Multi-omics joint analysis reveals that the Miao medicine Yindanxinnaotong formula attenuates non-alcoholic fatty liver disease

Phytomedicine, Journal Year: 2024, Volume and Issue: 135, P. 156026 - 156026

Published: Sept. 21, 2024

Language: Английский

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Mechanism and therapeutic potential of hippo signaling pathway in type 2 diabetes and its complications

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 183, P. 117817 - 117817

Published: Jan. 21, 2025

Language: Английский

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Enpp1 ameliorates MAFLD by regulating hepatocyte lipid metabolism through the AMPK/PPARα signaling pathway

Cell & Bioscience, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 19, 2025

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the leading chronic globally, and there are no approved pharmacotherapies to treat this disease. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) been found be related insulin resistance lipid accumulation. However, role mechanism of Enpp1 in development MAFLD remain unknown. Here we discovered that is lowly expressed patients by clinical investigation. Knocking out mice aggravated obesity, hepatic steatosis, these effects were reversed liver-specific overexpression. Through transcriptomic data mining experimental validation, demonstrated deficiency inhibited expression AMPK (energy receptor) PPARα (nuclear transcription factor for metabolism), thereby promoting synthesis factors mediating progression MAFLD. Mechanistically, enhanced activity increasing AMP-to-ATP ratio, which turn raised levels promoted its downstream metabolism factors. Pharmacological inhibition abolished effect on protein expression. This study indicate can effectively ameliorate through AMPK/PPARα signaling pathway-mediated metabolism, revealing significance as a promising therapeutic target against

Language: Английский

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Terazosin, a repurposed GPR119 agonist, ameliorates mitophagy and β‐cell function in NAFPD by inhibiting MST1‐Foxo3a signalling pathway

Cell Proliferation, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 16, 2024

Abstract GPR119 agonists are being developed to safeguard the function of pancreatic β‐cells, especially in context non‐alcoholic fatty pancreas disease (NAFPD) that is closely associated with β‐cell dysfunction. This study aims employ a drug repurposing strategy screen and explore their potential molecular mechanisms for enhancing NAFPD. MIN6 cells were stimulated palmitic acid (PA), NAFPD model was established −/− mice fed high‐fat diet (HFD). Terazosin, identified through screening, utilized assess its impact on via MST1‐Foxo3a pathway mitophagy. Terazosin selectively activated GPR119, leading increased cAMP ATP synthesis, consequently insulin secretion. administration improved high blood glucose, obesity, impaired mice. It inhibited upregulation expression tissue enhanced damaged mitophagy clearance, restoring autophagic flux, improving mitochondrial quantity structure β‐cells. Nevertheless, deficiency negated positive terazosin abolished inhibitory effect pathway. activates surface alleviating dysfunction by suppressing signalling could be considered priority treatment patients concomitant hypertension.

Language: Английский

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Acoustic Delivery of Plasma Low-Density Lipoprotein into Liver via ApoB100-Targeted Microbubbles Inhibits Atherosclerotic Plaque Growth

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(19), P. 24206 - 24220

Published: May 3, 2024

Atherosclerosis is the main risk factor for cardiovascular disease, which accounts majority of mortality worldwide. A significantly increased plasma level low-density lipoprotein cholesterol (LDL-C), surrounded by a monolayer phospholipids, free cholesterol, and one apolipoprotein B-100 (ApoB-100) in blood, plays most significant role driving development atherosclerosis. Commercially available cholesterol-lowering drugs are not sufficient preventing recurrent events. Developing alternative strategies to decrease levels desirable. Herein, we develop an approach reducing LDL-C using gas-filled microbubbles (MBs) that were coated with anti-ApoB100 antibodies. These targeted MBApoB100 could selectively capture LDL particles bloodstream through forming LDL-MBApoB100 complexes transport them liver degradation. Further immunofluorescence staining lipidomic analyses showed these may be taken up Kupffer cells delivered bile acids, greatly inhibiting atherosclerotic plaque growth. More importantly, ultrasound irradiation accumulated induce acoustic cavitation effects, enhancing delivery into accelerating their Our study provides strategy decreasing progression

Language: Английский

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Liquiritigenin regulates insulin sensitivity and ameliorates inflammatory responses in the nonalcoholic fatty liver by activation PI3K/AKT pathway

Chemical Biology & Drug Design, Journal Year: 2023, Volume and Issue: 102(4), P. 793 - 804

Published: July 16, 2023

Nonalcoholic fatty liver disease (NAFLD) is a prevalent long-term in the world. Liquiritigenin (LQ) protective against variety of hepatotoxins. Herein, we report potential mechanism LQ on high-fat diet (HFD) induced NAFLD. NAFLD mice model was established by HFD for 12 weeks, and treatment 1 week. Commercially available assay kits measure triglycerides (TG) total cholesterol (TC) levels. Plasm TC, TG, high-density-lipoprotein (HDL-C), low-density-lipoprotein (LDL-C) levels were also monitored biochemistry. Enzyme linked immunosorbent (ELISA) performed to analyze pro-inflammatory factors, intraperitoneal glucose tolerance test (IPGTT), insulin (IPITT), serum determined. GO KEGG pathway enrichment analysis employed overlapping genes targets development-related targets. Western blot key proteins enriched signaling pathway. showed significant increases hepatic TG plasm LDL-C blood lipids, while HDL-C significantly decreased, reversed their (p < 0.05). alleviated HFD-induced elevated IPGTT, IPITT, homeostasis assessment resistance (HOMA-IR). And factor suppressed LQ. PI3K/AKT enrichment, its p-PI3K p-AKT after We found first time that improves lipid accumulation, alleviates resistance, suppresses inflammatory responses mice, which might be associated with activation

Language: Английский

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STK4 is a prognostic biomarker correlated with immune infiltrates in clear cell renal cell carcinoma

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 20, 2023

Mammalian STE20-like kinase 1 (MST1/STK4/KRS2) is a highly conserved serine/threonine and central member of the Hippo signaling pathway. STK4 has been reported to play important roles in various tumors, but systematic comprehensive study its function clear cell renal carcinoma (ccRCC) not conducted.In this study, we used immunohistochemistry (IHC), western blot (WB), quantitative real-time PCR (qPCR) experiments, bioinformatics analysis comprehensively analyze expression, prognostic value, immune infiltration ccRCC.Analysis TCGA database showed that expression level gene ccRCC patients depended on tumor stage, grade, distant lymphatic metastasis. This was further confirmed by results IHC, WB, qPCR. In addition, receiver operating characteristic curve (ROC curve) elucidate diagnostic value patients. According findings TIMER database, high significantly associated with survival kidney cancer (including ccRCC) (p < 0.001), suggesting reliable predictor. We then set enrichment (GSEA) explore mechanisms behind ccRCC. found may role regulation interactions. Subsequently, performed STK4. The regulate development affecting NK pDC cells.STK4 be marker for help identify new strategies treating

Language: Английский

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Terazosin, a repurposed GPR119 agonist, ameliorates mitophagy and β-cell function in NAFPD by inhibiting MST1-Foxo3a signaling pathway

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: April 26, 2024

G protein-coupled receptor 119 (GPR119) agonists are being developed to safeguard the function of pancreatic β-cells, especially in context non-alcoholic fatty pancreas disease (NAFPD), closely associated with β-cell dysfunction arising from excessive fat accumulation pancreas. Drug repurposing technology, abandoning drawbacks traditional lengthy, costly, and low-market-probability development methods, has emerged as a new direction drug development. Here, we employed technology screen GPR119 explore their potential molecular mechanisms for enhancing NAFPD. Employing Schrodinger Suites design software, found that 3622 drugs, including α-1 adrenergic blocker Terazosin, can bind GPR119. Terazosin was further validated selectively activate GPR119, leading increased cAMP ATP synthesis, consequently insulin secretion. administration improved high blood glucose, obesity, impaired NAFPD mice. It inhibited upregulation MST1-Foxo3a expression tissue damaged mitophagy clearance, restoring autophagic flux, improving mitochondrial quantity structure β-cells. Notably, deficiency negated positive impact on mice, abolished its inhibitory effect pathway. In conclusions, is applicable agonists. enhances alleviating by suppressing signaling could be considered priority treatment patients concomitant hypertension.

Language: Английский

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Delivery of miRNAs Using Nanoparticles for the Treatment of Osteosarcoma

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 8641 - 8660

Published: Aug. 1, 2024

Osteosarcoma is the predominant primary malignant bone tumor that poses a significant global health challenge. MicroRNAs (miRNAs) regulate gene expression are associated with osteosarcoma pathogenesis. Thus, miRNAs potential therapeutic targets for osteosarcoma. Nanoparticles, widely used targeted drug delivery, facilitate miRNA-based treatment. Numerous studies have focused on miRNA delivery using nanoparticles to inhibit progress of Polymer-based, lipid-based, inorganic-based and extracellular vesicles were deliver treatment They can be modified enhance loading capabilities. Also, was combined traditional therapies, example chemotherapy, treat Consequently, offers promising avenues osteosarcoma, providing renewed hope patients. This review emphasizes utilizing in treatment, then introduced summarized detail. And it also discusses prospects clinical applications.

Language: Английский

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STK4, a novel prognostic biomarker, correlated with immune infiltrates in clear cell renal cell carcinoma

Research Square (Research Square), Journal Year: 2022, Volume and Issue: unknown

Published: Dec. 13, 2022

Abstract Background Mammalian STE20-like kinase 1 (MST1/STK4/KRS2) is a highly conservative serine/threonine kinase, as well core member of the Hippo signaling pathway. STK4 has been reported play important roles in mutiple tumors. However, there still no systematic and comprehensive study on role ccRCC. Methods In this study, experiments including Immunohistochemistry (IHC), western blot (WB), quantitative real-time-polymerase chain reaction (RT-PCR) combined with bioinformatics analysis were used to integrate expression, prognostic value, immune infiltration Results The findings from TCGA database revealed that expression its based tumor stage, grade, nodal metastasis status ccRCC was increased. results IHC, WB, RT-PCR further verified it. Additionally, receiver operating characteristic (ROC) curve clarify diagnositic value patients According Timer database, we found high significant (p < 0.001) association renal cancer (including ccRCC) survival, suggesting reliable predictors. Then, GSEA performed explore mechanism underlying functions We may immunoregulatory interactions. Subsequently, subjected analyses. suggested development by adjusting influencing NK pDCs cell. Conclusions be markers potential for finding novel strategies treatment

Language: Английский

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