Regeneration of Non-Alcoholic Fatty Liver Cells Using Chimeric FGF21/HGFR: A Novel Therapeutic Approach DOI Open Access
Sung Jun Kim, SoJung Kim, Jeongeun Hyun

et al.

Published: Dec. 15, 2023

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant ailment attributed to factors like obesity and diabetes. While ongoing research explores treatments for NAFLD, further investigation is imperative address this escalating health concern. NAFLD manifests hepatic steatosis, precipitating insulin resistance metabolic syndrome. This study aims validate the regenerative potential of chimeric fibroblast growth factor 21 (FGF21)-Hepatocyte Growth Factor Receptor (HGFR) in NAFLD-afflicted cells. AML12, murine hepatocyte cell line, was utilized gauge effects FGF21/HGFR expression. Polysaccharide accumulation affirmed through periodic acid-Schiff (PAS) staining, while LDL uptake microscopically observed with labeled LDL. mRNA analysis via RT-PCR revealed reduced expression key markers, including acetyl-CoA carboxylase 1 (ACC1) sterol regulatory element-binding protein (SREBP) cleavage-activating (SCAP), alongside elevated levels (HGF), nuclear 4 alpha (HNF4A), albumin (ALB). These findings affirm hepatoregenerative properties within AML12 cells, opening novel avenues therapeutic exploration.

Language: Английский

Noncoding RNAs in sepsis-associated acute liver injury: Roles, mechanisms, and therapeutic applications DOI Creative Commons

Jialian Wang,

Xingyu Tao, Zhengyang Liu

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107596 - 107596

Published: Jan. 10, 2025

Sepsis is a life-threatening syndrome characterized by organ dysfunction caused dysregulated host response to infection. Sepsis-associated acute liver injury (SA-ALI) frequent and serious complication of sepsis that considerably impacts both short-term long-term survival outcomes. In intensive care units (ICUs), the mortality rate patients with SA-ALI remains high, mostly due absence effective early diagnostic markers suitable therapeutic strategies. Recent studies have demonstrated importance non-coding RNAs (ncRNAs) in development progression SA-ALI. This review focuses on critical roles ncRNAs, including microRNAs (miRNAs), long (lncRNAs), circular (circRNAs), regulating "cytokine storms", oxidative stress, mitochondrial dysfunction, programmed cell death SA-ALI, summarizes current state limitations existing lncRNAs circRNAs By integrating advancements high-throughput sequencing technologies, this provides novel insights into dual potential ncRNAs as biomarkers targets, offers new ideas for diagnosis treatment research highlights challenges clinical translation.

Language: Английский

Citations

1
Single‐cell RNA sequencing reveals reduced intercellular adhesion molecule crosstalk between activated hepatic stellate cells and neutrophils alleviating liver fibrosis in hepatitis B virus transgenic mice post menstrual blood‐derived mesenchymal stem cell transplantation DOI Creative Commons
Lijun Chen, Yuqi Huang, Ning Zhang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 22, 2024

Abstract Liver fibrosis can cause hepatitis B virus (HBV)‐associated hepatocellular carcinoma. Menstrual blood‐derived mesenchymal stem cells (MenSCs) ameliorate liver through paracrine. Single‐cell RNA sequencing (scRNA‐seq) may be used to explore the roadmap of activated hepatic stellate cell (aHSC) inactivation target fibrosis. This study established HBV transgenic (HBV‐Tg) mouse model carbon tetrachloride (CCl 4 )‐induced and demonstrated that MenSCs migrated injured improve serological indices reduce fibrotic accumulation. RNA‐bulk analysis revealed mediated extracellular matrix accumulation adhesion. parenchymal nonparenchymal were identified by scRNA‐seq in control, CCl , MenSC groups, revealing heterogeneity fibroblasts/HSCs. A CellChat diminished intercellular adhesion molecule (ICAM) signaling is vital for therapy. Specifically, Icam1 aHSCs acted on Itgal / Itgb2 Itgam neutrophils, causing decreased The expression was higher group than control after therapy neutrophil clusters. Lcn2 Pglyrp1 Wfdc21 Mmp8 had high potential targets neutrophils. highlights interacting cells, corresponding molecules, underlying treating HBV‐associated

Language: Английский

Citations

6
Advances in molecular agents targeting toll-like receptor 4 signaling pathways for potential treatment of sepsis DOI
Yunyun Zheng, Yingying Gao,

Weiru Zhu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 268, P. 116300 - 116300

Published: March 1, 2024

Language: Английский

Citations

5
Comprehensive single-cell analysis deciphered the immunoregulatory mechanism of TPPU in alleviating sepsis-related acute liver injury DOI Creative Commons

Juan Li,

Mengjuan Xuan,

Li Yang

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
The dual role of neutrophils in sepsis-associated liver injury DOI Creative Commons
L. Z. Fang,

Yu Na Song,

Jiangtao Chen

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 28, 2025

Sepsis is often accompanied by liver injury and associated with an increase in the number of circulating hepatic neutrophils. In sepsis-associated injury, neutrophils exhibit phenotypic heterogeneity perform both pro- anti-inflammatory functions. Moreover, neutrophil dysfunction neutrophil-associated immunosuppression are also involved pathogenesis sepsis. Given complex functionality this cell type, aim review was to describe possible mechanistic role a brief introduction recruitment subsequent discussion potential contributions different subtypes injury.

Language: Английский

Citations

0
Comprehensive integration of diagnostic biomarker analysis and immune cell infiltration features in sepsis via machine learning and bioinformatics techniques DOI Creative Commons
Liuqing Yang,

Rui Xuan,

Dawei Xu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 10, 2025

Introduction Sepsis, a critical medical condition resulting from an irregular immune response to infection, leads life-threatening organ dysfunction. Despite advancements, the need for research into dependable diagnostic markers and precise therapeutic targets. Methods We screened out five gene expression datasets (GSE69063, GSE236713, GSE28750, GSE65682 GSE137340) Gene Expression Omnibus. First, we merged first two datasets. then identified differentially expressed genes (DEGs), which were subjected KEGG GO enrichment analyses. Following this, integrated DEGs with key modules as determined by Weighted Co-expression Network Analysis (WGCNA), identifying 262 overlapping genes. 12 core subsequently selected using three machine-learning algorithms: random forest (RF), Least Absolute Shrinkage Selection Operator (LASSO), Support Vector Machine-Recursive Feature Elimination (SVW-RFE). The utilization of receiver operating characteristic curve in conjunction nomogram model served authenticate discriminatory strength efficacy CIBERSORT was utilized evaluate inflammatory immunological sepsis. Astragalus, Salvia, Safflower are primary elements Xuebijing, commonly used clinical treatment Using Traditional Chinese Medicine Systems Pharmacology Database Platform (TCMSP), chemical constituents these herbs their target Results found that CD40LG is not only one identified, but also common active components quercetin, luteolin, apigenin herbs. extracted structure ingredients -flavonoids. Through docking analysis, further validated interaction between flavonoids CD40LG. Lastly, blood samples collected healthy individuals sepsis patients, without administration extraction peripheral mononuclear cells (PBMCs). By qPCR WB analysis. observed significant differences across groups. In this study, pinpointed candidate hub constructed its diagnosis. Discussion This provides potential evidence diagnosis offers insights pathogenesis disease progression

Language: Английский

Citations

0
Liver injury in sepsis: manifestations, mechanisms and emerging therapeutic strategies DOI Creative Commons

Xinqi Xu,

Tingyu Yang, Jie An

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 28, 2025

Sepsis is defined as a condition related to infection that manifests with multiorgan dysfunction, representing life-threatening state. Consequently, severe complications frequently occur, liver injury being one of the most prevalent serious sepsis. Liver dysfunction during sepsis serves an independent predictor mortality. This review provides comprehensive overview current research on sepsis-induced (SILI), encompassing clinical manifestations, diagnostic criteria, pathogenesis and therapeutic strategies associated this condition. SILI may manifest hypoxic hepatitis due ischemia shock, cholestasis resulting from abnormal bile metabolism, or duct sclerosis. The pathophysiology involves intricate interactions among inflammatory response, oxidative stress, cell death. All these factors complicate treatment represent potential targets for intervention. Furthermore, addresses limitations inherent in conventional therapies currently employed managing emphasizes novel targeted aimed at addressing fundamental mechanisms underlying

Language: Английский

Citations

0
Interleukin-6 overexpression and elevated granulocyte-to-lymphocyte ratio indicate hepatic stress in experimental group a Streptococcus sepsis DOI Creative Commons

Valerie Brunsch,

Wendy Bergmann‐Ewert, Brigitte Müller‐Hilke

et al.

Medical Microbiology and Immunology, Journal Year: 2025, Volume and Issue: 214(1)

Published: April 3, 2025

Language: Английский

Citations

0
Usp9x contributes to the development of sepsis-induced acute kidney injury by promoting inflammation and apoptosis in renal tubular epithelial cells via activation of the TLR4/nf-κb pathway DOI Creative Commons

Shuhao Gong,

Huawei Xiong,

Yingchao Lei

et al.

Renal Failure, Journal Year: 2024, Volume and Issue: 46(2)

Published: June 14, 2024

As a pattern recognition receptor, Toll-like receptor 4 (TLR4) is crucial for the development and progression of acute kidney injury (AKI). This study aims to explore whether deubiquitinase Usp9x influences TLR4/NF-B pathway cause sepsis-induced (S-AKI). The model AKI was established in Sprague-Dawley rats using cecal ligation puncture (CLP) method, while renal tubular epithelial cell NRK-52E stimulated with lipopolysaccharide (LPS) vitro. All plasmids were transfected into cells according indicated group. TLR4 predicted by online prediction software Ubibrowser. Subsequently, Western blot Pearson correlation analysis identified protein as potential candidate. Co-IP verified interaction between Usp9x. Further research revealed that overexpression inhibited degradation downregulating its ubiquitination modification levels. Both vivo vitro experiments observed interference effectively alleviated inflammatory response apoptosis (RTECs) induced CLP or LPS, whereas reversed this situation. Transfection sh-Usp9x suppressed expression proteins associated TLR4/NF-κB LPS. Moreover, effect transfection. Therefore, interacts TLR4, leading upregulation through deubiquitination modification, activation signaling pathway, thereby promoting inflammation contributing injury.

Language: Английский

Citations

3
LncRNA 220: A Novel Long Non-Coding RNA Regulates Autophagy and Apoptosis in Kupffer Cells via the miR-5101/PI3K/AKT/mTOR Axis in LPS-Induced Endotoxemic Liver Injury in Mice DOI Open Access
Ying Yang, Tian Tian, Shan Li

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 11210 - 11210

Published: July 7, 2023

Sepsis is a severe medical condition distinguished by immune systematic dysfunction and multiple organic injury, or even failure, resulting from an acute systemic inflammatory response. Acute liver injury (ALI) could be considered as notable outcome of sepsis. Studies have demonstrated the essential roles played long non-coding RNAs (lncRNAs) in mediating processes various diseases, including their ability to engage interactions with microRNAs (miRNAs) complexes competing endogenous RNA (ceRNA) modulate signaling pathways. In this study, newly discovered lncRNA, named 220, was identified function regulating autophagy apoptosis Kupffer cells treated lipopolysaccharide (LPS). This achieved through sponging miR-5101 ceRNA complex, via high-throughput sequencing. The expression 220 found significantly different hepatic tissues endotoxemic mice that were LPS for 8 h, ultimately modulating ALI process. Our studies collectively novel regulator acts on LPS-induced cells, thereby process induced LPS. Furthermore, validation our findings using clinical databases suggests potentially serve molecular target clinical, diagnostic, therapeutic significance septic injury.

Language: Английский

Citations

4