A new hope for cancer patients: Arthritis drug

Agencies
August 4, 2017

London, Aug 4: A simple drug used in the treatment of arthritis may provide hope for patients with blood cancer towards an affordable and effective treatment, a study has shown.

Polycythemia Vera is a type of blood cancer which causes an overproduction of red blood cells and causes itching, headaches, weight loss, fatigue and night sweats.

The researchers from the University of Sheffield in the UK discovered that methotrexate (MTX) - a drug on the World Health Organization list of essential medicines - works by directly inhibiting the molecular pathway responsible for causing cancer.

After initial tests carried on fruit fly cells, tests on human cells showed that MTX acts as a potent suppressor of JAK/STAT pathway - a signaling pathway whose misregulation is central to the development of Myeloproliferative neoplasms (MPNs), the collective term for progressive blood cancers like Polycythemia Vera.

MTX was found to suppress JAK/STAT pathway activation, even in cells carrying the mutated gene responsible for MPNs in patients, the researchers noted, in the paper published in the journal Haematologica.

Importantly, the latest tests conducted on mice showed that low-dose MTX suppresses JAK/STAT pathway activity and is able to normalise both the raised blood counts and the increase in spleen size associated with the disease in these mice.

"We have now shown pretty conclusively that we can use this approach to treat mouse models of human MPNs, results which provide a much more tangible prospect of success in humans," said Martin Zeidler, from the UK varsity.

"Repurposing MTX has the potential to provide a new, molecularly targeted treatment for MPN patients within a budget accessible to healthcare systems throughout the world," Zeidler added.

MTX has been used for 35 years to treat inflammatory diseases including rheumatoid arthritis, Crohn's disease, and psoriasis.

Diseases such as rheumatoid arthritis all feature inflammatory processes driven by JAK/STAT activity and the effectiveness of MTX in these inflammatory diseases may well be a consequence of its ability to dampen the JAK/STAT pathway.

The researchers now hope to conduct a full clinical trial early in 2018.

 

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Agencies
July 8,2020

Probiotics that broaden the mix of helpful bacteria in the gut may help to ease depression, say researchers.

Foods that broaden the profile of helpful bacteria in the gut are collectively known as probiotics. These "good bacteria" can be taken as supplements, or found naturally in yoghurts or fermented foods.

For the findings, the research team from the University of Brighton in the UK searched for relevant studies published in English between 2003 and 2019, which looked at the potential therapeutic contribution of pre-and probiotics in adults with depression and/or anxiety disorders.

Out of an initial haul of 71 studies, just seven met all the criteria for inclusion. All 7 investigated at least one probiotic strain; four looked at the effect of combinations of multiple strains.In all, 12 probiotic strains featured in the selected studies, primarily Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidium.

One study looked at combined pre-probiotic treatment, while one looked at prebiotic therapy by itself. The studies varied considerably in their design, methods used, and clinical considerations, but all of them concluded that probiotic supplements either alone or in combination with prebiotics may be linked to measurable reductions in depression.

And every study showed a significant fall or improvement in anxiety symptoms and clinically relevant changes in biochemical measures of anxiety or depression with probiotic or combined pre-probiotic use.

Of the 12 different probiotics investigated, 11 were potentially useful, the findings showed.'Probiotics may help reduce the production of inflammatory chemicals, such as cytokines, as is the case in inflammatory bowel disease, the researchers suggested.

"They may help direct the action of tryptophan, a chemical thought to be important in the gut-brain axis in psychiatric disorders," they added.

In this way, with a better understanding of the mechanisms, probiotics may prove to be a useful tool across a wide range of conditions," the authors wrote.

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Agencies
July 3,2020

Apart from the many benefits of doing exercise, new research has now found that exercise can slow down or prevent the development of macular degeneration and may benefit other common causes of vision loss, such as glaucoma and diabetic retinopathy.

The new study from the University of Virginia School of Medicine found that exercise reduced the harmful overgrowth of blood vessels in the eyes of lab mice by up to 45 per cent. This tangle of blood vessels is a key contributor to macular degeneration and several other eye diseases.

The study represents the first experimental evidence showing that exercise can reduce the severity of macular degeneration, a leading cause of vision loss, the scientists report. Ten million Americans are estimated to have the condition.

"There has long been a question about whether maintaining a healthy lifestyle can delay or prevent the development of macular degeneration. The way that question has historically been answered has been by taking surveys of people, asking them what they are eating and how much exercise they are performing," said researcher Bradley Gelfand, PhD, of UVA's Center for Advanced Vision Science.

"That is basically the most sophisticated study that has been done. The problem with that is that people are notoriously bad self-reporters ... and that can lead to conclusions that may or not be true. This [study] offers hard evidence from the lab for the very first time," Gelfand added.

Enticingly, the research found that the bar for receiving the benefits from exercise was relatively low - more exercise didn't mean more benefit.

"Mice are kind of like people in that they will do a spectrum of exercise. As long as they had a wheel and ran on it, there was a benefit. The benefit that they obtained is saturated at low levels of exercise," Gelfand said.

An initial test comparing mice that voluntarily exercised versus those that did not found that exercise reduced the blood vessel overgrowth by 45%. A second test, to confirm the findings, found a reduction of 32 per cent.

The scientists aren't certain exactly how exercise is preventing the blood vessel overgrowth. There could be a variety of factors at play, they say, including increased blood flow to the eyes.

Gelfand, of UVA's Department of Ophthalmology and Department of Biomedical Engineering, noted that the onset of vision loss is often associated with a decrease in exercise.

"It is fairly well known that as people's eyes and vision deteriorate, their tendency to engage in physical activity also goes down. It can be a challenging thing to study with older people. ... How much of that is one causing the other?" he said.
The researchers already have submitted grant proposals in hopes of obtaining funding to pursue their findings further.

"The next step is to look at how and why this happens, and to see if we can develop a pill or method that will give you the benefits of exercise without having to exercise," Gelfand said.

He explained, "We're talking about a fairly elderly population [of people with macular degeneration], many of whom may not be capable of conducting the type of exercise regimen that may be required to see some kind of benefit." (He urged people to consult their doctors before beginning any aggressive exercise program.)
Gelfand, a self-described couch potato, disclosed a secret motivation for the research: "One reason I wanted to do this study was sort of selfish. I was hoping to find some reason not to exercise," he joked. "It turned out exercise really is good for you."

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Agencies
May 14,2020

COVID-19 mostly kills through an overreaction of the immune system, whose function is precisely to fight infections, say scientists who have decoded the mechanisms, symptoms, and diagnosis of the disease caused by the SARS-Cov-2 coronavirus.

In a study published in the journal Frontiers in Public Health, the researchers explained step-by-step how the virus infects the airways, multiplies inside cells, and in severe cases causes the immune defences to overshoot with a "cytokine storm".

This storm is an over-activation of white blood cells, which release too-great amounts of cytokines -- inflammation-stimulating molecules --into the blood, they said.

"Similar to what happens after infection with SARS and MERS, data show that patients with severe COVID-19 may have a cytokine storm syndrome," said study author Daishun Liu, Professor at Zunyi Medical University in China.

"The rapidly increased cytokines attract an excess of immune cells such as lymphocytes and neutrophils, resulting in an infiltration of these cells into lung tissue and thus cause lung injury," Liu said.

The researchers explained that the cytokine storm ultimately causes high fever, excessive leakiness of blood vessels, and blood clotting inside the body.

It also causes extremely low blood pressure, lack of oxygen and excess acidity of the blood, and build-up of fluids in the lungs, they said.

The researchers noted that white blood cells are misdirected to attack and inflame even healthy tissue, leading to failure of the lungs, heart, liver, intestines, kidneys, and genitals.

This multiple organ dysfunction syndrome (MODS) may worsen and shutdown the lungs, a condition called acute respiratory distress syndrome, (ARDS), they said.

This, the researchers explained, happens due to the formation of a so-called hyaline membrane -- composed of debris of proteins and dead cells -- lining the lungs, which makes absorption of oxygen difficult.

Most deaths due to COVID-19 are therefore due to respiratory failure, they said.

The researchers explained that in the absence of a specific antiviral cure for COVID-19, the goal of treatment must be to the fight the symptoms, and lowering the mortality rate through intensive maintenance of organ function.

For example, an artificial liver blood purification system or renal replacement therapy can be used to filter the blood through mechanical means, they said.

The team noted that especially important are methods to supplement or replace lung function, for example with non-invasive mechanical ventilation through a mask, ventilation through a tube into the windpipe, the administration of heated and humidified oxygen via a tube in the nose, or a heart-lung bypass.

The researchers stressed the importance of preventing secondary infections.

They noted that SARS-Cov-2 also invades the intestines, where it causes inflammation and leakiness of the gut lining, allowing the opportunistic entry of other disease-causing microorganisms.

The researchers advocate that this should be prevented with nutritional support, for example with probiotics -- beneficial bacteria that protect against the establishment of harmful ones -- and nutrients and amino acids to improve the immune defences and function of the intestine.

"Because treatment for now relies on aggressive treatment of symptoms, preventative protection against secondary infections, such as bacteria and fungi, is particularly important to support organ function, especially in the heart, kidneys, and liver, to try and avoid further deterioration of their condition," Liu added.

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