أرشيف الوسم: Department of Medicine

Powering H. pylori pathogenesis | VUMC Reporter


by Leigh MacMillan

The bacterium Helicobacter pylori colonizes the stomach in half of the world’s population and increases the risk of gastric cancer.

Strains of H. pylori that contain a cluster of genes called the “cag PAI” are associated with higher risk. These strains synthesize a complex molecular machine known as a type IV secretion system (T4SS), which injects the oncoprotein CagA and other bacterial products into stomach cells.

Aung Soe Lin, Timothy Cover, MD, and colleagues have explored the roles of energy-generating ATPase proteins that are part of the T4SS.

They report in the February issue of Infection and Immunity that three ATPases (Cag-alpha, Cag-beta, and CagE) are each required for CagA translocation into host cells. In contrast, only two of the ATPases are required for the injection of other bacterial products that stimulate inflammatory signaling.

The findings provide new insights into the sources of energy used by this complex molecular machine linked to the pathogenesis of gastric cancer.

This research was supported by the National Institutes of Health (grants AI118932, CA116087, AI039657, AI112541) and the Department of Veterans Affairs.


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A step towards gastric most cancers | VUMC Reporter


by Sanjay Mishra

Helicobacter pylori infects roughly half of the world’s inhabitants and is the strongest recognized threat issue for growing gastric most cancers. Gastric most cancers is the third most deadly most cancers worldwide.

A cluster of genes known as the cag pathogenicity island renders some strains of H. pylori notably virulent. Nevertheless, it isn’t clear precisely how H. pylori induces gastric most cancers.

Now in a examine revealed within the Proceedings of the Nationwide Academy of Sciences, Lydia Wroblewski, PhD, Richard Peek, MD, and collaborators have proven that in chronically contaminated mice, carcinogenic strains of H. pylorimobilize a transmembrane protein that marks a definite inhabitants of progenitor cells known as Lrig1.

H. pylori was discovered to stimulate Lrig1-expressing progenitor cells in a cag-dependent method, and these reprogrammed cells gave rise to a full spectrum of differentiated cells. Furthermore, in human samples, Lrig1 expression was enhanced in gastric lesions with premalignant potential.

These findings present additional perception into the detrimental occasions that develop in response to H. pylori an infection.

This analysis was supported partially by grants from the Nationwide Institutes of Well being (DK058587, CA077955, CA116087, DK058404, DK101332) and by a VA Shared Funding Grant (IBX003097).


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All-in-one capsule helps scale back blood strain, ldl cholesterol | VUMC Reporter



by Craig Boerner

A single capsule containing low doses of three medicines to deal with hypertension and one to decrease ldl cholesterol decreased the estimated danger of heart problems by 25%, in keeping with a examine revealed within the New England Journal of Medication (NEJM).

“Polypills” for prevention of heart problems have beforehand been studied in low- and middle-income nations the place different well being care limitations exist, in keeping with senior creator Thomas Wang, MD, chief of the Division of Cardiovascular Medication at Vanderbilt College Medical Heart.

However the U.S. examine of largely low revenue, primarily black adults from a group well being heart in Cellular, Alabama, units up a dialog about the best way to lengthen these findings to different settings.

“The capsule could tackle a number of the limitations that contribute to disparities in well being primarily based on geography, socioeconomic class and different parameters that we all know have existed on this nation and different nations for some time now,” Wang stated. “Regardless of advances within the prevention and therapy of heart problems, it stays the No. 1 world killer of each women and men.”

The randomized, managed trial of adults with out heart problems enrolled 303 adults — 96% black, 60% feminine and 75% with an annual revenue under $15,000 — with half assigned to take a day by day polypill for 12 months and the opposite half assigned to proceed their common routine medical care.

Half of the examine individuals got here from the Southern Neighborhood Cohort Research, co-led by William Blot, PhD, a analysis professor of Medication at VUMC and co-senior creator of this examine. Adherence was 86% after one yr, primarily based on capsule counts.

Members underwent an ordinary medical examination, blood strain measurement, and blood ldl cholesterol testing throughout their preliminary go to, a two-month go to, and a 12-month go to.

On the finish of the yr, examine individuals who had taken the polypill had decreased blood strain by a median of seven mm Hg and decreased LDL levels of cholesterol as in contrast with individuals within the common care group, translating to an estimated 25% discount within the danger of experiencing a cardiovascular occasion.

“Sufferers searching for care at group well being facilities have historically been under-represented in scientific trials. We have to higher perceive what works and what doesn’t in these settings so we are able to enhance outcomes for our fellow residents who could be the most weak,” stated lead creator Daniel Muñoz, MD, a heart specialist at VUMC.

“We predict there are benefits to combining population-based methods just like the polypill with all the virtues of precision medication. It’s a operating begin for individuals who want entry to some medical care, however precision medication ought to nonetheless be used so as to add remedy and regulate remedy.”

The examine was funded by the American Coronary heart Affiliation Strategically Targeted Prevention Analysis Community and the Nationwide Institutes of Well being; ClinicalTrials.gov quantity NCT02278471.


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Potential prostate most cancers biomarkers | VUMC Reporter


by Leigh MacMillan

Biomarkers for screening and early detection of prostate most cancers — the most typical and second deadliest most cancers in U.S. males — are restricted. PSA (prostate-specific antigen) is extensively used however is controversial due to its unclear profit and contribution to prostate most cancers overdiagnosis.

Wei Zheng, MD, PhD, and colleagues used genetic instruments to seek for associations between genetically predicted blood protein ranges and prostate most cancers threat. They studied 79,194 circumstances and 61,112 controls of European ancestry from a number of prostate most cancers consortia.

They recognized a complete of 31 proteins related to prostate most cancers threat. 9 of the proteins are encoded by genes situated at GWAS-identified prostate most cancers threat loci, and a number of other have potential useful roles in prostate most cancers growth. For 28 of the proteins, gene modifications had been detected in tumor tissues from sufferers with prostate most cancers included in The Most cancers Genome Atlas program.

The big-scale research, reported in Most cancers Analysis, generates a listing of promising proteins as potential biomarkers for threat evaluation and early detection of prostate most cancers.

This analysis was supported partially by funds from the Anne Potter Wilson endowment and grants from the Nationwide Institutes of Well being (CA218892, CA160056).


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