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Diseases and Conditions

Unlocking the Mystery of Calciphylaxis: Researchers Identify Key Pathway Responsible for Rare and Serious Condition

The global burden of chronic kidney disease (CKD) is rising, with more than 800 million people affected worldwide. Vascular diseases in patients with CKD are unique and grouped as uremic vascular diseases. One of them, calciphylaxis, typically affects patients with end-stage, advanced kidney disease. It is a condition characterized by severe, painful and non-healing skin ulcers with no known cure. Researchers have now discovered a novel biological pathway, called the IL6 pathway, central to the skin lesion initiation and progression. Blocking this pathway they believe, will likely prevent progression of the skin ulcers and resolve the pain seen in patients with calciphylaxis.

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The global burden of chronic kidney disease (CKD) is growing at an alarming rate, affecting more than 800 million people worldwide. A unique aspect of vascular diseases in patients with CKD is the group known as uremic vascular diseases. One such condition, calciphylaxis, typically affects individuals with end-stage kidney disease and is characterized by severe, painful, and non-healing skin ulcers.

For the first time, researchers from Boston University Chobanian & Avedisian School of Medicine, in collaboration with Massachusetts General Hospital, have made a groundbreaking discovery. They identified a novel biological pathway called the IL6 pathway as central to the initiation and progression of calciphylaxis. This breakthrough finding opens up new possibilities for treatment.

According to Dr. Vipul Chitalia, corresponding author and professor of medicine, “This study reveals a pathological cycle between fat under the skin, sweat glands, and small blood vessels that keeps feeding onto itself. If this cycle isn’t stopped and remains unchecked, it will lead to the skin ulcers that won’t heal.” Dr. Chitalia emphasizes that blocking the IL6 pathway may prevent progression of the skin ulcers and resolve pain in patients with calciphylaxis.

In their study, researchers analyzed human calciphylaxis skin and blood samples for proteins and genes to understand disease-causing mechanisms. They then applied an FDA-approved drug to see if the disease-causing pathway could be suppressed. The findings suggest that drugs already available can block this pathway, potentially preventing further progression of the condition.

While more research is needed to confirm these results in human trials, this discovery brings new hope for patients with calciphylaxis. As Dr. Jean Francis, co-author and associate professor of medicine, notes, “Those drugs are likely to prevent progression of the skin ulcers and resolve the pain that we see in patients with calciphylaxis.”

These findings have been published online in Science Translational Medicine, shedding light on a rare and serious condition. Further research is necessary to fully understand the implications of this discovery and to bring about effective treatments for patients with calciphylaxis.

Cell Biology

Unlocking the Secrets of Deadly Tropical Diseases: A New Target for Treatment

The efforts of a research team give hope for new treatment approaches for dangerous tropical diseases. The researchers have compiled a high-precision inventory of the membrane proteins of cell organelles of the African sleeping sickness pathogen.

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The fight against deadly tropical diseases has taken a significant step forward with the discovery of a promising target for new treatments. Researchers from Bochum and Würzburg have made a groundbreaking find in their study on the African sleeping sickness pathogen Trypanosoma brucei, which also causes Chagas disease and leishmaniasis.

In a breakthrough study published in Cell Reports, the researchers compiled a high-precision inventory of the membrane proteins of the glycosomes, unique cell organelles essential for the survival of the parasites. “Some of these proteins contain components that are specific to parasites and differ significantly from those of the host cells,” explains Professor Ralf Erdmann.

The team’s success in identifying 28 glycosome membrane proteins with a high degree of reliability opens up new avenues for targeted treatment strategies against these poorly understood tropical diseases. A particular highlight was the discovery of TbPEX15, a membrane anchor for an essential protein import complex that differs significantly from its counterpart in humans.

This finding provides a valuable resource for biomedical research into glycosome biology and deepens our understanding of parasite biology. The researchers’ work gives hope for new treatment approaches for diseases that affect over 12 million people worldwide.

The study’s findings are a significant step forward in the fight against deadly tropical diseases, and further research could lead to the development of new therapies and treatments.

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Agriculture and Food

“Processed with Caution: Ultra-Processed Foods May Accelerate Early Signs of Parkinson’s Disease”

People who eat more ultra processed foods like cold breakfast cereal, cookies and hot dogs are more likely to have early signs of Parkinson’s disease when compared to those who eat very few ultra processed foods, according to a new study. The study does not prove that eating more ultra processed foods causes early signs of Parkinson’s disease; it only shows an association.

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Eating ultra-processed foods like cold breakfast cereal, cookies, and hot dogs may speed up early signs of Parkinson’s disease, according to a recent study published in Neurology. The research found that people who consumed more of these processed foods were more likely to experience early symptoms of the disease compared to those who ate very few.

The study analyzed data from over 42,000 participants with an average age of 48, who did not have Parkinson’s disease at the start of the study. They were followed up to 26 years and completed regular medical exams and health questionnaires. Researchers also reviewed food diaries that listed what participants ate and how often.

The team looked at several types of ultra-processed foods, including sauces, spreads, or condiments; packaged sweets; snacks or desserts; artificially or sugar-sweetened beverages; animal-based products; yogurt or dairy-based desserts; and packaged savory snacks. One serving was equivalent to a single can of soda, one ounce of potato chips, one slice of packaged cake, a single hot dog, or one tablespoon of ketchup.

Researchers divided participants into five groups based on how many ultra-processed foods they ate per day on average. The highest group consumed 11 or more servings daily, while the lowest group averaged fewer than three servings daily.

After adjusting for factors like age, physical activity, and smoking, researchers found that participants who ate 11 or more servings of ultra-processed food per day had a 2.5-fold higher likelihood of having three or more early signs of Parkinson’s disease compared to those consuming fewer than three servings per day.

When looking at individual symptoms, eating more ultra-processed foods was tied to an increased risk for nearly all symptoms except constipation. The study’s author, Xiang Gao, emphasized the importance of choosing whole, nutritious foods over processed ones to maintain brain health.

While the study suggests a link between ultra-processed food consumption and early signs of Parkinson’s disease, it does not prove causation. More research is needed to confirm these findings and understand the complex relationships between diet, lifestyle, and neurodegenerative diseases.

In the meantime, individuals can take steps to reduce their exposure to ultra-processed foods by:

* Reading labels carefully
* Choosing whole grains over refined ones
* Limiting sugary drinks and snacks
* Opting for fresh fruits and vegetables instead of packaged options
* Cooking meals from scratch using fresh ingredients

By making informed food choices, individuals can contribute to a healthier brain and potentially reduce their risk of developing neurodegenerative diseases like Parkinson’s.

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Brain Tumor

“Revolutionizing Lymphoma Treatment: Enhanced CAR T Cell Therapy Shows Promise in Small Study”

A phase I study of a next-generation CAR T cell therapy showed a 52 percent complete remission rate for patients with relapsed/refractory lymphoma.

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The article describes a groundbreaking study that has shown promising results in treating lymphoma patients who have resisted multiple rounds of other cancer treatments, including commercially available CAR T cell therapies. The new enhanced CAR T cell therapy, dubbed huCART19-IL18, was found to be highly effective in 81% of patients and resulted in complete remission in 52%. This is a significant improvement over traditional CAR T cell therapies, which have been shown to result in long-term remission in only around 50% of patients.

The study, led by researchers at the University of Pennsylvania, used a new process that shortens the manufacturing time for the CAR T cells to just three days. This means that patients with aggressive, fast-growing cancers can begin CAR T cell therapy quicker than is currently possible with standard manufacturing times of nine to 14 days.

The addition of interleukin 18 (IL18) to the CAR T cells enhanced their ability to attack cancer cells and protected them from immune suppression and T cell exhaustion. The researchers also found that the type of CAR T cell therapy patients previously received may impact the efficacy of huCART19-IL18.

This study represents a significant development in the ongoing evolution of CAR T cell therapy, as it is the first time a cytokine-enhanced CAR T has been tested in patients with blood cancer. The researchers believe that incorporating cytokine secretion into CAR T cell design will have broad implications for enhancing cellular therapies, even beyond blood cancers.

The study has already led to several other clinical trials being planned, including studies for acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). Another trial for non-Hodgkin’s lymphoma using a similar IL18-armored CAR T cell product is currently enrolling patients. On the manufacturing side, the team is partnering with a Penn spinout company to improve the process for how these CAR T cells are created and expanded in the laboratory before being reinfused into the patient.

Overall, this study has shown promise in treating lymphoma patients who have resisted multiple rounds of other cancer treatments, and further research is needed to fully understand its potential.

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