Pharmacotherapeutic options for metabolic dysfunction-associated steatotic liver disease: where are we today?

Expert Opinion on Pharmacotherapy, Journal Year: 2024, Volume and Issue: 25(9), P. 1249 - 1263

Published: June 12, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by hepatic steatosis and cardiometabolic risk factors like obesity, type 2 diabetes, dyslipidemia. Persistent metabolic injury may promote inflammatory processes resulting in steatohepatitis (MASH) fibrosis. Mechanistic insights helped to identify potential drug targets, thereby supporting the development of novel compounds modulating drivers.

Language: Английский

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Fructose-1,6-bisphosphatase 1 in cancer: Dual roles, mechanistic insights, and therapeutic potential – A comprehensive review

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 139273 - 139273

Published: Jan. 1, 2025

Language: Английский

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Deciphering Oxidative Stress in Cardiovascular Disease Progression: A Blueprint for Mechanistic Understanding and Therapeutic Innovation

Antioxidants, Journal Year: 2024, Volume and Issue: 14(1), P. 38 - 38

Published: Dec. 31, 2024

Oxidative stress plays a pivotal role in the pathogenesis and progression of cardiovascular diseases (CVDs). This review focuses on signaling pathways oxidative during development CVDs, delving into molecular regulatory networks underlying various disease stages, particularly apoptosis, inflammation, fibrosis, metabolic imbalance. By examining dual roles influences sex differences levels susceptibility, this study offers comprehensive understanding diseases. The integrates key findings from current research three ways. First, it outlines major CVDs associated with their respective pathways, emphasizing stress’s central pathology. Second, summarizes protective effects, mechanisms action, animal models antioxidants, offering insights future drug development. Third, discusses applications, advantages, limitations, potential targets gene therapy providing foundation for novel therapeutic strategies. These tables underscore systematic integrative nature while theoretical basis precision treatment CVDs. A contribution is differential effects across different stages addition to proposal innovative, multi-level intervention strategies, which open new avenues system.

Language: Английский

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Targeted drug delivery systems for atherosclerosis

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 23, 2025

Atherosclerosis is a complex cardiovascular disease driven by multiple factors, including aging, inflammation, oxidative stress, and plaque rupture. The progression of this often covert, emphasizing the need for early biomarkers effective intervention measures. In recent years, advancements in therapeutic strategies have highlighted potential targeting specific processes atherosclerosis, such as localization, macrophage activity, key enzymes. Based on this, review discusses role targeted drugs treatment atherosclerosis. It also focuses their clinical efficacy anti-atherosclerosis ability to provide more precise approaches. findings underscore that future research can concentrate exploring newer drug delivery systems further refine enhance long-term dynamic management

Language: Английский

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Integrative bioinformatics analysis for identifying the mitochondrial-related gene signature associated with immune infiltration in premature ovarian insufficiency

BMC Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 8, 2024

Premature ovarian insufficiency (POI) is a reproductive disorder characterized by the cessation of function before age 40. Although mitochondrial dysfunction and immune disorders are believed to contribute damage in POI, interplay between these factors remains understudied. In this research, transcriptomic data related POI were obtained from NCBI GEO database. Hub biomarkers identified through construction protein‒protein interaction (PPI) network further validated using RT‒qPCR Western blot. Moreover, their expression across various cell types was elucidated via single-cell RNA sequencing analysis. A comprehensive investigation profiles carried out correlation Furthermore, potential therapeutic agents predicted utilizing cMap total 119 mitochondria-related differentially expressed genes (MitoDEGs) shown be significantly enriched metabolic pathways. Among genes, Hadhb, Cpt1a, Mrpl12, Mrps7 confirmed both model human granulosa cells (GCs), where they found accumulate GCs theca cells. Immune analysis revealed variations macrophages, monocytes, 15 other control groups. Notably, strong correlations observed seven hub-MitoDEGs (Hadhb, Cpt2, Mrps7, Mrpl51, Eci1) functions, such as respiratory complexes, dynamics, mitophagy, metabolism, immune-related immunocytes. Additionally, nine drugs (calyculin, amodiaquine, eudesmic acid, cefotaxime, BX-912, prostratin, SCH-79797, HU-211, pizotifen) targeting key identified. Our results highlight crosstalk response development POI. The identification MitoDEGs could lead reliable for early diagnosis, monitoring, personalized treatment

Language: Английский

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The Identification of Key Genes and Biological Pathways in Cardiac Arrest by Integrated Bioinformatics and Next Generation Sequencing Data Analysis

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

Published: Aug. 19, 2024

Abstract Cardiac arrest (CA) is a common cause of death world wide. The disease has lacks effective treatment. Efforts have been made to elucidate the molecular pathogenesis CA, but mechanisms remain elusive. To identify key genes and pathways in next generation sequencing (NGS) GSE200117 dataset was downloaded from Gene Expression Omnibus (GEO) database. DESeq2 tool used recognize differentially expressed (DEGs). ontology (GO) REACTOME pathway enrichment analyses were performed analyze DEGs associated signal g:Profiler IID database construct protein-protein interaction (PPI) network, modules analysis using Cytoscape. A miRNA-hub gene regulatory network TF-hub then constructed screen miRNAs, TFs hub by miRNet NetworkAnalyst Cityscape software. Receiver operating characteristic curve (ROC) verified genes. In total, 844 identified, comprising 414 up regulated 430 down GO indicated that for CA mainly enriched organonitrogen compound metabolic process, response stimulus, translation immune system. Ten (up-regulated: HSPA8, HOXA1, INCA1 TP53; down-regulated: HSPB1, LMNA, SNCA, ADAMTSL4 PDLIM7) screened. We also predicted miRNAs (hsa-mir-1914-5p hsa-mir-598-3p) (JUN PRRX2) targeting This study uses series bioinformatics technologies obtain hug genes, TFs, related CA. These results provide us with new ideas finding biomarkers treatment methods

Language: Английский

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Identification of biomarkers and potential drug targets in osteoarthritis based on bioinformatics analysis and mendelian randomization

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 29, 2024

Background Osteoarthritis (OA) can lead to chronic joint pain, and currently there are no methods available for complete cure. Utilizing the Gene Expression Omnibus (GEO) database bioinformatics analysis combined with Mendelian randomization (MR) has been widely employed drug repurposing discovery of novel therapeutic targets. Therefore, our research focus is identify new diagnostic markers improved target sites. Methods expression data from different tissues synovial membrane, cartilage subchondral bone were collected through GEO screen out differential genes. Two-sample MR Analysis was used estimate causal effect quantitative trait loci (eQTL) on OA. Through intersection two, core genes obtained, which further screened by in vitro vivo molecular experimental verification. Finally, prediction docking verified medicinal value Results In utilizing approach, five exhibited significance across both analytical methods. These subjected analysis, revealing their close association immunological functions. Further refinement identified two (ARL4C GAPDH), whose levels found decrease OA pathology a protective thus demonstrating consistent trends. Support experiments also while revealed favorable interactions between drugs proteins, line existing structural data. Conclusion This study potential biomarkers targets utilization analysis. The findings suggest that ARL4C GAPDH may serve as targets, offering promise personalized treatment

Language: Английский

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Structure-Guided Design of Affinity/Covalent-Bond Dual-Driven Inhibitors Targeting the AMP Site of FBPase

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(22), P. 20421 - 20437

Published: Nov. 9, 2024

Fructose-1,6-bisphosphatase (FBPase) has attracted substantial interest as a target associated with cancer and type II diabetes. FBPase inhibitors targeting the AMP allosteric site have been documented, but their limited selectivity raised concerns about adverse effects. To address this issue, we designed affinity/covalent-bond dual-driven based on pharmacophore knowledge of pocket neighboring cysteine residue (C179) using cysteine-targeting reactivity warhead screen followed by structural optimization strategy. Pull-down Western Blotting assays confirmed direct in hepatic cells. X-ray cocrystallographic structure FBPase-

Language: Английский

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Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

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

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