Combinatorial chemistry & high throughput screening最新文献

{"title":"Qilianshupi Decoction Alleviate Epithelial-mesenchymal Transition to Treat Chronic Atrophic Gastritis.","authors":"Mengyi Shen, Chunxiao Wang, Jiapei Zhou, Jing Wang, Hongjie Xiang","doi":"10.2174/0113862073377282250716063813","DOIUrl":"https://doi.org/10.2174/0113862073377282250716063813","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic atrophic gastritis (CAG) is an important stage in the occurrence and development of gastric cancer, and the morbidity of CAG is increasing year by year. Qilianshupi Decoction (QLSP) is a Chinese herbal compound which has been proved to reverse CAG, but its mechanism remains unknown. We wanted to identify the main components of QLSP by mass spectrometry and liquid phase analysis, and investigate their potential pathways for CAG treatment in combination with network pharmacology.</p><p><strong>Methods: </strong>The main active components of QLSP were identified by liquid chromatography and mass spectrometry. Combined with network pharmacology, the targets where the drugs may act were identified and verified by animal experiments. Rats were randomly divided into control group, model group, QLSP low-dose group, QLSP medium-dose group, QLSP high-dose group and Weifushun group. Rat CAG model was prepared by \"N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) + ethanol intragastric + ranitidine feed\". After the test, gastric tissues were taken for pathological staining and immunohistochemistry.</p><p><strong>Results: </strong>We identified 51 prototype components of QLSP and found that QLSP treatment of CAG was closely related to p53. In animal experiments, CAG results in the decrease of Ecadherin and the increase of N-cadherin, Vimentin, p53, SMAD2 and TGF-β (p＜0.05). Both QLSP and Weifuchun can increase E-cadherin and decrease N-cadherin, Vimentin, p53, SMAD2 and TGF-β (p＜0.05).</p><p><strong>Discussion: </strong>QLSP, a traditional Chinese medicine formula with multi-component and multitarget characteristics, has been shown in our study to effectively regulate key EMT (epithelialmesenchymal transition) markers and their upstream/downstream regulators. In animal experiments, QLSP successfully reversed the EMT process in CAG model rats. This finding provides new therapeutic targets for CAG treatment, though several challenges remain in clinical translation: First, rat CAG models differ from human CAG in pathological features and disease progression, and species-specific physiological and metabolic variations may limit the extrapolation of these findings. Second, network pharmacology analysis identified IL-6, alongside TP53, as another critical target of QLSP in CAG intervention. Therefore, future studies should further clarify the molecular mechanisms by which QLSP modulates EMT via IL-6-related pathways and validate its efficacy through well-designed clinical trials, ultimately providing a comprehensive understanding of QLSP's therapeutic potential in CAG.</p><p><strong>Conclusion: </strong>QLSP inhibits epithelial-mesenchymal transition (EMT) in gastric mucosal epithelial cells and prevents CAG, possibly by regulating p53/TGF-β signaling pathway.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering Cellular Intricacies for Drug Discovery: A Synergistic Approach Combining Cryo-CLEM, Electromechanical Modeling, and AI-Guided Simulations.","authors":"Sijia Zhang, Jingsong Ai, Jiasheng Zhao, Zhiwei Yang","doi":"10.2174/0113862073413549250729080059","DOIUrl":"https://doi.org/10.2174/0113862073413549250729080059","url":null,"abstract":"<p><p>Biological membranes and their vesicular derivatives constitute dynamic nanoscale architectures critical to cellular function. Their electromechanical properties and molecular diversity govern processes ranging from vesicle trafficking and signal transduction to pathogen entry and organelle morphogenesis. While decades of foundational research have advanced our understanding of lipid bilayer assembly and membrane protein interactions, achieving a comprehensive, multiscale understanding of membrane dynamics, spanning molecular interactions to cellular-scale behavior, remains a paramount challenge in modern cell biology. This editorial presents recent breakthroughs at the intersection of three transformative domains: cryo- correlative light and electron microscopy (cryo-CLEM), electromechanical theory, and AI-driven simulation, to elucidate their collective impact on resolving membrane complexity. By integrating structural insights, the innovations are revolutionizing the drug discovery pipelines by accelerating candidate screening, reducing false-positive rates, optimizing assay design, and implementing high-density library strategies. It also critically evaluates technical challenges while proposing an actionable roadmap to unify these modalities into cohesive workflows, advancing both basic membrane research and translational therapeutic development.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in Precision Oncology: Harnessing High-Throughput Screening and Computational Strategies for Targeted Cancer Therapies.","authors":"Akshay Thakur, Kaunava Roy Chowdhury, Vir Vikram Sharma, Kuldeep Singh, Jeetendra Kumar Gupta, Divya Jain, Mukesh Chandra Sharma","doi":"10.2174/0113862073397811250716154921","DOIUrl":"https://doi.org/10.2174/0113862073397811250716154921","url":null,"abstract":"<p><p>Recent breakthroughs in precision medicine have significantly transformed the landscape of cancer treatment, propelling the development of individualized therapies characterized by enhanced therapeutic efficacy and reduced toxicity. This review examines the integration of high-throughput screening techniques with advanced computational methodologies, including artificial intelligence (AI) and machine learning, to expedite drug discovery and optimize treatment protocols in oncology. We explore the efficacy of targeted therapeutics, CAR T-cell therapies, and immune checkpoint inhibitors, alongside the role of combination therapies and biomarker identification in refining patient-specific treatment strategies. By aggregating scientific data from key databases, we evaluate the impact of in silico modeling on drug efficacy predictions, cost reduction, and time efficiency in the development process. This review highlights the collaborative potential of computational and synthetic approaches in redefining oncological pharmacotherapy and improving patient outcomes.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Up-to-Date Screening on the Tool of Quality by Design in Pharmaceutical Manufacturing.","authors":"Evren Algın Yapar, Merve Nur Özdemir","doi":"10.2174/0113862073388521250708101658","DOIUrl":"https://doi.org/10.2174/0113862073388521250708101658","url":null,"abstract":"<p><p>The process of developing innovative, safe, and effective treatments is timeconsuming, difficult, and expensive. The use of a Quality by Design approach, which emphasizes incorporating quality into pharmaceutical products during the design phase rather than testing, has resulted in higher product quality, reduced costs, and a shorter time to market. According to the guidelines of the International Council for Harmonization, quality by design is a methodical approach to medication development that begins with defined objectives. This scientific and data- driven, risk-based approach advances pharmaceutical development, production, and quality assurance. The two fundamental components of quality by design -quality risk management and knowledge management -work together to create an organized and efficient path to consistent pharmaceutical product quality. In this review, the impact of QbD on pharmaceutical products has been examined and reviewed by using data, which collected by a comprehensive literature search on QbD, QbD applied dosage forms, quality risk management in pharmaceutical manufacturing, process analytical technology in any field via Pubmed, ScienceDirect, ISI Web of Knowledge, Google Scholar, ICH related databases were used for research or review articles published in peer-reviewed journals from 2009 to 2025. For patents search, the European Patent Office (EPO) and the United States Patent, Trademark Office (USPTO), and the Google Patents databases were used. In this review, the concepts of quality risk management and knowledge management, which play an important role in quality by design, have also been presented with patents and recent developments in this field, in addition to future perspectives. In terms of industry application of the QbD approach, both for new and generic drug manufacturing processes are also examined.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Cross-sectional Study on Biochemical Alterations and Associated Metabolic Syndrome among Obese Subjects in Enugu Metropolis, Nigeria.","authors":"Ifeoma Chinwe Ikegwuonu, Fidelis Ikechukwu Edeh, Adanna Perpetua Ikebudu, Ijeoma Edith Nnaji, Cornelius Osinachi Ogu, Peace Nkiruka Ojiako, Samuel Onuzulike Ebede","doi":"10.2174/0113862073334393241007052046","DOIUrl":"https://doi.org/10.2174/0113862073334393241007052046","url":null,"abstract":"<p><strong>Background and objective: </strong>The co-occurrence of obesity and metabolic syndrome (MetS) is a global health concern. Key factors contributing to the emergence and prevalence of MetS include dyslipidemia, obesity, type 2 diabetes (T2D), race, and physical inactivity. This study investigated biochemical alterations and associated MetS of obese subjects residing in Enugu metropolis, Nigeria.</p><p><strong>Materials and methods: </strong>Two hundred and ten respondents (20-60 years old) were recruited for this cross-sectional study. A total of 105 obese and 105 normal-weight people were recruited as test and control groups, respectively. Hip circumference (HC), height, weight, and waist circumference (WC) were measured, and body mass index (BMI) was calculated. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were also measured. Five milliliters of fasting blood samples were collected and used for the determination of fasting blood sugar (FBS) and lipid profile using enzymatic colorimetric methods. Assessment of MetS was done using the National Cholesterol Education Program - Adult Treatment Panel 111 (NCEP-ATP 111) criteria. Data were analyzed using the Statistical Package for Social Science (SPSS) version 26.</p><p><strong>Results: </strong>There was a significant increase (P< 0.05) in the mean ± SD of WC, HC, BMI, SBP, DBP, FBS, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) in the obese compared to the normal weight individuals. Using the NCEP-ATP criteria, the prevalence rate of MetS was 74.3% and 8.6% for obese and normalweight individuals, respectively.</p><p><strong>Conclusion: </strong>The study concludes that obesity predisposes individuals to a higher risk of developing MetS.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Endurance Exercise Amends the Circulating MicroRNA Profile in Response to Exercise Dosage.","authors":"Fatma Hassan Abd Elbasset Mourgan, Ali Al Shamli, Wafaa Mohmoud Abdellatif Bekir, Eman Abdelhalim Mohamed Ali, Nana El Dawy Ahmed Hefny, Manaf AlMatar","doi":"10.2174/0113862073386622250710113810","DOIUrl":"https://doi.org/10.2174/0113862073386622250710113810","url":null,"abstract":"<p><strong>Introduction: </strong>Regular exercise, particularly continuous endurance activity, is known to help prevent and manage various chronic conditions. It remains unknown which cellular and molecular mechanisms underpin the adaptive response to exercise, despite new research suggesting that epigenetic mechanisms, particularly microRNAs (miRNAs), may play a role in the formation and regulation of exercise-related alterations. A \"fitness score\" was created by integrating the analysis of miRNAs as epigenetic biomarkers, genetic predispositions, and food and supplement consumption in order to gauge an individual's response to diet, exercise, and metabolic effects.</p><p><strong>Method: </strong>In response to a four-week sports intervention, we employed qPCR analysis to investigate genetic and epigenetic markers, including miR-21 and miR-146a, in capillary blood from 10 participants (mean age: 33 years, comprising 66.1% females and 33.9% males). A healthy, ageand sex-matched control group (n = 10) that did not receive any intervention was also used to study these biomarkers.</p><p><strong>Results: </strong>Significant differences (P < 0.05) were observed in the relative expression levels of two microRNAs, miR-21 and miR-146a. During the training period, expression levels increased in nine out of ten participants. Specifically, miR-21 expression rose from 1.125 ± 0.113 to 1.164 ± 0.205, and miR-146a expression increased from 1.103 ± 0.054 to 1.210 ± 0.217 following the intervention.</p><p><strong>Discussion: </strong>Our research reveals that, during a 4-week training cycle, the levels of specific microRNAs, such as miR-21 and miR-146a, fluctuate. The levels of these miRNAs significantly increased after the intense training session.</p><p><strong>Conclusion: </strong>Our findings suggest that a comprehensive examination of multiple biomarkers (miRNAs) may provide insights into a person's body composition, potential recovery, training adaptations, fitness, and dietary requirements. We demonstrated that these biomarkers can also be tested using a less invasive technique, in contrast to the majority of research that uses muscle biopsies.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Animal Experiments, Bioinformatics and Molecular Dynamics Stimulations to Explore the Potential Mechanism of Songyang Duanwu Tea Improving Metabolic Syndrome.","authors":"Suhong Chen, Chengliang Zhou, Huiying Wang, Simei Dong, Zhiyuan Li, Chuanjie Zhou, Wanqi Chen, Zhihao Ge, Xinglishang He, Bo Li, Jianping Wang, Luwei Xiao, Guiyuan Lv, Shuhua Shen","doi":"10.2174/0113862073367989250630102258","DOIUrl":"https://doi.org/10.2174/0113862073367989250630102258","url":null,"abstract":"<p><strong>Background: </strong>Metabolic syndrome (MetS) is a metabolic disorder characterized by the accumulation of various risk factors, including obesity, dyslipidemia, hypertension and so on. Songyang Duanwu Tea (SYT) has a high value in nutrition and health care, and it is widely used in traditional Chinese medicine for weight loss. Nevertheless, the mechanisms of SYT improving MetS remain to be elucidated. The objective of this study was to investigate the molecular targets and potential mechanisms by which SYT may improve MetS based on animal experiments and bioinformatics.</p><p><strong>Methods: </strong>MetS model mice were established by a high-fat, high-sugar, high-salt diet (HFSSD). Obesity, dyslipidemia, hypertension, hyperuricemia and non-alcoholic fatty liver disease (NAFLD) of MetS model mice were evaluated to assess the effect of SYT on the treatment effects of MetS. The bioactive components in SYT were identified by bioinformatics and verified by HPLC-QTOF-MS. The possible molecular targets and mechanisms of action were predicted and verified using bioinformatics.</p><p><strong>Results: </strong>SYT (1.2 g/kg) ameliorated obesity, dyslipidemia, hypertension, hyperuricemia and NAFLD in HFSSD-induced mice. Bioinformatics results suggested that the major bioactive components in SYT include the flavonoid components apigenin, kaempferol, luteolin and quercetin, and the polyphenolic component eugenol. HPLC-QTOF-MS further validated the presence of apigenin, kaempferol, luteolin and quercetin. These 4 bioactive components are involved in the regulation of SYT to improve MetS by regulating metabolism and attenuating inflammation, and the key targets include peroxisome proliferator-activated receptor gamma (PPARG), tumor necrosis factor alpha (TNFα), interleukin 1beta (IL1B) and interleukin 6 (IL6).</p><p><strong>Conclusion: </strong>SYT effectively improved the MetS model mice induced by HFSSD. The potential mechanism may regulate PPARG and attenuate inflammatory targets: TNFα, IL1B and IL6 through 4 flavonoid components: apigenin, kaempferol, luteolin and quercetin.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of Nanomedicine Research Proposals Received at ICMR: Gaps in Research and Further Opportunities.","authors":"Heena Tabassum, Ankita, Vishal Deo","doi":"10.2174/0113862073375405250702114943","DOIUrl":"https://doi.org/10.2174/0113862073375405250702114943","url":null,"abstract":"<p><strong>Introduction: </strong>Nanomedicine integrates nanotechnology with healthcare, offering targeted diagnostics, therapeutic solutions, and preventive applications. India, through agencies such as the Indian Council of Medical Research (ICMR), the Department of Biotechnology (DBT), and the Department of Science & Technology (DST), has prioritized nanomedicine to address public health challenges. Despite significant progress, gaps persist in clinical translation and interdisciplinary applications.</p><p><strong>Objective: </strong>To analyze the scope, gaps, and opportunities in nanomedicine research in India, focusing on ICMR-funded projects.</p><p><strong>Methods: </strong>Data on nanomedicine proposals submitted to ICMR (2018-2022) were reviewed using keyword-based searches from databases and survey responses from principal investigators. Metrics included funding trends, research objectives, and outcomes. Quantitative and qualitative analyses assessed scientific progress and translational potential.</p><p><strong>Results: </strong>Over the past five years, the ICMR has funded over 250 projects, with a focus on cancer therapy, infectious diseases, and diagnostics. Achievements include nanoparticle-based drug delivery systems and diagnostics, with notable innovations like Albupax® and gold nanoparticlebased sensors. Research activity increased over the years, with a slight slowdown during the COVID-19 period. Funding was primarily allocated to states with established research infrastructures, underscoring the need for more equitable support nationwide.</p><p><strong>Discussion: </strong>Nanomedicine research in India has made significant progress, primarily in cancer; however, limited research has been observed in non-cancer applications and long-term safety studies. Differences in funding across various regions and difficulties in turning ideas into marketable products were major problems. Integrating nanomedicine with genetic tools offers promise for more targeted treatments.</p><p><strong>Conclusion: </strong>The ICMR's support has advanced nanomedicine research in India, particularly in the field of oncology. To strengthen India's position in the field, future efforts must address unmet needs, including non-cancer applications, clinical translation, and regulatory harmonization. Collaborative initiatives and equitable funding distribution can accelerate advancements and strengthen the implementation of nanomedicine research.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gan-Jiang-Ling-Zhu Decoction Prevents Paigen's Diet-induced Lean Metabolic Dysfunction-associated Steatotic Liver disease by Regulating Bile Acid Metabolism.","authors":"Zansong Ma, Milian Chen, Ying Cao, Deji Song, Li Zhang","doi":"10.2174/0113862073379080250701164923","DOIUrl":"https://doi.org/10.2174/0113862073379080250701164923","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health concern, even among lean individuals. The Gan-Jiang-Ling-Zhu decoction (GZD), a traditional Chinese medicine formula, shows therapeutic potential against MASLD. This study investigated the efficacy of GZD in lean MASLD and explored its mechanisms of action.</p><p><strong>Methods: </strong>A lean MASLD mouse model was established using C57BL/6 mice fed with a cholesterol- rich Paigen's diet (PD). Following successful modeling, mice were administered GZD (1.8, 3.6, or 7.2 g/kg) or vehicle control. Body weight, food intake, and liver weight were monitored. Hepatic steatosis and lipid accumulation were assessed via H&E and Oil Red O staining, while serum enzymes were quantified biochemically. Gut microbiota composition was analyzed by 16S rRNA gene sequencing, and bile acid (BA) profiles in feces and serum were measured using UPLC-TQMS.</p><p><strong>Results: </strong>Twelve weeks of PD feeding induced a lean MASLD phenotype characterized by reduced body weight alongside hepatic steatosis and dyslipidemia. The GZD treatment dosedependently ameliorated liver steatosis and lipid accumulation, with the highest dose (7.2 g/kg) showing superior efficacy. GZD restored gut microbiota balance by reducing pathogenic bacteria and enriching taxa involved in BA metabolism, leading to increased fecal excretion of secondary BAs. Conversely, serum levels of secondary BAs were significantly reduced after GZD treatment.</p><p><strong>Discussion: </strong>Our study highlights the promising role of GZD in lean MASLD, the involvement of gut microbiota and related BA metabolism that aligns with emerging evidence that gut dysbiosis and disrupted BA homeostasis are central to MASLD pathogenesis, even in lean individuals. However, the mechanistic links between specific microbial changes, BA pool composition, and hepatic outcomes remain to be elucidated.</p><p><strong>Conclusion: </strong>GZD ameliorates hepatic steatosis in lean MASLD mice, an effect associated with modulation of gut microbiota composition and increased fecal excretion of secondary BAs. These findings suggest the potential of GZD as a therapeutic option for lean MASLD through gutliver axis regulation.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of DNA Replication Stress-Related Genes as Prognostic Biomarkers for Bladder Cancer.","authors":"Fei Zhang, Shuai Li, Zhijie Zhang, Jiulong Li, Huiqin Liu, Xudong Ma, Zhigang Yang","doi":"10.2174/0113862073396305250526102508","DOIUrl":"https://doi.org/10.2174/0113862073396305250526102508","url":null,"abstract":"<p><strong>Introduction: </strong>Bladder cancer (BLCA) is a highly aggressive malignancy with poor prognosis. DNA replication stress-related genes (DRSGs) hold prognostic significance in multiple cancers, and their expression patterns in BLCA may reveal novel biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>This study was designed using a public database and the Cancer Genome Atlas (TCGA). Genes associated with DNA replication stress in BLCA were discovered by analyzing data from the TCGA and GEO databases using bioinformatics tools. The prognostic gene expression profiles in BLCA cell lines were analyzed using Western blotting (WB). The motility capacity of BLCA cells was evaluated using the wound healing and Transwell migration assays, while cell growth was ascertained with the CCK-8 assay.</p><p><strong>Results: </strong>Five DRSGs with prognostic significance were identified, and a risk score model was constructed using univariate Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm. Kaplan-Meier (KM) analysis showed worse Overall Survival (OS) in the high-risk group (P < 0.05). Gene Set Enrichment Analysis (GSEA) indicated involvement in tumor-related pathways. The nomogram effectively predicted OS in both training and validation cohorts. WB and functional assays confirmed gene expression and effects on BLCA cell proliferation and migration.</p><p><strong>Discussion: </strong>This study first validates DRSGs' prognostic value in bladder cancer, highlighting potential biomarkers and targets. Limitations include reliance on public data and in vitro tests. Future research should use multicenter cohorts and animal models to confirm clinical relevance.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}