Clonal Haematopoiesis and Risk of Chronic Liver Disease

Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95% confidence interval (95% CI) [1.46, 2.79]; P \u3c 0.001). Individuals with CHIP were more likely to demonstrate liver inflammation and fibrosis detectable by magnetic resonance imaging compared to those without CHIP (odds ratio = 1.74, 95% CI [1.16, 2.60]; P = 0.007). to assess potential causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (odds ratio = 2.37, 95% CI [1.57, 3.6]; P \u3c 0.001). In a dietary model of non-alcoholic steatohepatitis, mice transplanted with Tet2-deficient haematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated by the NLRP3 inflammasome and increased levels of expression of downstream inflammatory cytokines in Tet2-deficient macrophages. In summary, clonal haematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression through an aberrant inflammatory response

Strategies and tools for the biotechnological valorization of glycerol to 1, 3-propanediol: challenges, recent advancements and future outlook

Global efforts towards decarbonization, environmental sustainability, and a growing impetus for exploiting renewable resources such as biomass have spurred the growth and usage of bio-based chemicals and fuels. In light of such developments, the biodiesel industry will likely flourish, as the transport sector is taking several initiatives to attain carbon-neutral mobility. However, this industry would inevitably generate glycerol as an abundant waste by-product. Despite being a renewable organic carbon source and assimilated by several prokaryotes, presently realizing glycerol-based biorefinery is a distant reality. Among several platform chemicals such as ethanol, lactic acid, succinic acid, 2, 3-butanediol etc., 1, 3-propanediol (1, 3-PDO) is the only chemical naturally produced by fermentation, with glycerol as a native substrate. The recent commercialization of glycerol-based 1, 3-PDO by Metabolic Explorer, France, has revived research interests in developing alternate cost-competitive, scalable and marketable bioprocesses. The current review outlines natural glycerol assimilating and 1, 3-PDO-producing microbes, their metabolic pathways, and associated genes. Later, technical barriers are carefully examined, such as the direct use of industrial glycerol as input material and genetic and metabolic issues related to microbes alleviating their industrial use. Biotechnological interventions exploited in the past five years, which can substantially circumvent these challenges, such as microbial bioprospecting, mutagenesis, metabolic, evolutionary and bioprocess engineering, including their combinations, are discussed in detail. The concluding section sheds light on some of the emerging and most promising breakthroughs which have resulted in evolving new, efficient, and robust microbial cell factories and/or bioprocesses for glycerol-based 1, 3-PDO production

AN EPIDEMIOLOGICAL STUDY OF DIETARY AND EXERCISE HABITS AS CO-RELATES OF HYPERTENSION IN PERSON AGED 45 AND ABOVE IN AGRA DISTRICT

Background: Due to changing lifestyle in Indian population prevalence of hypertension is increasing which needs modification in dietary and exercise habit of the general population. Objective: A study was designed to correlate dietary and exercise habits with hypertension in general population. Material and methods: Present study is a community based cross sectional study among persons aged more than 45 years in Agra district using PPS multi stage simple random sampling technique with a sample size of 553, which includes 260 persons from urban and 293 persons from rural area. Results: Out of 544 persons studied, overall prevalence of hypertension was found to be 36.21% which was 41.47% in urban and 31.47% in rural areas. Prevalence decreases significantly in person engaged in heavy physical activity (14.54%). Hypertension is more prevalent in non vegetarian diet (44.26%) as compared to vegetarian (33.88%) and very high in population consuming extra salt (73.77%). Conclusion: Prevalence of hypertension in this study is 36.21% and increases with lack of exercise and yoga, non vegetarian diet and consumption of extra salt in diet

Distinction of lymphoid and myeloid clonal hematopoiesis

Clonal hematopoiesis (CH) results from somatic genomic alterations that drive clonal expansion of blood cells. Somatic gene mutations associated with hematologic malignancies detected in hematopoietic cells of healthy individuals, referred to as CH of indeterminate potential (CHIP), have been associated with myeloid malignancies, while mosaic chromosomal alterations (mCAs) have been associated with lymphoid malignancies. Here, we analyzed CHIP in 55,383 individuals and autosomal mCAs in 420,969 individuals with no history of hematologic malignancies in the UK Biobank and Mass General Brigham Biobank. We distinguished myeloid and lymphoid somatic gene mutations, as well as myeloid and lymphoid mCAs, and found both to be associated with risk of lineage-specific hematologic malignancies. Further, we performed an integrated analysis of somatic alterations with peripheral blood count parameters to stratify the risk of incident myeloid and lymphoid malignancies. These genetic alterations can be readily detected in clinical sequencing panels and used with blood count parameters to identify individuals at high risk of developing hematologic malignancies