Plasma lipidomics and fungal peptide-based community analysis identifies distinct signatures of early mortality in acute liver failure.

Background And Aims: Acute liver failure (ALF) has high mortality predominantly due to compromised immune system and increase vulnerability to bacterial and fungal infections.

Method: Plasma lipidome and fungal peptide-based-community (mycobiome) analysis were performed in Discovery cohort (40-ALF, 5-healthy) and validated in a validation cohort of 230-ALF using High-resolution-mass-spectrometry, artificial-neural-network (ANN) and machine-learning (ML).

Results: Untargeted lipidomics identified 2,013 lipids across 8 lipid-groups.

Circulating bacterial peptides and linked metabolomic signatures are indicative of early mortality in pediatric cirrhosis.

Background: Patients with pediatric cirrhosis-sepsis (PC-S) attain early mortality. Plasma bacterial composition, the cognate metabolites, and their contribution to the deterioration of patients with PC-S to early mortality are unknown. We aimed to delineate the plasma metaproteome-metabolome landscape and identify molecular indicators capable of segregating patients with PC-S predisposed to early mortality in plasma, and we further validated the selected metabolite panel in paired 1-drop blood samples using untargeted metaproteomics-metabolomics by UHPLC-HRMS followed by validation using machine-learning algorithms.

Modulation of CD8T cells, NK cells and Th1cytokines by metabolic milieu in decline of HBV-viremia in pregnant women treated with tenofovir-disoproxil from second trimester of pregnancy.

High HBV DNA levels predispose to mother to child transmission (MTCT) of HBV. Early nucleotide analogue (NA) therapy can reduce HBV DNA and minimize MTCT. We analysed immune-metabolic profile in pregnant mothers who received NA from 2nd trimester compared with untreated mothers.

Comparative metabolome analysis reveals higher potential of haemoperfusion adsorption in providing favourable outcome in ACLF patients.

Background And Aims: Acute-on-chronic liver failure (ACLF) is a serious illness associated with altered metabolome, organ failure and high mortality. Need for therapies to improve the metabolic milieu and support liver regeneration are urgently needed.

Methods: We investigated the ability of haemoperfusion adsorption (HA) and therapeutic plasma exchange (TPE) in improving the metabolic profile and survival in ACLF patients.

A mitochondrial quality control mechanism reverses the phagosome maturation arrest caused by .

Phagosome maturation arrest (PMA) imposed by ( ) is a classic tool that helps evade macrophage anti-bacterial responses. The exclusion of RAB7, a small GTPase, from -phagosomes underscores PMA. Here we report an unexpected mechanism that triggers crosstalk between the mitochondrial quality control (MQC) and the phagosome maturation pathways that reverses the PMA.

Metabolic alterations unravel the maternofetal immune responses with disease severity in pregnant women infected with SARS-CoV-2.

Pregnancy being an immune compromised state, coronavirus disease of 2019 (COVID-19) disease poses high risk of premature delivery and threat to fetus. Plasma metabolome regulates immune cellular responses, therefore we aimed to analyze the change in plasma secretome, metabolome, and immune cells with disease severity in COVID-19 positive pregnant females and their cord blood. COVID-19 reverse transcriptase-polymerase chain reaction positive pregnant females (n = 112) with asymptomatic (Asy) (n = 82), mild (n = 21), or moderate (n = 9) disease, healthy pregnant (n = 18), COVID-19 positive nonpregnant females (n = 7) were included.

Early hepatic proteomic signatures reveal metabolic changes in high-fat-induced obesity in rats.

The prevalence of diet-related obesity is increasing dramatically worldwide, making it important to understand the associated metabolic alterations in the liver. It is well known that obesity is a multifactorial condition that is the result of complex integration between many gene expressions and dietary factors. Obesity alone or in conjunction with other chronic diseases such as diabetes and insulin resistance causes many health problems and is considered a major risk factor for developing non-alcoholic steatohepatitis (NASH) and cirrhosis.

Alters the Lipid Landscape of the Brain Cortex and Plasma to Ameliorate the Effect of Photothrombotic Stroke in a Mouse Model.

Stroke-like injuries in the brain result in not only cell death at the site of the injury but also other detrimental structural and molecular changes in regions around the stroke. A stroke-induced alteration in the lipid profile interferes with neuronal functions such as neurotransmission. Preventing these unfavorable changes is important for recovery.

SIRT2 inhibition by AGK2 enhances mycobacteria-specific stem cell memory responses by modulating beta-catenin and glycolysis.

Bacille Calmette-Guerin (BCG) generates limited long-lasting adaptive memory responses leading to short-lived protection against adult pulmonary tuberculosis (TB). Here, we show that host sirtuin 2 (SIRT2) inhibition by AGK2 significantly enhances the BCG vaccine efficacy during primary infection and TB recurrence through enhanced stem cell memory (T) responses. SIRT2 inhibition modulated the proteome landscape of CD4 T cells affecting pathways involved in cellular metabolism and T-cell differentiation.

Biomolecular map of albumin identifies signatures of severity and early mortality in acute liver failure.

Background & Aims: Acute liver failure (ALF) is associated with high mortality. Alterations in albumin structure and function have been shown to correlate with outcomes in cirrhosis. We undertook a biomolecular analysis of albumin to determine its correlation with hepatocellular injury and early mortality in ALF.

Withaferin A Protects against Primary and Recurrent Tuberculosis by Modulating Mycobacterium-Specific Host Immune Responses.

The fate of Mycobacterium tuberculosis infection is governed by immune signaling pathways that can either eliminate the pathogen or result in tuberculosis (TB). Anti-TB therapy (ATT) is extensive and is efficacious only against active, drug-sensitive strains of M. tuberculosis.

Berberine governs NOTCH3/AKT signaling to enrich lung-resident memory T cells during tuberculosis.

Stimulation of naïve T cells during primary infection or vaccination drives the differentiation and expansion of effector and memory T cells that mediate immediate and long-term protection. Despite self-reliant rescue from infection, BCG vaccination, and treatment, long-term memory is rarely established against Mycobacterium tuberculosis (M.tb) resulting in recurrent tuberculosis (TB).

Metabolomic analysis shows dysregulation in amino acid and NAD+ metabolism in palmitate treated hepatocytes and plasma of non-alcoholic fatty liver disease spectrum.

There is an alarming increase in incidence of fatty liver disease worldwide. The fatty liver disease spectrum disease ranges from simple steatosis (NAFL) to steatohepatitis (NASH) which culminates in cirrhosis and cancer. Altered metabolism is a hallmark feature associated with fatty liver disease and palmitic acid is the most abundant saturated fatty acid, therefore, the aim of this study was to compare metabolic profiles altered in hepatocytes treated with palmitic acid and also the differentially expressed plasma metabolites in spectrum of nonalcoholic fatty liver.

Plasma Proteomic Analysis Identified Proteins Associated with Faulty Neutrophils Functionality in Decompensated Cirrhosis Patients with Sepsis.

Decompensated cirrhosis (DC) is susceptible to infections and sepsis. Neutrophils and monocytes provide the first line of defense to encounter infection. We aimed to evaluate proteins related to neutrophils functionality in sepsis.

Downregulation of gamma subunit of TCP1 chaperonin of Leishmania donovani modulates extracellular vesicles-mediated macrophage microbicidal function.

T-complex protein-1 (TCP1) is a group II chaperonin, known to fold various proteins like actin and tubulin. In Leishmania donovani only one subunit that is gamma subunit (LdTCP1γ) has been functionally characterized as a homo-oligomeric complex that exhibits ATP-dependent protein folding. The gene is essential for the survival and infectivity of the parasite.

Bile multi-omics analysis classifies lipid species and microbial peptides predictive of carcinoma of gallbladder.

Background And Aims: Histopathological examination is the gold standard for detection of gallstone (GS) or gallbladder carcinoma (CAGB). Bile concentrated in the gallbladder (GB) is expected to recapitulate metagenomics and molecular changes associated with development of CAGB.

Approach And Results: Bile samples were screened for lipidomics and metaproteome (metagenomics) signatures capable of early detection of cancer in GB anomalies.

Unraveling of interacting protein network of chaperonin TCP1 gamma subunit of Leishmania donovani.

T-complex polypeptide-1 (TCP1) is a group II chaperonin that folds various cellular proteins. About 10% of cytosolic proteins in yeast have been shown to flux through the TCP1 protein complex indicating that it interacts and folds a plethora of substrate proteins that perform essential functions. In Leishmania donovani, the gamma subunit of TCP1 (LdTCP1γ) has been shown to form a homo-oligomeric complex and exhibited ATP-dependent protein folding activity.

Global metabolome profiling of COVID-19 respiratory specimen using high-resolution mass spectrometry (HRMS).

Here we describe a protocol for identifying metabolites in respiratory specimens of patients that are SARS-CoV-2 positive, SARS-CoV-2 negative, or H1N1 positive. This protocol provides step-by-step instructions on sample collection from patients, followed by metabolite extraction. We use ultra-high-pressure liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS) for data acquisition and describe the steps for data analysis.

Multi-omics analysis of respiratory specimen characterizes baseline molecular determinants associated with SARS-CoV-2 outcome.

Rapid diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection still remains a major challenge. A multi-omic approach was adopted to analyze the respiratory specimens of 20 SARS-CoV-2-positive, 20 negative and 15 H1N1 pdm 2009 positive cases. Increased basal level of MX1 (MX dynamin-like GTPase 1) and WARS (tryptophan-tRNA ligase) correlated with SARS-CoV-2 infection and its outcome.

Differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitis.

Background & Aims: In patients with severe alcoholic hepatitis (SAH), little is known about the profile of peripheral blood mononuclear cells (PBMCs) at baseline and during corticosteroid therapy, among those who can be treated successfully with steroids (steroid-responders [R] and those who cannot (steroid-non-responders [NR]); 2 groups with different outcomes.

Methods: We performed RNA-seq analysis in PBMCs from 32 patients with definite SAH, at baseline and after 7 days of corticosteroids. The data were sorted into R and NR (n = 16, each group) using the Lille model and 346 blood transcription modules (BTMs) were identified.

Characterization of a Bowman-Birk type trypsin inhibitor purified from seeds of Solanum surattense.

A Bowman-Birk type trypsin inhibitor protein (SSTI) from seeds of the medicinal plant Solanum surattense was isolated, purified and characterized. SSTI showed a single band on SDS-PAGE corresponding to 11.4 kDa molecular weight.

Albumin in Advanced Liver Diseases: The Good and Bad of a Drug!

Human serum albumin is the most abundant plasma protein, and it regulates diverse body functions. In patients with advanced and decompensated cirrhosis, serum albumin levels are low because of a reduction in the hepatocyte mass due to disease per se and multiple therapeutic interventions. Because of their oncotic and nononcotic properties, administration of human albumin solutions (HAS) have been found to be beneficial in patients undergoing large-volume paracentesis or who have hepatorenal syndrome or spontaneous bacterial peritonitis.