitutes the oldest direct evidence of fiber technology ever found.
A stone flake with three distinct twisted fibers preserved (indicated by the box).
M.-H. Moncel
When artifacts are recovered from archaeological sites, they are generally imaged using high powered microscopes to zoom in on tiny marks and details on the stones. Previously, plant fibers had been found on stones at this site, but they were too poorly preserved to be interpreted. When the team examined this particular flake, they were surprised to find three distinct twisted fibers, which were then twisted together in the opposite direction to form a 3-ply cord.
While it may not sound like much, this piece of string hints at something much more significant. For one, extracting and manipulating plant fibers requires working memory, as well as understanding plant seasonality and the concept of numbers. Also, such cords are the building blocks for creating other textiles, such as baskets, fabrics, and nets. Once adopted, these objects would have been indispensable in daily life.
This little piece of string provides unprecedented insight into the lives of our extinct relatives, which, despite an abundance of genetic, archaeological, and skeletal data, have been extremely difficult to interpret. It seems as though we humans arent as unique as we like to think.
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Sick bees social distance, but only within their own colony - Massive Science
Hope Realized – CU Anschutz Today
By daniellenierenberg
Not anymore.
Thanks to significant philanthropic support from The Sprout Foundation, a Denver-area foundation funded by Suzanne and Bob Fanch, and gifts from others including Wag and Annalee Schorr, the Ehlers-Danlos Syndrome Center of Excellence was launched in 2019. The goal of the center is to eventually develop a cure for EDS at the Gates Center for Regenerative Medicine, while better addressing the clinical needs of patients today through specialty care at Childrens Hospital Colorado. The clinical components of this new center address the critical need for patient-centered, coordinated EDS care where physicians come together to agree on the treatment plan, rather than leaving the patient and their family to determine the course of action.
Calla Winchell, left, with her grandfather, Dr. Wag Schorr, and her mother, Dr. Kate Schorr.
Simultaneously, the Gates Center for Regenerative Medicine scientists are conducting leading-edge research with the ultimate goal of finding a cure. Today, this research is aimed at discovering the genetic underpinnings of hypermobile EDS and leveraging this information to develop future therapies for patients like Calla.
The Fanches said, Sprout Foundation has funded research and the outstanding staff at the Gates Center for Regenerative Medicine to accelerate the cure for this life-changing disorder and also for clinical care to patients through the EDS Center of Excellence.
Joining in this effort are Callas own grandparents, Wag Schorr, an accomplished nephrologist and 1963 CU School of Medicine alumnus, and his wife, Annalee.
An essential component of the EDS Center of Excellence is a translational research program, which leverages existing campus resources and partnerships, including the Gates Center for Regenerative Medicine and the Colorado Center for Personalized Medicine.
The research program at the Gates Center is led by Dennis Roop, PhD, director of the Gates Center, in partnership with Ganna Bilousova, PhD, and Igor Kogut, PhD. The program brings EDS patients genetic information from clinical visits to the Gates Center where researchers are working on future treatments for the condition. In this virtuous cycle, patients inform future therapies in the lab that, in turn, could ultimately change lives back in the clinic.
Calla is one of those patients. She is motivated by the possibility of improving EDS research.
In preclinical models, scientists are collecting stem cells from Calla and other patients that indicate a possible mutation. These studies, using multiple patients, allow for a more accurate portrait of the errors in DNA. Early findings at the Gates Center suggest that a possible mutation for the hypermobile form of EDS may have been identified. The hope is that this research will lead to a potential treatment in the coming years.
Scientists are growing skin cells in the lab using Callas stem cells, with the EDS gene mutations removed. If successful, the modified stem cells will hook onto sites of inflammation and grow new cells restoring function to damaged tissues and organs. It sounds like science fiction, but it could be a reality at the CU Anschutz Medical Campus in the years to come.
The research advances taking place at the Gates Center will ultimately mean incredible hope and healing for people like Calla, and others with rare genetic disorders, who are eager to regain their health and their independence.
Im thrilled, she said. Im excited to receive coordinated care and treatments that will help me get back to my life. What if I could go to the grocery store and not have to use a wheelchair anymore?
By bringing research together with clinical care, the EDS Center of Excellence is helping turn such possibilities into realities.
Callas care plan is coordinated by a team of experts at the EDS multidisciplinary clinic at Childrens Hospital Colorado, led by the Medical Director of the Special Care Clinic Ellen Roy Elias, MD, in close collaboration with Kourtney Santucci, MD.
The clinic places the patient at the center of care, and brings forward all of the right health professionals required to determine a comprehensive care plan. In this model, the patient is seen by a team of specialists in a single day, with the goal of having a treatment plan at the end of the visit.
Callas grandfather, Dr. Schorr, says no more will Calla and others like her have to create a center of excellence for themselves as they traverse a complex and fragmented healthcare system to ensure their needs are met.
The pioneering work taking place at the EDS Center of Excellence began with Dr. Schorrs vision. In 2016, as a member of the Gates Center for Regenerative Medicine Advisory Board, Dr. Schorr approached director Dennis Roop and began laying the groundwork for research efforts in EDS, which he and Annalee funded later that year. Dr. Schorrs vision and commitment made it possible to develop the EDS Center of Excellence as a place to realize scientific advances in EDS research.
CU is poised for another breakthrough in medicine, said Dr. Schorr. I believe that EDS patients will soon have access to effective treatments, and possibly even a cure. If we are precise with our research and resources, we can resume our place at the forefront of the medical world. Thats our responsibility.
Another must, said Dr. Schorr, is to empower visionaries in their fields to pave the path toward new discoveries and major medical advances.
Leading this charge is CU School of Medicine Dean and Vice Chancellor for Health Affairs John Reilly, Jr., MD. Dean Reilly said, One of the great advantages of having our pediatric hospital partner, Childrens Hospital Colorado, and a research entity like the Gates Center on campus is the opportunity to collaborate. By bringing some of the best minds together to lead the next generation in EDS research, we get remarkable innovation, and leading-edge treatments and care. What our philanthropic partners have built here is inspiring, and together we are determined to bring hope to patients and their families. It has been exciting to see two families with a long friendship come together with a shared goal to create a center that will have a positive effect on so many patients and families.
With each new discovery at the EDS Center of Excellence, lives will improve through better care and better health. Each new discovery brings new opportunity for people with EDS to live lives they never knew they could have.
Guest Contributor: Courtney Keener, CU Anschutz Office of Advancement.
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Hope Realized - CU Anschutz Today
Impacts of COVID 19 on the Global Regenerative Medicine Market Size: Global Industry Analysis, Growth, Top Companies Revenue, MRFR Reveals Insights…
By daniellenierenberg
(MENAFN - GetNews) Market Research Future (MRFR) collected data on several factors including implications of COVID 19 Impact on Regenerative Medicine Market and demographic challenges, showed how it could move forward in the coming years.
Regenerative Medicine Market Outlook
Global regenerative medicine market is growing continually, witnessing a massive uptake. Market growth primarily attributes to the increasing advancement in healthcare technology and the growing prevalence of chronic diseases. Besides, improvements in the field of regenerative medicine and stem cell technology drive the growth of the market excellently.
Moreover, the rising uptake of therapeutics such as stem cell biology, cellular therapy, tissue engineering in applications, including cord blood, oncology, urology, orthopedics, neurology, dermatology, and others accelerate the market growth. According to Market Research Future (MRFR), the global regenerative medicine market is poised to grow at 25.4% CAGR throughout the forecast period (2016 2022).
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Additionally, the rising uptake of stem cell & tissue engineering processes in the treatment of health issues ranging from orthopedics, musculoskeletal & spine, dental, and skin/integumentary to cancer, neurology, and cardiology substantiate the market growth. Furthermore, the increasing rate of road accidents, injuries, and trauma cases drive the market exponentially, driving the demand for transplants & surgical reconstruction procedures.
On the other hand, factors such as the lack of awareness, skilled professionals, and stringent regulatory policies are projected to act as significant impeders for market growth. Nevertheless, funding support for the development of regenerative medicines would support the growth of the market throughout the predicted period. Also, widening application areas of regenerative medicines in the field of stem cell reconstructive and skin grafting would increase the market growth.
Global Regenerative Medicine Market Segments
The analysis is segmented into four dynamics;
By Material : Synthetic Materials, Genetically Engineered Materials, Pharmaceuticals, and others.
By Therapy : Stem Cell Biology, Cellular Therapy, Tissue Engineering, and others.
By Application : Cord Blood, Oncology, Urology, Orthopedics, Neurology, Dermatology, and others.
By Regions : Americas, Europe, Asia Pacific, Middle East & Africa, and Rest-of-the-World.
Regenerative Medicine Market Regional Analysis
North America is projected to continue dominating the global regenerative medicine market throughout the forecast period. In 2015, North America accounted for more than 44% of the overall market share. This huge market growth attributes to the presence of a large number of major players and pharma & biotechnology companies. Moreover, huge investments made by public & private organizations drive the regenerative medicine industry in the region.
Besides, the rising prevalence of chronic diseases and orthopedic issues and increasing clinical trials to evaluate the therapeutic potential of products foster regional market growth. Also, the well-spread awareness towards the therapeutic potency of regenerative medicines impacts the market growth positively. The North American regenerative medicine market is expected to grow at a robust CAGR of 22.3% over the review period.
Europe stands second in the global regenerative medicine market. Factors such as the increasing per capita healthcare expenses and penetration of healthcare sectors in the region boost the market growth. Additionally, the rising government support and R & D funding in the life science developments substantiate the regional market growth. Markets in the UK, Germany, and France, contribute to the regional market majorly. The European regenerative medicine market is estimated to grow at 22.5% CAGR during the assessment period.
The Asia Pacific regenerative medicine market has emerged as a rapidly growing market. Factors such as the large advances in biotechnology and increasing government support for R & D are fostering the growth of the regional market. Regenerative medicine markets in highly populated countries such as China, India, and Japan support the regional market growth excellently, heading with huge technological advances. The APAC Regenerative Medicine market is predicted to demonstrate huge growth potential.
Global Regenerative Medicine Market - Competitive Analysis
The well-established regenerative medicine market appears to be highly competitive with the presence of several notable players. To gain a larger competitive advantage, market players incorporate strategic initiatives such as mergers & acquisitions, expansions, and product/technology launch. Also, they make substantial investments to drive R & D to develop their capabilities and to expand their global footprints. Simultaneously, R & D funding programs initiated by the governments to enhance regenerative medicine capabilities are offering high growth potential. This is further going to attract several new entrants to the market and intensify the market competition further.
Regenerative Medicine Market Major Players:
Players active in the global regenerative medicine market include Osiris Therapeutics, Cook Biotech, Organogenesis, Baxter International, Inc., Stryker and RTI surgical, LifeSciences, CryoLife, Advanced Cell Technology, Sanofi, BioMimetic Therapeutics, Medtronic, StemCellsInc, and LifeCell Kinetic Concepts, among others.
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Regenerative Medicine Industry/Innovations/Related News:
March 15, 2020 - Research team at the University of Sheffield published their study on stem cell mutations that could improve regenerative medicine in the magazine Stem Cell Reports.' Their study gives new insights into the cause of mutations in pluripotent stem cells and potential ways of stopping these mutations from occurring. It also suggests ways to reduce the likelihood of variations occurring in these cells when cultured.There is considerable interest in using Pluripotent stem cells to produce cells that can replace diseased or damaged tissues in applications referred to as regenerative medicine.
Pharmaceutical Industry Related Reports
Global Anti-viral drugs Market Information, by application (hepatitis, HIV/AIDS, herpes, influenza and others) and by mechanism of action (nucleotide polymerase inhibitors, reverse transcriptase inhibitors, protease inhibitors and others) - Forecast to 2022: https://www.marketresearchfuture.com/reports/anti-viral-drugs-market-2454
Drug allergy market information: by type (immunologic, nonimmunologic, and others), diagnosis (skin tests, blood tests, and others), by treatment (antihistamines, corticosteroids, and others), by end user- global forecast till 2023: https://www.marketresearchfuture.com/reports/drug-allergy-market-4033
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MRFR team have supreme objective to provide the optimum quality market research and intelligence services to our clients. Our market research studies by Components, Application, Logistics and market players for global, regional, and country level market segments, enable our clients to see more, know more, and do more, which help to answer all their most important questions.
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Buckeye butterflies get their color from their scales – Massive Science
By daniellenierenberg
Last week, Christian Cooper was birdwatching in Central Park. Upon rightfully asking a woman to leash her dog in a protected area, a verbal altercation ensued and the woman called the police on Cooper, highlighting how dangerous the outdoors can be for Black birdwatchers.
Sadly, Christian Coopers experience is not an uncommon one. This tale resonated deeply with Black birdwatchers and nature enthusiasts, prompting the BlackAFInSTEM group (founded by Jason Ward) to launch #BlackBirdersWeek.
Starting from May 31, the #BlackBirdersWeek aims to celebrate Black nature enthusiasts and amplify their voices through various photo challenges (#PostABird, #BlackWomenWhoBird) and livestream chats. The co-founders of this week-long initiative include Anna Gifty Opoku-Agyeman, Danielle Belleny, Sheridan Alford, Tykee James, Joseph Saunders and Chelsea Connor.
It is upsetting to see that it is still so unsafe for a lot of Black people to go outside, and to do what they love doing outside, says Connor, who is a herpetologist, artist and science communicator. A lot of us in the [BlackAFInSTEM] group are nature biologists. We have to go outside for work to do fieldwork, collect our data and look at the animals we study out there.
Connors research focuses on the differences in diet between native and invasive anole species found in Dominica. Anoles are a family of small to large lizards, where males often have a dewlap (a brightly colored flap of skin that extends from their throat).
We wanted to highlight Black birders, amplify their voices, and make sure that people can see us. We want Black birders to be visible. We want people to know were out here. We bird as well. Its not just for one race. It is important that we feel safe in the environment that we work in, says Connor.
The BlackAFInSTEM group joined Twitter this past weekend, and has already amassed over 5,000 followers. At the time of writing this, #BlackBirdersWeek has kicked off with their first photo challenge: asking individuals to share their photos out in nature using #BlackInNature.
The response has been amazing I dont even know how to describe it [] Its just amazing to see the support were getting, and how our colleagues are amplifying our voices, says Connor. It is so vital that people hear our side of the story that people hear what it is like just being Black, existing and doing some of the things that we love.
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Buckeye butterflies get their color from their scales - Massive Science
Study reveals birth defects caused by flame retardant – University of Georgia
By daniellenierenberg
Research focuses on mans exposure prior to conception
A new study from the University of Georgia has shown that exposure to a now-banned flame retardant can alter the genetic code in sperm, leading to major health defects in children of exposed parents.
Published recently in Scientific Reports, the study is the first to investigate how polybrominated biphenyl-153 (PBB153), the primary chemical component of the flame retardant FireMaster, impacts paternal reproduction.
In 1973, an estimated 6.5 million Michigan residents were exposed to PBB153 when FireMaster was accidentally sent to state grain mills where it made its way into the food supply. In the decades since, a range of health problems including skin discoloration, headache, dizziness, joint pain and even some cancers have been linked to the exposure.
More striking, the children of those who were exposed seemed to experience a host of health issues as well, including reports of hernia or buildup in the scrotum for newborn sons and a higher chance of stillbirth or miscarriage among adult daughters.
Yet, little work has been done to understand how the chemical exposure could have impacted genes passed from an exposed father, said study author Katherine Greeson.
It is still a relatively new idea that a mans exposures prior to conception can impact the health of his children, said Greeson, an environmental health science doctoral student in Charles Easleys lab at UGAs College of Public Health and Regenerative Bioscience Center.
Most studies where a toxic effect is observed in children look only to the mothers and the same has been true of studies conducted on PBB153, she said.
Greeson and a team of researchers from UGA and Emory University used a unique combination of observational and laboratory approaches to demonstrate how PBB153 acted on sperm cells.
Typically, scientific studies are either epidemiological in nature and inherently observational or focus on bench science, but in this study, we did both, said Greeson.
This approach allowed the researchers to mimic the known blood exposure levels of PBB153 in a lab environment.
We were uniquely able to recreate this effect using our previously characterized human stem cell model for spermatogenesis, she said, which allowed us to study the mechanism that causes this effect in humans.
The team looked at the expression of different genes in their human spermatogenesis model after dosing with PBB153 and found marked alterations in gene expression between dosed and undosed cells, specifically at genes important to development, such as embryonic organ, limb, muscle, and nervous system development.
PBB153 causes changes to the DNA in sperm in a way that changes how the genes are turned on and off, said Greeson. PBB153 seems to turn on these genes in sperm which should be turned off, said Greeson, which may explain some of the endocrine-related health issues observed in the children of exposed parents.
Though the study used this model to directly replicate exposure to PBB153, Greeson says this approach could be used to better understand the impact of other environmental exposures on reproduction, including large-scale accidental exposures to toxic chemicals or everyday exposures.
Hopefully this work will lead to more studies combining epidemiology and bench science in the future, which will tell us more about why were seeing an effect from an environmental exposure in human populations and encourage experimental studies to more closely mimic human exposures, she said.
The study, Detrimental Effects of Flame Retardant, PBB153, Exposure on Sperm and Future Generations, published May 22. It is available online.
Excerpt from:
Study reveals birth defects caused by flame retardant - University of Georgia
The 15 Best New Products to Try in Isolation This Month – InStyle
By daniellenierenberg
My summer countdown usually starts on the first day of fall. However, with social distancing still in place and travel completely off the cards for the foreseeable future, it's tough to get excited about what's arguably the best time of year.
Throughout quarantine, beauty products have given me a little bit of comfort and madethe stressand challenges of our current reality seem more manageable.
But even though everyone'sdaily routines have changed and the beauty industry has been greatly impacted by COVID-19, brands haven't stopped launching new products.
RELATED:Shopping for Makeup Post COVID-19 Lockdown Will Never Be the Same
This month's just-launched and soon-to-launch makeup, skincare, and haircare products include a number of treatments that are perfect for taking a time out and indulging in a little TLC in isolation. Briogeo's repairing hair mask, HoliFrog's glow-boosting cleanser, and Gucci Westman'svelvety eyeshadows are just a few examples.
Ahead, 15 new beauty products to give yourself some extra self-care while stuck at home.
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The 15 Best New Products to Try in Isolation This Month - InStyle
Genetic features pave way for targeted BPDCN therapies – Dermatology Times
By daniellenierenberg
Researchers are learning more about genetic aberrations common in the rare but clinically aggressive hematological cancer blastic plasmacytoid dendritic cell neoplasm. There is one targeted therapy approved by the U.S. Food and Drug Administration: Elzonris (tagraxofusp-erzs, Stemline). However, more treatment options are needed to improve the cancers clinical outcome, according to a review published May 2020 in Critical Reviews Oncology/Hematology.1
Dermatologists might be the first providers to encounter patients with blastic plasmacytoid dendritic cell neoplasm because more than 70% of these patients have cutaneous lesions. Those lesions often are asymptomatic and vary in size. The skin lesions tend to have nodules, plaques or bruise-like areas, a brown to violet color and might be solitary or multifocal, according to the authors.
Blastic plasmacytoid dendritic cell neoplasm often originates from type 2 myeloid-derived resting plasmacytoid dendritic cell precursors. Recent research suggests providers can diagnose the cancer when patients express at least four of five plasmacytoid dendritic cell specific markers, CD4, CD56, CD123, TCL1 and BDCA-2, without expressing myeloid, T-cell or B-cell lineage markers.
Commonly, [blastic plasmacytoid dendritic cell neoplasm] is characterized by high CD123 expression, aberrant NF-B [nuclear factor-B] activation, dependence on TCF4-/BRD4-network, and deregulated cholesterol metabolism, they wrote.
Despite advancing knowledge about the cancer type, patients median overall survival remains at 12 to 14 months, according to the paper. Conventional treatment approaches include chemotherapy, radiotherapy and ultimately hematopoietic stem cell transplantation. The challenges with conventional therapies are while blastic plasmacytoid dendritic cell neoplasm is sensitive to some chemotherapy regimens, patient relapse is high at more than 60%. And many patients with blastic plasmacytoid dendritic cell neoplasm are too old or frail to have intensive chemotherapy or hematopoietic stem cell transplantation, according to the authors.
Recently, the most attractive agent for [blastic plasmacytoid dendritic cell neoplasm] is tagraxofusp, which is composed of the catalytic and translocation domains of diphtheria toxin (DT) fused to interleukin-3 (IL-3), the authors wrote.
Blastic plasmacytoid dendritic cell neoplasm cells overexpress interleukin-3 receptor subunit alpha (IL3RA, also called CD123). Elzonris, or tagraxofusp-erzs, is a CD123-directed cytotoxin given intravenously, which is used to treat blastic plasmacytoid dendritic cell neoplasm in adults and in pediatric patients 2 years and older.
Researchers reported in a study of 47 blastic plasmacytoid dendritic cell neoplasm patients published in 2019 in the New England Journal of Medicine that tagraxofusp led to clinical responses in untreated and relapsed patients.2 The overall response rate with tagraxofusp was 90% and the primary outcome of complete response and clinical complete response was 72% among the previously untreated patients. Overall response was 67% in the previously treated patients. Serious adverse events including capillary leak syndrome, hepatic dysfunction and thrombocytopenia were common, according to the NEJM paper.
More targeted therapies are needed to treat blastic plasmacytoid dendritic cell neoplasm, but many potential therapeutic agents are not advancing to clinical trials, according to authors of the paper in Critical Reviews Oncology/Hematology.
Common blastic plasmacytoid dendritic cell neoplasm characteristics are genetically heterogeneous and provide valuable drug targets, according to the authors.
Apart from aberrant activation of NF-B signaling pathway, which is highly dependent on TCF4- and BRD4- transcriptional networks, cholesterol metabolism deregulation and CD123 expression, defects of DNA damage repair and mitosis are new, potential common features of the cancer. Corresponding therapies might be promising, the authors wrote.
Venetoclax, anti-CD123 CAR-T, XmAb14045 and IMGN632 are in clinical trials for blastic plasmacytoid dendritic cell neoplasm. But the authors noted that bortezomib, lenalidomide, 5-aza and pralatrexate could easily be pushed to the front line of the cancers treatment.
Disclosures:
The authors report no relevant disclosures.
References:
1. Zhang X, Sun J, Yang M, Wang L, Jin J. New perspectives in genetics and targeted therapy for blastic plasmacytoid dendritic cell neoplasm. Crit Rev Oncol Hematol. 2020 May;149:102928.2. Pemmaraju N, Lane AA, Sweet KL, et al. Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm. N Engl J Med. 2019;380(17):1628-1637.
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Genetic features pave way for targeted BPDCN therapies - Dermatology Times
Ageing: An expos on what really causes us to show our age – The South African
By daniellenierenberg
Most people are seeking the secret to anti-ageing, but did you ever wonder how the skin actually ages or how you could slow the process down?
Ageing is a natural process accompanied by a continuous alteration of the body. Your body produces visible changes in its structure, function and vulnerability to environmental stress and disease. Genetics, as well as the lifestyle we lead, play a big role in the ageing process.
Your skin is an organ, and its function is to regulate the excretion of metabolic waste products, regulate the bodies temperature as well as containing receptors for pain, tactile sensation, and pressure. Therefore, the health and appearance of your skin, like the health of your other organs correspond with your lifestyle and dietary habits, as well as with age-related factors such as the imbalance of hormones.
Ageing of the skin can be influenced by many factors including ultraviolet radiation, excess alcohol consumption, tobacco abuse, and environmental pollution.
What a lot of people dont realise is that as their body weight increases and their blood sugar levels rise, biochemical reactions interrupt the structural framework of their skin. With all these factors combined they lead to cumulative deterioration in the appearance of the skin as well as the function of the skin.
Within the skin ageing is associated with a loss of fibrous tissue, a slower rate of cellular renewal, and a reduced vascular and glandular network. The barrier function that maintains cellular hydration also becomes impaired. The subcutaneous tissue (known as the hypodermis or the third layer of the skin) flattens.
The rate at which these functions decline can be more than 50% by middle age depending upon ones genetic makeup, lifestyle and normal physiological functions within the skin. If we dont take action to support our skins intrinsic defence systems, the youthful qualities of our skin will deteriorate rapidly. Luckily for us, we can harness insights gathered through the latest scientific innovations and slow or potentially reverse the signs and symptoms of accelerated skin ageing.
Intrinsic skin ageing is primarily determined by genetic factors, hormonal imbalances and metabolic reactions like oxidative stress. Signs of intrinsic ageing include skin sagging, thinning and cracking, and the appearance of fine lines and wrinkles.
There are numerous external factors that affect the skin and cause signs and symptoms of premature ageing. Generally, most premature ageing is caused by over-exposure to the suns UV rays. However, there are other contributing factors, for example, atmospheric factors such as air pollution, visible light and infrared radiation. Lifestyle choices such as smoking, chronic stress and excessive alcohol consumption can lead to older-looking skin.
The most common signs of extrinsic ageing are thinning of the skin, laxity, fragility and the increased appearance of wrinkles.
As the skin is a visual organ, the beauty industrys main objective is to improve the appearance of skin with extensive topical treatments and products. However, often overlooked is the need to support the health and beauty of the skin from within.
Ideally one should centre their diet upon fruits, vegetables, whole grains, legumes, monounsaturated fats (like those found in olive oil), and a healthy ratio of omega-3 to omega-6 polyunsaturated fatty acids. Generally, consumption of shellfish, fish rich in omega 3 fatty acids, regular tea drinking, and greater consumption of fruits and vegetables have been known to be associated with improved skin health.
Gut health is crucial to healthy skin. The human skin hosts a variety of microorganisms, collectively known as the skin microbiota. Within the skin, there is a complex network of interactions between the microbes and cells. Friendly bacteria, such as Lactobacillus and Bifidobacteria are well researched for effectively treating infections, promoting healthy immunity, and reducing inflammation in the skin. Oral pre- and probiotics help to rebalance the skin microbiota and optimise the skin barrier function.
In addition, oral probiotics boost cellular antioxidant capacity and combat inflammation in general. Probiotics also help to neutralise toxic byproducts, defend the lining of the intestine, increase the bioavailability of some nutrients and reinforce the intestinal barrier against infectious microbes that may harm healthy skin.
Cosmeceuticals are topical products that exert both cosmetic and therapeutic benefits which have continued to evolve in order to ward off the signs of skin ageing. Some of the most popular topicals include exfoliating and depigmenting agents, antioxidants and regenerating products, such as peptides and stem cells.
Sunscreens (with dual protection against UVA and UVB in a photostable complex) are the most important topical as they protect us from the UV damage caused by the sun. Sun exposure is definitely one of the biggest contributing factors to premature ageing and is actually known as photo-ageing.
Another phenomenal topical is retinoids which have proven their safety and efficacy in reducing photo-damaged skin and are a popular treatment for anti-ageing. Retinoids help combat and reverse the visual effects of ageing, such as wrinkles, laxity, and discolouration. Retinoids accelerate cell turnover and can also improve blemishes and the appearance of pores.
The use of alpha-hydroxy acids (AHAs) has also been known to improve skin texture and reduce the signs of ageing by promoting the shedding of our superficial dead skin cells which in turn helps to restore hydration and a smoother texture. Whats nice about alpha-hydroxy acids is that they can pretty much treat any skin condition or concern because there are so many different types of acids. Theres literally something for everything. The most common ingredients used in product formulations and peels include citric acid, glycolic acid, lactic acid, malic acid, pyruvic acid as well as tartaric acid.
Antioxidants are being increasingly used in anti-ageing skincare. Topical antioxidants are effective in fending off damaging free radicals and reducing inflammation within the skin. A few popular ones used are ascorbic acid (vitamin C,) tocopherols (vitamin E,) alpha-lipoic acid and coenzyme Q10. Emerging natural antioxidants proving effective include EGCG (from green tea), resveratrol, Centella Asiatica (Gotu Kola,) proanthocyanidins (grapeseed,) curcumin, pomegranate, silymarin/silibinin (milk thistle), coffeeberry, melatonin, and marine-based ingredients.
Within the skin, the deterioration of collagen results in the formation of protein fragments, called peptides. These peptides are then recognised by collagen-producing cells, which respond by increasing collagen production in order to repair the damaged skin. However, as we age this positive feedback between skin breakdown and the initiation of new collagen formation becomes inefficient. Therefore by applying specialised peptides to your skin topically you can effectively trick collagen-producing cells into boosting collagen production. There are many other active ingredients used in topical products that are focused on anti-ageing among other things.
So basically all we need to do is protect the skin from the inside by consuming nutrient-packed foods as well as reducing our exposure to extrinsic factors that cause premature ageing along with using topical skincare products. Not as difficult as we may have thought, hey?
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Stem cell therapy: a potential approach for treatment of influenza virus and coronavirus-induced acute lung injury – BMC Blogs Network
By daniellenierenberg
Acute lung injury (ALI) is a devastating disease process involving pulmonary edema and atelectasis caused by capillary membrane injury [1]. The main clinical manifestation is the acute onset of hypoxic respiratory failure, which can subsequently trigger a cascade of serious complications and even death [2]. Thus, ALI causes a considerable financial burden for health care systems throughout the world. ALI can result from various causes, including multiple traumas, large-volume blood transfusions, and bacterial and viral infections [2, 3]. A variety of viruses, including influenza virus, coronavirus (CoV), adenovirus, cytomegalovirus (CMV), and respiratory syncytial virus (RSV), are associated with ALI [4]. Importantly, most viruses, whose hosts are various animal species, can cause severe and rapidly spreading human infections. In the early 2000s, several outbreaks of influenza virus and CoV emerged, causing human respiratory and intestinal diseases worldwide, including the more recent SARS-CoV-2 infection [5,6,7]. To date, SARS-CoV-2 has affected more than 80,000 people, causing nearly 3300 deaths in China and more than 1,800,000 people, causing nearly 110,000 deaths all over the world (http://2019ncov.chinacdc.cn/2019-nCoV/).
Infectious respiratory diseases caused by different viruses are associated with similar respiratory symptoms ranging from the common cold to severe acute respiratory syndrome [8]. This makes the clinical distinction between different agents involved in infection very difficult [8, 9]. Currently, the clinical experience mainly includes antibacterial and antiviral drug treatment derived from handling several outbreaks of influenza virus and human CoVs. Numerous agents have been identified to inhibit the entry and/or replication of these viruses in cell culture or animal models [10]. Although these antiviral drugs can effectively prevent and eliminate the virus, the full recovery from pneumonia and ALI depends on the resistance of the patient. Recently, stem cell-based therapy has become a potential approved tool for the treatment of virus-induced lung injury [11,12,13]. Here, we will give a brief overview of influenza virus and CoVs and then present the cell-based therapeutic options for lung injury caused by different kinds of viruses.
Influenza virus and human CoV are the two most threatening viruses for infectious lung injury [14]. These pathogens can be transmitted through direct or indirect physical contact, droplets, or aerosols, with increasing evidence suggesting that airborne transmission, including via droplets or aerosols, enhances the efficiency of viral transmission among humans and causes uncontrolled infectious disease [15]. Throughout human history, outbreaks and occasional pandemics caused by influenza virus and CoV have led to approximately hundreds of millions of deaths worldwide [16].
Influenza virus is a well-known human pathogen that has a negative-sense RNA genome [17]. According to its distinct antigenic properties, the influenza virus can be divided into 4 subtypes, types A, B, C, and D. Influenza A virus (IAV) lineages in animal populations cause economically important respiratory disease. Little is known about the other human influenza virus types B, C, and D [18]. Further subtypes are characterized by the genetic and antigenic properties of the hemagglutinin (HA) and neuraminidase (NA) glycoproteins [19]. Sporadic and seasonal infections in swine with avian influenza viruses of various subtypes have been reported. The most recent human pandemic virusesH1N1 from swine and H5N1 from aviancause severe respiratory tract disease and lung injury in humans [20, 21].
CoVs, a large family of single-stranded RNA viruses, typically affect the respiratory tract of mammals, including humans. CoVs are further divided into four genera: alpha-, beta-, gamma-, and delta-CoVs. Alpha- and beta-CoVs can infect mammals, and gamma- and delta-CoVs tend to infect birds, but some of these viruses can also be transmitted to mammals [22]. Human CoVs were considered relatively harmless respiratory pathogens in the past. Infections with the human CoV strains 229E, OC43, NL63, and HKU1 usually result in mild respiratory illness, such as the common cold [23]. In contrast, the CoV responsible for the 2002 severe acute respiratory syndrome (SARS-CoV), the 2012 Middle East respiratory syndrome CoV (MERS-CoV), and, more recently, the SARS-CoV-2 have received global attention owing to their genetic variation and rapid spread in human populations [5,6,7].
Usually, the influenza virus can enter the columnar epithelial cells of the respiratory tract, such as the trachea, bronchi, and bronchioles. Subsequently, the influenza virus begins to replicate for an asymptomatic period of time and then migrate to the lung tissue to cause acute lung and respiratory injury [24]. Similar to those with influenza virus infection, patients with SARS, MERS, or SARS-CoV-2 present with various clinical features, ranging from asymptomatic or mild respiratory illness to severe ALI, even with multiple organ failure [5,6,7]. The pathogenesis of ALI caused by influenza virus and human CoV is often associated with rapid viral replication, marked inflammatory cell infiltration, and elevated proinflammatory cytokine/chemokine responses [25]. Interestingly, in IAV- and human CoV-infected individuals, the pulmonary pathology always involves diffuse alveolar damage, but viral RNA is present in only a subset of patients [26]. Some studies suggest that an overly exaggerated immune response, rather than uncontrolled viral spread, is the primary cause in fatal cases caused by virus infection [27]. Several immune cell types have been found to contribute to damaging host responses, providing novel approaches for therapeutic intervention [28].
IAV infection, the most common cause of viral pneumonia, causes substantial seasonal and pandemic morbidity and mortality [29]. Currently, antiviral drugs are the primary treatment strategy for influenza-induced pneumonia. However, antiviral drugs cannot repair damaged lung cells. Here, we summarize the present studies of stem cell therapy for influenza virus-induced lung injury.
Mesenchymal stem/stromal cells (MSCs) constitute a heterogeneous subset of stromal regenerative cells that can be harvested from several adult tissue types, including bone marrow, umbilical cord, adipose, and endometrium [30]. They retain the expression of the markers CD29, CD73, CD90, and CD105 and have a rapid proliferation rate, low immunogenicity, and low tumorigenicity [30]. MSCs also have self-renewal and multidifferentiation capabilities and exert immunomodulatory and tissue repair effects by secreting trophic factors, cytokines, and chemokines [31]. Due to these beneficial biological properties, MSCs and their derivatives are attractive as cellular therapies for various inflammatory diseases, including virus-induced lung injury.
Several studies on IAV-infected animal models have shown the beneficial effects of the administration of different tissue-derived MSCs [32,33,34,35]. H5N1 virus infection reduces alveolar fluid clearance (AFC) and enhances alveolar protein permeability (APP) in human alveolar epithelial cells, which can be inhibited by coculture with human bone marrow-derived MSCs (BMSCs) [32]. Mechanistically, this process can be mediated by human BMSC secreted angiopoietin-1 (Ang1) and keratinocyte growth factor (KGF) [32]. Moreover, in vivo experiments have shown that human BMSCs have a significant anti-inflammatory effect by increasing the number of M2 macrophages and releasing various cytokines and chemokines, such as interleukin (IL)-1, IL-4, IL-6, IL-8, and IL-17 [32]. Similar anti-inflammatory effects have been achieved in another virus-induced lung injury model. The intravenous injection of mouse BMSCs into H9N2 virus-infected mice significantly attenuates H9N2 virus-induced pulmonary inflammation by reducing chemokine (GM-CSF, MCP-1, KC, MIP-1, and MIG) and proinflammatory cytokine (IL-1, IL-6, TNF-, and IFN-) levels, as well as reducing inflammatory cell recruitment into the lungs [33]. Another study on human BMSCs cocultured with CD8+ T cells showed that MSCs inhibit the proliferation of virus-specific CD8+ T cells and the release of IFN- by specific CD8+ T cells [36].
In addition, human umbilical cord-derived MSCs (UC-MSCs) were found to have a similar effect as BMSCs on AFC, APP, and inflammation by secreting growth factors, including Ang1 and hepatocyte growth factor (HGF), in an in vitro lung injury model induced by H5N1 virus [34]. UC-MSCs also promote lung injury mouse survival, increase the body weight, and decreased the APP levels and inflammation in vivo [34]. Unlike Ang1, KGF, and HGF mentioned above, basic fibroblast growth factor 2 (FGF2) plays an important role in lung injury therapy via immunoregulation. The administration of the recombinant FGF2 protein improves H1N1-induced mouse lung injury and promotes the survival of infected mice by recruiting and activating neutrophils via the FGFR2-PI3K-AKT-NFB signaling pathway [37]. FGF2-overexpressing MSCs have an enhanced therapeutic effect on lipopolysaccharide-induced ALI, as assessed by the proinflammatory factor level, neutrophil quantity, and histopathological index of the lung [38].
MSCs secrete various soluble factors and extracellular vesicles (EVs), which carry lipids, proteins, DNA, mRNA, microRNAs, small RNAs, and organelles. These biologically active components can be transferred to recipient cells to exert anti-inflammatory, antiapoptotic, and tissue regeneration functions [39]. EVs isolated from conditioned medium of pig BMSCs have been demonstrated to have anti-apoptosis, anti-inflammation, and antiviral replication functions in H1N1-affected lung epithelial cells and alleviate H1N1-induced lung injury in pigs [35]. Moreover, the preincubation of EVs with RNase abrogates their anti-influenza activity, suggesting that the anti-influenza activity of EVs is due to the transfer of RNAs from EVs to epithelial cells [35]. Exosomes are a subset of EVs that are 50200nm in diameter and positive for CD63 and CD81 [40]. Exosomes isolated from the conditioned medium of UC-MSCs restore the impaired AFC and decreased APP in alveolar epithelial cells affected by H5N1 virus [34]. In addition, the ability of UC-MSCs to increase AFC is superior to that of exosomes, which indicates that other components secreted by UC-MSCs have synergistic effects with exosomes [34].
Despite accumulating evidence demonstrating the therapeutic effects of MSC administration in various preclinical models of lung injury, some studies have shown contrasting results. Darwish and colleagues proved that neither the prophylactic nor therapeutic administration of murine or human BMSCs could decrease pulmonary inflammation or prevent the progression of ALI in H1N1 virus-infected mice [41]. In addition, combining MSC administration with the antiviral agent oseltamivir was also found to be ineffective [41]. Similar negative results were obtained in another preclinical study. Murine or human BMSCs were administered intravenously to H1N1-induced ARDS mice [42]. Although murine BMSCs prevented influenza-induced thrombocytosis and caused a modest reduction in lung viral load, murine or human BMSCs failed to improve influenza-mediated lung injury as assessed by weight loss, the lung water content, and bronchoalveolar lavage inflammation and histology, which is consistent with Darwishs findings [42]. However, the mild reduction in viral load observed in response to murine BMSC treatment suggests that, on balance, MSCs are mildly immunostimulatory in this model [42]. Although there are some controversial incidents in preclinical research, the transplant of menstrual-blood-derived MSCs into patients with H7N9-induced ARDS was conducted at a single center through an open-label clinical trial (http://www.chictr.org.cn/). MSC transplantation significantly lowered the mortality and did not result in harmful effects in the bodies of the patients [43]. This clinic study suggests that MSCs significantly improve the survival rate of influenza virus-induced lung injury.
The effects of exogenous MSCs are exerted through their isolation and injection into test animals. There are also some stem/progenitor cells that can be activated to proliferate when various tissues are injured. Basal cells (BCs), distributed throughout the pseudostratified epithelium from the trachea to the bronchioles, are a class of multipotent tissue-specific stem cells from various organs, including the skin, esophagus, and olfactory and airway epithelia [44, 45]. Previously, TPR63+/KRT5+ BCs were shown to self-renew and divide into club cells and ciliated cells to maintain the pseudostratified epithelium of proximal airways [46]. Several studies have shown that TPR63+/KRT5+ BCs play a key role in lung repair and regeneration after influenza virus infection. When animals typically recover from H1N1 influenza infection, TPR63+/KRT5+ BCs accumulate robustly in the lung parenchyma and initiate an injury repair process to maintain normal lung function by differentiating into mature epithelium [47]. Lineage-negative epithelial stem/progenitor (LNEP) cells, present in the normal distal lung, can activate a TPR63+/KRT5+ remodeling program through Notch signaling after H1N1 influenza infection [48]. Moreover, a population of SOX2+/SCGB1A/KRT5 progenitor cells can generate nascent KRT5+ cells as an early response to airway injury upon H1N1 influenza virus infection [49]. In addition, a rare p63+Krt5 progenitor cell population also responds to H1N1 virus-induced severe injury [50]. This evidence suggests that these endogenous lung stem/progenitor cells (LSCs) play a critical role in the repopulation of damaged lung tissue following severe influenza virus infection (Table2).
Taken together, the present in vitro (Table1) and in vivo (Table2) results show that MSCs and LSCs are potential cell sources to treat influenza virus-induced lung injury.
Lung injury caused by SARS, MERS, or SARS-CoV-2 poses major clinical management challenges because there is no specific treatment that has been proven to be effective for each infection. Currently, virus- and host-based therapies are the main methods of treatment for spreading CoV infections. Virus- and host-based therapies include monoclonal antibodies and antiviral drugs that target the key proteins and pathways that mediate viral entry and replication [51].The major challenges in the clinical development of novel drugs include a limited number of suitable animal models for SARS-CoV, MERS-CoV, and SARS-CoV-2 infections and the current absence of new SARS and MERS cases [51]. Although the number of cases of SARS-CoV-2-induced pneumonia patients is continuously increasing, antibiotic and antiviral drugs are the primary methods to treat SARS-CoV-2-infected patients. Similar to that of IAV, human CoV-mediated damage to the respiratory epithelium results from both intrinsic viral pathogenicity and a robust host immune response. The excessive immune response contributes to viral clearance and can also worsen the severity of lung injury, including the demise of lung cells [52]. However, the present treatment approaches have a limited effect on lung inflammation and regeneration.
Stem cell therapy for influenza virus-induced lung injury shows promise in preclinical models. Although it is difficult to establish preclinical models of CoV-induced lung injury, we consider stem cell therapies to be effective approaches to improve human CoV-induced lung injury. Acute inflammatory responses are one of the major underlying mechanisms for virus-induced lung injury. Innate immune cells, including neutrophils and inflammatory monocytes-macrophages (IMMs), are major innate leukocyte subsets that protect against viral lung infections [53]. Both neutrophils and IMMs are rapidly recruited to the site of infection and play crucial roles in the host defense against viruses. Neutrophils and IMMs can activate Toll-like receptors (TLRs) and produce interferons (IFNs) and other cytokines/chemokines [54]. There are two functional effects produced by the recruitment of neutrophils and IMMs: the orchestration of effective adaptive T cell responses and the secretion of inflammatory cytokines/chemokines [55]. However, excessive inflammatory cytokine and chemokine secretion impairs antiviral T cell responses, leading to ineffective viral clearance and reduced survival [56].
MSCs are known to suppress both innate and adaptive immune responses. MSCs have been suggested to inhibit many kinds of immune cells, including T cells, B cells, dendritic cells (DCs), and natural killer (NK) cells in vitro and in vivo [57] (Fig.1). Several molecules, including IL-1, TNF-, and INF-, most of which are produced by inflammatory cells, are reported to be involved in MSC-mediated immunosuppression [58]. Furthermore, MSCs can produce numerous immunosuppressive molecules, such as IL-6, PGE2, IDO, and IL-10, in response to inflammatory stimuli. PGE2 has been reported to mediate the MSC-mediated suppression of T cells, NK cells, and macrophages. Moreover, PGE2 has been found to act with IDO to alter the proliferation of T cells and NK cells [59]. In contrast, MSCs have come to be recognized as one type of adult stem cell actively participating in tissue repair by closely interacting with inflammatory cells and various other cell types [60]. Numerous reports have demonstrated that MSCs can release an array of growth and inhibitory factors, such as EGF, FGF, PDGF, and VEGF, and express several leukocyte chemokines, such as CXCL9, CCL2, CXCL10, and CXCL11. These factors provide an important microenvironment to activate adaptive immunity for lung repair [61]. Thus, the dual functions of MSCs may improve lung recovery after human CoV-induced ALI. Recently, MSCs was transplanted intravenously to enrolled patients with COVID-19 pneumonia. After treatment, the pulmonary function and symptoms of these patients were significantly improved. Meanwhile, the peripheral lymphocytes were increased, the C-reactive protein decreased, the level of TNF- was significantly decreased, and the overactivated cytokine-secreting immune cells disappeared. In addition, a group of regulatory DC cell population dramatically increased. Thus, the intravenous transplantation of MSCs was effective for treatment in patients with COVID-19 pneumonia [62, 63].
Stem cell therapies for treatment of influenza virus and coronavirus-induced lung injury. CoVs, coronavirus; MSCs, mesenchymal stem/stromal cells; LSCs, lung stem/progenitor cells; NK cells, natural killer cells; DC cells, dendritic cells
In addition, endogenous LSCs also play an important role in lung cell reconstitution after virus-induced ALI. In particular, TPR63+/KRT5+ airway BCs comprise approximately equal numbers of stem cells and committed precursors and give rise to differentiated luminal cells during steady state and epithelial repair after lung injury [44, 64]. Research has shown that KRT5+ cells repopulate damaged alveolar parenchyma following influenza virus infection [47]. However, there is still little evidence for the role of altered TPR63+/KRT5+ stem cells during lung injury repair caused by human CoVs.
In summary, exogenous MSCs may modulate human CoV-induced lung injury repair and regeneration through their immunoregulatory properties. These cells are capable of interacting with various types of immune cell, including neutrophils, macrophages, T cells, B cells, NK cells, and DCs. Furthermore, viral infections can activate endogenous LSCs to produce new lung cells and maintain lung function (Fig.1). Thus, we propose that MSCs and LSCs are two potential cell sources for treating human CoV-induced lung injury.
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Stem cell therapy: a potential approach for treatment of influenza virus and coronavirus-induced acute lung injury - BMC Blogs Network
AUGUSTMAN Grooming Awards 2020 Part IV: Best Head-To-Toe Treatment Services For Gentlemen – AUGUSTMAN
By daniellenierenberg
Introducing the best in mens grooming for the year. The fourth and final segment in this series is a compilation of trusted head-to-toe treatment services every gentleman should indulge in to look and feel your best.Sometimes its better to leave things to an experts hands.
Treatment: CO2 Skin Renewal Facial Treatment, Porcelain
This treatment helps to deal with adult skin issues ranging from acne to ageing. To address the latter, a combination of a C02 mask and cryoprobes work to promote collagen production, boost blood circulation and tighten sagging skin. A hydrating enzyme mask then restores moisture and dissolves acne-causing grime and debris. Theres nothing to complain about when we left the compound with improved skin.Available at Porcelain for $298.50
Treatment: The Ultimate Shave Experience, Truefitt + Hill
We found out why people say its better to leave things to the experts. At this salon, the barber put us through an aromatic hot towel treatment to both soften our facial hair and help us relax. Swift and gentle strokes of the straight razor gave us a close shave, leaving our skin baby smooth and looking dapper fresh. We also appreciate the massage, which made us forget our worries and feel good to be alive.Available at Truefitt + Hill for $80
Treatment: Miracle Stem Cell Treatment, PHS Hairscience
This may not be as effective as a hair transplant, but it is a much less painful alternative to revive dormant hair follicles. The treatment uses the brands potent Miracle Stem Cell Solution, which contains a blend of growth factors, botanical stem cells and nutrients that nourish the scalp and encourage hair growth. DHT blockers neutralise the effects of androgen, the hormonal culprit behind hair loss.Available at PHS Hairscience for $297
Treatment: Rescue & Release Massage, Raffles Spa
Whether you pick the 60- or 90- minute option, this massage provides soothing relief from the tensions that city life inflicts. Swedish techniques were used to loosen tight knots, and this release of built-up tension left us feeling calmer and more in touch with our senses. The luxurious oils used in the treatment also left our skin feeling moisturised and nourished. Make time to use the baths to reap fuller relaxation benefits.Available at Raffles Hotel from $245
Minoxidil Market will witness over 100 million units demand by 2024 – Cole of Duty
By daniellenierenberg
According to the latest research report by Global Market Insights, Inc., minoxidil market size is projected to surpass US$ 1 billion by 2024.
Frontrunners in the Minoxidil industry:
Nanz Med Science Pharma Private Limited, Bakul Group of companies, Kumar Organic Products Limited, Changzhou Tianhua Pharmaceutical Co. Ltd., Par Pharmaceuticals, Provizer Pharma, Metapharmaceutical Ind. S.L., Pharhome International Limited, LOY Pharma Lab, Inc., Maruti Futuristic Pharma Pvt. Ltd., Dr. R. Pfleger Chemical Factory GmbH, Renata Limited, McNeil Consumer Healthcare
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https://www.gminsights.com/request-sample/detail/750
2% product segment is likely to provide a positive impetus to the industry forecast as it is believed to bolster effectiveness and enhance quality of hair growth. Apparently, 2% formulation triggers the hair growth via dermal papilla and epithelial cells. Given it seemingly has minimal side effects to the skin, the product is said to be apt for patients with sensitive skin.
2% solution tends to reduce baldness at the receding hairline and at the front as the product offsets hair thinning and boosts hair growth. Prominently, soaring adoption of topical supplementation to improve hair density is expected to spur demand for 2% solution.
5% product is also expected to impel minoxidil market size as demand for high dosage medicines with minimal side effects continues to rise unabated. 5% solution is said to be highly efficacious in hair growth, thereby spurring growth of adipose-derived stem cells (ASCs) and reducing hair thinning. Stakeholders are increasingly being involved in product development to negate irritation and burning sensation.
According to the American Hair Loss Association, more than 80% of men suffer from hair loss by the age of 50. Strikingly, 40% of the 21 million women who are inflicted with hair loss problems opt for active treatments. As it pans out, North America minoxidil market size is expected to expand substantially. Prevalence of oral medication and skepticism towards surgical procedures are anticipated to bolster North America minoxidil market share.
Growth Drivers:
Pitfalls & Challenges:
Make an inquiry for purchasing this report @ https://www.gminsights.com/inquiry-before-buying/750
Geographies covered:
U.S., Canada, Germany, UK, France, Italy, Spain, Russia, Poland, China, India, Japan, South Korea, Indonesia, Thailand, Malaysia, Australia, Brazil, Mexico, Argentina, Saudi Arabia, UAE, South Africa
Stakeholders will continue to invest in APAC minoxidil market as number of people with thin hair line problem has soared drastically in the region. According to reports from United Nations Economic & Social Commission for Asia and the Pacific (ESCAP) in North & Central Asia, population ratio aged 60 or above will rise to 24% by 2050up 8% from 2016. As regions such as APAC and Europe witness an uptick in middle-age population, minoxidil market value will rise significantly in the next half a decade.
New product roll outs and mergers & acquisitions are expected to grab headlines among leading companies such as Renata Ltd., Kumar Organic Products, McNeil PPC, Par Pharmaceuticals, and Dr. R.P Fletcher Chemical Factory, among others. For instance, Kumar Organic Products Ltd. inaugurated a new office in Switzerland in February 2018 to expand market footprints.
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Minoxidil Market will witness over 100 million units demand by 2024 - Cole of Duty
KEYTRUDA (pembrolizumab) plus LENVIMA (lenvatinib) Combination Demonstrated Clinically Meaningful Tumor Response Rates in Unresectable Hepatocellular…
By daniellenierenberg
KENILWORTH, N.J. & WOODCLIFF LAKE, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Eisai today announced new data from analyses of two trials evaluating KEYTRUDA, Mercks anti-PD-1 therapy, plus LENVIMA, an orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai. In the KEYNOTE-524/Study 116 and KEYNOTE-146/Study 111 trials, the KEYTRUDA plus LENVIMA combination demonstrated clinically meaningful objective response rates (ORR) in patients with unresectable hepatocellular carcinoma (HCC) with no prior systemic therapy and in patients with metastatic clear cell renal cell carcinoma (ccRCC) who progressed following immune checkpoint inhibitor therapy, respectively.
The tumor response rates demonstrated with KEYTRUDA plus LENVIMA in these studies underscore the potential of this combination regimen in certain types of hepatocellular and renal cell carcinoma, said Dr. Jonathan Cheng, Vice President, Oncology Clinical Research, Merck Research Laboratories. KEYTRUDA plus LENVIMA is an important pillar of our broad oncology research program, and we continue to advance the study of the combination across multiple types of cancers and stages of disease.
As data from our combination trials continue to read out, our enthusiasm for and belief in the potential of KEYTRUDA plus LENVIMA are strengthened by the growing body of evidence observed in multiple advanced cancers, said Dr. Takashi Owa, Chief Medicine Creation and Chief Discovery Officer, Oncology Business Group at Eisai. Our ongoing clinical study efforts on this combination exemplify our commitment to following the science and exploring possible solutions for patients affected by difficult-to-treat cancers.
Results from KEYNOTE-524/Study 116 (Abstract #4519) are being presented in a poster discussion session, and results from KEYNOTE-146/Study 111 (Abstract #5008) are being presented in an oral abstract session of the Virtual Scientific Program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting.
KEYNOTE-524/Study 116 Trial Design and Data (Abstract #4519)
KEYNOTE-524/Study 116 (ClinicalTrials.gov, NCT03006926) is a Phase 1b, open-label, single-arm trial evaluating the KEYTRUDA plus LENVIMA combination in 100 patients with unresectable HCC with no prior systemic therapy. Patients were treated with KEYTRUDA 200 mg intravenously every three weeks in combination with LENVIMA 8 or 12 mg (based on baseline body weight 60 kilograms or 60 kilograms, respectively) orally once daily. The primary endpoints are ORR and duration of response (DOR) by modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST v1.1 per independent imaging review (IIR). Secondary endpoints include progression-free survival (PFS), time to progression (TTP) and overall survival (OS). At data cutoff (Oct. 31, 2019) and a median duration of follow-up of 10.6 months (95% CI: 9.2-11.5), 37 patients were still on study treatment (KEYTRUDA plus LENVIMA: n=34; LENVIMA only: n=3), and median duration of treatment exposure to the KEYTRUDA plus LENVIMA combination was 7.9 months (range: 0.2-31.1).
The final analysis of the studys primary endpoints showed the KEYTRUDA plus LENVIMA combination demonstrated an ORR of 36% (n=36) (95% CI: 26.6-46.2), with a complete response rate of 1% (n=1) and a partial response rate of 35% (n=35), and a median DOR of 12.6 months (95% CI: 6.9-not estimable [NE]), using RECIST v1.1 criteria per IIR. As assessed using mRECIST criteria per IIR, the KEYTRUDA plus LENVIMA combination demonstrated an ORR of 46% (n=46) (95% CI: 36.0-56.3), with a complete response rate of 11% (n=11) and a partial response rate of 35% (n=35), and a median DOR of 8.6 months (95% CI: 6.9-NE).
Treatment-related adverse events (TRAEs) led to discontinuation of KEYTRUDA and LENVIMA in 6% of patients, discontinuation of KEYTRUDA in 10% of patients, and discontinuation of LENVIMA in 14% of patients. Grade 3 TRAEs occurred in 67% of patients (Grade 3: 63%; Grade 4: 1%; Grade 5: 3%). There was one Grade 4 TRAE (leukopenia/neutropenia), and there were three Grade 5 treatment-related deaths (acute respiratory failure/acute respiratory distress syndrome, intestinal perforation and abnormal hepatic function; n=1 for each). The most common TRAEs of any grade (20%) were hypertension (36%), diarrhea (35%), fatigue (30%), decreased appetite (28%), hypothyroidism (25%), palmar-plantar erythrodysesthesia syndrome (23%), decreased weight (22%), dysphonia (21%), increased aspartate aminotransferase (20%) and proteinuria (20%).
KEYNOTE-146/Study 111 Trial Design and Data from the RCC Cohort (Abstract #5008)
KEYNOTE-146/Study 111 (ClinicalTrials.gov, NCT02501096) is a Phase 1b/2, open-label, single-arm trial evaluating the KEYTRUDA plus LENVIMA combination in patients with selected solid tumors. Results from the RCC cohort of the Phase 2 part of the study are based on 104 patients with metastatic ccRCC with disease progression following PD-1/PD-L1 immune checkpoint inhibitor therapy using RECIST v1.1 criteria. Patients were treated with KEYTRUDA 200 mg intravenously every three weeks in combination with LENVIMA 20 mg orally once daily until unacceptable toxicity or disease progression. The primary endpoint is ORR at week 24 by immune-related RECIST (irRECIST) per investigator review. Secondary endpoints include ORR, PFS, OS, safety and tolerability for a maximum of 35 cycles/treatments (approximately two years).
At data cutoff (Apr. 9, 2020), results from the Phase 2 part of the study showed the KEYTRUDA plus LENVIMA combination demonstrated an ORR at week 24 of 51% (95% CI: 41-61) by irRECIST per investigator review. As assessed by irRECIST per investigator review, ORR was 55% (95% CI: 45-65), with a partial response rate of 55%, a stable disease rate of 36% and a progressive disease rate of 5% (5% were not evaluable). Median DOR was 12 months (95% CI: 9-18). Median PFS was 11.7 months (95% CI: 9.4-17.7), and the 12-month PFS rate was 45% (95% CI: 32-57). Median OS was not reached (NR) (95% CI:16.7-NR), and the 12-month OS rate was 77% (95% CI: 67-85).
As assessed by RECIST v1.1 per investigator review, ORR was 52% (95% CI: 42-62), with a partial response rate of 52%, a stable disease rate of 38% and a progressive disease rate of 6% (5% were not evaluable). Median DOR was 12 months (95% CI: 9-18). Median PFS was 11.3 months (95% CI: 7.6-17.7), and the 12-month PFS rate was 44% (95% CI: 31-55).
TRAEs led to discontinuation of KEYTRUDA and LENVIMA in 15% of patients, discontinuation of KEYTRUDA in 12% of patients, and discontinuation of LENVIMA in 12% of patients (2% due to proteinuria). The most common TRAEs that led to dose reduction of LENVIMA were fatigue (14%), diarrhea (10%) and proteinuria (9%). Grade 4 TRAEs included lipase increased, diverticulitis, large intestine perforation and myocardial infarction, and there were two Grade 5 treatment-related deaths of upper gastrointestinal hemorrhage and sudden death. The most common TRAEs of any grade (20%) were fatigue (53%), diarrhea (46%), proteinuria (39%), dysphonia (35%), hypertension (34%), nausea (32%), stomatitis (32%), arthralgia (29%), decreased appetite (28%), palmar-plantar erythrodysesthesia syndrome (25%), hypothyroidism (23%) and headache (22%).
About KEYTRUDA (pembrolizumab) Injection, 100 mg
KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA (pembrolizumab) Indications
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
Small Cell Lung Cancer
KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High (MSI-H) Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.
Gastric Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.
Cervical Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
Endometrial Carcinoma
KEYTRUDA, in combination with LENVIMA, is indicated for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.
Selected Important Safety Information for KEYTRUDA
Immune-Mediated Pneumonitis
KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.
Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.
Immune-Mediated Colitis
KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.
Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)
Immune-Mediated Hepatitis
KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.
Hepatotoxicity in Combination With Axitinib
KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.
Immune-Mediated Endocrinopathies
KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.
Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.
Immune-Mediated Nephritis and Renal Dysfunction
KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.
Immune-Mediated Skin Reactions
Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.
Other Immune-Mediated Adverse Reactions
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.
The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.
Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.
Infusion-Related Reactions
KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.
Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptorblocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.
In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.
Increased Mortality in Patients With Multiple Myeloma
In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.
Embryofetal Toxicity
Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.
Adverse Reactions
In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).
In KEYNOTE-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).
In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).
In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).
In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.
In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).
In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).
Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.
In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).
In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).
In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.
In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those 1% included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).
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KEYTRUDA (pembrolizumab) plus LENVIMA (lenvatinib) Combination Demonstrated Clinically Meaningful Tumor Response Rates in Unresectable Hepatocellular...
Research at MDI Biological Laboratory explores novel pathways of regeneration and tumorigenesis – Bangor Daily News
By daniellenierenberg
BAR HARBOR Research by scientists at the MDI Biological Laboratoryis opening up new approaches to promoting tissue regeneration in organs damaged by disease or injury.
In recent years, research in regenerative biology has focused on stem cell therapies that reprogram the bodys own cells to replace damaged tissue, which is a complicated process because it involves turning genes in the cells nucleus on and off.
A recent paper in the journal Genetics by MDI Biological Laboratory scientist Elisabeth Marnik, Ph.D., a postdoctoral fellow in the laboratory of Dustin Updike, Ph.D., offers insight into an alternate pathway to regeneration: by recreating the properties of germ cells.
Germ cells, which are the precursors to the sperm and egg, are considered immortal because they are the only cells in the body with the potential to create an entirely new organism. The stem cell-like ability of germ cells to turn into any type of cell is called totipotency.
By getting a handle on what makes germ cells totipotent, we can promote regeneration by unlocking the stem cell-like properties of other cell types, said Updike. Our research shows that such cells can be reprogrammed by manipulating their cytoplasmic composition and chemistry, which would seem to be safer and easier than changing the DNA within a cells nucleus.
Using the tiny, soil-dwelling nematode worm, C. elegans, as a model, the Updike lab studies organelles called germ granules that reside in the cytoplasm (the contents of the cell outside of the nucleus) of germ cells. These organelles, which are conserved from nematodes to humans, are one of the keys to the remarkable attributes of germ cells, including the ability to differentiate into other types of cells.
In their recent paper entitled Germline Maintenance Through the Multifaceted Activities of GLH/Vasa in Caenorhabditis elegans P Granules, Updike and his team describe the intriguing and elusive role of Vasa proteins within germ granules in determining whether a cell is destined to become a germ cell with totipotent capabilities or a specific type of cell, like those that comprise muscle, nerves or skin.
Because of the role of Vasa proteins in preserving totipotency, an increased understanding of how such proteins work could lead to unprecedented approaches to de-differentiating cell types to promote regeneration; or alternatively, to new methods to turn off totipotency when it is no longer desirable, as in the case of cancer.
The increase in chronic and degenerative diseases caused by the aging of the population is driving demand for new therapies, said MDI Biological Laboratory President Hermann Haller, M.D. Dustins research on germ granules offers another route to repairing damaged tissues and organs in cases where therapeutic options are limited or non-existent, as well as an increased understanding of cancer.
Because of the complexity of the cellular chemistry, research on Vasa and other proteins found in germ granules is often overlooked, but that is rapidly changing especially among pharmaceutical companies as more scientists realize the impact and potential of such research, not only for regenerative medicine but also for an understanding of tumorigenesis, or cancer development, Updike said.
Recent research has found that some cancers are accompanied by the mis-expression of germ granule proteins, which are normally found only in germ cells. The mis-expression of these germ-granule proteins seems to promote the immortal properties of germ cells, and consequently tumorigenesis, with some germ-granule proteins now serving as prognosis markers for different types of cancer, Updike said.
Updike is a former postdoctoral researcher in the laboratory of Susan Strome, Ph.D., at University of California, Santa Cruz. Strome, who was inducted into the National Academy of Sciences last year, first discovered P granules more than 30 years ago. She credits Updike, who has published several seminal papers on the subject, with great imagination, determination and excellent technical skill in the pursuit of his goal of elucidating the function and biochemistry of these tiny organelles.
The lead author of the new study from the Updike laboratory, Elisabeth A. Marnik, Ph.D., will be launching her own laboratory at Husson University in Bangor, Maine, this fall. Other contributors include J. Heath Fuqua, Catherine S. Sharp, Jesse D. Rochester, Emily L. Xu and Sarah E. Holbrook. Their research was conducted at the Kathryn W. Davis Center for Regenerative Biology and Medicine at the MDI Biological Laboratory.
Updikes research is supported by a grant (R01 GM-113933) from the National Institute of General Medical Sciences (NIGMS), an institute of the National Institutes of Health (NIH). The equipment and cores used for part of the study were supported by NIGMS-NIH Centers of Biomedical Research Excellence and IDeA Networks of Biomedical Research Excellence grants P20 GM-104318 and P20 GM-203423, respectively.
We aim to improve human health and healthspan by uncovering basic mechanisms of tissue repair, aging and regeneration, translating our discoveries for the benefit of society and developing the next generation of scientific leaders. For more information, please visitmdibl.org.
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Research at MDI Biological Laboratory explores novel pathways of regeneration and tumorigenesis - Bangor Daily News
Regenerative Medicine Market to Exhibit a CAGR of 26.1% by 2026; Rising Prevalence of Genetic Disorders to Fuel Demand, states Fortune Business…
By daniellenierenberg
Pune, May 27, 2020 (GLOBE NEWSWIRE) -- The global regenerative medicine market size is expected to reach USD 151,949.5 billion by 2026, exhibiting a CAGR of 26.1% during the forecast period. The growing R&D investment by key players for the development of innovative regenerative therapies can be a vital factor enabling the growth of the market during the forecast period, states Fortune Business Insights in a report, titled Regenerative Medicine Market Size, Share and Industry Analysis By Product (Cell Therapy, Gene Therapy, Tissue Engineering, Platelet Rich Plasma), By Application (Orthopaedics, Wound Care, Oncology), By Distribution Channel (Hospitals, Clinics) & Regional Forecast, 2019 2026 the market size stood at USD 23,841.5 Million in 2018. The growing organ transplantation surgeries will spur opportunities for the market during the forecast period.
Request a Sample Copy of the Research Report: https://www.fortunebusinessinsights.com/enquiry/request-sample-pdf/regenerative-medicine-market-100970
Market Driver:
Escalating Cases of Genetic Disorders to Augment Growth
The increasing prevalence of chronic disorders can be an essential factor enabling the growth of the market. Similarly, the growing incidence of genetic disorders will fuel demand for the market. The growing investment in R&D activities by major market players will have a positive impact on the regenerative medicine market growth during the forecast period. For instance, in March 2018, SanBio Group, a leader in regenerative medicine and therapies for neurological disorders announced that it has made a deal with Hitachi Chemical Advanced Therapeutics Solutions, LLC, a cell manufacturing company for the development and manufacturing of innovative regenerative medicines.
Furthermore, the rising cases of neurological disorders will influence the healthy growth of the market. The growing healthcare expenditure in developed and developing countries will boost the market in the forthcoming years. The ongoing clinical trials and robust pipeline products in stem cell andgene therapy will contribute tremendously to the growth of the market. The rising utilization of skin substitutes, grafts, bone matrix, and other tissue-engineered regenerative medicine in orthopedic and neurosurgical applications will augment the growth of the market.
An Overview of the Impact of COVID-19 on this Market:
The emergence of COVID-19 has brought the world to a standstill. We understand that this health crisis has brought an unprecedented impact on businesses across industries. However, this too shall pass. Rising support from governments and several companies can help in the fight against this highly contagious disease. There are some industries that are struggling and some are thriving. Overall, almost every sector is anticipated to be impacted by the pandemic.
We are taking continuous efforts to help your business sustain and grow during COVID-19 pandemics. Based on our experience and expertise, we will offer you an impact analysis of coronavirus outbreak across industries to help you prepare for the future.
To get the short-term and long-term impact of COVID-19 on this Market.
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Regional Analysis:
Development of Novel Therapies to Favor Growth in North America
The market in North America generated a revenue of USD 9,128.2 million in 2018 and is predicted to grow rapidly during the forecast period owing to the presence of major pharmaceutical companies. The growing launch of novel therapeutics and the availability of advanced technologies along with clinical trials will support growth in North America. Asia Pacific is expected to witness a high growth rate during the forecast period owing to the
developing healthcare infrastructure and facilities. The increasing stem cell research in developing countries such as India, Japan China will contribute positively to the growth of the market. For instance, In April 2013, the Japan Ministry of Health, Labor, and Welfare approved Regenerative Medicine law. The growing number of clinical developments of regenerative and cell-based therapies will drive the market in the region. The increasing government initiatives for human embryonic stem cell research and development will further encourage growth in the region. The surge in geriatric patients, the evolving lifestyle of people, and the growing need for novel therapies are factors likely to aid the expansion of the market in Asia Pacific.
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Key Development:
2018: Novartis announced that it has received EUs approval for one-time gene therapy Luxturna, to restore vision in people with rare and genetically-associated retinal disease.
List of the Key Companies Operating in the Regenerative Medicine Market are:
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Regenerative Medicine Market to Exhibit a CAGR of 26.1% by 2026; Rising Prevalence of Genetic Disorders to Fuel Demand, states Fortune Business...
BREAKTHROUGH! Scientists Discover Particular Protein that Could Block Cancer Growth – Science Times
By daniellenierenberg
The Faculty of Health and Medical Sciences at the University of Copenhagen recently discovered how a particular protein, Phosphoprotein phosphatase 2A (PP2A), inhibits tumor development in mice.
Proteins are complex molecules in cells that are necessary for the function, structure, and regulation of the body's organs and tissues. Proteins have five primary functions: antibodies, enzymes, messengers, structural components, and transport or storage of atoms or small molecules.
Professor Jakob Nilsson, from the Novo Nordisk Foundation Center for Protein Research, explained that PP2A is called a household protein as it can be commonly found in most places. Everything that lives with simple cells or complex cells contain PP2A.
The PP2A Protein is also being studied by pharmaceutical companies as it is known to show unique patterns of kinase opposition, or simply, it is a tumor suppressor. Protein kinases are enzymes that induce change, switching active proteins into an inactive form.
While there is still insufficient research on which specific types of proteins PP2A regulates to prevent cancer, results from the new data do gain more insight.
Other tumor suppressor proteins include the retinoblastoma protein (pRb) and the p53 gene. Both regulate the cycling behavior of cells in a process called cell proliferation and growth are known as cell cycle progression.
Rb has a vital part in regulation G1/S transition, which is the 'start' checkpoint which controls the production of starter kinase proteins. What follows is Rb's 'role in the functioning of normal andcancer stem cells,' as well as its effect on the 'energy metabolism of cancer cells.'
According to a study called Nanostructures for Cancer Therapy, P53 is a protein that can 'respond to hypoxia, DNA damage, and loss of normal cell contacts when activated,' as it mediates the growth and death of cells.
The same study notes, 'targeting p53-MDM2 interaction would be attractive in cancer therapy.'
Read Also: Metformin, a Drug for Diabetes, is Investigated for Cancer-Causing Contaminant
Associate Professor Marie Kveiborg from the Biotech Research and Innovation Centre notes that what is new about their study is that they can show how the specific PP2AB56 'selects the phosphate groups that shall be removed from other proteins,' while it turns off the enzyme ADAM17. ADAM17 being switched off resulted in 'inhibition of tumor growth in mice.'
A disintegrin and metalloprotease domain 17 (ADAM17) is a protein-coding gene associated with diseases including inflammatory skin (psoriasis), inflammatory bowel disease (Crohn's disease), and breast cancer. The test mice were all injected with three variations of ADAM17 cells.
On the day of injection, '4T1 A17wt, I762A, and LEE cells,' all ADAM17 variants, were given and the scientists monitored tumor growth through time.
When they began observing how PP2A-B56 interacted with ADAM17, 'none of the mice injected with ADAM17 LEE cells reached tumor endpoint criteria, as opposed to ADAM17 wt or I762A injected mice, which exhibited only 50% survival by the end of the experiment.'
The newly discovered data on cancer research will hopefully develop into studies with human tumors, expressed by the researchers. The scientists concluded, 'the B56 inhibitor displays excellent specificity toward the PP2AB56 holoenzyme family.' As a result, scientists also want to make additional research to determine if PP2A also can regulate other proteins with its tumor suppressor function.
Read Also:Will COVID-19 End Scientific Breakthroughs?
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BREAKTHROUGH! Scientists Discover Particular Protein that Could Block Cancer Growth - Science Times
Cancer Stem Cells Reliance on a Key Amino Acid Could Be an Exploitable Weakness – On Cancer – Memorial Sloan Kettering
By daniellenierenberg
By Matthew Tontonoz Tuesday, May 26, 2020
Starving skin cancer tumors of serine increases cancer stem cell differentiation in mice. In this image, skin stem cells undergoing differentiation are magenta and those remaining as stem cells are green.
Summary
A team of scientists at the Sloan Kettering Institute and The Rockefeller University has discovered that cancer stem cells rely on a steady external supply of the amino acid serine. This dependency makes them vulnerable to restrictions on this supply, a discovery that could potentially be exploited therapeutically.
In recent years, cancer biologists have come to understand that metabolism the way that cells acquire and use nutrients can directly affect their tendency to become cancerous.
SKI cell biologist Lydia Finley and colleagues in the Elaine Fuchs lab at The Rockefeller University have now deepened knowledge of this relationship in the context of squamous cell carcinoma, a cancer that arises from stem cells in the skin. Using mouse models and cells growing in tissue culture, they found that the amount of the amino acid serine present in a stem cells environment influences its decision to keep dividing or to grow up (differentiate). Differentiated cells generally do not form cancer.
The stem cells that give rise to squamous cell carcinoma seem to be highly dependent on extracellular serine for their growth, Dr. Finley says. Trying to starve these cells of this source of serine could be a strategy to try to curb their growth by forcing them to differentiate.
A normal stem cell will respond to a shortage of extracellular serine by synthesizing more. Atthe same time, they will begin differentiating: The biochemical pathways involved with serine synthesis interact with proteins called histones that wrap DNA like a spool of thread and allow specific genes to be turned on. Stem cells with cancer-predisposing mutations, on the other hand, seem intent onavoiding new serine synthesis.
Cancer stem cells heightened reliance on extracellular serine reflects what Dr. Finley calls metabolic rewiring: By relying on extracellular serine, the cancer stem cells can avoid serine synthesis, with the happy side effect (for the cancer cell) that the path toward differentiation is blocked.
Our findings link the nutrients that a skin stem cell consumes to their identity and their ability to initiate a tumor, says Sanjeethan Baksh, a Tri-Institutional MD/PhD student in the Fuchs lab and the papers first author. Not only do nutrients allow stem cells and cancer cells to grow, but our study also shows that metabolism directly regulates gene expression programs important for cancer stem cell identity.
Although restricting serine in the diet is not feasible in humans, the team is currently looking for ways that they might be able to interfere with cancer stem cells ability to take up serine in the hope of curbing cancer growth.
The findings were reported on May 25 in the journal Nature Cell Biology.
This study received financial support from the Howard Hughes Medical Institute, the National Institutes of Health (grants R01-AR31737, F31CA236465, F30CA236239-01, and 1F32AR073105), the Human Frontiers Science Program, the European Molecular Biology Organization, NYSTEM (CO29559), The Starr Foundation, the Damon Runyon Cancer Research Foundation, the Concern Foundation, the Anna Fuller Fund, The Edward Mallinckrodt, Jr. Foundation, and the Memorial Sloan Kettering Cancer Center Support Grant P30 CA008748. The study authors declare no competing interests.
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Cancer Stem Cells Reliance on a Key Amino Acid Could Be an Exploitable Weakness - On Cancer - Memorial Sloan Kettering
‘The Alchemy Of Us’ Examines Inventions And How They’ve Shaped Human Life – WSHU
By daniellenierenberg
Science has fascinated Ainissa Ramirez ever since she watched her very first episode of the PBS kids science show 3-2-1 Contact. It changed the way she looked at the world and put her on a career path.
Today Ramirez is a materials scientist. Shes done research at Bell Labs and has taught at Yale and MIT. Shes also on a quest to transform our understanding of inventions: how they came to be and how they've changed our lives. In her new book, The Alchemy of Us, she writes, In order to create the finest version of ourselves we need to think critically about the tools that surround us.
WSHUs Morning Edition Host Tom Kuser recently spoke to Ainissa Ramirez. Below is a transcript of their conversation.
I understand you were inspired to write this book after a particularly challenging glass blowing class.What happened during that class?
Well theres a wonderful studio not far from me, in Branford. I live in New Haven, and I wanted to take some glass blowing classes, just on my bucket list. It was fun but I was also very scared. Usually I would take a small amount of glass and make a small vase.
But one day I came in in a very bad mood and actually took a lot of glass on the end of my pipe. As I was making this piece, all I had to do was one last step.But I wasnt really paying attention because I was talking to a friend.And the glass piece fell on the floor.My instructor came by and he fixed it, he reattached it to my pipe.And we were able to put it back together, although it now had a flattened side.
But as it was cooling and as I was calming down, I thought a little bit about what had happened. I was shaping the glass but the glass was actually shaping me.I came to the class in a bad mood and I was leaving in a better mood.It might feel a little existential, but I just said, I wonder how materials and humans have been shaping each other over the eons.So thats what compelled me to write my book, The Alchemy of Us.
Its clear in reading your book that this is not a dry scientific tome.You tell some very compelling stories about fascinating characters who played very significant roles in innovations that changed and are still changing our culture for better and for worse.
The eight chapters highlightspecific innovations. The chapter called CONVEY explores the development of the telegraph.SEE is all about the invention of artificial light and in CAPTURE, you focus on photography.With so many inventions over the millennia, how did you focus on just eight?
[Laugh] Yeah.It could have been much, much longer. In the architecture of the book, I was looking for stories and they had to show how humans changed.And as you mentioned the chapters are given titles that are verbs. So when I was hunting for various stories, I found eight very compelling stories to do that.There are other materials that I could have focused on but these seem to sing the loudest.So thats how I selected it.Each material had to show how it impacted culture by changing the human experience.
In your first chapter INTERACT, you take on time itself through clocks and how they now control our sleep.How did that happen?
INTERACT is one of my favorite chapters because it starts off with a woman who sold time.
Yes. I never heard that story before and I found it fascinating.
In the 19th century, when we became more and more obsessed with time, someone actually had a job where they would walk around with a watch that was certified from the Royal Observatory and show it to different businesses.Now before Ruth Bellville had her business, people slept differently.We used to sleep in two different segments.We would go to bed at 9:00. Go to sleep for about 3 1/2 hours, wake up for about an hour, do something around the house, read, talk to our neighbors who were also up, and then go back to sleep for another 3 1/2 hours.
These segments were called first and second sleep, and everyone slept that way. And if you read old books, youll see words like first sleep and second sleep and thats what they mean. As we became more obsessed with time, we had to wake up earlier so one of those segments got truncated and also with the development of electrical lights the first segment got truncated and they consolidated and that type of sleep is how we sleep today.
And that, you point out, has an impact on health.
Oh absolutely.A lot of people say they have a form of insomnia, and historians actually think its harkening back to this old way of sleeping. And also in terms of our health, the artificial light also seems to be also impacting our health because our bodies actually have two modes.We have a daytime mode and a nighttime mode.
How the body knows which mode to be in is based on blue light.Now when our ancestors were alive they lived by sunlight, which has a lot of blue in it, and candlelight which has less. But we live under artificial lights all the time.And when we're in daytime mode our bodies are actually in growth mode and thats actually impacting us because our cells will respond to that growth mode in ways that we dont necessarily want.
You bring up the chapter about the electric light or artificial light, and of course you include Thomas Edison in the chapter which is called SEE. But it seems that your protagonist, I guess I can call him that, is really an inventor named William Wallace of Ansonia, Connecticut.Why is he a player in this story?
Well, I really loved William Wallace because if you read books about Edison, very thick books, youll always see William Wallace as a footnote. And I said, Who is this guy? I found out that Edison actually came to Ansonia and he met William Wallace.Wallace had created an early version of the electric light, it was an arc light so it was very, very bright, it was like a searchlight, so it wasnt really useful for the home, but Edison saw this and said, Hey, I think Ill start working on electric lights.And then he went back to Menlo Park in New Jersey and created his incandescent bulb. But he wouldnt have had that idea if he didnt come to Connecticut. And most people in Connecticut dont know this. That Edison came up here. So thats why I highlighted William Wallace. I wanted this little known inventor to get his moment in the sun.
You mention the day Thomas Edison came to meet Wallace in Ansonia was really the beginning of a period of darkness for Wallace because he was cut out of the invention process from beyond that time.
That is absolutely right.Wallace thought his moment had come.The great Wizard of Menlo Park came to visit him to see what he had created.And Wallace had created not only this fantastic light, he created a special generator which transmitted the water power from the Naugatuck River into electricity because there wasnt any electricity in the homes yet. And so Edison said well I want one of these electrical systems.He brought it back to his place in Menlo Park and he cut Wallace out of the deal.He just bought the units from Wallace and never included Wallace in his inventions moving forward.
You also talk about the things that weve lost along with what we gained through these innovations. For example with the light bulb, we lost darkness.Tell us about that down side.
Well our ancestors used to look and see thousands of stars.Now if you and I look up, well see about fifty. Recently I went on a trip and I went to a place that was very, very dark.And the starred sky is amazing.You feel very small and you feel connected to nature.So I do talk about how that has happened.As a result of having all these lights, this abundance of lights, it really disconnects us from really seeing how beautiful the night sky is.
And one of the illustrations you use, when talking about the effect on the environment is the life cycle of the lighting bug or the firefly.
Yeah, well on the East Coast were very lucky.We have this wonderful bug, the lightning bug or firefly. But it ends up on the West Coast the fireflies dont make it that far. And the number of fireflies has been decreasing and the reason is because of the lights. Fireflies speak to each other through a Morse code of flashes but its really important that they see each other in a dark sky. They can see each other, connect, and make future fireflies.But when theres a street light overhead, the female firefly doesnt know to flash back to the male firefly so they dont meet. So thats why their numbers are decreasing.Even though artificial lights are convenient for us, for humans, theyre really making things difficult for fireflies.
Since you mentioned the Morse Code that the fireflies use,Id like to jump over to CONVEY, the third chapter in the book about telegraph wires and the invention of the telegraph with Samuel B. Morse.You connect Morse with a number of things in culture that have changed over the years, including the way we write and also, a lack of personal social interaction due to things like texting and emails.Could you connect those dots for us?
Sure.When Morse was first making his telegraph he would work with his assistant (Alfred Vail). And he would chide him and say, condense your language, which was harsh language back in those days.And what he was trying to tell Vail is to not write so much when sending a message.
What Vail would do or what Morse would do, is they would write their letters by longhand and then convertall the letters in the alphabet in the word to dots and dashes, and type in those dots and dashes, figure out what those dots and dashes mean and then write out the word. That took a lot of time.
And so Morse would get a message from Vail and it would be dash, four dots and another dot and youd convert it and youd seek the word the. Thats a lot of work for a word that doesnt do very much.So he was telling Vail to shorten what youre saying in the message that youre transmitting.
It ends up that telegraphs become very popular in society and telegraph officers would tell customers to be brief because the telegraph was great at sending information long distances but it couldnt handle a lot of messages. And so the officers wanted customers to just send very short messages so they could keep it available for the next set of customers.
Telegraphs became popular in newsrooms and editors would tell their reporters to be succinct, again one of the limitation of their prose was because of the telegraph. Now there was one reporter that really loved this style of writing with short declarative sentences. His name was Earnest Hemingway.So the way that he writes is a style that was designed by the use of the telegraph. So this is how one technology, this technology of the telegraph has changed language.
Now the other thing that you mention is about how the telegraph has squeezed out the human part. Morse use to write very, very long letters and used wonderful prose that described everything around him. But when you use the telegraph, you dont have that luxury.
And so the progeny of the telegraph is text messages.
And again when we as humans communicate, we use a lot of different ways of getting a message across besides words.We can look at body language, we can look at peoples eyes.And as a result of communicating in this one-dimensional way, what historians, linguists and scholars are concerned with is that were reducing our ability to empathize.
So thats one of the things that I also point to in The Alchemy of Us, is that this technology is useful in getting information across but its deteriorating our ability to be human with each other, that is to empathize and relate to one another.
Your chapter about photography, called CAPTURE explores several stories and several dimensions of how photography affected culture in the years following its invention and development.One Id like to talk about, you explaining how the development of film actually contributed to the stereotyping of African Americans. Can you please connect those dots for us.
Well it ends up that the most photographed person in the world at one point was Frederick Douglass.Not Lincoln, not Twain. Frederick Douglass. Now why was he so crazy about getting selfies of himself? Well he was trying to use his image as a way to combat the negative stereotypes about African Americans. here were a lot of characters that were hand-drawn and they would show people with exaggerated expressions, with eyes that were white and were bugging out and wide smiles.And if youve ever seen a photograph of Frederick Douglass he looks so regal, hes a handsome looking guy he wanted to combat that image.And so thats the reason why every time he went by a portraiture place for pictures, he would go in to take his pictures because those pictures would also be sold.And so he wanted to use this as a way to combat that stereotype.
Maybe you could talk a bit more about the technical issue that resulted in film really all the way into the later part of the 20th century resulting in film that did not expose correctly darker skin.
Ok thats a very good question.In the 1950s, 1960s, African American mothers were looking at class photos of their children and they saw something that didnt look right. The black children did not come out as well as the white children.And African American mothers they asked manufactures of film to fix this. What they had seen is that actually there was a bias in the film. The film was tailormade or was optimized for people with lighter skin because the main customer were people of lighter complexion.Initially camera film was egalitarian because it was homemade chemistry that you could do in your kitchen. Whoever took a picture, their likeness would be depicted.But as it became manufactured by companies, they tailored the process so that it was optimized for a certain population.And this is what these African American mothers saw in the 1950s.
And so after some chiding, not from these African American mothers, even though they wrote letters. It was only when two businesses, furniture manufacturers and confectioners that made chocolate, when they told this manufacturer that they had to change their film, that changes happened.
Because they wanted their chocolates of different flavors, you know, white chocolate, milk chocolate, dark chocolate.They wanted people to be able to discern those different types of chocolate and in the current form of the film.That wasnt happening. So eventually the formulation was changed so that the film was democratic and could pick up different hues of chocolate as well as different hues of skin.
And I cant let you go without asking for your perspective on the COVID-19 pandemic.Im wondering if theres an innovation from our past that might have created this unfortunate situation?
I dont know if theres an innovation in our past.Weve benefited from not having pandemics because weve got tremendous medicines.And weve got new technologies that can do things that couldnt happen as quickly in the past.We can trace. We can test.So weve got things to combat it a little bit better. Were not actually using them as well as we could, but technologies can definitely help.
From your vantage point as a scientist and a science communicator, how do you see this pandemictransforming perhaps science and our culture looking forward?
This pandemic is also because people feel disconnected from science.I think if people were a little bit more informed about how things work, they would adhere, they would comply a little bit more.Because weve had a little bit of a breakdown with how we teach science, STEM in particular, we dont see how were part of a global system, that what you do affects me.As scientists we forgot to teach that and so as a result, people dont see that their actions actually have some ripple effect outward.
So thats kind of what I see as the impact.And I hope that going forward science, science communicators and also society in general will just realize that theres an ecology, that what you do affects other people although you may not be able to see them.
My ignorance is showing here now.You are a materials scientist.Can you explain just what that is?
I tell people Im an atom whisperer. Materials science sits where chemistry and physics overlap. So chemistry is interested in how things bond and physicists are interested in how materials behave in different situations and I want to show how one thing is linked to the other.So that is what materials science is. Its not very well-known but a lot of the things you take for granted like the cell phone and the fact that this phone call being made by microphone, thats all materials science.
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'The Alchemy Of Us' Examines Inventions And How They've Shaped Human Life - WSHU
Advancements in Medical Skin Care Products Market to boost Revenues Through COVID-19 Crisis Phase and Forecast 2017 2025 – WaterCloud News
By daniellenierenberg
New York City, United States The change during the COVID-19 pandemic has overhauled our dependence on pattern setting developments, for instance, expanded reality, computer generated reality, and the Healthcare web of things. The unfulfilled cash related targets are persuading the relationship to grasp robotization and forefront advancements to stay ahead in the market competition. Associations are utilizing this open entryway by recognizing step by step operational needs and showing robotization in it to make an automated structure as far as might be feasible
Medical skin care products are used for beautifying or to address some other skin care problems. The cosmetic industry is booming and skin care forms a very huge part of this industry. The aesthetic appearance is so important that people spend a lot on skin care products and treatment. People being more technologically aware of the various new skin care products trending in the market. In addition to the aesthetic application, the medical skin care products are also used to address issues such as acne, pimples or scars.
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Medical Skin Care Products Market: Drivers and Restraints
The medical skin care products is primarily driven by the need of natural based active ingredients products which are now trending in the market. Consumers demand medical skin care products which favor health and environment. Moreover, the consumers are updated with the trends so that various companies end up providing such products to satisfy the customers. For instance, a single product face mask has thousands of different variants. This offers consumers different options to select the product depending on the skin type. Moreover, the market players catering to the medical skin care products are offering products with advanced technologies. For instance, Santinov launched the CICABEL mask using stem cell material based on advanced technologies. The stem cells used in the skin care product helps to to protect and activate the cells and promote the proliferation of skin epidermal cells and the anagenesis of skin fibrosis.
Medical Skin Care Products Market: Segmentation
On the basis of product type the medical skin care products market can be segmented as:
On the basis of application, the medical skin care products market can be segment as:
On the basis of distribution channel, the medical skin care products market can be segment as:
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Medical Skin Care Products Market: Overview
Medical skin care products are used to address basic skin problems ranging from acne to scars. There are various advancements in the ingredients used to offer skin care products to the consumers. For instance, the use of hyaluronic acid and retinoids is the latest development in the industry. The anti-aging creams are at the forefront as the help treating issues such as wrinkles, scars, acne, and sun damage. Another, product in demand is the probiotic skincare which include lactobacillus and bifidobacterium.
Medical Skin Care Products Market: Region-wise Outlook
In terms of geography, medical skin care products market has been divided into five regions including North- America, Asia- Pacific, Middle-East & Africa, Latin America and Europe. North America dominated the global medical skin care products market as international players are acquiring domestic companies to make their hold strong in the U.S. LOral is accelerating its U.S. market by signing a definitive agreement with Valeant Pharmaceuticals International Inc. to acquire CeraVe, AcneFree and Ambi skin-care brands for US$ 1.3 billion. The acquisition is expected LOreal to get hold of the brands in the price-accessible segment. Asia Pacific is expected to be the fastest growing region owing to the increasing disposable income and rising awareness towards the skin care products.
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Medical Skin Care Products Market: Key Market Participants
Some of the medical skin care products market participants are ,
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Advancements in Medical Skin Care Products Market to boost Revenues Through COVID-19 Crisis Phase and Forecast 2017 2025 - WaterCloud News
COVID-19: The Prevention Prescription – The New Indian Express
By daniellenierenberg
The health focus today is squarely on the bodys natural defense system. Until there is a vaccination, preventative measures are all we can turn to. Ayurveda can help, experts believe, especially a technique thats been gaining popularity. It's called Photo Bio Modulation (PBM). Availableat Indus Valley AyurvedicCentre (IVAC) in Mysore, itsan emerging medical practicein which exposure to low-level laser light or light-emitting diodes stimulates cellular function. This results in beneficial clinical outcomes for various conditions and diseases, primarily low immunity, in addition to lung disorders, respiratory disorders, joint problems, skin issues, and stress.
How does it work?Also known as Low-Level Laser Therapy (LLLT), it increases the production of Adenosine Triphosphate (ATP) in the mitochondria of the cells, which scavenges the free radicals. By doing so, it stimulates stem cell proliferation, lymph nodes associated with respiratory tract, the immune system and stimulates local tissues to support lung function leading to protection from asthma, bronchitis, pneumonia and Chronic Obstructive Pulmonary Disease, says Dr Talavane Krishna, Founder,President, IVAC.
Nasal ApplicationWhile PBM is gaining prominence now, processes such as nasal application, part of Panchakarma (five actions) treatment, have been a standard Ayurvedic antidote to viruses for aeons. One has to apply different herbal powders, liquid extracts, medicated ghee or oil inside the nostrils. Medications like Anu Taila, sesame or coconut oil, Brahmi ghrutha etc are antimicrobial and act as a protective filter inside the nose and throatthe primary entry point for the viruses. This simple procedure could be a daily practice for both adults and children.
Oil pulling Likewise, oil pulling with sesame or coconut oil as a daily oral health practice is useful. It involves swishing a teaspoon of oil in the mouth for three-five minutes and then spitting the oil, followed by washing/brushing the mouth. This kills bacteria that may lead to tooth decay, bad breath, and gum disease.
Rasayana This is one of the eight major branches of Ayurveda. Popularly known as a form of rejuvenation therapy, not only does it focus on anti-aging, but also immunity. This is accomplished by taking certain Ayurvedic preparations, food based on body constitution, and following an Ayurvedic way of life. This increases Ojas, the very essence of the bodys immunity. Medicines include single herbs like Ashwagandha, Shatavari, Amrita, and formulations like Chyavanaprash, Triphala, Makaradhwaja, notto mention regular body-mind detoxifications like Panchakarma and Rejuvenation.
Balance is keyKeeping the body alignedwith its natural rhythms is a prerequisite to the success of your health. For this, Ayurvedic principles namely Dhincharya (daily regime) and Rithucharya (seasonal regime) are crucial. Dhinacharya looks at aspects such as oral hygiene, yoga, pranayama, meditation, diet, bowel movements and more. Ritucharya describes the various changes in our body during the different seasonsand its effect on health. Italso teaches us how to keepa good balance.
The importance of dietcannot be negated, therefore ensure you add ginger, garlic, pepper, turmeric, clove, cumin, fenugreek and cinnamon in your food as all these ingredients build the immunesystem and bring aboutperfect balance, says Gita Ramesh, Joint MD, Kairali Ayurvedic Group.Dont forget to take warm showers and apply sesame oil on the entire body before the morning bath. Allow nostrils to be lubricated by application of cow ghee or oil, and do warm turmeric water gargles regularly, says Dr Aruna Bhide, Senior Ayurveda Doctor and Consultant, Mercure Goa Devaaya Retreat. Breathing exerciseslike Anulom vilom pranayama (alternate breathing), Kapal bhati (forceful exhalation) and Nadi shuddhi pranayama are beneficial too. Keep in mind to exercise until you sweat as this is the best way to excrete toxins.
Potions for healing(Do consult an Ayurvedic doctor)
Indukantha Kashyam Prevents the recurrence of debilitating diseases and keeps the body healthyVilwadi GulikaA tablet used as a treatment for insect bites, rodent bites, gastroenteritis etc.
Chyawanprash High in Vitamin C, it aids in the production of haemoglobinand white blood cells
Kushmandarasayana Comes in a herbal jam form and is used in respiratory conditions
TriphalaGhritam Support bowel health and aids digestion. As an antioxidant, its also thought to detoxify the body and support immunity.
AshwagandhaIt has demonstrated excellent immune-boosting effects, and has also shown to encourage anti-inflammatory and disease-fighting immune cells, thatkeep illnesses at bay
Amrita Used as a blood purifierMakaradhwaja A mineral-based preparation used for its aphrodisiac characteristics, it enhances the effectiveness of several medicines
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COVID-19: The Prevention Prescription - The New Indian Express