Ischemic heart disease (characterized by decreased blood supply to the heart muscle) is one of the leading causes of death worldwide.It manifests as a coronary artery occlusion, which in turn leads to myocardial infarction, accompanied by death of myocardial cells.This overloads the surviving heart muscle and eventually leads to heart failure.In addition, other causes can also cause heart failure, including chronic hypertension, which is also characterized by the gradual loss of cardiomyocytes, and experimental inhibition of programmed cell death can improve heart function.Clinically, the effective treatment to solve the fundamental problem of heart loss is heart transplantation.The new discovery that stem cells and progenitor cells have regenerative potential to treat and prevent heart failure has changed experimental research and caused explosive growth in clinical research.

Heart RegenerationAlthough heart cells have a slight ability to regenerate.However, it is generally believed that the regenerative capacity of the human heart muscle is seriously insufficient, and it is not enough to make up for the severe loss of myocardium caused by catastrophic myocardial infarction or other heart disease.Studies have found that the heart of some vertebrates (such as zebrafish and salamanders) does undergo a regenerative reaction after injury;under normal conditions, mouse and human cardiomyocytes rarely divide.But after a serious injury, the remaining cardiomyocytes will start DNA synthesis and re-enter the cell cycle.Therefore, the division of existing cardiomyocytes seems to be the most important factor for heart regeneration in mice and humans.The dedifferentiation of cardiomyocytes near the damaged area occurs before their proliferation and is characterized by the loss of expression of myocardial contractile proteins (such as -myosin heavy chain and troponin T). Studies find zebrafish heart regeneration may be mainly caused by undifferentiated stem cells or progenitor cells from the outer layer of the heart (epithelium).Further research on salamanders and zebrafish will more clearly define whether cardiac regeneration in these organisms requires dedifferentiation, proliferation and subsequent cardiomyocyte differentiation, or whether regeneration is driven by the recruitment of stem cells to the injured site.In contrast, in mammalian hearts, cardiomyocytes rarely divide after a myocardial infarction, although transgene overexpression of specific genes in mice increases the division of cardiomyocytes.

There is strong evidence that endothelial cells are renewed by bone marrow-derived progenitor cells, but the idea that cardiomyocytes are renewed by such cells has been heatedly debated. Less controversial is that adult mammalian heart muscle has a resident cardiac stem cell (CSC) population, which has the potential to differentiate into cardiomyocytes and other cell types (such as endothelial and vascular smooth muscle cells). The study found that CSCs can support the basic turnover of cardiomyocytes, but this turnover occurs at a very low rate without damage. CSCs have high proliferation and differentiation potential in vitro, and it may be a promising therapeutic direction to expand autologous CSCs in vitro or stimulate the regeneration of these cells in vivo.

The recognition that there is indeed a regeneration mechanism in the mammalian myocardium has aroused intense attention. Researchers have discovered that it may hinder the existence of aplastic disorders, including ischemia, inflammation and fibrosis at various stages of myocardial infarction. This unfavorable microenvironment may prevent the activation of resident CSCs, thereby reducing the success rate of exogenous cell therapy. Certain components of the inflammatory response may be essential to promote angiogenesis and progenitor cell recruitment, but excessive inflammation may also prevent the recruitment and survival of progenitor cells. Similarly, after myocardial infarction, a certain degree of fibrosis is required to prevent myocardial rupture, but dense fibrosis presents a strong physical barrier to regenerative cells.

Which Stem Cells Are Used In Heart Therapy?Perhaps the most confusing aspect of current cardiac regeneration is the different cell types, which are considered to be candidates for cardiac therapy.Multiple cell candidates reflect that human research on cell regeneration is not deep enough, so further research and exploration are needed.

Figure 1. Many cell types and mechanisms have been proposed for cardiac therapy.

Skeletal MyoblastOne of the earliest cell-based cardiac regeneration strategies was to inject autologous skeletal muscle myoblasts into ischemic myocardium.Myoblasts are resistant to ischemia, and can be differentiated into myotubes (but not into cardiomyocytes) in the laboratory animal experiments and improve ventricular function.The myocardial tube will not integrate with the surviving cardiomyocytes, so it will not beat synchronously with the surrounding myocardium.However, related clinical trials were terminated due to lack of efficacy, so it is unlikely that skeletal myoblasts will actually regenerate the heart muscle.Interestingly, studies found that mouse skeletal muscle contains a large number of non-satellite cells, which can differentiate into spontaneous pulsatile cells with cardiomyocyte characteristics, but no one has found similar cells in human skeletal muscle.

Bone Marrow-Derived Cells

In stem cell cardiac therapy, it was first reported that adult stem cells or progenitor cells transplanted into the infarcted heart of mice that can differentiate into cardiac myocytes are a subset of hematopoietic cells derived from bone marrow. The first evidence that adult bone marrow-derived progenitor cells are involved in the formation of cardiomyocytes in the adult human heart is based on reports of Y chromosome-positive cardiomyocytes in male recipients of transplanted female donor hearts. Animal studies using labeled hematopoietic stem cells for bone marrow transplantation and subsequent myocardial infarction have shown that cardiomyocytes are derived from transplanted cells, but the proportion is extremely low. Moreover, other studies in animals have not demonstrated that hematopoietic progenitor cells can differentiate into cardiomyocytes or improve heart function. Therefore, there is currently no consensus on whether bone marrow-derived progenitor cells differentiate into cardiomyocytes in vivo.

Embryonic stem cell

Embryonic stem (ES) cells are prototype stem cells.They clearly meet all the requirements of stem cells: cloning, self-renewal and multi-potency.ES cells can differentiate into any type of cells present in an adult organism, so it has the potential to completely regenerate the heart muscle.The two obstacles facing the clinical application of ES therapy are immune rejection and the tendency of injecting ES cells to form teratomas.With the increase in knowledge of ES cell differentiation and cardiac embryonic development pathways, ES cell differentiation may become more controllable.Methods to limit teratoma formation include genetic selection of differentiated ES cells, or differentiation of ES cells into cardiomyocytes or endothelial cells in vitro before injection.For example, tumor necrosis factor promotes the differentiation of ES cells into cardiomyocytes.If the differentiated ES cells are delivered to the myocardium in a rich survival mixture, they can survive and improve myocardial function.The inherent difficulty in controlling the growth and differentiation of ES cells and other pluripotent stem cells is that the timing of activating specific signaling pathways may be crucial.For example, recent studies on mouse and zebrafish embryos have shown that the role of the Wnt--catenin pathway in heart development depends on the stage of development.

Endogenous cardiac stem cells

Because allogeneic cells face immunological challenges that may require immune rejection, the isolation of endogenous adult mammalian CSCs based on cell surface markers has attracted great interest. However, no clear CSC mark has been determined so far. Mammalian heart muscle includes a small percentage of stem cells expressing cell surface markers Kitor Scal. In addition, some side population cells also express Kit and / or Sca1, and like Kit +CSC and Sca1 +CSC, side population cells can produce cardiomyocytes in vitro and in vivo. In addition to Kit +CSC, Sca1+CSC and side population cells, the fourth type of CSC also expresses the transcription factor Isl1. The tracer experiments showed that during embryonic heart development, cells expressing Isl1can differentiate into endothelial cells, endocardial cells, smooth muscle cells, conduction system cells, right ventricular myogenic cells and atrial myogenic cells. There are also cells that express Isl1 in the heart of adult mammals, but they are limited to the right atrium, are found in fewer numbers than the embryonic heart, and have unknown physiological effects. Recently, epicardial-derived progenitor cells with angiogenic potential have been described.

Stem cell therapy for heart disease faces some challenges.The most important question to be answered in preclinical research is which stem or progenitor cells are the best choice for treatment.So far, under certain circumstances (acute myocardial infarction), bone marrow-derived progenitor cell therapy has proven to be safe and beneficial, but the regeneration potential of this cell is still controversial.CSC may have the potential to target patients, but isolation and cultivation procedures are still in the early stages of development.ES cells have the greatest differentiation potential, but face moral barriers and the greatest risk of teratoma formation.Whether ES cell derivatives will be rejected by the hosts immune response is still under debate.However, in principle, rejection can be avoided by using cells from a pool of only 150 donors with different HLA types.If new technologies for reprogramming human and mouse fibroblasts into ES-like cells can be used, the use of patient-reprogrammed cells can reduce or even eliminate immune rejection.When designing a more rational cell-based treatment for heart disease, a key issue is to understand the mechanism by which each stem or progenitor cell type can affect myocardial function.Similarly, different cardiology, such as acute myocardial infarction and chronic ischemic cardiomyopathy, may require different types of stem or progenitor cells.

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Whether youre blasting the heat or AC (or both, because, April), staying inside all day puts you on the fast track to dry skin. Unless youve got a humidifier decorating your WFH space, the air in your home is ripe for sucking the moisture straight out of your face. And while diligently slathering on moisturizer every hour on the hour is certainly one way to hold in the hydration, the easiest method to hydrate skin at home is actually by repurposing your hydrating sleep mask for use during waking hours.

No, were not talking sleeping eye masks. Think of sleep masks, which came to us by way of K-beauty and popularized over the last few years, as a sort of jacket for your skin. Unlike regular masks, they dont need to be washed off, and they create a protective boundary between your skin and environment thats even tougher to permeate than your usual skin products. We recommend using a concentrated mask during the day when working from home, because your skin is so susceptible to losing moisture if you dont adequately hydrate it, says Glow Recipe founder Sarah Lee. Because overnight masks are usually very hydrating with nourishing properties, it really helps to keep that moisture retained throughout the hours. Because of this, its also a great way to maximize the ingredients youre getting from the products youre applying underneath it.

A sleep mask should be the final layer after your usual skin-care routine, and can go on either on top of your moisturizer or in place of it. Scroll through for our favorite picks worth dedicating a spot to in your routine.

This influencer-approved mask is chock full of vitamins (C and E, to be specific) and amino acids that give dull, sleepy skin an instant boost. Its got antioxidants to help protect from free-radical damage, and ceramides to really lock in the moisture it provides.

A combination of watermelon and hyaluronic acid helps to infuse moisture in the skin, and a mixture of AHAs (including glycloic and lactic acids) clear away the top layer of dead skin cells to help moisture penetrate more deeply. The jelly texture is ultra light so that you wont feel like youve got some goopy mask on your face all day long, and can you beat the packaging?

This drugstore beauty buy is not only immensely hydrating (and under $20), but it also leaves behind a pearlescent finish that will make you look luminous while you work. Its formulated with skin-soothing niacinamide and moisture-drawing humectants to hydrate and brighten as it absorbs.

Thanks to its barely-there, water-based formula, this jelly mask absorbs almost immediately into your skin. In addition to highly concentrated mineral water, its also packed with calming and brightening ingredients like orange flower, rose, sandalwood, apricot, and evening primrose. Thirsty pores will drink it right up.

With this mask, youll be waking up, spending your day,and going to sleep beautiful. Its got all kinds of nourishing, natural ingredients like quinoa, mushrooms, and floral stem cells, and is infused with aromatherapy elements to help keep you calm throughout the work day.

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Repurpose your sleep masks to keep WFH skin fresh and hydrated all day - Well+Good

Skin Stem Cells Comments Off on Repurpose your sleep masks to keep WFH skin fresh and hydrated all day – Well+Good | April 25th, 2020

Insulin injections cancontrol diabetes, but patients still experience serious complications such as kidney disease and skin infections. Transplanting pancreatic tissues containing functional insulin-producing beta cells is of limited use, because donors are scarce and patients must take immunosuppressant drugs afterward.

Now, scientists atWashington University in St. Louis havedeveloped a way to use gene editing system CRISPR-Cas9 to edit a mutation in human-induced pluripotent stem cells (iPSCs) and then turnthem into beta cells. When transplanted into mice, the cells reversed preexisting diabetes in a lasting way, according to results published in the journal Science Translational Medicine.

While the researchers used cells from patients with Wolfram syndromea rare childhood diabetes caused by mutations in the WFS1 genethey argue that the combination of a gene therapy with stem cells could potentially treat other forms of diabetes as well.

Virtual Clinical Trials Online

This virtual event will bring together industry experts to discuss the increasing pace of pharmaceutical innovation, the need to maintain data quality and integrity as new technologies are implemented and understand regulatory challenges to ensure compliance.

One of the biggest challenges we faced was differentiating our patient cells into beta cells. Previous approaches do not allow for this robust differentiation. We use our new differentiation protocol targeting different development and signaling pathways to generate our cells, the studys lead author, Kristina Maxwell, explained in a video statement.

Making pancreatic beta cells from patient-derived stem cells requires precise activation and repression of specific pathways, and atthe right times, to guide the development process. In a recent Nature Biotechnology study, the team described a successful method that leverages the link between a complex known as actin cytoskeleton and the expression of transcription factors that drive pancreatic cell differentiation.

This time, the researchers applied the technology to iPSCs from two patients with Wolfram syndrome. They used CRISPR to correct the mutated WFS1 gene in the cells and differentiated the edited iPSCs into fully functional beta cells.

After transplanting the corrected beta cells into diabetic mice, the animals saw their blood glucose drop quickly, suggesting the disease had been reversed. The effect lasted for the entire six-month observation period, the scientists reported. By comparison, those receiving unedited cells from patients were unable to achieve glycemic control.

RELATED:CRISPR Therapeutics, ViaCyte team up on gene-edited diabetes treatment

The idea of editing stem cells with CRISPR has already attracted interest in the biopharma industry. Back in 2018, CRISPR Therapeutics penned a deal with ViaCyte to develop off-the-shelf, gene-editing stem cell therapies for diabetes. Rather than editing iPSCs from particular patients themselves to correct a faulty gene, the pairs lead project used CRISPR to edit healthy cells so that they lackedthe B2M gene and expressed PD-L1 to protect against immune attack. The two companies unveiled positive preclinical data inSeptember.

Other research groups working on gene therapy or stem cells for diabetes include a Harvard University scientist and his startup Semma Therapeutics, whichdeveloped a method for selecting beta cells out of a mixture of cells developed from PSCs. Scientists at the University of Wisconsin-Madison recently proposed that removing the IRE1-alpha gene in beta cells could prevent immune T cells from attacking them in mice with Type 1 diabetes.

The Washington University team hopes its technology may help Type 1 diabetes patients whose disease is caused by multiple genetic and environmental factors as well as the Type 2 form linked to obesity and insulin resistance.

We can generate a virtually unlimited number of beta cells from patients with diabetes to test and discover new drugs to hopefully stop or even reverse this disease, Jeffrey Millman, the studys co-senior author, said in the video statement. Perhaps most importantly, this technology now allows for the potential use of gene therapy in combination with the patients own cells to treat their own diabetes by transplantation of lab-grown beta cells.

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Reversing diabetes with CRISPR and patient-derived stem cells - FierceBiotech

Skin Stem Cells Comments Off on Reversing diabetes with CRISPR and patient-derived stem cells – FierceBiotech | April 25th, 2020

The global Cosmetic Skin Care market reached ~US$ xx Mn in 2019and is anticipated grow at a CAGR of xx% over the forecast period 2019-2029. In this Cosmetic Skin Care market study, the following years are considered to predict the market footprint:

The business intelligence study of the Cosmetic Skin Care market covers the estimation size of the market both in terms of value (Mn/Bn USD) and volume (x units). In a bid to recognize the growth prospects in the Cosmetic Skin Care market, the market study has been geographically fragmented into important regions that are progressing faster than the overall market. Each segment of the Cosmetic Skin Care market has been individually analyzed on the basis of pricing, distribution, and demand prospect for the Global region.

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below:

Global Cosmetic Skin Care Market, Product Analysis

Global Cosmetic Skin Care Market, Application Analysis

In addition the report provides cross-sectional analysis of all the above segments with respect to the following geographical markets:

Global Cosmetic Skin Care Market, by Geography

Each market player encompassed in the Cosmetic Skin Care market study is assessed according to its market share, production footprint, current launches, agreements, ongoing R&D projects, and business tactics. In addition, the Cosmetic Skin Care market study scrutinizes the strengths, weaknesses, opportunities and threats (SWOT) analysis.

COVID-19 Impact on Cosmetic Skin Care Market

Adapting to the recent novel COVID-19 pandemic, the impact of the COVID-19 pandemic on the global Cosmetic Skin Care market is included in the present report. The influence of the novel coronavirus pandemic on the growth of the Cosmetic Skin Care market is analyzed and depicted in the report.

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What insights readers can gather from the Cosmetic Skin Care market report?

The Cosmetic Skin Care market report answers the following queries:

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Why Choose Cosmetic Skin Care Market Report?

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Potential Impact of COVID-19 on Cosmetic Skin Care Market to Show Outstanding Growth by 2025 Profiling Global Players Industry Developments, Outlook,...

Skin Stem Cells Comments Off on Potential Impact of COVID-19 on Cosmetic Skin Care Market to Show Outstanding Growth by 2025 Profiling Global Players Industry Developments, Outlook,… | April 25th, 2020

The coronavirus crisis is affecting every aspect of our lives, including the condition of our skin. Have you noticed that your skin is particularly spotty, irritated and angry lately? That's another thing you can blame on COVID-19.

Express.co.ukspoke to Dr. Luca Russo, Dermatologist at Urban Retreat, to find out why.Dr. Russo says there are several reasons for your unexpected breakouts.He said: "There might be several reasons for noticing a tendency to break out during this national emergency."It's probably to do with what's going on inside, and what you're putting in your body, says Dr. Russo.

READ MORE- Coronavirus symptoms: Man reveals skin-related warning sign

Are you up all night worrying about the virus?Dr. Russo says: "The most likely cause of your breakout is stress."During such uncertain and stressful times, our system copes with increased production of Cortisol."Cortisol is an androgen hormone that is released when we are facing unusual challenges and prepare us to "fight'."However, it will also increase the sugar level in the bloodstream and production of sebum that might be a cause of the breakout."

In order to prevent breakouts that stem from high levels of stress, you'll need to calm yourself down.Dr Russo recommends doing activities that allow you to relax and unwind, such as yoga.He also suggests exercising regularly, so it's time to start making use of that daily government-approved walk, cycle, or run.

If you hate exercising, don't worry, the antidote to high cortisol levels doesn't have to be physical.Laughing, a solid night of sleep, or practising your favourite hobby are all effective options.

Having a soak in the bath and doing a face-mask may help you feel more in control of your skin.

This relief may cause a decrease in oil production and pimples.

DON'T MISS...How to help your brain through the coronavirus crisis stress [EXPLAINER]Coronavirus: How to look after your mental health during lockdown [EXPLAINER]Lockdown exercise: The eight exercises you can do at home [INFORMER]

Can you honestly say you have been eating well throughout the lockdown?Most people have stocked up on sugary treats and salty snacks in order to cheer themselves up in the face of COVID-19.And what about the good-old "support local businesses" excuse you use every time you order a greasy takeaway?Dr Russo says: "During isolation food becomes one of the few focal points of the day with more consumption of comfort food."Just like any other organ in your body, a poor diet affects your skin negatively.The body breaks down our food into tiny particles of proteins, fats, and carbs, and circulates it to the organs that need them.These nutrients make their way to your skin too, impacting its condition.It makes sense that inflammatory foods, such as sweets, some dairy, processed meat, and refined carbohydrates, will cause a flare-up in your complexion.

Dr. Russo says: "To improve your skin, you must eat well."Eat foods that are packed with vitamins and proteins and snack on fruit and veg."Drinking lots of water will replace the moisture that is lost through sweat and other processes, keeping your skin hydrated.If you fill up on foods rich in healthy oils and omega-3 fatty acids, you will improve the collagen production in your skin.This makes your skin smoother, suppler, and will help you in the longterm by preventing premature ageing.These oils and fats are found in fish, nuts, olive oil, and many more commonly found items.

During the lockdown, we're stuck inside all day and often don't get a chance to let our skin feel the sun.Dr. Russo says: "At the moment, skin isn't being exposed to natural light much at all."When your skin is exposed to natural light, the production of Vitamin D is increased."Endorphins are also produced, and this boosts your immune system and well-being."Make sure you get some fresh air every day, in order to reap these benefits of the sun.The sun is a great natural resource to improve your skin, but make sure you protect yourself with sun protection before you go out.You should wear an SPF of at least 30 on your face whenever you leave the house or are in front of a window for a prolonged amount of time.

Most people are shunning makeup in favour of the natural look since no one other than our household is going to see our faces.This means you may be tempted to skip your cleansing routine and go straight to bed once the day is over.

If you normally get facials and now can't, this may also be why you are breaking out or seeing changes.Dr. Russo explains: "You have probably been unable to receive professional treatments over this time, and this will contribute towards your breakouts."Dr. Russo recommends continuing with your normal skincare routine.He says: "Carry on as normal, but add an exfoliating cleanser to your routine."Exfoliating cleansers make your skincare routine shorter, by combining exfoliating and cleansing in one step.They remove dead skin cells and any build-up of dirt and oil in one go.There are hundreds of physical exfoliating cleansers on the market, as well as chemical exfoliating cleansers, so take your pick!

While surgical masks are thought to protect us against coronavirus, they're not great for our skin, said Dr. Russo.Wearing a mask over your face for many hours is damaging to your skin, especially when it's hot outside.The mask offers the perfect spot for bacteria and germs to harbour.Try double cleansing on the lower half of your face if you've worn a surgical mask for a prolonged period of time.

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Breakouts: Why is my skin worse during the coronavirus pandemic? - Express

Skin Stem Cells Comments Off on Breakouts: Why is my skin worse during the coronavirus pandemic? – Express | April 25th, 2020

Doctors are hoping stem cell therapy could be a weapon in the fight against coronavirus. On Friday, regenerative medicine company Mesoblast announced a 300-person trial to determine whether stem cell treatments will work in COVID-19 patients suffering from severe lung inflammation.

One hospital in New York tried it as an experiment with 12 patients, 10 of whom were able to come off of ventilators.

"What we saw in the very first patient was that within four hours of getting the cells, a lot of her parameters started to get better," Dr. Karen Osman, who led the team at Mount Sinai, told CBS News' Adriana Diaz.

The doctor said she was encouraged by the results, though she was hesitant to link the stem cell procedure to her patients' recovery.

"We don't know" if the 10 people removed from ventilators would not have gotten had they not gotten the stem cells, she said. "And we would never dare to claim that it was related to the cells."

She explained that only a "randomized controlled trial" would be the only way "to make a true comparison."

Luis Naranjo, a 60-year-old COVID-19 survivor, was one of Mount Sinai's stem cell trial success stories. He told Diaz in Spanish that he was feeling "much better."

Naranjo's daughter, Paola, brought him to the emergency room, fearful she would not see her father again. Like so many families struck by the coronavirus, she was not allowed inside with him.

"I forgot to tell him that I love him," she said. "All I said was go inside, I hope you feel better."

During his hospital stay, Naranjo was unconscious and on a ventilator for 14 days.

Doctors proposed giving him stem cells from bone marrow in hopes it would suppress the severe lung inflammation caused by the virus.

Now, Naranjo credits the doctors who treated him for his survival. Though income from his family's jewelry business has been cut off and they found themselves falling behind on rent, Naranjo said he is focused primarily on his recovery and regaining the 25 pounds he lost at the hospital.

Although stem cell treatment, usually reserved for other diseases like rheumatoid arthritis, might end up being another step toward helping coronavirus patients recover, Dr. Osman was quick to say it would not be a "miracle treatment."

"The miracle treatment will be a vaccine," she said.

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Doctors experiment with stem cell therapy on COVID-19 patients - KTVQ Billings News

Bone Marrow Stem Cells Comments Off on Doctors experiment with stem cell therapy on COVID-19 patients – KTVQ Billings News | April 25th, 2020

In some patients, COVID-19 has triggered a cytokine storm, an immune system response in which the body attacks its own cells. Jung painted a picture of a boxing match in which "fighter" immune cells are being called upon to battle the virus. This battle generates lots of fluid, waste and pus, making it difficult for the alveoli to pick up the oxygen a person breathes in, leading to multi-organ failure.

"These immune cells, neutrophils and other fighter immune cells, are like that. They don't care if it's a virus or our own cells. If you're infected, they're all enemies," Jung said. "So what they're going to do is they're going to start to kill everybody, basically."

Why exactly some people's immune systems go into overdrive, Jung said, is unknown, but he said it can happen to anybody.

"If we are up to the level where we can fight well without going into a coma or anything, then 14 days later, our body can provide an antibody," Jung said. "An antibody will neutralize this virus very quietly."

Strengthening the immune system

Eating certain foods can help keep your immune cells strong. Jung said vegetables, for example, stimulate the circulation of blood cells from bone marrow.

"Those bioactive reagents can support our immune systems by sending them the appropriate amount of stem cells, just in case some tissue cells are damaged and we need to replenish them. For example, if your lung cell has been damaged and they need to be replaced, that could be done by the stem cell that has been moved from the bone marrow and located around the lung area," said Jung, who encourages eating a variety of different colored vegetables.

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BCU biology professor offers tips to prevent COVID-19 infection - Sioux City Journal

Bone Marrow Stem Cells Comments Off on BCU biology professor offers tips to prevent COVID-19 infection – Sioux City Journal | April 25th, 2020

Wed, Apr 22, 2020 - 5:50 AM

PATIENTS from around the world have benefited from Parkway Cancer Centre's (PCC) comprehensive and holistic approach to treating haematological cancers, or cancers of the blood. The field of haematology covers a broad spectrum of blood disorders, with the World Health Organization estimating that there are as many as 72 types and sub-types of this form of cancer.

With one of the largest and most experienced teams of haematologists in Singapore - comprising three oncologists and one paediatric oncologist - PCC is able to offer specialised care for the management of a wide range of adult and childhood conditions, including leukaemia and lymphoma, among many others.

Significantly, this core group of haematologists is supported by dedicated transplant physicians, oncology and transplant nurses, transplant coordinators, counsellors and allied health professionals. The breadth of its resources allows PCC to adopt a holistic approach to care that enhances the patient journey and results in better healthcare outcomes.

Treatments provided by the haematology oncology team range from intensive chemotherapy, molecular targeted therapy and novel immunotherapy to stem cell transplantation. For each patient, the team devises a personalised treatment plan that aims to optimise clinical outcomes.

"In all diseases, especially cancers, it is important to be able to see patients as individuals in need of treatment that extends beyond specialised investigations and medications. This is best achieved by a multidisciplinary team approach that identifies the patient's medical and emotional needs, preferences and values," said Dr Colin Phipps Diong, Senior Consultant, Haematology Oncology at PCC.

"We are able to draw on the collective expertise of our multidisciplinary team and use our knowledge bank of experience gleaned from successfully treating some of the most challenging and complex cases. Being at the fore of medical advancements gives us the capability and confidence to provide our patients with current treatment options," he added.

A Pioneer in Bone Marrow Transplantation

Reflecting the depth of its expertise in this specialised field, PCC is the only private healthcare provider that offers a comprehensive adult and paediatric blood and bone marrow transplant programme. Indeed, the centre's haematology team performed the first bone marrow transplant in a private hospital setting in Singapore more than two decades ago.

Bone marrow transplantation, known formally as haematopoietic stem cell transplantation, is a specialised procedure which has proven to be effective in treating many types of cancers, as well as blood and autoimmune disorders such as leukaemia and lymphoma.

Since the 1950s, more than one million transplants have been performed globally, with the success of the procedure largely dependent on the skill and experience of the multidisciplinary transplant team. Transplant specialists at the PCC Haematology and Stem Cell Transplant Centre perform transplants from family members, unrelated donors, and cord blood, for a range of conditions, both non-malignant (thalassaemia, aplastic anaemia) and malignant (acute leukaemias, lymphoma, myeloma).

These specialists have extensive experience in bone marrow transplants in both adult and paediatric patients, having trained and worked at some of the leading transplant centres around the world.

Even though stem cell transplantation has been proven to save lives, there are still risks associated with the procedure. At PCC, these risks are clearly explained to the patients and caregivers before they consent to the procedure. "Complex treatment decisions are regularly discussed between the transplant physicians to formulate an optimal plan for our patients," explained Dr Diong.

The transplantation process involves several important stages: Conditioning where the patient receives chemotherapy and/or radiation to kill the diseased cells and to change the immune system; infusion of healthy stem cells into the body to replace the damaged cells; engraftment, when the transplanted stem cells begin to grow and produce healthy red and white blood cells and platelets over the course of two to four weeks; and post-transplant recovery where the "new" immune system matures and develops the ability to fight infections and blood cancer cells.

Looking ahead, PCC will continue to develop its expertise and services to stay ahead of the curve in treating haematological cancers. "We are always looking ahead. It is important that we build our team further to broaden our regional footprint and expand services to bring our patients access to cutting-edge science like CAR T-cell therapies," said Dr Diong.

"In this regard, we strive to develop services, infrastructure, and facilities that are internationally accredited together with our partners in Parkway. At the same time we will continue to work with all stakeholders to ensure that cost is manageable and more patients have access to our transplant services."

PCC's holistic philosophy

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A leader in treating haematological cancers - The Business Times

Bone Marrow Stem Cells Comments Off on A leader in treating haematological cancers – The Business Times | April 25th, 2020

The lungs are ground zero, but COVID-19 also tears through organ systems from brain to blood vessels.

Science's COVID-19 coverage is supported by the Pulitzer Center.

The coronavirus wreaked extensive damage (yellow) on the lungs of a 59-year-old man who died at George Washington University Hospital, as seen in a 3D model based on computed tomography scans.

On rounds in a 20-bed intensive care unit one recent day, physician Joshua Denson assessed two patients with seizures, many with respiratory failure, and others whose kidneys were on a dangerous downhill slide. Days earlier, his rounds had been interrupted as his team tried, and failed, to resuscitate a young woman whose heart had stopped. All of the patients shared one thing, says Denson, a pulmonary and critical care physician at the Tulane University School of Medicine. They are all COVID positive.

As the number of confirmed cases of COVID-19 approaches 2.5 million globally and deaths surpass 166,000, clinicians and pathologists are struggling to understand the damage wrought by the coronavirus as it tears through the body. They are realizing that although the lungs are ground zero, the virus' reach can extend to many organs including the heart and blood vessels, kidneys, gut, and brain.

[The disease] can attack almost anything in the body with devastating consequences, says cardiologist Harlan Krumholz of Yale University and Yale-New Haven Hospital, who is leading multiple efforts to gather clinical data on COVID-19. Its ferocity is breathtaking and humbling.

Understanding the rampage could help doctors on the front lines treat the roughly 5% of infected people who become desperately and sometimes mysteriously ill. Does a dangerous, newly observed tendency to blood clotting transform some mild cases into life-threatening emergencies? Is an overzealous immune response behind the worst cases, suggesting treatment with immune-suppressing drugs could help? And what explains the startlingly low blood oxygen that some physicians are reporting in patients who nonetheless are not gasping for breath? Taking a systems approach may be beneficial as we start thinking about therapies, says Nilam Mangalmurti, a pulmonary intensivist at the Hospital of the University of Pennsylvania (HUP).

What follows is a snapshot of the fast-evolving understanding of how the virus attacks cells around the body. Despite the more than 1500 papers now spilling into journals and onto preprint servers every week, a clear picture is elusive, as the virus acts like no pathogen humanity has ever seen. Without larger, controlled studies that are only now being launched, scientists must pull information from small studies and case reports, often published at warp speed and not yet peer reviewed. We need to keep a very open mind as this phenomenon goes forward, says Nancy Reau, a liver transplant physician who has been treating COVID-19 patients at Rush University Medical Center. We are still learning.

WHEN AN INFECTED PERSON expels virus-laden droplets and someone else inhales them, the novel coronavirus, called SARS-CoV-2, enters the nose and throat. It finds a welcome home in the lining of the nose, according to a recent arXiv preprint, because cells there are rich in a cell-surface receptor called angiotensin-converting enzyme 2 (ACE2). Throughout the body, the presence of ACE2, which normally helps regulate blood pressure, marks tissues potentially vulnerable to infection, because the virus requires that receptor to enter a cell. Once inside, the virus hijacks the cell's machinery, making myriad copies of itself and invading new cells.

As the virus multiplies, an infected person may shed copious amounts of it, especially during the first week or so. Symptoms may be absent at this point. Or the virus' new victim may develop a fever, dry cough, sore throat, loss of smell and taste, or head and body aches.

If the immune system doesn't beat back SARS-CoV-2 during this initial phase, the virus then marches down the windpipe to attack the lungs, where it can turn deadly. The thinner, distant branches of the lung's respiratory tree end in tiny air sacs called alveoli, each lined by a single layer of cells that are also rich in ACE2 receptors.

Normally, oxygen crosses the alveoli into the capillaries, tiny blood vessels that lie beside the air sacs; the oxygen is then carried to the rest of the body. But as the immune system wars with the invader, the battle itself disrupts healthy oxygen transfer. Frontline white blood cells release inflammatory molecules called chemokines, which in turn summon more immune cells that target and kill virus-infected cells, leaving a stew of fluid and dead cellspusbehind (see graphic, below). This is the underlying pathology of pneumonia, with its corresponding symptoms: coughing; fever; and rapid, shallow respiration. Some COVID-19 patients recover, sometimes with no more support than oxygen breathed in through nasal prongs.

But others deteriorate, often suddenly, developing a condition called acute respiratory distress syndrome. Oxygen levels in their blood plummet, and they struggle ever harder to breathe. On x-rays and computed tomography scans, their lungs are riddled with white opacities where black spaceairshould be. Commonly, these patients end up on ventilators. Many die, and survivors may face long-term complications (see sidebar, p. 359). Autopsies show their alveoli became stuffed with fluid, white blood cells, mucus, and the detritus of destroyed lung cells.

Some clinicians suspect the driving force in many gravely ill patients' downhill trajectories is a disastrous overreaction of the immune system known as a cytokine storm, which other viral infections are known to trigger. Cytokines are chemical signaling molecules that guide a healthy immune response; but in a cytokine storm, levels of certain cytokines soar far beyond what's needed, and immune cells start to attack healthy tissues. Blood vessels leak, blood pressure drops, clots form, and catastrophic organ failure can ensue.

Some studies have shown elevated levels of these inflammation-inducing cytokines in the blood of hospitalized COVID-19 patients. The real morbidity and mortality of this disease is probably driven by this out of proportion inflammatory response to the virus, says Jamie Garfield, a pulmonologist who cares for COVID-19 patients at Temple University Hospital.

But others aren't convinced. There seems to have been a quick move to associate COVID-19 with these hyperinflammatory states. I haven't really seen convincing data that that is the case, says Joseph Levitt, a pulmonary critical care physician at the Stanford University School of Medicine.

He's also worried that efforts to dampen a cytokine response could backfire. Several drugs targeting specific cytokines are in clinical trials in COVID-19 patients. But Levitt fears those drugs may suppress the immune response that the body needs to fight off the virus. There's a real risk that we allow more viral replication, Levitt says.

Meanwhile, other scientists are zeroing in on an entirely different organ system that they say is driving some patients' rapid deterioration: the heart and blood vessels.

IN BRESCIA, ITALY, a 53-year-old woman walked into the emergency room of her local hospital with all the classic symptoms of a heart attack, including telltale signs in her electrocardiogram and high levels of a blood marker suggesting damaged cardiac muscles. Further tests showed cardiac swelling and scarring, and a left ventriclenormally the powerhouse chamber of the heartso weak that it could only pump one-third its normal amount of blood. But when doctors injected dye in her coronary arteries, looking for the blockage that signifies a heart attack, they found none. Another test revealed the real cause: COVID-19.

How the virus attacks the heart and blood vessels is a mystery, but dozens of preprints and papers attest that such damage is common. A 25 March paper in JAMA Cardiology found heart damage in nearly 20% of patients out of 416 hospitalized for COVID-19 in Wuhan, China. In another Wuhan study, 44% of 36 patients admitted to the intensive care unit (ICU) had arrhythmias.

The disruption seems to extend to the blood itself. Among 184 COVID-19 patients in a Dutch ICU, 38% had blood that clotted abnormally, and almost one-third already had clots, according to a 10 April paper in Thrombosis Research. Blood clots can break apart and land in the lungs, blocking vital arteriesa condition known as pulmonary embolism, which has reportedly killed COVID-19 patients. Clots from arteries can also lodge in the brain, causing stroke. Many patients have dramatically high levels of D-dimer, a byproduct of blood clots, says Behnood Bikdeli, a cardiovascular medicine fellow at Columbia University Medical Center.

The more we look, the more likely it becomes that blood clots are a major player in the disease severity and mortality from COVID-19, Bikdeli says.

Infection may also lead to blood vessel constriction. Reports are emerging of ischemia in the fingers and toesa reduction in blood flow that can lead to swollen, painful digits and tissue death.

In the lungs, blood vessel constriction might help explain anecdotal reports of a perplexing phenomenon seen in pneumonia caused by COVID-19: Some patients have extremely low blood-oxygen levels and yet are not gasping for breath. In this scenario, oxygen uptake is impeded by constricted blood vessels rather than by clogged alveoli. One theory is that the virus affects the vascular biology and that's why we see these really low oxygen levels, Levitt says.

If COVID-19 targets blood vessels, that could also help explain why patients with pre-existing damage to those vessels, for example from diabetes and high blood pressure, face higher risk of serious disease. Recent Centers for Disease Control and Prevention (CDC) data on hospitalized patients in 14 U.S. states found that about one-third had chronic lung diseasebut nearly as many had diabetes, and fully half had pre-existing high blood pressure.

Mangalmurti says she has been shocked by the fact that we don't have a huge number of asthmatics or patients with other respiratory diseases in her hospital's ICU. It's very striking to us that risk factors seem to be vascular: diabetes, obesity, age, hypertension.

Scientists are struggling to understand exactly what causes the cardiovascular damage. The virus may directly attack the lining of the heart and blood vessels, which, like the nose and alveoli, are rich in ACE2 receptors. By altering the delicate balance of hormones that help regulate blood pressure, the virus might constrict blood vessels going to the lungs. Another possibility is that lack of oxygen, due to the chaos in the lungs, damages blood vessels. Or a cytokine storm could ravage the heart as it does other organs.

We're still at the beginning, Krumholz says. We really don't understand who is vulnerable, why some people are affected so severely, why it comes on so rapidly and why it is so hard [for some] to recover.

THE WORLDWIDE FEARS of ventilator shortages for failing lungs have received plenty of attention. Not so a scramble for another type of equipment: kidney dialysis machines. If these folks are not dying of lung failure, they're dying of renal failure, says neurologist Jennifer Frontera of New York University's Langone Medical Center, which has treated thousands of COVID-19 patients. Her hospital is developing a dialysis protocol with a different kind of machine to support more patients. What she and her colleagues are seeing suggests the virus may target the kidneys, which are abundantly endowed with ACE2 receptors.

According to one preprint, 27% of 85 hospitalized patients in Wuhan had kidney failure. Another preprint reported that 59% of nearly 200 hospitalized COVID-19 patients in China's Hubei and Sichuan provinces had protein in their urine, and 44% had blood; both suggest kidney damage. Those with acute kidney injury were more than five times as likely to die as COVID-19 patients without it, that preprint reported.

The lung is the primary battle zone. But a fraction of the virus possibly attacks the kidney. And as on the real battlefield, if two places are being attacked at the same time, each place gets worse, says co-author Hongbo Jia, a neuroscientist at the Chinese Academy of Sciences's Suzhou Institute of Biomedical Engineering and Technology.

One study identified viral particles in electron micrographs of kidneys from autopsies, suggesting a direct viral attack. But kidney injury may also be collateral damage. Ventilators boost the risk of kidney damage, as do antiviral compounds including remdesivir, which is being deployed experimentally in COVID-19 patients. Cytokine storms can also dramatically reduce blood flow to the kidney, causing often-fatal damage. And pre-existing diseases like diabetes can increase the chances of kidney injury. There is a whole bucket of people who already have some chronic kidney disease who are at higher risk for acute kidney injury, says Suzanne Watnick, chief medical officer at Northwest Kidney Centers.

ANOTHER STRIKING SET of symptoms in COVID-19 patients centers on the brain and nervous system. Frontera says 5% to 10% of coronavirus patients at her hospital have neurological symptoms. But she says that is probably a gross underestimate of the number whose brains are struggling, especially because many are sedated and on ventilators.

Frontera has seen patients with the brain inflammation encephalitis, seizures, and a sympathetic storm, a hyperreaction of the sympathetic nervous system that causes seizurelike symptoms and is most common after a traumatic brain injury. Some people with COVID-19 briefly lose consciousness. Others have strokes. Many report losing their sense of smell and taste. And Frontera and others wonder whether, in some cases, infection depresses the brain stem reflex that senses oxygen starvationanother explanation for anecdotal observations that some patients aren't gasping for air, despite dangerously low blood oxygen levels.

ACE2 receptors are present in the neural cortex and brain stem, says Robert Stevens, an intensive care physician at Johns Hopkins Medicine. And the coronavirus behind the 2003 severe acute respiratory syndrome (SARS) epidemica close cousin of today's culpritwas able to infiltrate neurons and sometimes caused encephalitis. On 3 April, a case study in the International Journal of Infectious Diseases, from a team in Japan, reported traces of new coronavirus in the cerebrospinal fluid of a COVID-19 patient who developed meningitis and encephalitis, suggesting it, too, can penetrate the central nervous system.

But other factors could be damaging the brain. For example, a cytokine storm could cause brain swelling. The blood's exaggerated tendency to clot could trigger strokes. The challenge now is to shift from conjecture to confidence, at a time when staff are focused on saving lives, and even neurologic assessments like inducing the gag reflex or transporting patients for brain scans risk spreading the virus.

Last month, Sherry Chou, a neurologist at the University of Pittsburgh Medical Center, began to organize a worldwide consortium that now includes 50 centers to draw neurological data from care patients already receive. Early goals are simple: Identify the prevalence of neurologic complications in hospitalized patients and document how they fare. Longer term, Chou and her colleagues hope to gather scans and data from lab tests to better understand the virus' impact on the nervous system, including the brain.

No one knows when or how the virus might penetrate the brain. But Chou speculates about a possible invasion route: through the nose, then upward and through the olfactory bulbexplaining reports of a loss of smellwhich connects to the brain. It's a nice sounding theory, she says. We really have to go and prove that.

A 58-year-old woman with COVID-19 developed encephalitis, with tissue damage in the brain (arrows).

Most neurological symptoms are reported from colleague to colleague by word of mouth, Chou adds. I don't think anybody, and certainly not me, can say we're experts.

IN EARLY MARCH, a 71-year-old Michigan woman returned from a Nile River cruise with bloody diarrhea, vomiting, and abdominal pain. Initially doctors suspected she had a common stomach bug, such as Salmonella. But after she developed a cough, doctors took a nasal swab and found her positive for the novel coronavirus. A stool sample positive for viral RNA, as well as signs of colon injury seen in an endoscopy, pointed to a gastrointestinal (GI) infection with the coronavirus, according to a paper posted online in The American Journal of Gastroenterology (AJG).

Her case adds to a growing body of evidence suggesting the new coronavirus, like its cousin SARS, can infect the lining of the lower digestive tract, where ACE2 receptors are abundant. Viral RNA has been found in as many as 53% of sampled patients' stool samples. And in a paper in press at Gastroenterology, a Chinese team reported finding the virus' protein shell in gastric, duodenal, and rectal cells in biopsies from a COVID-19 patient. I think it probably does replicate in the gastrointestinal tract, says Mary Estes, a virologist at Baylor College of Medicine.

Recent reports suggest up to half of patients, averaging about 20% across studies, experience diarrhea, says Brennan Spiegel of Cedars-Sinai Medical Center in Los Angeles, coeditor-in-chief of AJG. GI symptoms aren't on CDC's list of COVID-19 symptoms, which could cause some COVID-19 cases to go undetected, Spiegel and others say. If you mainly have fever and diarrhea, you won't be tested for COVID, says Douglas Corley of Kaiser Permanente, Northern California, co-editor of Gastroenterology.

The presence of virus in the GI tract raises the unsettling possibility that it could be passed on through feces. But it's not yet clear whether stool contains intact, infectious virus, or only RNA and proteins. To date, We have no evidence that fecal transmission is important, says coronavirus expert Stanley Perlman of the University of Iowa. CDC says that, based on experiences with SARS and with the coronavirus that causes Middle East respiratory syndrome, the risk from fecal transmission is probably low.

The intestines are not the end of the disease's march through the body. For example, up to one-third of hospitalized patients develop conjunctivitispink, watery eyesalthough it's not clear that the virus directly invades the eye.

Other reports suggest liver damage: More than half of COVID-19 patients hospitalized in two Chinese centers had elevated levels of enzymes indicating injury to the liver or bile ducts. But several experts told Science that direct viral invasion isn't likely the culprit. They say other events in a failing body, like drugs or an immune system in overdrive, are more likely causes of the liver damage.

This map of the devastation that COVID-19 can inflict on the body is still just a sketch. It will take years of painstaking research to sharpen the picture of its reach, and the cascade of effects in the body's complex and interconnected systems that it might set in motion. As science races ahead, from probing tissues under microscopes to testing drugs on patients, the hope is for treatments more wily than the virus that has stopped the world in its tracks.

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A rampage through the body - Science Magazine

Cardiac Stem Cells Comments Off on A rampage through the body – Science Magazine | April 25th, 2020

Dispositiu per a realitzar registres electrofisiolgics amb les llums LED incorporades per lus doptogentica.

Equip investigador.

Researchers from Lund University (Sweeden) and the Institute of Neurosciences of the University of Barcelona (UBNeuro) have recovered, through cell therapy, the mobility and sensibility of mice that suffered a cardiovascular accident. The results of this study were published in the journal Proceedings of the National Academy of Sciences (PNAS).

Researchers used an ischemic model of ictus in mice to which they transferred stem cells obtained from the skin of a healthy human donor. The cells were reprogramed to become neuronal progenitors of the damaged area of the brain, specifically the brain cortex. Six months after the transplant, researchers could observe how the new cells had repaired the damage that was caused by the cerebrovascular injury. In addition, the sensor and motor problems resulting from the stroke had been reversed as well.

We observed that the fibers of the cells that were put in the cortical area grew and created connections in brain areas that are far from the transplant area, notes Daniel Tornero, researcher in the Laboratory of Stem Cells and Regenerative Medicine in UBNeuro. To identify the transplanted cells, researches used different techniques that enable the monitoring so as to prove the connection in damaged circuits is right. Although there is a lot of work to do -the researcher adds-, the study sheds light on the possibility of replacing the damaged cells for new healthy cells in patients with ictus.

This is the last study of a series of three articles in which the researchers used cell therapy to work on brain healing. Previous studies showed it is possible to transplant nervous cells derived from human stem cells or reprogrammed cells in the brain of mice affected by cardiovascular injuries. However, researchers did not know whether the transformed cells could create new connections in the mice brains and restore the movement and feelings of touch.

The next step is to understand how the transplant affects intellectual functions such as memory, and the potential adverse effects, concludes Tornero.

Article reference:

S. Palma-Tortosa, D. l Tornero, M. Grnning Hansen, E. Monni, M. Hajy, S. Kartsivadze, S. Aktay, O. Tsupykov, M. Parmar, K. Deisseroth, G. Skibo, O. Lindvall, y Z. Kokaia. Activity in grafted human iPS cellderived corticalneurons integrated in stroke-injured rat brain regulatesmotor behavior. Proceedings of the National Academy of Sciences (PNAS). Doi: doi: 10.1073/pnas.2000690117

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Researchers use cell therapy to recover damaged brain areas in mice that suffered - Mirage News

Skin Stem Cells Comments Off on Researchers use cell therapy to recover damaged brain areas in mice that suffered – Mirage News | April 25th, 2020

Using induced pluripotent stem cells produced from the skin of a patient with a rare, genetic form of insulin-dependent diabetes calledWolfram syndrome, researchers transformed the human stem cells into insulin-producing cells and used the gene-editing tool CRISPR-Cas9 to correct a genetic defect that had caused the syndrome. They then implanted the cells into lab mice and cured the unrelenting diabetes in those mice.

The findings, from researchers at Washington University School of Medicine in St. Louis, suggest the CRISPR-Cas9 technique may hold promise as a treatment for diabetes, particularly the forms caused by a single gene mutation, and it also may be useful one day in some patients with the more common forms of diabetes, such as type 1 and type 2.

The study is published online April 22 in the journal Science Translational Medicine.

Patients with Wolfram syndrome develop diabetes during childhood or adolescence and quickly require insulin-replacement therapy, requiring insulin injections multiple times each day. Most go on to develop problems with vision and balance, as well as other issues, and in many patients, the syndrome contributes to an early death.

This is the first time CRISPR has been used to fix a patients diabetes-causing genetic defect and successfully reverse diabetes, said co-senior investigatorJeffrey R. Millman, PhD, an assistant professor of medicine and of biomedical engineering at Washington University. For this study, we used cells from a patient with Wolfram syndrome because, conceptually, we knew it would be easier to correct a defect caused by a single gene. But we see this as a stepping stone toward applying gene therapy to a broader population of patients with diabetes.

Wolfram syndrome is caused by mutations to a single gene, providing the researchers an opportunity to determine whether combining stem cell technology with CRISPR to correct the genetic error also might correct the diabetes caused by the mutation.

A few years ago, Millman and his colleagues discovered how to convert human stem cells into pancreatic beta cells. When such cells encounter blood sugar, they secrete insulin. Recently, those same researchers developed a new technique to more efficiently convert human stem cells into beta cells that are considerably better at controlling blood sugar.

In this study, they took the additional steps of deriving these cells from patients and using the CRISPR-Cas9 gene-editing tool on those cells to correct a mutation to the gene that causes Wolfram syndrome (WFS1). Then, the researchers compared the gene-edited cells to insulin-secreting beta cells from the same batch of stem cells that had not undergone editing with CRISPR.

In the test tube and in mice with a severe form of diabetes, the newly grown beta cells that were edited with CRISPR more efficiently secreted insulin in response to glucose. Diabetes disappeared quickly in mice with the CRISPR-edited cells implanted beneath the skin, and the animals blood sugar levels remained in normal range for the entire six months they were monitored. Animals receiving unedited beta cells remained diabetic. Their newly implanted beta cells could produce insulin, just not enough to reverse their diabetes.

We basically were able to use these cells to cure the problem, making normal beta cells by correcting this mutation, said co-senior investigatorFumihiko Urano, MD, PhD, the Samuel E. Schechter Professor of Medicine and a professor of pathology and immunology. Its a proof of concept demonstrating that correcting gene defects that cause or contribute to diabetes in this case, in the Wolfram syndrome gene we can make beta cells that more effectively control blood sugar. Its also possible that by correcting the genetic defects in these cells, we may correct other problems Wolfram syndrome patients experience, such as visual impairment and neurodegeneration.

In the future, using CRISPR to correct certain mutations in beta cells may help patients whose diabetes is the result of multiple genetic and environmental factors, such as type 1, caused by an autoimmune process that destroys beta cells, and type 2, which is closely linked to obesity and a systemic process called insulin resistance.

Were excited about the fact that we were able to combine these two technologies growing beta cells from induced pluripotent stem cells and using CRISPR to correct genetic defects, Millman said. In fact, we found that corrected beta cells were indistinguishable from beta cells made from the stem cells of healthy people without diabetes.

Moving forward, the process of making beta cells from stem cells should get easier, the researchers said. For example, the scientists have developed less intrusive methods, making induced pluripotent stem cells from blood and they are working on developing stem cells from urine samples.

In the future, Urano said, we may be able to take a few milliliters of urine from a patient, make stem cells that we then can grow into beta cells, correct mutations in those cells with CRISPR, transplant them back into the patient, and cure their diabetes in our clinic. Genetic testing in patients with diabetes will guide us to identify genes that should be corrected, which will lead to a personalized regenerative gene therapy.

Reference:

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Diabetes Reversed in Mice With CRISPR-Edited Stem Cells From Patients - Technology Networks

Skin Stem Cells Comments Off on Diabetes Reversed in Mice With CRISPR-Edited Stem Cells From Patients – Technology Networks | April 24th, 2020

Induced pluripotent stem cells made to produce insulin and CRISPR, used to correct a genetic defect, cured Wolfram syndrome in mice.

Using induced pluripotent stem cells (iPSCs) produced from the skin of a patient with a rare, genetic form of insulin-dependent diabetes called Wolfram syndrome, researchers transformed the human stem cells into insulin-producing cells and used CRISPR-Cas9 to correct a genetic defect that had caused the syndrome. They then implanted the cells into lab mice and cured the unrelenting diabetes in those models.

The findings, from researchers at Washington University School of Medicine in St. Louis, US, suggest this CRISPR-Cas9 technique may hold promise as a treatment for diabetes, particularly the forms caused by a single gene mutation and it also may be useful one day in some patients with the more common forms of diabetes, such as type 1 and type 2.

This is the first time CRISPR has been used to fix a patients diabetes-causing genetic defect and successfully reverse diabetes, said co-senior investigator Dr Jeffrey Millman, an assistant professor of medicine and of biomedical engineering at Washington University. For this study, we used cells from a patient with Wolfram syndrome because, conceptually, we knew it would be easier to correct a defect caused by a single gene. But we see this as a stepping stone toward applying gene therapy to a broader population of patients with diabetes.

Wolfram syndrome is caused by mutations to a single gene, providing the researchers an opportunity to determine whether combining stem cell technology with CRISPR to correct the genetic error also might correct the diabetes caused by the mutation.

Researchers at Washington University School of Medicine in St. Louis have transformed stem cells into insulin-producing cells. They used the CRISPR gene-editing tool to correct a defect that caused a form of diabetes, and implanted the cells into mice to reverse diabetes in the animals. Shown is a microscopic image of insulin-secreting beta cells (insulin is green) that were made from stem cells produced from the skin of a patient with Wolfram syndrome [credit: Millman lab Washington University].

Millman and his colleagues had previously discovered how to convert human stem cells into pancreatic beta cells. When such cells encounter blood sugar, they secrete insulin. Recently, these researchers developed a new technique to more efficiently convert human stem cells into beta cells that are considerably better at controlling blood sugar.

In this study, they took the additional steps of deriving these cells from patients and using the CRISPR-Cas9 gene-editing tool on those cells to correct a mutation to the gene that causes Wolfram syndrome (WFS1). Then, the researchers compared the gene-edited cells to insulin-secreting beta cells from the same batch of stem cells that had not undergone editing with CRISPR.

In the test tube and in mice with a severe form of diabetes, the newly grown beta cells that were edited with CRISPR more efficiently secreted insulin in response to glucose. Diabetes disappeared in mice with the CRISPR-edited cells implanted beneath the skin and the animals blood sugar levels remained in normal range for the entire six months they were monitored. Animals receiving unedited beta cells remained diabetic. Although their newly implanted beta cells could produce insulin, it was not enough to reverse their diabetes.

We basically were able to use these cells to cure the problem, making normal beta cells by correcting this mutation, said co-senior investigator Dr Fumihiko Urano, the Samuel E. Schechter Professor of Medicine and a professor of pathology and immunology. Its a proof of concept demonstrating that correcting gene defects that cause or contribute to diabetes in this case, in the Wolfram syndrome gene we can make beta cells that more effectively control blood sugar. Its also possible that by correcting the genetic defects in these cells, we may correct other problems Wolfram syndrome patients experience, such as visual impairment and neurodegeneration.

Were excited about the fact that we were able to combine these two technologies growing beta cells from induced pluripotent stem cells and using CRISPR to correct genetic defects, Millman said. In fact, we found that corrected beta cells were indistinguishable from beta cells made from the stem cells of healthy people without diabetes.

Moving forward, the process of making beta cells from stem cells should get easier, the researchers said. For example, the scientists have developed less intrusive methods, making iPSCs from blood and they are working on developing stem cells from urine samples.

The study is published in Science Translational Medicine.

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Induced pluripotent stem cells and CRISPR reversed diabetes in mice - Drug Target Review

Skin Stem Cells Comments Off on Induced pluripotent stem cells and CRISPR reversed diabetes in mice – Drug Target Review | April 24th, 2020

Most breast cancers utilize the female hormone estrogen to grow, so drug-induced estrogen deprivation is used as a treatment in many patients. However, cancer will recur in one-third of these patients. A research team at Dartmouths and Dartmouth-Hitchcocks Norris Cotton Cancer Center, led by Todd W. Miller, PhD, is trying to understand why dormant breast cancer cells survive despite being starved of estrogen. The team discovered that an anti-diabetes drug, metformin, which is being tested in many clinical trials as an anti-cancer agent, actually activated fat metabolism that protected dormant breast cancer cells during estrogen deprivation. The findings suggest that the drug has context-dependent effects on cancer cells. The results, entitled AMPK activation by metformin promotes survival of dormant ER+ breast cancer cells, are newly published online inClinical Cancer Research, a journal of the American Association for Cancer Research.

Knowledge that metformin has context-dependent effects on cancer cells will inform a better understanding of ongoing and prior clinical trials testing metformin, and help shape the design of trials moving forward. Our study indicates that the development of drugs targeting fat metabolism is warranted for breast cancer. Most excitingly, anti-angina drugs that block fat metabolism may be quickly repurposed as potential treatments for cancer and tested in clinical trials, says Miller.

Next steps include clinical trials testing drugs that block fat metabolism in breast cancer. Were also designing preclinical studies to further dissect the roles of fat metabolism in breast and other cancers, with the goal of identifying more refined therapeutic targets that will selectively kill cancer cells and not harm healthy cells, notes Miller.

Reference:Hampsch, et al. (2020) AMPK activation by metformin promotes survival of dormant ER+ breast cancer cells. Clinical Cancer Research DOI: 10.1158/1078-0432.CCR-20-0269.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Team Reveal Key to the Survival of Dormant Breast Cancer Cells - Technology Networks

Skin Stem Cells Comments Off on Team Reveal Key to the Survival of Dormant Breast Cancer Cells – Technology Networks | April 24th, 2020

Good morning,

Crucial data gaps are hurting Canadas ability to fight the COVID-19 pandemic, leaving Canadians in the dark about who is being infected or struggling with the devastated economy.

Canada has a long-standing problem of information gaps, The Globe and Mail found in a year-long series, and that has left us vulnerable during public health crises before. But now, these blind spots could blunt the federal economic rescue effort, hide inequities in deaths from the disease and slow our emergence from self-isolation in the months ahead.

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Father Victor Fernandes puts on personal protection equipment prior to visiting with a patient in the COVID-19 intensive care unit at St. Paul's hospital in downtown Vancouver on April 21, 2020.

JONATHAN HAYWARD/The Canadian Press

This is the daily Morning Update newsletter. If youre reading this on the web, or it was forwarded to you from someone else, you can sign up for Morning Update and more than 20 more Globe newsletters on our newsletter signup page.

Nova Scotia shooting: Premier Stephen McNeil is urging his mourning province to help investigators unravel questions around a gunmans weekend rampage. A new tip line was created specifically for the killings. He acknowledged there is anger over the RCMPs decision not to use the provincial emergency alert system during the 12-hour manhunt, but he asked people to be patient, and wait for answers.

New details are emerging about the chaos that ensued as police tried to capture the killer disguised as an RCMP officer. Audio recordings of first responders communicating on two-way radios provide a glimpse of frantic attempts to help the first victims in the village of Portapique.

A couple pays their respects at a memorial in Portapique, N.S., on April 22, 2020.

Andrew Vaughan/The Canadian Press

Economy: Saskatchewan has laid out a detailed, comprehensive plan to reopen its economy, and is the first province in the country to do so. On May 4, the five phases will begin, opening non-essential medical procedures, and the reopening of provincial parks, campgrounds and golf courses.

In Quebec, Premier Franois Legault is preparing to lay the groundwork next week for a plan to gradually restart the provinces economy and get children back to school.

Rent: Ottawa is proposing to offer commercial rent relief, in the form of loans for landlords of small and medium-sized businesses, that would cover up to 75 per cent of tenants payments for three months, according to sources familiar with the negotiations.

When it comes to investment properties, small landlords across Canada might not qualify for government assistance and are scrambling to figure out how to accommodate rent reductions while making their mortgage payments.

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World news:

Researchers at the University of Oxford are racing to develop a vaccine for COVID-19 and plan to make a million doses of it this summer. The team has been working since January, and clinical trials involving more than 500 volunteers began yesterday. The testing is expected to take several months, but the researchers have already teamed up with manufacturers globally to produce the doses September and millions more by the end of the year. The Globes Paul Waldie reports.

An aerial view of people queuing outside a bank in downtown Quito, Ecuador, on April 22, 2020.

RODRIGO BUENDIA/AFP/Getty Images

Got a news tip that youd like us to look into? E-mail us at tips@globeandmail.com Need to share documents securely? Reach out via SecureDrop

Scheer, Tories refrain from criticizing MP accused of racist comments: People of Asian descent have faced a spike in hate crimes and slurs since the COVID-19 pandemic began in China last year and experts say the comments from an elected official give licence for the attacks to continue.

Child protection organizations seeing significant uptick in predators: In dark-web forums, sexual predators are increasingly discussing the COVID-19 pandemic as an opportunity to exploit children online as they spend more time out of school and on the internet.

Ontarios Serious Fraud Office investigates Bondfield: A special unit of Ontario police officers and prosecutors launched the investigation in 2019, looking into allegations of wrongdoing by a major builder of hospitals, transit stations and other public infrastructure across the province.

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Parents of teen girls killed by Paul Bernardo seek to obtain his file with the parole board: The two families filed for judicial review this month after their requests for the documents under access to information legislation were denied.

MPs seek to overcome hurdle in getting WHO adviser to testify: A parliamentary committee scrutinizing the response to the pandemic is working to get key World Health Organization adviser Bruce Aylward to testify. The WHOs legal counsel has said that Dr. Aylward cannot testify unless he receives authorization from WHO Director-General Tedros Adhanom Ghebreyesus.

World stocks fall on worries over EU stimulus details, coronavirus drug: Global shares fell on Friday, spurred by delays to an agreement on divisive details of the European Unions stimulus package and doubts about progress in the development of drugs to treat COVID-19. In Europe, Britains FTSE 100 was down 0.93 per cent around 6 a.m. ET. Germanys DAX and Frances CAC 40 fell 1.07 per cent and 1.03 per cent, respectively. In Asia, Japans Nikkei fell 0.86 per cent. Hong Kongs Hang Seng fell 0.61 per cent. New York futures were flat. The Canadian dollar was trading at 71.05 U.S. cents.

Canada must protect itself from Americas response to COVID-19

Robyn Urback: It is not implausible that Mr. Trump would retaliate in some sort of petty but potentially grave economic way on supply lines for essential goods, for example if Canada refuses to lift restrictions on non-essential travel if and when the President decides that time is up.

This Ramadan, in solitude, will be more meaningful than ever

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Fatima Al Fahim: But the pandemic need not dampen Ramadan spirits. Physical distancing gives us a reminder of the true meaning of the holy month.

The world has a big China problem now

Campbell Clark: We dont know precisely what happened in China in the early days of COVID-19, but we know some whistle-blowers were stifled and, for whatever reason, officials waited for days to tell the world after learning they faced a serious epidemic.

By Brian Gable

Brian Gable/The Globe and Mail

What you really need is a room edit, not a reno

Especially while in isolation, you may be looking for curatorial guidance, but are keen to avoid the expense of a full interiors overhaul. Some people would rather rip out a wall or buy a bigger house, when all it often takes is reimaging and reworking what you already have, says Joanna Teplin, the Nashville co-founder of the Home Edit. If you want to remodel, read about how you might be able to make the change with what you already have.

Snuppy, right, the first male dog cloned from adult cells by somatic nuclear cell transfer, and the male Afghan hound from which an adult skin cell was taken to clone Snuppy, are seen in this handout photo released in Seoul on Aug. 3, 2005.

Seoul National University via Reuters

Snuppy worlds first cloned dog is born

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If he were born today, Snuppy would be dubbed, in internet lingo, a very good pupper or an excellent doggo. Instead, Snuppy, the first successful clone of a dog, had to settle for merely being hailed as a breakthrough in biotechnology. A team of 45 South Korean researchers, led by stem-cell researcher Hwang Woo-suk, produced the pup using a process called somatic cell nuclear transfer with a cell from the ear of a male Afghan dog, Tai. Snuppy was named for Seoul National University (SNU) and puppy. While other mammals had been cloned successfully starting with Dolly the sheep in 1996 cloning mans best friend proved more challenging. The achievement suggested that, given time and expertise, almost any mammal could be reproduced. Defying concerns that clones would be rife with ailments, Snuppy was generally healthy. He fathered 10 pups by artificial insemination and produced, by stem-cell clone, a litter with three surviving pups. Snuppy died of cancer, a common fate in dogs, just days after his 10th birthday in 2015. Jessie Willms

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Morning Update: Canadas data gaps are hurting our ability to fight the pandemic - The Globe and Mail

Skin Stem Cells Comments Off on Morning Update: Canadas data gaps are hurting our ability to fight the pandemic – The Globe and Mail | April 24th, 2020

Findings confirmed that patient-specific autologous dendritic cell vaccines (DCV) induced a different immune response associated with longer survival than autologous tumor cell vaccines (TCV)

IRVINE, Calif.--(BUSINESS WIRE)-- AIVITA Biomedical, Inc., a biotechnology company specializing in innovative cell therapy applications, announced today the publication of a paper titled, Cytokine network analysis of immune responses before and after autologous dendritic cell and tumor cell vaccine immunotherapies in a randomized trial, in the Journal of Translational Medicine. Robert O. Dillman, M.D., chief medical officer at AIVITA, and Gabriel I Nistor, M.D., chief scientific officer at AIVITA, authored the article.

The publication provides insight into the innate and adaptive immune responses induced by patient-specific autologous dendritic cell vaccines (DCV) and autologous tumor cell vaccines (TCV), and their impact on survival. DCV was associated with a multipronged innate and adaptive immune response and correlated with improved survival compared to TCV.

In a randomized Phase 2 trial conducted in patients with melanoma, blood samples were obtained at one week before and one week after a course of three weekly injections, which either included dendritic cells loaded ex vivo with antigens from autologous irradiated tumor-initiating cells (DCV), or autologous irradiated tumor-initiating cells alone (TCV). Cytokine network analysis techniques used to analyze the serologic immune responses generated by each immunotherapy confirmed they triggered differing responses. The results help provide insight into a potential underlying immunologic mechanism of action that contributes to improved survival in DCV-treated patients.

This analysis reinforces conclusions from our patient-specific cancer vaccine survival data, which suggested that ex-vivo processing of the same tumor antigens by autologous dendritic cells induces a more advantageous immune response than antigen-only based tumor cell vaccines, said Dr. Nistor. This is reassuring as we continue to further optimize our unique approach in which we use enhanced autologous dendritic cells for targeting each patients own tumor.

AIVITA is currently conducting three independent clinical studies investigating its platform immunotherapy in patients with ovarian cancer, glioblastoma and melanoma. AIVITA uses 100% of proceeds from the sale of its ROOT of SKIN skincare line to support the development of its cancer therapeutic pipeline.

About AIVITAS Clinical Trials

OVARIAN CANCER

AIVITAs ovarian Phase 2 double-blind study is active and enrolling approximately 99 patients who are being randomized in a 2:1 ratio to receive either the autologous tumor-initiating cell-targeting immunotherapy or autologous monocytes as a comparator.

Patients eligible for randomization and treatment will be those (1) who have undergone debulking surgery, (2) for whom a cell line has been established, (3) who have undergone leukapheresis from which sufficient monocytes were obtained, (4) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), and (5) who have completed primary therapy. The trial is not open to patients with recurrent ovarian cancer.

For additional information about AIVITAs AVOVA-1 trial patients can visit: http://www.clinicaltrials.gov/ct2/show/NCT02033616

GLIOBLASTOMA

AIVITAs glioblastoma Phase 2 single-arm study is active and is enrolling approximately 55 patients to receive the tumor-initiating cell-targeting immunotherapy.

Patients eligible for treatment will be those (1) who have recovered from surgery such that they are about to begin concurrent chemotherapy and radiation therapy (CT/RT), (2) for whom an autologous tumor cell line has been established, (3) have a Karnofsky Performance Status of > 70 and (4) have undergone successful leukapheresis from which peripheral blood mononuclear cells (PBMC) were obtained that can be used to generate dendritic cells (DC). The trial is not open to patients with recurrent glioblastoma.

For additional information about AIVITAs AV-GBM-1 trial please visit: http://www.clinicaltrials.gov/ct2/show/NCT03400917

MELANOMA

AIVITAs melanoma Phase 1B open-label, single-arm study will establish the safety of administering anti-PD1 monoclonal antibodies in combination with AIVITAs tumor-initiating cell-targeting immunotherapy in patients with measurable metastatic melanoma. The study will also track efficacy of the treatment for the estimated 14 to 20 patients. This trial is not yet open for enrollment.

Patients eligible for treatment will be those (1) for whom a cell line has been established, (2) who have undergone leukapheresis from which sufficient monocytes were obtained, (3) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), (4) who have either never received treatment for metastatic melanoma or were previously treated with enzymatic inhibitors of the BRAF/MEK pathway because of BRAF600E/K mutations and (5) are about to initiate anti-PD1 monotherapy.

For additional information about AIVITAs AV-MEL-1 trial please visit: http://www.clinicaltrials.gov/ct2/show/NCT03743298

About AIVITA Biomedical

AIVITA Biomedical is a privately held company engaged in the advancement of commercial and clinical-stage programs utilizing curative and regenerative medicines. Founded in 2016 by pioneers in the stem cell industry, AIVITA Biomedical utilizes its expertise in stem cell growth and directed, high-purity differentiation to enable safe, efficient and economical manufacturing systems which support its therapeutic pipeline and commercial line of skin care products. All proceeds from the sale of AIVITAs skin care products support the treatment of people with cancer.

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AIVITA Biomedical Publishes Study Comparing Immune Responses and Associated Survivals Induced by Dendritic and Tumor Cell Vaccines - BioSpace

Skin Stem Cells Comments Off on AIVITA Biomedical Publishes Study Comparing Immune Responses and Associated Survivals Induced by Dendritic and Tumor Cell Vaccines – BioSpace | April 24th, 2020

New research results show promise in treating people who are blind.

The National Eye Institute funded the study, which is research considered to be ethical.

Dr. David Prentice of the Charlotte Lozier Institute says there have been discussions over using adult stem cells to restore sight, which he calls a different tack for advancing science and medicine.

It's still an ethical way to go about this, he observes. There's no embryonic stem cells, no fetal tissue, none of this unethical type of research direction.

What the scientists did was turn a skin cell directly into a photoreceptor for vision then transplanted it.

Prenticeadvises the testing is very preliminary after the experiment on mice.

But what they find was when they transplanted this newly formed type of vision cell into the eyes of these blind mice, he says, they restored their vision.

The researchers applied chemicals that transformed one cell type into another needed for vision, and there is now potential to help people with all forms of vision blindness or vision correction, which would include macular degeneration and other retinal disorders.

Editor's note: Original posting attribute comments to wrong person.

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Lozier praises promising, and ethical, blindness study - OneNewsNow

Skin Stem Cells Comments Off on Lozier praises promising, and ethical, blindness study – OneNewsNow | April 24th, 2020

Just because you cant head to a nail salon right now doesnt mean you should neglect your hands, feet and nails. Plus, the excessive hand washing youve been doing still the most reliable way to protect yourself and your family from Covid-19 can also strip skin of its natural oils and leave it dry. Heres what you can do:

If youre lazy, just use a body scrub in the shower, starting from the feet up. But for a little DIY pampering, start with a foot soak to soften rough heels and soles, then use a foot scrub.

This is important, especially for the hands, as the skin there is thinner than the rest of the body. Its also one of the first places to show signs of ageing. Plus, if the skin on your hands and feet are extremely dry, it could develop micro cracks that allow germs in, making you unwell.

Did you know that massaging cuticle oil on your cuticles and nails every day can improve blood flow to the nail matrix (the root), which makes your nails strong and healthy? If you tend to forget, keep the bottle by your WFH work desk or at your bedside as a nightly reminder.

Here are seven treats to get your hands, feet and nails looking great, when youre stuck at home:

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The Body Shop ? Almond Hand And Nail Cream 30ml 95.000 Order WA : 0878 8850 6509 #thebodyshop #bodybutter #vitamin #moisturizer #showergel #edt #parfum #bodymist #sabunmandi #sabuncair #makeup #teatree #vitamine #strawberry #vanilla #mango #tbs #thebodyshopsurabaya #thebodyshopalmondhandcream #handcreamthebodyshop #almondhandcream #almond #pelembab #thebodyshop #handcream #krimtangan #pelembabtangan Pelembap khusus tangan dan kuku dengan aroma sweet almond. Membantu membuat tangan dan kuku menjadi lembap, lembut, dan tampak sehat.

A post shared by haii rek ? (@mbakaysurabaya) on Feb 27, 2020 at 11:38am PST

Sweet almond oil and shea butter nourish skin, strengthen nails, and keep your hands soft.

Available atwww.thebodyshop.com/en-sg/and when stores re-open, at The Body Shop.

Not everyone likes using a thick, heavy cream, especially when you dont have the aircon on when you work from home. The heat just makes it all the more sticky.

This lotion is lightweight yet intensively hydrates hands with organic shea butter, USDA-certified organic jojoba seed oil and rice bran oil, yet remains lightweight on the skin.

The latter ingredient contains vitamin E, which protects your hands against UV damagewhich helps give added projection if you work by the window.

Available atwww.thann.com.sg

ALSO READ:9 nail products to help you get a salon-quality manicure at home

A five-oil blend of jojoba, sunflower, argan, pomegranate and tamu moisturise dry cuticles, keeping nails healthy, and soothing skin. We love the rollerball for fuss-free application and the delicate citrus and rose geranium scent.

Available atwww.net-a-porter.com

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#???? #??? . ???? ????? ??!! ???? ????, ???? ????, ???? ????, ????? #legspa #?? #????? #cureprogram #?????? #?

A post shared by ???(????PT? WEgym) (@n___hyunwoo) on Feb 15, 2019 at 11:14pm PST

You wear the mask like socks that reach up to mid-shin, taping the tabs down for a snug fit. The inside of the mask contains its formula of 7 essential oils and 11 herbs (including spearmint, eucalyptus, grapefruit, bergamot, juniper and thyme) to relieve tired feet and legs, and keep them soft and hydrated.

Available atwww.ksisters.sg

View this post on Instagram

I’m not a big “exfoliate in the shower person,”but the smell of this product is divine and makes me want to buff my bits? @aesopskincare #aesop #aesopbodyscrub #aesopredemptionbodyscrub #aesopscrub #bodyscrub #skincare #beauty #aesopskincare #scrub

A post shared by Susan B (@susybliving) on May 17, 2019 at 9:40am PDT

For quick exfoliation in the shower, use this creamy body scrub. It contains finely milled pumice stone and bamboo stem to gently buff away dead skin cells and dirt. Skin feels smoother and softer, from top to toe.

Available atwww.aesop.com/sg/andwww.net-a-porter.com

View this post on Instagram

So for those of who missed my stories early last week, I wanted to start a fun @drunkelephant tag myself so I came up with #silisaturday ? I have been really enjoying lathering myself up with the new Sili Body Lotion. It is so light, absorbs quickly into the skin but your skin is still left feeling hydrated & soft - no greasy residue, which is something I hate in a lot of body lotions / body butters. There is a very subtle sweet almond scent but you have to really look for it in order to smell it. I remember opening the bottle to smell it and didn’t at first; but the smell was more noticeable once I started actually applying it. I can’t wait to get my hands on the rest of the new hair & body collection - I’ll have a review up soon of the Marula Detangler Spray once I’ve used it a bit more to really get a solid opinion! ? . . Show me your #silisaturday photos & I will be sharing them on my stories! ?? . . #drunkelephant #drunkelephantskincare #drunkelephantforlife #drunkelephantsili #silibodylotion #skin #cleanbeauty #cleanskincare #acleanbreak #skincare #skincareroutine #skincareproducts #skincaretips #skincarejunkie #skincarecommunity #skincareroutines #skincareblogger #skincaretipsandtricks #skincareaddict #skincarelover #skincareobsessed #skincareregime #skincarereview

A post shared by Jennifer (@makeupxdanseee) on Apr 4, 2020 at 11:55am PDT

A body lotion is the easiest way to ensure that every bit of skin gets hydration, not just your hands and feet. This one contains nourishing plant oils and butters, together with amino acids, ceramides and antioxidants that lock in moisture, soothe dryness and itch, and protect skin from free radical damage.

Available atwww.sephora.sgand when stores re-open, at Sephora.

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Werbung- Happy Sunday Ihr Lieben ? was macht Ihr heute? Bei uns ist es recht kühl und Dauerregen? Ideales Wetter für ein bisschen Me-Time zuhause. Sonntag ist eh immer mein Pflege-Tag mit Masken, Baden, Peelings und Co. Ich habe vor kurzem diese neuen Gold Masken für Hände und Füße?von Starskin zugeschickt bekommen. Kennt Ihr die Marke schon? Benutzt Ihr solche Hand & Fuß Masken? Ich habe das tatsächlich noch nie probiert ? Bin immer zu ungeduldig für sowas. PS: Es freut mich, dass soviele beim Gewinnspiel mitmachen ? Daher kommt wahrscheinlich auch schon nächste Woche das nächste für Euch ??Ich wünsche Euch einen schönen Sonntag ?? #instabeauty #instamakeup #makeup #makeupadicct #makeupjunkie #skincare #starskin #starskingold #starskinsquad #starskinmask #starskinbeauty #beautyaddict #beautyjunkie #beautyblogger_de #bblogger #cosmetics #cosmetic #highendlove #blogger_de #starskinthegoldmask

A post shared by I L O N K A T I M M (@highendloveblog) on Aug 18, 2019 at 3:17am PDT

An intensive treatment for your hands, the mask contains two layers: The inner layer contains Bulgarian rose, shea butter and rose hip oil to nourish while the outer protective foil creates a warming effect to enhance absorption of the active ingredients. Hands are soft, supple and conditioned in 15 minutes.

Available atwww.sephora.sgand when stores re-open, at Sephora.

For the latest updates on the coronavirus, visithere.

This article was first published in Her World Online.

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How to care for your nails at home now that you can't go to the salon - AsiaOne

Skin Stem Cells Comments Off on How to care for your nails at home now that you can’t go to the salon – AsiaOne | April 24th, 2020

- Phase 3 REACH2 data demonstrate that ruxolitinib (Jakafi) improves outcomes across a range of efficacy measures in patients with steroid-refractory acute graft-versus-host disease (GVHD) compared to best available therapy (BAT)

- Results show a significantly greater overall response rate (ORR) in patients treated with ruxolitinib (62%) compared to BAT (39%) 1,2

- GVHD is a serious and common complication of allogeneic stem cell transplants with a one-year mortality rate as high as 80% in patients who develop acute GVHD3-5

- The results, published in The New England Journal of Medicine, were also selected for an oral presentation during the Presidential Symposium at the European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting to be held 30 August to 2 September in Madrid, Spain

Incyte (Nasdaq:INCY) today announced that data from the Phase 3 REACH2 study have been published in The New England Journal of Medicine demonstrating that ruxolitinib (Jakafi) improves outcomes across a range of efficacy measures in patients with steroid-refractory acute graft-versus-host disease (GVHD) compared to best available therapy (BAT). The results of REACH2, the first Phase 3 study of ruxolitinib in acute GVHD to have met its primary endpoint, reinforce findings from the previously-reported Phase 2 REACH1 study.

In REACH2, patients treated with ruxolitinib experienced a significantly greater overall response rate (ORR) vs. BAT (62% vs. 39%; p<0.001) at Day 28, the primary endpoint of the study. For the key secondary endpoints, patients treated with ruxolitinib maintained significantly higher durable ORR (40% vs. 22%; p<0.001) at Day 56. In addition, ruxolitinib was associated with longer median failure free survival (FFS) than BAT (5.0 months vs. 1.0 months; hazard ratio 0.46, 95% CI, 0.35 to 0.60) and showed a positive trend with other secondary endpoints, including duration of response1,2.

No new safety signals were observed, and the ruxolitinib safety profile in REACH2 was consistent with that seen in previously reported studies in steroid-refractory acute GVHD. The most frequently reported adverse events among study participants were thrombocytopenia and anemia. While 38% and 9% of patients required ruxolitinib and BAT dose modifications, the number of patients who discontinued treatment due to AEs was low (11% and 5%, respectively)1,2.

"The results from the REACH2 study reinforce findings from the pivotal REACH1 trial and demonstrate the potential that ruxolitinib has to effectively and safely improve outcomes for patients with GVHD," said Peter Langmuir, M.D., Group Vice President, Oncology Targeted Therapies, Incyte. "We are committed to continuing our research in GVHD with the goal of providing more effective treatment options for patients living with this disease, and look forward to the results of the REACH3 study in steroid-refractory chronic GVHD later this year."

The REACH2 data were also accepted as an oral presentation as part of the Presidential Symposium at the European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting to be held 30 August to 2 September in Madrid, Spain.

"Patients with acute graft-versus-host disease face life-threatening challenges with limited treatment options, particularly for the nearly half of individuals who do not respond to initial steroid therapy," said Robert Zeiser, University Hospital Freiburg, Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg, Germany. "These new data from REACH2 showing superiority of ruxolitinib over current standard-of-care therapies add to a growing body of evidence on how targeting the JAK pathway can be an effective strategy in this difficult-to-treat condition."

In 2019, Jakafi (ruxolitinib) was approved by the U.S. Food and Drug Administration for the treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older, based on the positive results of the Phase 2 REACH1 trial6. The Phase 3 REACH3 study in patients with steroid-refractory chronic GVHD is ongoing and results are expected in the second half of this year. Jakafi is marketed by Incyte in the U.S.; ruxolitinib (Jakavi) is licensed to Novartis ex-U.S.

The NEJM publication of the REACH2 results is available online.

Story continues

About REACH2

REACH2 (NCT02913261), a randomized, open-label, multicenter Phase 3 study sponsored by Novartis and conducted in collaboration with and co-funded by Incyte , is evaluating the safety and efficacy of ruxolitinib compared with best available therapy in patients with steroid-refractory acute GVHD.

The primary endpoint was overall response rate (ORR) at Day 28, defined as the proportion of patients demonstrating a best overall response (complete response or partial response). Secondary endpoints include durable ORR at Day 56, ORR at Day 14, duration of response, overall survival and event-free survival, among others. For more information about the study, please visit https://clinicaltrials.gov/ct2/show/NCT02913261.

About REACH

The REACH clinical trial program evaluating ruxolitinib in patients with steroid-refractory GVHD, includes the randomized pivotal Phase 3 REACH2 and REACH3 trials, conducted in collaboration with Novartis. The ongoing REACH3 trial is evaluating patients with steroid-refractory chronic GVHD with results expected later this year. For more information about the REACH3 study, please visit https://clinicaltrials.gov/ct2/show/NCT03112603.

The REACH program was initiated with the Incyte-sponsored REACH1 trial, a prospective, open-label, single-cohort, multicenter, pivotal Phase 2 trial (NCT02953678) evaluating Jakafi in combination with corticosteroids in patients with steroid-refractory grade II-IV acute GVHD. For more information about the study, including trial results, please visit https://clinicaltrials.gov/show/NCT02953678.

About Jakafi (ruxolitinib)

Jakafi is a first-in-class JAK1/JAK2 inhibitor approved by the U.S. FDA for the treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea, in adults with intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF and for the treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older.

Jakafi is marketed by Incyte in the United States and by Novartis as Jakavi (ruxolitinib) outside the United States. Jakafi is a registered trademark of Incyte Corporation. Jakavi is a registered trademark of Novartis AG in countries outside the United States.

Important Safety Information

Jakafi can cause serious side effects, including:

Low blood counts: Jakafi (ruxolitinib) may cause your platelet, red blood cell, or white blood cell counts to be lowered. If you develop bleeding, stop taking Jakafi and call your healthcare provider. Your healthcare provider will perform blood tests to check your blood counts before you start Jakafi and regularly during your treatment. Your healthcare provider may change your dose of Jakafi or stop your treatment based on the results of your blood tests. Tell your healthcare provider right away if you develop or have worsening symptoms such as unusual bleeding, bruising, tiredness, shortness of breath, or a fever.

Infection: You may be at risk for developing a serious infection during treatment with Jakafi. Tell your healthcare provider if you develop any of the following symptoms of infection: chills, nausea, vomiting, aches, weakness, fever, painful skin rash or blisters.

Skin cancers: Some people who take Jakafi have developed certain types of non-melanoma skin cancers. Tell your healthcare provider if you develop any new or changing skin lesions.

Increases in cholesterol: You may have changes in your blood cholesterol levels. Your healthcare provider will do blood tests to check your cholesterol levels during your treatment with Jakafi.

The most common side effects of Jakafi include: for certain types of MF and PV - low platelet or low red blood cell counts, bruising, dizziness, headache, and diarrhea; and for acute GVHD low platelet, red or white blood cell counts, infections, and fluid retention.

These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. Tell your healthcare provider about any side effect that bothers you or that does not go away.

Before taking Jakafi, tell your healthcare provider about: all the medications, vitamins, and herbal supplements you are taking and all your medical conditions, including if you have an infection, have or had tuberculosis (TB), or have been in close contact with someone who has TB, have or had hepatitis B, have or had liver or kidney problems, are on dialysis, have a high level of fat in your blood (high blood cholesterol or triglycerides), had skin cancer or have any other medical condition. Take Jakafi exactly as your healthcare provider tells you. Do not change or stop taking Jakafi without first talking to your healthcare provider.

Women should not take Jakafi while pregnant or planning to become pregnant. Do not breast-feed during treatment with Jakafi and for 2 weeks after the final dose.

Full Prescribing Information, which includes a more complete discussion of the risks associated with Jakafi, is available at http://www.jakafi.com.

About Incyte

Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com and follow @Incyte.

Forward-Looking Statements

Except for the historical information set forth herein, the matters set forth in this press release, including statements about the REACH2 data, when results from the REACH3 study will be available, the effect of the REACH2 results on patients with GVHD, and the overall REACH program, contain predictions, estimates and other forward-looking statements.

These forward-looking statements are based on the Companys current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: unanticipated delays; further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials; determinations made by the FDA; the Companys dependence on its relationships with its collaboration partners; the efficacy or safety of the Companys products and the products of the Companys collaboration partners; the acceptance of the Companys products and the products of the Companys collaboration partners in the marketplace; market competition; sales, marketing, manufacturing and distribution requirements; greater than expected expenses; expenses relating to litigation or strategic activities; and other risks detailed from time to time in the Companys reports filed with the Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2019. The Company disclaims any intent or obligation to update these forward-looking statements.

References

View source version on businesswire.com: https://www.businesswire.com/news/home/20200422005739/en/

Contacts

Incyte Contacts Media Jenifer Antonacci+1 302 498 7036jantonacci@incyte.com

Catalina Loveman+1 302 498 6171cloveman@incyte.com

Investors Michael Booth, DPhil+1 302 498 5914mbooth@incyte.com

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Incyte Announces Pivotal REACH2 Study Data Published in NEJM Highlight Superior Efficacy of Ruxolitinib (Jakafi) versus Best Available Therapy in...

Skin Stem Cells Comments Off on Incyte Announces Pivotal REACH2 Study Data Published in NEJM Highlight Superior Efficacy of Ruxolitinib (Jakafi) versus Best Available Therapy in… | April 24th, 2020

A few weeks afterreceiving chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, many patientsexperience prolonged reductions in blood cell counts, possibly making them morevulnerable to infections.

Two recent studies characterized the extent and duration of postCAR-T cytopenia among patients receiving CAR-T therapy for hematological malignancies with 1 study offering insights on some of the possible factors that may influence hematological count recovery.

Whats important to know is that by day 90, mostpatients recover, noted UroosaIbrahim, MD, stemcell transplantation and cellular therapy fellow at the Tisch Cancer Instituteof the Icahn School of Medicine at Mount Sinai,New York, who coauthored 1 of the studies. Were supporting them for [approximately]3 months [with treatment], but then theyll recover, which is good to know.

One study by MemorialSloan Kettering Cancer Center (MSKCC) researchers followed 83 adult patientswho received CAR-T therapy: 40 patients received 1 of 2 Food and DrugAdministration (FDA)-approved therapies, axicabtageneciloleucel (axi-cel; Yescarta) ortisagenlecleucel (tisa-cel; Kymriah), to treat relapsed/refractory B-cell lymphoma.

The remainder comprised 37 patients with relapsed/refractory B-cell acute lymphoblastic leukemia who were currently enrolled in a clinical trial in which they received an experimental CAR-T therapy where cells express the 19-28z CAR construct (ClinicalTrials.gov Identifier: NCT01044069), and 6 multiple myeloma patients who received a different experimental CAR-T construct that targets the B-cell maturation antigen (BCMA) (ClinicalTrials.gov Identifier: NCT03070327). The findings were presented at the annual Transplantation and Cellular Therapy Meetings of ASCT and CIBMTR in February 2020.1

By 1 month, theresearchers observed that 24% of patients experienced a complete recovery ofhemoglobin, platelets, absolute neutrophil count, and white blood cell counts recovery being defined as reaching safe levels, and without requiringtransfusions or treatment with growth factors.

Recovery of hemoglobinwas noted in 61% of patients, platelets in 51% of patients, absolute neutrophilcount in 33% of patients, and white blood cell count in 28% of patients.Examining 41 patients at 3 months, those figures were 93%, 90%, 81%, and 59%,respectively, and overall, 56% saw a complete blood count recovery.

The results werebroadly consistent with recent research by Dr Ibrahim and Keren Osman, MD,associate professor and director of medicine at the Icahn School of Medicine atMount Sinai and director of cellular therapy service in the bone marrow andstem cell transplantation program at the schools Tisch Cancer Institute. Thatstudy comprised 50 patients 41 with multiple myeloma and 9 with diffuse largeB-cell lymphoma who received either axicabtagene ciloleucel, or 1 of 2 experimentalanti-BCMA CAR-T therapies, bb2121 or bb21217.

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What Factors Influence Hematological Recovery in Patients Who Receive CAR-T Therapies? - Cancer Therapy Advisor

Bone Marrow Stem Cells Comments Off on What Factors Influence Hematological Recovery in Patients Who Receive CAR-T Therapies? – Cancer Therapy Advisor | April 24th, 2020

Alumni members of National Institute of Technology - Tiruchi (NIT-T) holding key positions in tech companies across the globe have responded overwhelmingly through their knowledge support, innovative devices, fund mobilisation, and production of personal protection equipment for dealing with the COVID-19 pandemic.

An associate of Global Consortium of Cell Therapy Companies, Stempeutics, an Indian stem cell company of which B. N Manohar, an alumnus of ECE 1977 batch is the Chief Executive Officer, will shortly be supplying clinical-grade Mesenchymal Stem Cells (multi-potent stem cells found in the bone marrow used for making and repairing skeletal tissues) to those in need. Manufactured in the Manipal GMP facility under approval of Drug Controller General of India, the multi-potent stem cells have been found to reduce the symptoms of pneumonia induced by COVID-19 and halt its advancement to Acute Respiratory Distress Syndrome, NIT-T Director Mini Shaji Thomas said.

S. K. Ramesh, an alumnus of 1981 batch ECE holding a senior position in California State University, Northridge, is involved along with his colleagues in creation of life saving face shields and other personal protection equipment for donating the same to healthcare workers in hospitals throughout Southern California.

Blooom Energy, founded by K. R. Sridhar, who had completed his mechanical engineering degree from the then Regional Engineering College Tiruchi, and subsequently did his masters degree in Nuclear Engineering, and Ph.D. in Mechanical Engineering from the University of Illinois, Urbana-Champaign, has undertaken the task of repairing ventilators on a bulk scale in partnership with Stanford Health Care.

Chief Innovation Officer at Dulso, United Arab Emirates, Madhumohan Sreeram, an alumnus of NIT-T who had completed B.Tech in Chemical Engineering in 1982, has been in the forefront in carrying out sanitisation of the municipality of Dubai after identifying a suitable disinfectant QUATPLUS TB, which is a Quaternary Ammonium Compound product approved by United States Environmental Protection Agency and American chemistry councils Center Biocide Chemistry (CBC) and has been listed in their recommended EPA pre-approved products for COVID-9 disinfection application.

Richard Sekar, an alumnus who had completed Production Engineering in 1983 leads Warriors Against Virus a team of 371 volunteers in the Bay Area, USA, for stitching facial masks for hospital requirement. IcarusNova, of which Sapna Behar, an alumna (1990, EEE), is the Director and Founder, has partnered with LifeSignals to design a wireless biosensor-based patch, with ISO 13485 accreditation, for early detection and continuous monitoring of COVID-19 symptoms. The patches when affixed on the chest area can monitor the temperature, breathing rate, trace ECG and heart rate as a real time data. The data can be transferred to the users phone through an app. The system reduces the risk of contamination between patients and other individuals.

Admiral Superintendent of Naval Dockyard, Vishakapatnam, Sreekumar Nair (ECE, 1986), has led a team to design an innovative portable multi-feed oxygen manifold using a six-way radial header fitted to a single cylinder. This becomes essential when the existing hospital facilities for critical care management becomes limited and a need arises for catering to multiple patients. Rapid trials have been done at Naval Hospital INHS Kalyani. The entire assembly could be set up within 30 minutes.

Appreciating the efforts of the alumni members, Prof. Mini Shaji Thomas said the various contributions in diverse sectors was a matter of pride.

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Robust response by NIT-T alumni to tackle Covid-19 pandemic - The Hindu

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