Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis DOI Open Access
Basavaraj Vastrad, Chanabasayya Vastrad

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 17, 2024

Abstract Acute kidney injury (AKI) is a type of renal disease occurs frequently in hospitalized patients, which may cause abnormal function and structure with increase serum creatinine level or without reduced urine output. With the incidence AKI increasing. However, molecular mechanisms have not been elucidated. It significant to further explore AKI. We downloaded GSE139061 next generation sequancing (NGS) dataset from Gene Expression Omnibus (GEO) database. Limma R bioconductor package was used screen differentially expressed genes (DEGs). Then, enrichment analysis DEGs Ontology (GO) REACTOME pathways analyzed by g:Profiler. Next, protein-protein interaction (PPI) network modules constructed analysed, hub were identified. miRNA-hub gene regulatory TF-hub built. also validated identified via receiver operating characteristic (ROC) curve analysis. Overall, 956 identified, including 478 up regulated down genes. The functions involve primary metabolic process, small molecule striated muscle contraction metabolism. Topological PPI module revealed that genes, PPP1CC, RPS2, MDFI, BMI1, RPL23A, VCAM1, ALB, SNCA, DPP4 RPL26L1, might be involved development networks miRNAs TFs hsa-mir-510-3p, hsa-mir-6086 mir-146a-5p, MAX PAX2, Various known newtherapeutic targets obtained results current investigation beneficial for diagnosis treatment

Language: Английский

Drug Advances in NAFLD: Individual and Combination Treatment Strategies of Natural Products and Small-Synthetic-Molecule Drugs DOI Creative Commons

Xing Wan,

Jingyuan Ma,

He Bai

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 140 - 140

Published: Jan. 17, 2025

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic and is closely associated with metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), syndrome. However, effective treatment strategies for NAFLD are still lacking. In recent years, progress been made in understanding pathogenesis of NAFLD, identifying multiple therapeutic targets providing new directions drug development. This review summarizes advances focusing on mechanisms action natural products, small-synthetic-molecule drugs, combination therapy strategies. aims to provide insights treating NAFLD.

Language: Английский

Citations

2
Quercetin exerts anti-tumor immune mechanism by regulating IL-6/JAK2/STAT3 signaling pathway to deplete Treg cells DOI
Yu‐Pei Liao, Xiaoqing Xie, Chu Zhang

et al.

Toxicon, Journal Year: 2024, Volume and Issue: 243, P. 107747 - 107747

Published: May 1, 2024

Language: Английский

Citations

10
Role of FXR in the development of NAFLD and intervention strategies of small molecules DOI

Jiachan Long,

Yuanhang Xu,

Xuerong Zhang

et al.

Archives of Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 757, P. 110024 - 110024

Published: May 3, 2024

Language: Английский

Citations

7
TGR5 deficiency in excitatory neurons ameliorates Alzheimer’s pathology by regulating APP processing DOI Creative Commons
Chenli Li, Liangjie Wang,

Wenting Xie

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(26)

Published: June 28, 2024

Bile acids (BAs) metabolism has a significant impact on the pathogenesis of Alzheimer’s disease (AD). We found that deoxycholic acid (DCA) increased in brains AD mice at an early stage. The enhanced production DCA induces up-regulation bile receptor Takeda G protein-coupled (TGR5), which is also specifically neurons mouse accumulation exogenous impairs cognitive function wild-type mice, but not TGR5 knockout mice. This suggests primary mediating these effects DCA. Furthermore, excitatory neuron-specific ameliorates Aβ pathology and cognition impairments underlying mechanism linking relies downstream effectors APP production, succinctly concluded as “p-STAT3–APH1–γ-secretase” signaling pathway. Our studies identified critical role pathological development AD.

Language: Английский

Citations

7
Jujuboside A through YY1/CYP2E1 signaling alleviated type 2 diabetes-associated fatty liver disease by ameliorating hepatic lipid accumulation, inflammation, and oxidative stress DOI
Wenjing Zhang, Cheng Qian,

Longxiang Yin

et al.

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 400, P. 111157 - 111157

Published: July 24, 2024

Language: Английский

Citations

6
Emerging mechanisms of non-alcoholic steatohepatitis and novel drug therapies DOI
Hao Chen, Yang Zhou, Haiping Hao

et al.

Chinese Journal of Natural Medicines, Journal Year: 2024, Volume and Issue: 22(8), P. 724 - 745

Published: Aug. 1, 2024

Language: Английский

Citations

5
Human diet‐derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization DOI
Qichao Hu, Wenwen Zhang, Feng Wei

et al.

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 38(1), P. 280 - 304

Published: Oct. 23, 2023

Abstract This review focuses on the potential ameliorative effects of polyphenolic compounds derived from human diet hepatic diseases. It discusses molecular mechanisms and recent advancements in clinical applications. Edible polyphenols have been found to play a therapeutic role, particularly liver injury, fibrosis, NAFLD/NASH, HCC. In regulation exhibit anti‐inflammatory antioxidant effects, primarily targeting TGF‐β, NF‐κB/TLR4, PI3K/AKT, Nrf2/HO‐1 signaling pathways. effectively reverse fibrotic process by inhibiting activation stellate cells (HSC). Furthermore, show efficacy against NAFLD/NASH lipid oxidation accumulation, mediated through AMPK, SIRT, PPARγ Moreover, several anti‐HCC activity suppressing tumor cell proliferation metastasis. inhibition involves blocking Akt Wnt signaling, as well epithelial‐mesenchymal transition (EMT). Additionally, trials nutritional evidence support notion that certain can improve disease associated metabolic disorders. However, further fundamental research are warranted validate dietary polyphenols.

Language: Английский

Citations

11
Dendrobium nobile Lindl. alkaloids improve lipid metabolism by increasing LDL uptake through regulation of the LXRα/IDOL/LDLR pathway and inhibition of PCSK9 expression in HepG2 cells DOI Open Access
Jian Sun,

H Liu,

Mengli Zhang

et al.

Experimental and Therapeutic Medicine, Journal Year: 2025, Volume and Issue: 29(3)

Published: Jan. 9, 2025

Dendrobium nobile Lindl. alkaloids (DNLA) are active ingredients that can be extracted from the traditional Chinese herb Nobile Lindl. DNLA exhibits hypoglycemic and antihyperlipidemia effects. However, to best of our knowledge, specific molecular mechanism by which regulate lipid metabolism remains unclear. The aim present study was investigate effect on lipopolysaccharide (LPS)‑induced in HepG2 cells its potential mechanism. were treated with LPS or without different concentrations (0, 0.035, 0.35 3.5 µg/ml) for 48 h. Cell viability then detected using Counting Kit‑8 assay. 1,1'‑dioctadecyl‑3,3,3',3'‑tetramethyl‑indocarbocyanideperchlorate‑low‑density lipoprotein (LDL) uptake assay used examine LDL uptake. In addition, possible mechanisms explored western blot analysis. combination rosuvastatin calcium expression levels receptor (LDLR) proprotein convertase subtilisin/Kexin type 9 (PCSK9) examined. results indicated stimulation reduced cells, decreased intracellular LDLR content, increased inducible degrader (IDOL) liver X (LXR)α. intervention reversed all aforementioned LPS‑induced effects cells. Additional mechanistic experiments revealed exerted mainly regulating LXRα/IDOL/LDLR pathway. It shown also PCSK9, sterol regulatory element binding protein 2 hepatocyte nuclear factor 1α. PCSK9 calcium‑induced Notably, able decrease 3‑hydroxy‑­3‑methylglutaryl‑coenzyme A reductase increase cytochrome p450 7A1 at level, rate‑limiting enzymes cholesterol synthesis metabolism. Collectively, these data suggested could enhance increasing through pathway alleviate induced LPS, suggesting benefit improving disorders.

Language: Английский

Citations

0
The mechanism study of quercetin isolated from Zanthoxylum bungeanum maxim. inhibiting ferroptosis and alleviating MAFLD through p38 MAPK/ERK signaling pathway based on lipidomics and transcriptomics DOI Creative Commons
Yan Chen,

Fajian Ren,

Nannan Yang

et al.

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

Published: March 31, 2025

As a resource with variety of medicinal and edible values, Zanthoxylum bungeanum Maxim has been found to improve high-fat diet-induced metabolic-associated fatty liver disease (MAFLD). The aim this study was predict the main active metabolites in Z. Maxim. Based on network analysis, explore validate their potential mechanisms action through lipidomics transcriptomic techniques. MAFLD mouse model cell were established evaluate effect components MAFLD. Serum biochemical indexes, pathological staining observation, lipid group transcriptome used verify mechanism Quercetin can regulate mice Glycerophospholipid metabolic pathway, thereby improving accumulation injury. At same time, quercetin also by reducing oleic acid-induced HepG2 cells, inhibit ferroptosis p38 MAPK/ERK signaling alleviating progression isolated from ameliorative effects MAFLD, probably mainly affecting pathways MAPK pathways.

Language: Английский

Citations

0
A Metabolomics Study of the Effects of Eleutheroside B on Glucose and Lipid Metabolism in a Zebrafish Diabetes Model DOI Creative Commons

Xuelian Dong,

Qiang Chen,

Wen-Yan Chi

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(7), P. 1545 - 1545

Published: March 29, 2024

(1) Background: Diabetes is a common metabolic disease that seriously endangers human health. In the present study, we investigated therapeutic effects of active ingredient Eleutheroside B (EB) from traditional Chinese medicine on diabetes mellitus in zebrafish model. Concomitant hepatic injury was also analysed, along with study possible molecular mechanisms using metabolomics technology. This work should provide some theoretical references for future experimental studies. (2) Methods: A model constructed by soaking 1.75% glucose solution and feeding high-fat diet. The intervention drug groups were metformin (100 μg∙mL−1) EB (50, 100, 150 via water-soluble exposure 30 days. Glucose, TG, TC, LDL-C, HDL-C evaluated different treatment groups. GLUT4 protein expression each group, liver observed HE staining. Metabolomics techniques used to investigate mechanism which regulates endogenous markers pathways during development diabetes. (3) Results: All diabetic showed significantly reduced body mass index (BMI) improved blood lipid profiles. found upregulate ameliorate caused studies causes changes profile zebrafish. These related regulation purine metabolism, cytochrome P450, caffeine arginine proline mTOR signalling pathway, insulin resistance, glycerophospholipid metabolism. (4) Conclusions: has hypoglycaemic effect as well improving disorders glycolipid action may involve

Language: Английский

Citations

3