Inhibition of hepatic oxalate overproduction ameliorates metabolic dysfunction-associated steatohepatitis.

The incidence of metabolic dysfunction-associated steatohepatitis (MASH) is on the rise, and with limited pharmacological therapy available, identification of new metabolic targets is urgently needed. Oxalate is a terminal metabolite produced from glyoxylate by hepatic lactate dehydrogenase (LDHA). The liver-specific alanine-glyoxylate aminotransferase (AGXT) detoxifies glyoxylate, preventing oxalate accumulation.

Enhanced venous thrombosis and hypercoagulability in murine and human metabolic dysfunction-associated steatohepatitis.

Background: Patients with metabolic dysfunction-associated steatohepatitis (MASH) are at an increased risk of developing venous thromboembolic events, including deep vein thrombosis (DVT). To date, the study of DVT in MASH has been hampered by the lack of reliable models that mimic the pathologic aspects of human disease.

Objectives: To evaluate DVT severity and hypercoagulability in murine and human MASH.

Involvement of Sirt1-FoxO3a-Bnip3 axis and autophagy mediated mitochondrial turnover in according protection to hyperglycemic NRK-52E cells by Berberine.

Aberrant accumulation of dysfunctional mitochondria in renal cells during hyperglycemia signifies perturbed autophagy and mitochondrial turnover. This study aims to focus on the underlying mechanism involved in autophagy and mitophagy inducing efficacy of Berberine (isoquinoline alkaloid) in hyperglycemic NRK-52E cells. Berberine mediated protection to hyperglycemic cells prevented alteration in mitochondrial structure and function.

Interactions between integrin α9β1 and VCAM-1 promote neutrophil hyperactivation and mediate poststroke DVT.

Venous thromboembolic events are significant contributors to morbidity and mortality in patients with stroke. Neutrophils are among the first cells in the blood to respond to stroke and are known to promote deep vein thrombosis (DVT). Integrin α9 is a transmembrane glycoprotein highly expressed on neutrophils and stabilizes neutrophil adhesion to activated endothelium via vascular cell adhesion molecule 1 (VCAM-1).

CD14 Blockade Does Not Improve Outcomes of Deep Vein Thrombosis Following Inferior Vena Cava Stenosis in Mice.

Background: Neutrophil-mediated persistent inflammation and neutrophil extracellular trap formation (NETosis) promote deep vein thrombosis (DVT). CD14, a co-receptor for toll-like receptor 4 (TLR4), is actively synthesized by neutrophils, and the CD14/TLR4 signaling pathway has been implicated in proinflammatory cytokine overproduction and several aspects of thromboinflammation. The role of CD14 in the pathogenesis of DVT remains unclear.

Amino Acid Metabolism and Atherosclerotic Cardiovascular Disease.

Despite significant advances in medical treatments and drug development, atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death worldwide. Dysregulated lipid metabolism is a well-established driver of ASCVD. Unfortunately, even with potent lipid-lowering therapies, ASCVD-related deaths have continued to increase over the past decade, highlighting an incomplete understanding of the underlying risk factors and mechanisms of ASCVD.

Serine synthesis via reversed SHMT2 activity drives glycine depletion and acetaminophen hepatotoxicity in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one-third of the global population. Understanding the metabolic pathways involved can provide insights into disease progression and treatment. Untargeted metabolomics of livers from mice with early-stage steatosis uncovered decreased methylated metabolites, suggesting altered one-carbon metabolism.

Chitosan/alginate nanogel potentiate berberine uptake and enhance oxidative stress mediated apoptotic cell death in HepG2 cells.

Biopolymer-based nanoscale drug delivery systems have become a promising approach to overcome the limitations associated with conventional chemotherapeutics used for cancer treatment. Herein, we reported to develop a hydrophilic nanogel (NG) composed of Chitosan (Chi) and sodium alginate (Alg) using the ion gelation method for delivering Berberine hydrochloride (BBR), an alkaloid obtained from Berberis aristata roots. The use of different nanocarriers for BBR delivery has been reported previously, but the bioavailability of these carriers was limited due to phagocytic uptake and poor systemic delivery.

STE20-type kinases MST3 and MST4 promote the progression of hepatocellular carcinoma: Evidence from human cell culture and expression profiling of liver biopsies.

Hepatocellular carcinoma (HCC) is one of the most fatal and fastest growing malignancies. Recently, nonalcoholic steatohepatitis (NASH), characterized by liver steatosis, inflammation, cell injury (hepatocyte ballooning), and different stages of fibrosis, has emerged as a major catalyst for HCC. Because the STE20-type kinases, MST3 and MST4, have been described as critical molecular regulators of NASH pathophysiology, we here focused on determining the relevance of these proteins in human HCC.

AMP-activated protein kinase: An energy sensor and survival mechanism in the reinstatement of metabolic homeostasis.

Cells are programmed to favorably respond towards the nutrient availability by adapting their metabolism to meet energy demands. AMP-activated protein kinase (AMPK) is a highly conserved serine/threonine energy-sensing kinase. It gets activated upon a decrease in the cellular energy status as reflected by an increased AMP/ATP ratio, ADP, and also during the conditions of glucose starvation without change in the adenine nucelotide ratio.

Silencing of STE20-type kinase TAOK1 confers protection against hepatocellular lipotoxicity through metabolic rewiring.

Background: NAFLD has become the leading cause of chronic liver disease worldwide afflicting about one quarter of the adult population. NASH is a severe subtype of NAFLD, which in addition to hepatic steatosis connotes liver inflammation and hepatocyte ballooning. In light of the exponentially increasing prevalence of NAFLD, it is imperative to gain a better understanding of its molecular pathogenesis.

Inhibition of MAP4K4 signaling initiates metabolic reprogramming to protect hepatocytes from lipotoxic damage.

The primary hepatic consequence of obesity is non-alcoholic fatty liver disease (NAFLD), affecting about 25% of the global adult population. Non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD characterized by liver lipid accumulation, inflammation, and hepatocyte ballooning, with a different degree of hepatic fibrosis. In the light of rapidly increasing prevalence of NAFLD and NASH, there is an urgent need for improved understanding of the molecular pathogenesis of these diseases.

STE20-type kinase TAOK3 regulates hepatic lipid partitioning.

Objective: Nonalcoholic fatty liver disease (NAFLD), defined by excessive lipid storage in hepatocytes, has recently emerged as a leading global cause of chronic liver disease. The aim of this study was to examine the role of STE20-type protein kinase TAOK3, which has previously been shown to associate with hepatic lipid droplets, in the initiation and aggravation of human NAFLD.

Methods: The correlation between TAOK3 mRNA expression and the severity of NAFLD was investigated in liver biopsies from 62 individuals.

Antagonizing STK25 Signaling Suppresses the Development of Hepatocellular Carcinoma Through Targeting Metabolic, Inflammatory, and Pro-Oncogenic Pathways.

Background & Aims: Hepatocellular carcinoma (HCC) is one of the most fatal and fastest-growing cancers. Recently, nonalcoholic steatohepatitis (NASH) has been recognized as a major catalyst for HCC. Thus, additional research is critically needed to identify mechanisms involved in NASH-induced hepatocarcinogenesis, to advance the prevention and treatment of NASH-driven HCC.

Phytochemical profiling and cytotoxic evaluation of L. against human liver cancer cell line.

L. (Lamiaceae) is a medicinal plant, widely distributed in the tropical and subtropical regions and commonly used in traditional medicine. The current study was focused to evaluate the cytotoxic potential of aqueous extract of root of (AEPS) against human hepatoblastoma cancer cell line (Hep G2).

Berbamine induced activation of the SIRT1/LKB1/AMPK signaling axis attenuates the development of hepatic steatosis in high-fat diet-induced NAFLD rats.

Non-alcoholic fatty liver disease (NAFLD), a chronic metabolic disorder is concomitant with oxidative stress and inflammation. This study aimed to assess the effects of berbamine (BBM), a natural bisbenzylisoquinoline alkaloid with manifold biological activities and pharmacological effects on lipid, cholesterol and glucose metabolism in a rat model of NAFLD, and to explicate the potential mechanisms underlying its activity. BBM administration alleviated the increase in the body weight and liver index of HFD rats.

Berbamine induced AMPK activation regulates mTOR/SREBP-1c axis and Nrf2/ARE pathway to allay lipid accumulation and oxidative stress in steatotic HepG2 cells.

Non-alcoholic fatty liver disease is emanating as a global cataclysm. This study was designed to investigate the antioxidative, anti-inflammatory and fat metabolism-regulating potential of berbamine (BBM), a natural bis-benzylisoquinoline alkaloid. BBM attenuated intracellular lipid accumulation in oleic-acid exposed HepG2 cells (0.

Activation of autophagic flux via LKB1/AMPK/mTOR axis against xenoestrogen Bisphenol-A exposure in primary rat hepatocytes.

Bisphenol-A, an endocrine disruptive chemical widely used to manufacture polycarbonate plastics and epoxy resins, acts via multiple mechanisms that perturb cellular and molecular functions. BPA has the potential to induce hepatotoxicity via generation of ROS and oxidative stress. However, the mechanism of BPA induced oxidative stress and autophagy is still ambiguous at molecular and cellular levels.

Entrenching role of cell cycle checkpoints and autophagy for maintenance of genomic integrity.

Genomic integrity of the cell is crucial for the successful transmission of genetic information to the offspring and its survival. Persistent DNA damage induced by endogenous and exogenous agents leads to various metabolic manifestations. To combat this, eukaryotes have developed complex DNA damage response (DDR) pathway which senses the DNA damage and activates an arsenal of enzymes for the repair of damaged DNA.