Deciphering the link between skin allergies and the gut microbiota

The number of microorganisms hosted in our digestive tracts is 10 to 100 times greater than that of all the cells that make up our bodies, and the delicately balanced ecosystem they constitute may be modified by our diet and medication. Epidemiological data of various kinds suggest a link between changes in gut microbiota composition and the development of allergic diseases, like eczema, at body sites far removed from the intestine. But an explanation for this association had been lacking until now. The lead researchers focused their attention on mice deprived of the MAVS gene, which plays a key role in the detection of viruses by the immune system. They noted an altered gut microbiota and severe allergic skin reactions in these mice. To demonstrate a relationship between the two phenomena, the researchers transferred the altered microbiota to normal mice. The latter in turn developed severe allergic reactions, showing that the transplanted gut bacteria were responsible. Furthermore, the biologists revealed that such modification of the gut microbiota led to greater intestinal permeability, which allowed certain intestinal bacteria to migrate to the spleen and lymph nodes and increased the severity of allergic skin reactions. These findings shed light on the unexpected role played by an antiviral protein in the maintenance of gut microbiota equilibrium. By showing that changes in the gut microbiota exacerbate the allergic response in the skin, this research sets the stage for the development of new therapies. This approach is already being investigated for other diseases, like cancer.

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New mechanism of action in a first-line drug for diabetes

The effect of metformin on hepatic glucose production is most likely transmitted through the mitochondrial respiratory chain. However, up to now the mechanism through which the drug increases glucose uptake in muscle tissue has been unknown. Lead researcher now demonstrated in cell cultures and in an animal model that metformin directly binds to the lipid phosphatase SHIP2, reducing its activity. The reduction in SHIP2 activity increased glucose uptake in muscle cells and decreased cell death in podocytes, or glomerular epithelial cells. The lipid phosphatase SHIP2 suppresses the insulin signaling pathway. Prior studies have demonstrated through animal models that individuals suffering from diabetes have elevated levels of SHIP2 in their kidney, muscle and adipose tissue. This reduces the ability of tissue to react to insulin signaling and reduces its glucose uptake. Elevated SHIP2 concentration also increases programmed cell death in podocytes.Their analysis revealed that in patients with type 2 diabetes who were not taking metformin, SHIP2 activity in the kidneys was elevated, in addition to which their podocyte loss was remarkable. In patients taking metformin, SHIP2 activity did not deviate from people without diabetes, while podocyte loss was also lower than in patients using another drug therapy. Lead researcher said that the lipid phosphatase SHIP2 has a significant role in regulating glucose metabolism and cell death in podocytes. So, regulating SHIP2 activity with metformin or another suitable pharmaceutical agent is crucial in managing type 2 diabetes and particularly in preventing related diabetic kidney disease. Metformin's mechanism of action is being enthusiastically investigated due to its diverse effects on the body, making it potentially useful in treating diseases other than diabetes in the future. Better understanding of the mechanism also helps target the therapy precisely to those patient groups that will benefit from it. Patients with this type of diabetes are at an exceptionally high risk of also contracting diabetic kidney disease. The researchers estimate that it would be this group in particular that would benefit from metformin. Our findings prove that metformin could protect patients from renal damage by suppressing SHIP2 activity. This introduces a new, direct mechanism of action, through which metformin protects the kidneys from damage. New mechanisms of action can expand metformin's indications for use outside diabetes in treating, among other disorders, cancer and cardiovascular diseases.

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Brain training app helps reduce OCD symptoms

One of the most common types of Obsessive compulsive disorder (OCD), affecting up to 46% of OCD patients, is characterized by severe contamination fears and excessive washing behavior. The behaviors can have a serious impact on people's lives, their mental health, their relationships and their ability to hold down jobs. OCD is treated using a combination of medication such as Prozac and a form cognitive behavioral therapy ('talking therapy') termed 'exposure and response prevention'. These treatments are not particularly effective, however as many as 40% of patients fail to show a good response to either treatment. This may be in part because often people with OCD have suffered for years prior to receiving a diagnosis and treatment. Another difficulty is that patients may fail to attend exposure and response prevention therapy as they find it too stressful to undertake. For these reasons, researchers developed a new treatment to help people with contamination fears and excessive washing. The intervention, which can be delivered through a smartphone app, involves patients watching videos of themselves washing their hands or touching fake contaminated surfaces. The researchers used healthy volunteers rather than OCD patients in their study to ensure that the intervention did not potentially worsen symptoms. The participants were divided into three groups: the first group watched videos on their smartphones of themselves washing their hands; the second group watched similar videos but of themselves touching fake contaminated surfaces; and the third, control group watched themselves making neutral hand movements on their smartphones. After only one week of viewing their brief 30 second videos four times a day, participants from both of the first two groups that is, those who had watched the hand washing video and those with the exposure and response prevention video, improved in terms of reductions in OCD symptoms and showed greater cognitive flexibility compared with the neutral control group. On average, participants in the first two groups saw their Yale-Brown Obsessive Compulsive Scale (YBOCS) scores improve by around 21%.Researcher said that, Participants told that the smartphone washing app allowed them to easily engage in their daily activities. This technology will allow people to gain help at any time within the environment where they live or work, rather than having to wait for appointments. The use of smartphone videos allows the treatment to be personalized to the individual. The smartphone app is not currently available for public use. Further research is required before the researchers can show conclusively that it is effective at helping patients with OCD.

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First genetic risk factor for erectile dysfunction identified

Erectile dysfunction(ED), the inability to obtain and maintain an erection sufficient for sexual activity, is a common and costly condition of men of primarily middle and older ages. The disease is linked to many causes, such as neurological, hormonal and vascular factors. Genetics also are suspected as a factor in about one-third of erectile dysfunction cases, but researchers have failed to make an association with any specific genomic locations until now. The new study found that variations in a specific place in the genome called a genetic locus near the SIM1 gene are significantly associated with an increased risk of erectile dysfunction. The researchers ruled out that the risk was due to other known risk factors for ED, such as body mass index, or differences in how men describe their erectile dysfunction. The study found that variations in the SIM1 locus were associated with a 26 percent increased risk of ED. It has been difficult to study in part because of the differences in how patients report their symptoms. To overcome this challenge, the study looked to see whether the SIM1 locus was a risk factor when considering differences in how men reported their ED to their doctors. The study found that this location was indeed a risk factor for ED, whether the disorder was defined through clinical diagnoses, prescriptions history, or study participant self-report. The study then identified a biological role for this location in ED susceptibility. The SIM1 gene is known to be part of a signaling pathway that plays a central role in body weight regulation and sexual function. Research team shows that the implicated location physically interacts with the promoter of the SIM1 gene, and that variants in this location alter the function of a master gene regulator, called an enhancer. The promoter is like a light switch, and an enhancer acts like the fuse box. Because the ED risk locus showed enhancer activity and interacted with the SIM1 promoter, the risk locus likely influences the expression of the SIM1 gene, turning it on and off when needed. The study highlights the potential of SIM1 as a target for the development of new treatments for ED, which are needed because about half of all men who try currently available pharmaceutical treatments for ED don't respond to them. Lead researcher said that, this study points to a new research direction for ED that could help us identify other key genetic variants that trigger the disease and lead to investigations to better understand the precise mechanisms by which they operate.

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New research shown that by using a combination of immunotherapy and chemotherapy the body's own immune system can be tuned to attack triple-negative breast cancer, extending survival by up to ten months. The research also showed that the combined treatment reduced the risk of death or the cancer progressing by up to 40 per cent. Triple-negative breast cancer often affects young women, with many people diagnosed in their 40s or 50s. The standard treatment is chemotherapy, which most patients quickly develop resistance to. If the disease spreads to other parts of the body, survival is often only 12 to 15 months. The new treatment combines standard weekly chemotherapy with the immunotherapy medication atezolizumab which is given once every two weeks. The combination works by chemotherapy 'roughening up' the surface of the cancer, which enables the immune system to better recognize and therefore fight the cancer as a foreign object. Lead researcher said that, these results are a massive step forward & changing how triple-negative breast cancer is treated in proving for the first time that immune therapy has a substantial survival benefit. In a combined treatment approach, using chemotherapy to tear away the tumor’s 'immune-protective cloak' to expose it as well as enabling people's own immune system to get at it. Based on the results of this trial this new treatment is currently under review by health authorities and will hopefully become available in the NHS in the near future.

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Eating leafy greens could help prevent macular degeneration

The research showed that people who ate between 100 to 142 mgs of vegetable nitrates each day had a 35% lower risk of developing early Age-related Macular Degeneration (AMD) than people who ate less than 69mgs of vegetable nitrates each day. Lead Researcher said the link between vegetable nitrates and macular degeneration could have important implications. This is the first time the effects of dietary nitrates on macular degeneration risk have been measured. People who ate 100 to 142 mgs of vegetable nitrates every day had a reduced risk of developing early signs of macular degeneration compared with people who ate fewer nitrates. Lead researcher said that, Green leafy vegetables and beetroot could be a simple strategy to reduce the risk of early macular degeneration. Spinach has approximately 20mg of nitrate per 100g, while beetroot has nearly 15mg of nitrate per 100g. The research did not show any additional benefits for people who exceeded 142mgs of dietary nitrate each day. It also did not show any significant connections between vegetable nitrates and late stage AMD, or between non-vegetable nitrates and AMD risk. Age is the strongest known risk factor and the disease is more likely to occur after the age of 50. There is currently no cure for the disease. It is one of the world's largest epidemiology studies, measuring diet and lifestyle factors against health outcomes and a range of chronic diseases. This research aims to understand why eye diseases occur, as well as the genetic and environmental conditions that may threaten vision.

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