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Sigrid Therapeutics Prevents Type 2 Diabetes Using Silica Powder in the… – Labiotech.eu

Posted: February 9, 2020 at 7:52 pm

In Stockholm, Sweden, Sigrid Therapeutics is developing an ingestible silica powder that can treat type 2 diabetes and obesity without being absorbed in the gut.

Mission: To produce the first prophylactic silica-based treatment for type 2 diabetes that does not enter the bloodstream.

Some people have higher blood sugar levels than normal, but not high enough to be diagnosed with type 2 diabetes. This condition, known as prediabetes, leads to full-blown type 2 diabetes in around 70% of cases. Current therapies for type 2 diabetes focus on treatment rather than prevention an issue that Sigrid Therapeutics aims to address.

If you look at big pharma companies, they are not interested in type 2 diabetes prevention because if you prevent something, you wont make much money, Eric Johnston, CTO of Sigrid Therapeutics, told me.

Sigrids answer to this problem is a powder of porous white particles made from silica. People take the powder classed as a medical device with water into the gut, where it interferes with digestive enzymes and slows down the absorption of cholesterol and glucose into the blood.

Sigrid completed the first-in-human trial of the powder last year, where it significantly reduced blood sugar levels in people with prediabetes to a similar degree to current glucose-lowering drugs in this patient population, though with a better safety profile.

There are already drugs that can also block digestive enzymes, such as the anti-obesity drug orlistat inhibiting fat absorption. However, these drugs often have a very strong effect on a single enzyme and this can lead to side-effects such as diarrhea. In contrast, the powder showed no increased safety risks except for occasional feelings of being bloated. According to Johnston, this is because the powder blocks the enzymes more weakly than current drugs, but also blocks more enzymes at the same time.

Its like a cheese slicer it takes thin slices but it takes everything, he said.

The treatment is considered a medical device rather than a drug because the silica particles are too big to enter the bloodstream. As a consequence, Sigrid doesnt need to carry out phase I to phase III trials. The company now aims to launch a small clinical trial at the end of 2020 to prove its mode of action in the human setting. Johnston thinks it will then have enough evidence to earn EU regulatory approval with a CE mark in around 2021.

What we think:

This powder treatment, if approved, could take a stride in the direction of preventing type 2 diabetes, which is the focus of a huge healthcare market.

The powder is unlike many diabetes treatments in current use. It resembles nanoparticles an active area of research in cancer and other conditions but the silica particles in Sigrids therapy cant enter the blood like nanoparticles do. It also has an effect not unlike that seen with weight loss surgery, a drastic intervention that is sometimes used in very obese people.

One major challenge for an unusual treatment like this one was the manufacturing, according to Johnston. Sigrid is now in negotiation with three of the worlds largest silica producers to mass-produce the powder.

Over the next ten years, Johnston told me that treatments like Sigrids will combine with growing public awareness of unhealthy lifestyles to make diabetes prevention much more prominent than it has been so far. I believe prevention is the future, he said. If you can prevent people from developing type 2 diabetes, that will save society a lot of money and it will help a lot of people.

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After years of skyrocketing costs, lawmakers across the US push for caps on life-saving insulin payments – WQAD Moline

Posted: February 9, 2020 at 7:52 pm

(CNN) It costs between $2.28 and $3.42 for drug makers tomanufactureinsulin. Yet, people with diabetes pay hundreds of dollars for the life-saving drug.

After years of skyrocketing costs, lawmakers across the US have begun a push to cap the cost of insulin.

This week, Virginias House of Delegates almost unanimouslypasseda bill preventing insurance companies from charging a co-pay over $30 for a 30-day supply of insulin. The bipartisan bill passed with a vote 98-1 and is now awaiting approval from the state Senate and Democratic Gov. Ralph Northam.

The week before, Tennessee lawmakersintroduceda similar bipartisan bill that aims to ensure a patient does not have to pay any more than $100 for a 30-day supply of insulin even if they are not insured.

This is not a political issue. Everyone that is affected by this disease either directly or their family members, their friends, their loved ones, their coworkers, those folks that have this disease need this insulin, Tennessee state Rep. Matthew Hill, a Republican, told reporters onTuesdaywhile discussing the bill.

Its not right, its just not right that something we know can help people and has been around as a treatment for over 100 years, in the last five years it has continued to increase exponentially, Hill said.

IllinoisandColoradohave passed similar bills setting payment caps on the drug.

The Pharmaceutical Research and Manufacturers of America (PhRMA) represents most of the nations largest drug and biopharmaceutical research companies, including the three major manufacturers of insulin in the US.

Although PhRMA has not taken a position on these specific proposals, broadly speaking we support addressing the misaligned incentives in the pharmaceutical supply chain that have resulted in some patients with diabetes paying more for their insulin than their insurance company, PhRMA said in a statement to CNN.

According to the US Centers for Disease Control and Prevention, more than30 millionpeople in the United States nearly one in every 10 Americans have diabetes. Another estimated 84 million are prediabetic and could require insulin later in life.

Insulin is needed to treat all people with both type 1 diabetes and some people with type 2 diabetes.

Type 1 diabetes develops when the bodys immune system destroys pancreatic beta cells, the only cells in the body that make insulin. There is no way to prevent Type 1 diabetes.

Type 2 is associated with obesity, older age, family history, poor diet and physical inactivity. And thats its most common form, accounting for about 90% to 95% of all diagnosed cases of diabetes in adults.

Either way, people with diabetes take insulin to stay alive.

And while very little about the way insulin is produced has changed, the prices have skyrocketed some more thantriplingover the past 10 years. As a result, as many asone in fourpeople who take insulin skip doses because they cannot afford the medication that is keeping them alive.

People need this medicine to live, to survive. We wouldnt charge somebody $300 for a bottle of water if they needed to drink. Why wouldnt we do the same for a life saving drug? Tennessee state Rep. Jason Hodges, a Democrat,saidon Tuesday.

And as the number of people living with diabetes continues to rise, studies have predicted that the access to insulin needed to meet growing demand willfall short.

By 2030, 79 million adults with type 2 diabetes are expected to need insulin to manage their condition and if current levels of access remain, only half of them will be able to be able to get an adequate supply, according to a modeling study in the journal Lancet Diabetes and Endocrinology.

The study predicted that the number of adults with type 2 diabetes will rise from 406 million in 2018 to 511 million in 2030. The United States will have the third highest numbers globally, with 32 million people predicted to be living with the condition in 2030.

However, not all people with diabetes require insulin. Of that global total of 511 million, 79 million were predicted to be in need of insulin to manage their diabetes a 20% rise in the demand for insulin and only 38 million are likely to have access to it, based on current resources.

The countrys leading manufacturers of insulin are Eli Lilly, Novo Nordisk and Sanofi, whose executives wereordered to testifyon Capitol Hill last year regarding the rising prices of their drugs.

We are engaged with the administration and with health plans to identify approaches to help lower costs for patients, Sanofi spokesperson Nicolas Kressmann told CNN.

As a matter of policy, Sanofi supports capping patient out-of-pocket costs for insulin because of unjustified cost-shifting from health plans to patients who need insulin to manage their diabetes.

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Dear Dietitian Is the glycemic index diet a good option for diabetes? – Kiowa County Press

Posted: February 9, 2020 at 7:52 pm

Dear Dietitian,

I have had diabetes for fifteen years and have kept it under good control. But recently, my blood sugars have been higher, around 200 during the day. My daughter thinks I should try the glycemic index diet. What do you think?

Terry

Dear Terry,

The glycemic index diet was introduced by Jenkins et al. in the early 1980s as a ranking system for carbohydrates based on their immediate impact on blood glucose levels (1). It was developed as a meal-planning guide for people with diabetes, with emphasis on low glycemic index foods. The premise is to choose low GI foods to help control blood sugar levels and avoid spikes. The GI concept has since expanded to include weight loss and disease prevention.

The GI system ranks foods from 0 to 100; the smaller the number, the less impact it has on your blood sugar. Glucose is given the value of 100; all other foods are ranked comparatively to glucose. The GI values are classified as low, medium, and high. Below are examples of foods in each category (2):

Critics of the GI classification say it is not a measure of good nutrition. For example, the GI of ice cream, a food high in calories and fat, is low while the GI of watermelon is high when it is low in calories and a good source of vitamin A.

Glycemic index only tells part of the story. It is the glycemic load (GL) concept that gives us a more real-life predictor of carbohydrate consumption. The GL considers the glycemic index of a food as well as the amount of glucose a portion will deliver (3). As a frame of reference, a GL higher then 20 is considered high, between 11 and 19 is medium, and 10 or less is considered low (4). It is recommended to consume a total GL of 100 or less each day.

Studies on GI and its impact on health-related outcomes have mixed results. The American Diabetes Association states that the overall amount of carbohydrates consumed is more important than GI (5). The glycemic index diet is still debated among dietitians, with this RDN not recommending it. It's a complex system when carb counting is much easier and effective.

Perhaps a simpler way of keeping track of foods that drastically raise your blood sugar is to keep a log. Then you can avoid these foods or modify them. For instance, some people complain that white rice spikes their blood sugar levels. In this case, you have three choices: avoid it, eat a smaller portion, or switch to brown rice.

The bottom line is do what works for you. Maintaining healthy glucose levels and a healthy weight are of utmost importance in diabetes management. Talk to your doctor or dietitian if your blood sugar levels remains high.

Until next time, be healthy!

Dear Dietitian

2,4 Glycemic index and glycemic load (n.d.) Retrieved fromhttps://lpi.oregonstate.edu/mic/food-beverages/glycemic-index-glycemic-load

5.Glycemic index and diabetes (n.d.) Retrieved fromhttps://www.diabetes.org/glycemic-index-and-diabetes

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Menopause Hormone Therapy Found to Delay Type 2 Diabetes – Medscape

Posted: February 9, 2020 at 7:52 pm

EXPERT ANALYSIS FROM THE WCIRDC 2019

LOS ANGELES Although menopausal hormone therapy is not approved for the prevention of type 2 diabetes because of its complex balance of risks and benefits, it should not be withheld from women with increased risk of type 2 diabetes who seek treatment for menopausal symptoms, according toFranck Mauvais-Jarvis, MD.

"During the menopause transition, women accumulate metabolic disturbances, including visceral obesity, systemic inflammation, insulin resistance, dyslipidemia, and hypertension," Dr. Mauvais-Jarvis, director of the Tulane Diabetes Research Program at Tulane University Health Sciences Center, New Orleans, said at the Annual World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. "They also lose muscle mass. Some of these abnormalities are partially explained by chronological aging, but they are also caused by estrogen deficiency. There's a synergism between aging and estrogen deficiency."

The best evidence of this synergy comes from older trials. Nearly 30 years ago, researchers examined the association between postmenopausal hormone use and the subsequent incidence of noninsulin dependent diabetes in a prospective cohort of 21,028 postmenopausal U.S. women aged 30-55 years, who were enrolled in the Nurse's Health Study and followed for 12 years (Ann Epidemiol. 1992;2[5]:665-73). They found that study participants on hormone therapy experienced a 20% reduction in the incidence of type 2 diabetes. In a more recent trial, researchers examined the association between use of hormone therapy and new-onset diabetes in 63,624 postmenopausal women who were enrolled in the prospective French cohort of the Etude Epidemiologique de Femmes de la Mutuelle Gnrale de l'Education Nationale (E3N) and followed for 15 years (Diabetologia. 2009;52[10]:2092-100). It found that study participants on hormone therapy experienced a 20% reduction in the incidence of type 2 diabetes.

In the Heart and Estrogen/Progestin Replacement Study, researchers evaluated the effect of hormone therapy on fasting glucose level and incident diabetes in 2,763 postmenopausal women with coronary heart disease (Ann Intern Med. 2003;138[1]:1-9). At 20 U.S. centers, the study participants received 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone, or placebo, and were followed for 4 years. The researchers found that the use of hormone therapy reduced the incidence of diabetes by 35%.

According to Dr. Mauvais-Jarvis, the strongest data come from the Women's Health Initiative (WHI), a randomized, double-blind trial that compared the effect of daily 0.625 mg conjugated estrogen plus 2.5 mg medroxyprogesterone acetate with that of placebo during 5.6 years of follow-up (Diabetologia. 2004; 47[7]:1175-87). It showed a 20% decrease in the incidence of diabetes at 5 years. More recently, researchers found that, whether WHI participants took estrogen plus medroxyprogesterone or estrogen alone, the protection from diabetes was present (N Engl J Med. 2016;374:803-6).

In 2006, researchers published results from a meta-analysis of 107 trials in an effort to quantify the effects of hormone therapy on components of metabolic syndrome in postmenopausal women (Diabetes Obes Metab. 2006;8[5]:538-54). In women without diabetes, hormone therapy reduced the HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) score by 13% and incidence of type 2 diabetes by 30%. In women with diabetes, hormone therapy reduced fasting glucose by 11% and HOMA-IR by 36%.

The mechanisms by which estrogens improve glucose homeostasis are yet to be fully understood. "One of the most important [mechanisms] is a decrease in abdominal fat, which improves insulin resistance and systemic inflammation," Dr. Mauvais-Jarvis said. "However, in the WHI, it was clear that the improvement in HOMA-IR was independent from the body weight and fat. Estrogen has also been found to increase insulin clearance and sensitivity, increase glucose disposal and effectiveness and decrease sarcopenia. There are fewer than 20 studies looking at beta-cell function. Half of them have shown that estrogen improves insulin secretion."

Route of estrogen administration also comes into play. For example, oral estrogens increase liver exposure to estrogen, increase triglycerides, and increase clotting factors. "That is why oral estrogens are not indicated in women with risk of deep venous thrombosis," Dr. Mauvais-Jarvis said. "They also increase inflammatory factors like C-reactive protein. Advantages are that they decrease LDL cholesterol levels and increase HDL cholesterol levels more than transdermal estrogen does."

The main advantage with transdermal delivery of estrogen, he continued, is that it does not raise triglycerides, clotting factors, or inflammatory factors, and it confers less exposure to the liver. "That's why it's the preferred way of administration in women who are obese, who have a risk of DVT, or who have cardiovascular risk factors," he said. "It has a lower suppression of hepatic glucose production, it increases circulating estradiol, and the delivery to nonhepatic tissue is increased. The oral form of estrogen is cheaper, compared with the transdermal form, though. This is a factor that is always taken into account."

Dr. Mauvais-Jarvis and colleagues were first to evaluate the effect of conjugated estrogens plus bazedoxifene in mice (Mol Metab. 2014;3[2]:177-90). "The idea was that by combining estrogen and bazedoxifene, you have the beneficial effect of estrogen in the tissues but you block estrogen in the breast and in the uterus, and therefore, you prevent the risk of cancer," he said. "We found that tissue-selective estrogen complexes with bazedoxifene prevent metabolic dysfunction in female mice. It increased energy expenditure and decreased fatty liver."

In a subsequent pilot study, he and his colleagues assessed the effect of 12 weeks' treatment with bazedoxifene/conjugated estrogens, compared with placebo, on glucose homeostasis and body composition in 12 postmenopausal women (NCT02237079). "We did not find any significant alterations in the IVGTT [Intravenous Glucose Tolerance Test] but we observed improved fasting beta-cell function and serum glucose in menopausal women with obesity," Dr. Mauvais-Jarvis said (J Endocr Soc. 2019;3[8]:1583-94).

In a separate, randomized, double-blind, placebo-controlled, crossover trial that he and his colleagues performed in eight postmenopausal women with obesity, the primary endpoint was insulin action as measured by a two-step hyperinsulinemic-euglycemic clamp. Secondary endpoints were body composition, basal metabolic rate, ectopic fat, and metabolome. "We did not find any difference in systemic insulin action, ectopic fat, or energy expenditure," he said. "But we found something very interesting. We did a metabolic analysis and found that oral estrogens increase hepatic de novo lipogenesis and liver triacylglycerol production. In other words, the oral estrogens were increasing [triacylglycerol] synthesis from glucose, but it does not accumulate in the liver."

Dr. Mauvais-Jarvis disclosed that he has received research support from the National Institutes of Health, the American Diabetes Association, the Department of Veterans Affairs, and Pfizer.

This story originally appeared onMDedge.com.

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Type 2 diabetes: Best drink to lower blood sugar – and other natural remedies to help – Express

Posted: February 9, 2020 at 7:52 pm

Type 2 diabetes occurs when the body doesnt produce or use enough insulin a hormone that absorbs glucose into cells to be used up as energy. Hyperglycemia (the medical term for high blood sugar levels) can damage blood vessels, increasing the risk of a stroke.

Gudrun Jonsson, dietary advisor to Nibble Protein creators of low-GI snacks and author of international bestseller Gut Reaction, shared her knowledge on seven natural ways to bring that blood sugar reading right down, one of these being to drink water.

Detailing how the body can misread dehydration as hunger signals, due to the same part of the brain regulating both hunger and thirst, Gudrun said: Water is the perfect beverage to help combat high blood sugar levels as it has no calorific value and zero additives.

Drinking more water will help your kidneys flush out the excess sugar in your system through urine.

Diabetes UK note that urinating too frequently can indicate blood sugar levels are currently too high.

Diabetes UK explains how the glycaemic index (GI) tells us whether a food raises blood glucose levels quickly, moderately or slowly which is useful when managing diabetes.

The GI index runs from 0 to 100, adds the charity. Slowly absorbed carbohydrates have a low GI rating (55 or below).

Research has shown that choosing low-GI foods can particularly help manage long-term blood glucose levels in people with Type 2 diabetes.

Echoing Diabetes UK, Gudrun stated: Eating food on the low end of the GI has been shown to lower blood sugar levels.

Unfortunately, lots of the sweet treats we crave are high GI, so switching these for healthier

options can help.

Try Nibble Proteins Brownie Bites which are made with dried plum puree as opposed to dates, meaning theyre far lower in sugar which can help to stabilise your blood sugar.

Gudrun asserted: Studies have shown that when we are fatigued our blood sugar levels are higher.

Feeling tired makes us more likely to crave fast-releasing energy-rich food that are high in sugar, which only makes our blood sugar levels higher, putting us at an even greater risk of high blood sugar levels.

The only way to prevent high blood sugar levels through lack of sleep is to sleep more.

Practices such as meditation and a digital detox before going to bed are great ways to help the mind and body prepare for a restful night.

Although carbohydrates are an essential macronutrient to healthy nutrition, Gudrun advised people with type 2 diabetes to keep track of how many carbohydrate-rich foods you eat throughout the day and see where you can swap them for other fibre-rich alternatives.

Gudrun recommends eating fibre-rich foods, such as green beans, as it help our bodies slow down the absorption of sugar.

She said: Fibre helps prevent the so-called sugar rushes and fluctuations in energy levels that our bodies go through when we digest sugar-rich foods, because it doesnt use insulin in the digestion process and is a slow release energy source.

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Anti-inflammatory "switch" could treat diabetes, MS and aging itself – New Atlas

Posted: February 9, 2020 at 7:52 pm

Inflammation is the bodys way of fighting off threats, but if it gets out of hand it can lead to painful chronic inflammation, and even contribute to diseases like Alzheimers and diabetes. Now, researchers at UC Berkeley have identified a molecular switch in mice that could effectively turn off that reaction, potentially reversing these conditions and possibly even aging itself.

At the heart of the study is whats known as the NLRP3 inflammasome. This group of immune proteins keeps a watchful eye out for infections and other invaders to the body, and if it detects something it launches an inflammatory response to fight it off.

Normally this is an important function of the immune system, but sometimes the body stays in this heightened state for too long, causing chronic inflammation. This can not only cause pain and discomfort, but can lead to other chronic conditions like multiple sclerosis, cancer, diabetes, Alzheimers and Parkinsons.

But on the new study, the researchers found a way to essentially switch off the NLRP3 inflammasome. This is done through a process called deacetylation, where a fragment of molecular matter is removed.

This acetylation can serve as a switch, says Danica Chen, senior author of the study. So, when it is acetylated, this inflammasome is on. When it is deacetylated, the inflammasome is off.

Specifically, the team found that a protein called SIRT2 acted as the switch. They engineered mice that were unable to produce SIRT2, and over two years compared their health to a control group. They found that the test animals showed more signs of inflammation, and had higher insulin resistance a problem that arises during type 2 diabetes.

In other tests, the team studied two groups of older mice that had had their immune systems effectively rebooted. The animals immune systems were reconstituted to have either the acetylated or deacetylated versions of the NLRP3 inflammasome. The differences were then compared after six weeks, and the researchers found that the deacetylated mice had better insulin resistance than the control group.

The team says that the study shows how drugs that effectively switch off NLRP3 could help treat conditions associated with inflammation, including diabetes, multiple sclerosis, Alzheimers, and Parkinsons. Another molecule, dubbed MCC950, has already been fairly successful in trials as an NLRP3 blocker, and in the long run these kinds of drugs could even be applied to aging itself.

My lab is very interested in understanding the reversibility of aging, says Chen. Now, we are asking: to what extent can aging be reversed? And we are doing that by looking at physiological conditions, like inflammation and insulin resistance, that have been associated with aging-related degeneration and diseases.

The research was published in the journal Cell Metabolism.

Source: UC Berkeley

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Type 2 diabetes symptoms: Sign in your fingernails that could signal the chronic condition – Express

Posted: February 9, 2020 at 7:52 pm

The risk of type 2 diabetes increases with age, with ethnicity playing a factor too.

To demonstrate, Diabetes UK says the risk of developing the disease increases if youre white and more than 40-years-old.

This risk is the same for African-Caribbean, Black African, or South Asian people who are over the age of 25.

Genetics has a role as well, with those who have a close relative (parent, sibling or child) who has the condition being two to six times more likely to get type 2 diabetes.

Lifestyle factors can have a great influence on whether someone develops type 2 diabetes or not.

Smoking can contribute to the disease developing as well as a host of other health consequences.

As can drinking too much (with the recommended weekly allowance being 14 units).

Not moving about enough can also increase the chances of type 2 diabetes.

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Diabetes Pen Market Booming by Size, Revenue, Trends and Top Growing Companies 2026 – Instant Tech News

Posted: February 9, 2020 at 7:52 pm

Verified Market Research offers its latest report on the Diabetes Pen Market that includes a comprehensive analysis of a range of subjects such as market opportunities, competition, segmentation, regional expansion, and market dynamics. It prepares players also as investors to require competent decisions and plan for growth beforehand. This report is predicted to assist the reader understand the market with reference to its various drivers, restraints, trends, and opportunities to equip them in making careful business decisions.

Global Diabetes Pen Market was valued at USD 5.86 billion in 2016 and is projected to reach USD 11.19 billion by 2025, growing at a CAGR of 7.45% from 2017 to 2025.

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Kidney stem cells isolated from urine could be regenerative therapies – Drug Target Review

Posted: February 9, 2020 at 7:51 pm

Research into alternative stem cell sources has identified urine derived renal progenitor cells (UdRPCs) as a possible option for use in regenerative kidney therapies in the future.

Scientists have demonstrated their protocol for the reproducible isolation of kidney stem cells from human urine. These urine derived renal progenitor cells (UdRPCs) could be used to provide easier access to stem cells for regenerative kidney therapies and modelling diseases for R&D.

A shortage of donor organs and the risks and pain associated with bone marrow stem cell extractions and third trimester amniotic fluid collection have encouraged researchers to find alternative sources of stem cells. According to scientists, several laboratories have indicated urine could be an alternative source, at least for kidney stem cells, so the researchers from Heinrich Heine University-Duesseldorf (HHU) Germany,set out to complete a comprehensive molecular and cellular analysis of these cells.

UdRPCs should be considered as the choice of renal stem cells for facilitating the study of nephrogenesis, nephrotoxicity, disease modelling and drug development

Their study, published in Scientific Reports, revealed that UdRPCs isolated from ten individuals express both markers typically seen in bone marrow-derived mesenchymal stem cells (MSCs) and renal stem cells. The renal stem cell markers, according to the paper, allow UdRPCs to be differentiated into cell types present in the kidney, eg, podocytes and the proximal and distal tubules. The study also showed that these progenitor cells have similar properties to amniotic fluid-derived stem cells (AFCs).

Wasco Wruck, bioinformatician and co-author of the study, said: It is amazing that these valuable cells can be isolated from urine and comparing all the genes expressed in UdRPCs with that derived from kidney biopies we could confirm their renal and renal progenitor cell properties and origin.

According to Martina Bohndorf, a study co-author, UdRPCs can also be easily and efficiently reprogrammed into induced pluripotent stem cells using a non-viral integration-free and safe method.

Dr James Adjaye, study senior author and professor at the Institute for Stem Cell Research and Regenerative Medicine (ISRM) in the medical faculty of HHU, revealed that one of the most promising options in the near future is the use of transplantable renal stem cells (UdRPCs) for treatment of kidney diseases as a complementary option to kidney organs. He concluded that human UdRPCs should be considered as the choice of renal stem cells for facilitating the study of nephrogenesis, nephrotoxicity, disease modelling and drug development.

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Mutated blood stem cell receptors could be therapeutic targets for leukaemia – Drug Target Review

Posted: February 9, 2020 at 7:51 pm

news

Researchers have identified that in leukaemia, mutated receptors allow blood stem cells to activate one another without the proper signal and suggest this discovery could lead to targeted novel therapies.

Research into cell signalling has shown that in leukaemia, mutations in the cytokine receptors of blood stem cells triggers an overproduction of blood cells, causing the condition. The scientists hope this discovery will pave the way for targeted novel therapeutics in future.

In the study, published in Science, the research team discovered that while blood stem cells are normally regulated by cytokines, mutations can allow them to be activated without the correct signals, prompting the development of blood cells to spiral out of control.

The researchers used super-resolution fluorescent microscopy to study the way blood stem cells communicate with each other in real time. They observed cytokines binding to designated cell surface receptors, pairing the blood stem cells up and causing the production of blood cells. But when cells with mutations affecting these receptors were introduced, the cells paired up without cytokines and produced an imbalance of healthy platelets, white and red blood cells.

Professor Ian Hitchcock from the York Biomedical Research Institute and the Department of Biology at the University of York, UK, explained: Our bodies produce billions of blood cells every day via a process of cells signalling between each other. Cytokines act like a factory supervisor, tightly regulating this process and controlling the development and proliferation of the different blood cell types.

Our observations led us to a previously unknown mechanism for how individual mutations trigger blood stem cells to start signalling independently of cytokines, causing the normal system to become out of control and leading to diseases like leukaemia. Understanding this mechanism may enable the identification of targets for the development of new drugs.

Professor Ilpo Vattulainen from the University of Helsinki, Finland, added: Our biomolecular simulations unveiled surprising features concerning the orientation of active receptor pairs at the plasma membrane, explaining how mutations render activation possible without a ligand (eg, cytokine). These predictions were subsequently confirmed experimentally.

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Mutated blood stem cell receptors could be therapeutic targets for leukaemia - Drug Target Review

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