Neutrophil extracellular traps in homeostasis and disease

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 20, 2024

Language: Английский

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Gut Microbiota at the Crossroad of Hepatic Oxidative Stress and MASLD

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 56 - 56

Published: Jan. 6, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic condition marked by excessive lipid accumulation in hepatic tissue. This disorder can lead to range of pathological outcomes, including metabolic steatohepatitis (MASH) and cirrhosis. Despite extensive research, the molecular mechanisms driving MASLD initiation progression remain incompletely understood. Oxidative stress peroxidation are pivotal "multiple parallel hit model", contributing cell death tissue damage. Gut microbiota plays substantial role modulating oxidative through multiple pathways: impairing intestinal barrier, which results bacterial translocation inflammation; modifying bile acid structure, impacts signaling cascades involved lipidic metabolism; influencing hepatocytes' ferroptosis, form programmed death; regulating trimethylamine N-oxide (TMAO) activating platelet function, both recently identified as pathogenetic factors MASH progression. Moreover, various exogenous impact gut its involvement MASLD-related stress, such air pollution, physical activity, cigarette smoke, alcohol, dietary patterns. manuscript aims provide state-of-the-art overview focused on intricate interplay between microbiota, peroxidation, pathogenesis, offering insights into potential strategies prevent associated complications.

Language: Английский

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Nicotinamide Adenine Dinucleotide Phosphate Oxidases and Metabolic Dysfunction-Associated Steatotic Liver Disease

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 83 - 83

Published: Jan. 13, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by lipid accumulation in the due to an excess their supplies or impairment management. While some patients remain stable for years, a proportion of them progress up steatohepatitis (MASH). MASLD links with systemic pathways being associated metabolic and non-metabolic diseases. Although represents first hit MASLD, pathophysiology its development progression MASH remains not completely understood. Oxidative stress has received particular attention recent as most oxidative process occurs liver, which also target stress-induced damage. Growing evidence linked activity nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) increased production reactive oxygen species damage fibrosis. NOX acts both hepatocytes non-parenchymal hepatic cells, contributing hepatocyte lipotoxicity, impaired microcirculation, stellate, mesenchymal stem cells activation proliferation. This review aims summarize current knowledge on involvement MASLD-MASH transition, focusing role isoforms, suggest targeting therapeutic approach MASLD.

Language: Английский

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Elevated platelet distribution width and diabetes may serve as preoperative predictors of microvascular invasion in primary hepatocellular carcinoma

Journal of Cancer Research and Clinical Oncology, Journal Year: 2025, Volume and Issue: 151(3)

Published: March 14, 2025

Hepatocellular carcinoma (HCC) is one of the malignancies with increasing incidence globally, and microvascular invasion (MVI) a crucial determinant prognosis in patients. This study aimed to investigate platelet distribution width (PDW) diabetes mellitus as indicators for predicting preoperative MVI HCC, providing more accurate predictive tools clinicians guide treatment strategies improve patient survival quality life. A retrospective was conducted, including 1357 patients who underwent hepatectomy HCC between January 2008 December 2014 at Eastern Hepatobiliary Surgery Hospital China. Clinical, pathological, radiological data, PDW status, were collected. Univariate multivariate logistic regression analyses performed identify risk factors establish model. The performance model evaluated through nomograms internal validation. analysis revealed significant associations mellitus, presence liver cirrhosis, prealbumin level, tumor diameter, number tumors, HBV DNA viral load > 104, ≥ 17. Multivariate identified 17 independent MVI. Based on these findings, established, demonstrating high accuracy stability both training validation cohorts. confirmed reliable established corresponding Future research should further explore underlying mechanisms enhance clinical advance field treatment.

Language: Английский

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Neutrophil extracellular traps mediate pathophysiology of hepatic cells during liver injury

The Anatomical Record, Journal Year: 2025, Volume and Issue: unknown

Published: April 12, 2025

Neutrophil extracellular traps (NETs) are web-like, bactericidal structures produced by neutrophils and composed principally of DNA, histones, elastase, myeloperoxidase, among other components. NET formation is an innate immune response that beneficial for pathogen killing clearance. However, excessive clearance defects can lead to inflammation induce damage host organs. NETs also implicated in the development noninfectious inflammatory disorders, such as liver injury chronic diseases. The parenchyma contains hepatocytes, sinusoidal endothelial cells, Kupffer hepatic stellate cells. Each these cells possesses unique functions, their interactions with result pathophysiological changes contributing injury. This review updates findings related modes action molecular mechanisms which modulate pathophysiology various potentiate article reviews roles ischemia reperfusion injury, hepatocellular carcinoma pathogenesis, cancer metastasis. Last, we examine data determine whether crosstalk during identify future research directions.

Language: Английский

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Tumor‑associated macrophages activated in the tumor environment of hepatocellular carcinoma: Characterization and treatment (Review)

International Journal of Oncology, Journal Year: 2024, Volume and Issue: 65(4)

Published: Sept. 5, 2024

Hepatocellular carcinoma (HCC) tissue is rich in dendritic cells, T B macrophages, natural killer cells and cellular stroma. Together they form the tumor microenvironment (TME), which also numerous cytokines. Tumor‑associated macrophages (TAMs) are involved regulation of development. TAMs HCC receive stimuli different directions, polarize directions release cytokines to regulate development HCC. mostly divided into two cell phenotypes: M1 M2. secrete pro‑inflammatory mediators, M2 a variety anti‑inflammatory pro‑tumorigenic substances. The TAM polarization tumors Both direct indirect methods for discussed. indirectly support by promoting peripheral angiogenesis regulating immune TME. In terms between present review mainly focuses on molecular mechanism. both proliferation apoptosis quantitative changes HCC, stimulate related invasive migratory ability stemness cells. aims identify immunotherapeutic options based mechanisms TME

Language: Английский

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Advanced Liver-on-a-Chip Model for Evaluating Drug Metabolism and Hepatotoxicity

Biosensors, Journal Year: 2024, Volume and Issue: 14(9), P. 435 - 435

Published: Sept. 6, 2024

The liver has many important functions, including the biotransformation of drugs and detoxification human organism. As such, it is also exposed to harmful substances, which leads disorders diseases such as cirrhosis. For these reasons, seems consider metabolism direct effects on when evaluating efficacy new drugs. Accordingly, we have developed an advanced in vitro model using organ-on-a-chip approach that replicates morphological functional features vivo. created can metabolize drugs, demonstrated two widely used anticancer 5-fluorouracil (5FU) capecitabine (CAP). In addition, best our knowledge, are first who evaluate not only viability model-building cells but their cytochrome P450 activity albumin production. Our study brings hope properly drug at level.

Language: Английский

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Influence of nuclear factor κB and adenosine monophosphate-activated protein kinase on the vascular bed of the liver under the conditions of modeling chronic alcoholic hepatitis

Regulatory Mechanisms in Biosystems, Journal Year: 2024, Volume and Issue: 15(3), P. 410 - 415

Published: June 17, 2024

Chronic alcohol use activates the transcription factor κB (NF-κB) in liver sinusoidal endothelial cells (LSECs), macrophages and other of parenchyma, which controls regulation expression pro-inflammatory cytokines that activate signaling pathways immune inflammation vascular tone. AMP-activated protein kinase (AMPK) is an important immunometabolic regulatory and, as a metabolic sensor, AMPK may be involved blood flow. The aim work was to find out effect modulators on morphometric parameters bed rats under conditions modeling chronic alcoholic hepatitis. Simulation hepatitis leads violation exchange metabolites between central interlobular veins, creates prerequisites for development hypoxic damage hepatocytes, evidenced by decrease diameters lobular arterioles venules. Administration ammonium pyrrolidinedithiocarbamate bacterial lipopolysaccharide, affect NF-κB hepatitis, helps restore increase lumens introduction phenformin doxorubicin, prevents arteries intensification circulation.

Language: Английский

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