LA JOLLA, Calif., June 24, 2021 (SEND2PRESS NEWSWIRE) – Scientists are pursuing a new strategy to understand the source of inflammation in chronic diseases at the molecular level. They discover that early genes in cells regulate inflammatory networks before disease occurs. Dr. Marcelo Freire, Associate Professor of Genomic Medicine and Infectious Diseases at the J. Craig Venter Institute, is one of the scientists conducting this provocative research and is the lead and senior author of a recent study entitled “Transcriptomics of type 2 diabetic and healthy human” . Neutrophils. “
Type 2 diabetes (T2D) is a chronic inflammatory disease affecting approximately 415 million people worldwide and increasing its prevalence in adults, increasing the risk of developing comorbid conditions such as inflammatory lesions of the limbs, eyes, and periodontal tissue. In fact, patients with diabetes are more prone to developing severe forms of COVID-19. Recently, neutrophils have also been associated with inflammatory pathways in Sars-CoV-2 infections.
This shows that diabetics do not respond to microbial / viral and metabolic challenges due to deficiencies in immune cells. However, clinicians are unable to accurately predict which patients will develop chronic inflammatory and associated diseases.
“Understanding the immune and lipid mechanisms of diabetes can improve our understanding of the disease,” says Freire. “We found that abnormal inflammation is a molecular source of chronic disease in type 2 diabetes and that it is reversible.”
In laboratory studies, the researchers identified two pathways that dysregulate inflammation in type 2 diabetes. Through a global analysis of RNA (transcriptomics) from cells of the innate immune system, they discovered novel immune and lipid-related genes that are chronically suppressed.
Although chronic diseases such as type 2 diabetes have excellent therapeutic options that focus on blood sugar levels and insulin, none currently have the ability to control the disease-associated chronic inflammation.
In this study, human neutrophils (the most common leukocytes in the blood) were examined using transcriptomics for the first time. This new study of human neutrophils provides the scientific community with access to regulatory signatures and mechanistic information about health and disease.
“A joint effort has been made to expand knowledge in our and other laboratories, to expand the field of neutrophils, and to investigate the source of inflammation in other organs,” says Freire.
Inflammatory networks derived from neutrophils can be instructive for the early diagnosis of diabetics and the future development of therapeutics.
For this work, the researchers treated human cells ex vivo with a novel fatty acid, resolvin E1 (RvE1), which is known for its dissolution-promoting functions. The use of this exogenous therapeutic showed that type 2 diabetics are not irreversibly harmed and that the treatments that reduce chronic inflammation can save the phenotype. With expertise in inflammation and the receptor-ligand axis, Freire’s team was able to test human cells with a tailored amount of RvE1 to further advance precision medicine.
In addition to RNA sequencing (transcriptomics) and analysis of complete neutrophil transcriptomes, the team used cell cultures to increase the levels of RvE1 in both healthy and diabetic neutrophils, or saturated in diabetic patients only changed after certain levels of RvE1 were added, which shows that chronically inflamed cells respond
“There’s a lot more research to be done, but what unresolved inflammation is doing should be a starting point for developing new biomarkers for the severity and treatment of chronic diseases,” says Dr. Sarah Kleinstein, first author of the study.
Freire agrees that the research is just beginning and includes future plans to deepen its understanding of diabetic heterogeneity and diagnostic / therapeutic development.
“Our goal is to find a better way to monitor and treat chronic inflammation,” says Freire.
Read an accelerated article preview of the study in BMC Immunology here: https://bmcimmunol.biomedcentral.com/articles/10.1186/s12865-021-00428-6
Via the J. Craig Venture Institute
The J. Craig Venter Institute (JCVI) is a world leader in genomics with 160 scientists and staff who are brave innovators who fearlessly pursue revolutionary ideas. It is registered as a 501 (c) (3) non-profit organization and has a long track record of creativity and an interdisciplinary approach to genomics. It seeks to accelerate basic scientific research in order to make advances in human health and environmental sustainability.
More information about JCVI: https://www.jcvi.org/
NEWS SOURCE: J. Craig Venter Institute
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