Mammalian Ste20-like kinase 1 regulates AMPK to mitigate the progression of non-alcoholic fatty liver disease DOI Creative Commons
Lijuan Wang, Chenglei Zhang, Jie Ma

и другие.

European journal of medical research, Год журнала: 2025, Номер 30(1)

Опубликована: Апрель 17, 2025

Abstract Background Non-alcoholic steatohepatitis (NASH) progression is strongly associated with deteriorating hepatic function, primarily driven by free cholesterol (FC) accumulation-induced lipotoxicity. Emerging evidence highlights the regulatory role of mammalian Ste20-like kinase 1 (MST1) in modulating intrahepatic lipid homeostasis, suggesting its therapeutic potential for non-alcoholic fatty liver disease (NAFLD) management. This investigation seeks to elucidate pathophysiological mechanisms through which MST1 modulates NASH progression. Methods The experimental design employed two murine genetic models—wild-type (WT) controls and MST1-knockout (MST1-KO) specimens—subjected a nutritionally modified Western diet (WD) enriched saturated fats, simple carbohydrates, dietary induce pathogenesis. Lentiviral transduction techniques facilitated targeted overexpression WT animals maintained on this regimen. Parallel vitro investigations utilized HepG2 hepatocyte cultures exposed acid (FFA) cocktails comprising palmitic oleic acids, coupled CRISPR-mediated suppression complementary gain-of-function manipulations delineate molecular mechanisms. Results triggers sterol biosynthesis activation, resulting pathological FC overload concurrent transcriptional suppression. Genetic ablation amplifies retention potentiates histopathological inflammation, while reconstitution mitigates steatotic deposition attenuates inflammatory cascades. Mechanistic profiling revealed MST1-mediated AMPKα phosphorylation at Thr172, suppresses cholesterogenic enzyme expression via element-binding transcription factor 2 (SREBP2) axis modulation. cascade demonstrates dose-dependent inhibition HMGCR activity, resolving FC-induced hepatotoxicity. Crucially, orchestrates AMPK/SREBP2 crosstalk maintain knockout models exhibiting 67% elevated SREBP2 nuclear translocation compared controls. Conclusions involving AMPK emerges as promising modality metabolism. It significant arresting cascades extracellular matrix remodeling characteristic studies confirm that effectively de novo lipogenesis enhancing efflux capacity, thereby establishing dual-target strategy against both metabolic dysfunction fibrotic transformation preclinical models.

Язык: Английский

Role of MLIP in burn-induced sepsis and insights into sepsis-associated cancer progression DOI Creative Commons
Zhiwei Li, Qian Wang, Ying Liu

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 14, 2025

Introduction Burn-induced sepsis is a critical clinical challenge marked by systemic inflammation, immune dysregulation, and high mortality. Macrophage-driven inflammatory pathways are central to pathogenesis, while cell metabolic reprogramming plays key role in both cancer progression. Methods Bioinformatics analyses using GEO, TCGA, GTEx datasets identified MLIP-modulated genes linked responses prognosis. In vitro , LPS-stimulated HUVEC cells were used study MLIP’s effects on inflammation macrophage function through viability, ROS levels, cytokine expression, qRT-PCR, immunofluorescence assays. Results associated with immune-related cancer. Epigenetic analysis showed MLIP expression regulated promoter methylation chromatin accessibility. Prognostic revealed impact survival outcomes across types. reduced oxidative stress, hyperactivation. Conclusions regulates immune-metabolic dynamics burn-induced sepsis, influencing activity stress. Its suggests as potential therapeutic target linking modulation Further research evasion tumor metabolism may inform novel strategies.

Язык: Английский

Процитировано

0
SPRY1 regulates macrophage M1 polarization in skin aging and melanoma prognosis DOI

Rongxin Zhao,

Xun Zhang,

Yingnan Geng

и другие.

Translational Oncology, Год журнала: 2025, Номер 54, С. 102331 - 102331

Опубликована: Фев. 28, 2025

Язык: Английский

Процитировано

0
Single-cell sequencing reveals PHLDA1-positive smooth muscle cells promote local invasion in head and neck squamous cell carcinoma DOI
Bing Guo, Xutao Wen,

Shun Yu

и другие.

Translational Oncology, Год журнала: 2025, Номер 55, С. 102301 - 102301

Опубликована: Март 25, 2025

Язык: Английский

Процитировано

0
Interaction between post-tumor inflammation and vascular smooth muscle cell dysfunction in sepsis-induced cardiomyopathy DOI Creative Commons
Rui Liu, Lina Jia, Yu Lin

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 10, 2025

Background Sepsis-induced cardiomyopathy (SIC) presents a critical complication in cancer patients, contributing notably to heart failure and elevated mortality rates. While its clinical relevance is well-documented, the intricate molecular mechanisms that link sepsis, tumor-driven inflammation, cardiac dysfunction remain inadequately explored. This study aims elucidate interaction between post-tumor intratumor heterogeneity, of VSMC SIC, as well evaluate therapeutic potential exercise training specific pharmacological interventions. Methods Transcriptomic data from NCBI GEO databases were analyzed identify differentially expressed genes (DEGs) associated with SIC. Weighted gene co-expression network analysis (WGCNA), ontology (GO), KEGG pathway enrichment analyses utilized biological significance these genes. Molecular docking dynamics simulations used investigate drug-target interactions, immune infiltration mutation carried out by means platforms like TIMER 2.0 DepMap comprehend influence DVL1 on responsiveness. Results Through utilization datasets, we discovered core exhibited remarkable up-regulated expression both SIC diverse kinds cancers, which poor prognosis inflammatory responses. revealed Digoxin could bind reduce oxidative stress The module related was identified WGCNA, demonstrated distinctive cell patterns impact immunotherapeutic resistance. Conclusions regulator other cancers and, therefore, can serve target. present suggests targeted therapies enhance response regimens may be novel tool during particularly patients. drugs, Digoxin, require further vivo studies confirm their effects efforts improve outcomes immunotherapy-resistant

Язык: Английский

Процитировано

0
Mammalian Ste20-like kinase 1 regulates AMPK to mitigate the progression of non-alcoholic fatty liver disease DOI Creative Commons
Lijuan Wang, Chenglei Zhang, Jie Ma

и другие.

European journal of medical research, Год журнала: 2025, Номер 30(1)

Опубликована: Апрель 17, 2025

Abstract Background Non-alcoholic steatohepatitis (NASH) progression is strongly associated with deteriorating hepatic function, primarily driven by free cholesterol (FC) accumulation-induced lipotoxicity. Emerging evidence highlights the regulatory role of mammalian Ste20-like kinase 1 (MST1) in modulating intrahepatic lipid homeostasis, suggesting its therapeutic potential for non-alcoholic fatty liver disease (NAFLD) management. This investigation seeks to elucidate pathophysiological mechanisms through which MST1 modulates NASH progression. Methods The experimental design employed two murine genetic models—wild-type (WT) controls and MST1-knockout (MST1-KO) specimens—subjected a nutritionally modified Western diet (WD) enriched saturated fats, simple carbohydrates, dietary induce pathogenesis. Lentiviral transduction techniques facilitated targeted overexpression WT animals maintained on this regimen. Parallel vitro investigations utilized HepG2 hepatocyte cultures exposed acid (FFA) cocktails comprising palmitic oleic acids, coupled CRISPR-mediated suppression complementary gain-of-function manipulations delineate molecular mechanisms. Results triggers sterol biosynthesis activation, resulting pathological FC overload concurrent transcriptional suppression. Genetic ablation amplifies retention potentiates histopathological inflammation, while reconstitution mitigates steatotic deposition attenuates inflammatory cascades. Mechanistic profiling revealed MST1-mediated AMPKα phosphorylation at Thr172, suppresses cholesterogenic enzyme expression via element-binding transcription factor 2 (SREBP2) axis modulation. cascade demonstrates dose-dependent inhibition HMGCR activity, resolving FC-induced hepatotoxicity. Crucially, orchestrates AMPK/SREBP2 crosstalk maintain knockout models exhibiting 67% elevated SREBP2 nuclear translocation compared controls. Conclusions involving AMPK emerges as promising modality metabolism. It significant arresting cascades extracellular matrix remodeling characteristic studies confirm that effectively de novo lipogenesis enhancing efflux capacity, thereby establishing dual-target strategy against both metabolic dysfunction fibrotic transformation preclinical models.

Язык: Английский

Процитировано

0