Combinatorial chemistry & high throughput screening最新文献

{"title":"CircDUSP22 Attenuates the Ferroptosis of Prostate Cancer Cells via miR-18a-5p/SLC7A11/GPX4 Signaling.","authors":"Hua Jiang, He Zhang, Songsong Jiang","doi":"10.2174/0113862073324077240624094140","DOIUrl":"https://doi.org/10.2174/0113862073324077240624094140","url":null,"abstract":"<p><strong>Background: </strong>According to current worldwide cancer data, Prostate Cancer (PC) ranks as the second most common type of cancer and is the fifth leading cause of cancer-related mortality among men worldwide. PC in China has the 10th highest number of new cases and the 13th highest fatality rate, both of which show an ongoing annual increase. One of the significant challenges with prostate cancer is the difficulty in early detection, often resulting in diagnosis at intermediate or late stages, complicating treatment. Although hormonal therapy is initially successful in controlling the progression of prostate cancer, almost all tumors that respond to hormones eventually transform into Castration-resistant Prostate Cancer (CRPC) within 18-24 months of hormonal therapy. This poses clinical difficulties due to an absence of successful therapeutic approaches. Therefore, understanding the fundamental mechanisms of prostate cancer development, identifying effective therapeutic targets, and discovering reliable molecular biomarkers are crucial objectives.</p><p><strong>Methods: </strong>CircRNA expression in plasma was assessed in 4 samples obtained from patients with Benign Prostatic Hyperplasia (BPH), and PC was detected through microarray probes. Statistical analysis of the expression of circDUSP22 and clinicopathological features was conducted. The investigation of target genes was conducted using luciferase reporter assays and bioinformatics analysis. The expression levels of circDUSP22, miR-18a-5p, and Solute Carrier Family 7 member 11 (SLC7A11) were assessed using a quantitative Real-time Polymerase Chain Reaction (qRT-PCR) assay. Cell invasion, migration, colony formation, and proliferation were evaluated using Transwell, wound healing, colony formation, and CCK-8 assays, respectively. RNA Immunoprecipitation (RIP) and dual-luciferase reporter assays were used to examine the connections among circDUSP22, miR-18a-5p, and SLC7A11. The impact of circDUSP22 on the expression of ferroptosis-related proteins, specifically SLC7A11, as well as its effects on Fe2+ and ROS were also examined.</p><p><strong>Results: </strong>In both plasma samples and PCa cell lines, there was a substantial elevation of circDUSP22 and SLC7A11 expression and a decline in miR-18a-5p expression. Suppression of circDUSP22 significantly impeded the migration, invasion, and proliferation of PC cells in vitro. The target gene of miR-18a-5p, SLC7A11, was found to be upregulated as an effect of circDUSP22's competitive binding to miR-18a-5p. Cellular experiments demonstrated that interference with circDUSP22 expression in DU145 and PC-3 cells led to increased ferroptosis and decreased SLC7A11 expression. The modulation of prostate cancer cell proliferation was reversed by either overexpressing SLC7A11 or inhibiting miR-18a-5p in response to the silencing of circDUSP22.</p><p><strong>Conclusion: </strong>The circDUSP22 has been found to have a substantial effect on the","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589825","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":"In silico Screening and in vitro Cytotoxicity Study of Achyranthes aspera Phytochemicals Against Oral Cancer: A Possible Step towards the Development of Anti-cancer Agents.","authors":"Juveriya Israr, Mohsin Ali Khan, Sankalp Misra, Divya Gupta, Nootan Singh, Rumana Ahmad, Sahabjada Siddiqui","doi":"10.2174/0113862073289916240503051643","DOIUrl":"https://doi.org/10.2174/0113862073289916240503051643","url":null,"abstract":"<p><strong>Background: </strong>Oral cancer poses a significant threat to public health worldwide. In addition, because many chemotherapy treatments have negative side effects, natural herbs may be beneficial for oral cancer therapy. Achyranthes aspera (AA), a potential medicinal herb, exerts various pharmacological and biochemical activities.</p><p><strong>Objective: </strong>The present study aimed to predict the anti-oral cancer potential of AA using in silico tools and cell death by in vitro testing.</p><p><strong>Methods: </strong>A total of fourteen bioactive constituents from AA herb were selected using phytochemical databases. The toxicity of AA herb extract was analysed through MTT assay against oral carcinoma A253 cell line. The binding activities of the phytocomponents against serine/ threonine-specific protein kinases isoforms, namely Akt1 (PDB ID: 3qkk) and Akt2 (PDB ID: 2jdo) proteins, were analysed using Discovery Studio 2021 and PyRx docking software.</p><p><strong>Results: </strong>Cell viability data revealed that AA extract decreased the viability and reduced the number of live cells of the oral carcinoma A253 cell line in a dose-dependent manner. The halfmaximal concentration (IC50) value of AA was assessed as 204.74 μg/ml. Based on binding affinity, saponin C (-CDOCKER energy = -77.9862), oleanolic acid (-CDOCKER energy = - 49.4349), spinasterol (-CDOCKER energy = -38.1246), 36,47-dihydroxyhenpentacontan-4-one (-CDOCKER energy = -32.4386), and 20-hydroxyecdysone (-CDOCKER energy = -31.9138) were identified as the best compounds against Akt1, while, compounds saponin C (-CDOCKER energy = -134.412), oleanolic acid (-CDOCKER energy = -90.0846), spinasterol (-CDOCKER energy = -78.3213), 20-hydroxyecdysone (-CDOCKER energy = -80.1049), and ecdysone (- CDOCKER energy = -73.3885) were identified as Akt2 inhibitors. These top compounds fulfilled drug score values, pharmacokinetic and physicochemical characteristics, and druglikeness parameters.</p><p><strong>Conclusion: </strong>The present findings reveal that the lead phytomolecules of AA could be effective and developed as a prospective drug against oral cancer.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589826","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":"The Protective Effect of Melatonin on LPS-Induced Myocardial Injury via the Caspase-11/GSDMD Pathway.","authors":"Boqun Cui, Fei Gao, Duomao Lin, Yang Yu, Chengbin Wang, Jun Ma","doi":"10.2174/0113862073284989240510062817","DOIUrl":"https://doi.org/10.2174/0113862073284989240510062817","url":null,"abstract":"<p><strong>Background: </strong>Melatonin (MT) has been demonstrated to have cardioprotective effects. Nevertheless, the precise mechanism through which MT provides protection against the etiology of LPS-induced myocardial injury remains uncertain. In this investigation, our objective was to explore the impact of MT on LPS-induced myocardial injury in an in vitro setting.</p><p><strong>Methods: </strong>H9C2 cells were categorized into four groups: a control group (H9C2 group), an MT group, an LPS group, and an MT + LPS group. The H9C2 group received treatment with sterile saline solution, the LPS group was exposed to 5 μg/mL LPS for 24 hours, the MT + LPS group underwent pretreatment with 150 μmol/L MT for 2 hours, followed by exposure to 5 μg/mL LPS for 24 hours, and the MT group received only 150 μmol/L MT for 2 hours. Cell viability and lactate dehydrogenase (LDH) release were assessed using the CCK-8 assay and LDH activity assay, respectively. The levels of reactive oxygen species (ROS) were quantified in each group of cells, and the percentage of propidium iodide (PI)-stained apoptotic cells was determined by flow cytometry. The mRNA levels of caspase11, GSDMD, and IL-18 in each group of cells were quantified.</p><p><strong>Results: </strong>MT treatment significantly protected H9C2 cells from LPS-induced damage, as evidenced by decreased LDH release. LPS treatment markedly increased ROS levels in H9C2 cells, which were subsequently reduced by MT. LPS caused a substantial decrease in superoxide dismutase (SOD) activity and a significant increase in malondialdehyde (MDA) levels, while MT treatment significantly reversed these effects. Additionally, MT markedly enhanced the proportion of viable H9C2 cells compared to LPS-treated controls, as evidenced by the PI staining assay. LPS upregulated both mRNA levels and protein levels of IL-18 in H9C2 cells. However, MT treatment effectively mitigated this LPS-induced increase. Furthermore, MT significantly decreased LPS-induced protein levels of cleaved-caspase 11 and GSDMD-N in H9C2 cells.</p><p><strong>Conclusion: </strong>Overall, our findings suggest that MT inhibits the Caspase11-GSDMD signaling pathway via pyroptosis-related proteins (caspase-11 and GSDMD-N) and reduces the expression of inflammation-related cytokines (IL-18), thereby exerting a protective effect on H9C2 cells after LPS injury.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579190","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":"Jiawei Duhuo Jisheng Mixture Mitigates Osteoarthritis Progression in Rabbits by Inhibiting Inflammation: A Network Pharmacology and Experimental Approach.","authors":"Tan Kaiyun, Xu Xiaotong, Lu Min, Wu Yongrong, Tan Xuyi, Shen Fu, Ge Jinwen, Kuang Gaoyan","doi":"10.2174/0113862073298262240705045345","DOIUrl":"https://doi.org/10.2174/0113862073298262240705045345","url":null,"abstract":"<p><strong>Background: </strong>Knee osteoarthritis (KOA) is a common degenerative joint disease characterized by cartilage degradation, inflammation, and pain. Traditional Chinese Medicine, including JDJM (a herbal formula derived from the renowned Du Huo Ji Sheng Tang), has been used to alleviate symptoms of KOA, but its underlying mechanisms remain unclear.</p><p><strong>Objective: </strong>This study aims to elucidate the potential therapeutic mechanisms of JDJM in treating KOA through network pharmacology, weighted gene co-expression network analysis (WGCNA), molecular docking, and experimental validation in animal models.</p><p><strong>Methods: </strong>The active compounds of JDJM were identified through TCMSP database searches, and their potential targets were predicted using network pharmacology. WGCNA was employed to identify key modules and hub genes associated with KOA. Molecular docking was performed to assess the binding affinities of key compounds to critical inflammatory targets. Molecular dynamics (MD) simulations were used to evaluate the stability of the protein-ligand complexes. An experimental KOA model in rabbits was used to validate the therapeutic effects of JDJM. Histopathological examinations and inflammatory marker analyses were conducted to confirm the findings.</p><p><strong>Results: </strong>Network pharmacology and WGCNA analyses identified 21 key targets and pathways potentially involved in the therapeutic effects of JDJM. Molecular docking results showed that Glyasperin C had the highest docking scores with EGF and IL-1β, followed by Stigmasterol with IL-6, Myricanone with INS, and Sesamin with VEGFA. MD simulations confirmed the stability of these protein-ligand complexes, indicating strong and stable interactions. In the rabbit KOA model, JDJM treatment significantly improved knee joint morphology and reduced the levels of inflammatory markers, such as IL-6 and TNF-α. Histopathological analysis revealed reduced cartilage degradation and inflammation in the JDJM-treated group compared to controls.</p><p><strong>Conclusion: </strong>JDJM exhibits promising anti-inflammatory and cartilage-protective effects, making it a potential therapeutic option for KOA patients. Further experimental and clinical studies are warranted to confirm these findings and translate them into clinical practice.</p>.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579189","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 Ethnopharmacological Survey on Medicinally Important Plants of Genus Salvia.","authors":"Bapu R Thorat, Suraj N Mali, Susmita Yadav, Vikas Gambhire, Dnyaneshwar T Nagre","doi":"10.2174/0113862073315816240627050225","DOIUrl":"10.2174/0113862073315816240627050225","url":null,"abstract":"<p><p>Lamiaceae (Labiatae) is a medicinally significant plant family featuring key species like Salvia aegyptiaca, S. cabulica, S. coccinea, S. glutinosa, S. officinalis, S. haematodes, S. hians, S. lanata, S. macrosiphon, S. moorcroftiana, S. spinosa, S. sclarea, and S. plebeia. These species exhibit diverse pharmacological activities attributed to essential oils and phytochemi-cals, including antioxidant, antiasthmatic, antitumor, anti-inflammatory, analgesic, etc. This re-view covers extensive phytomedicinal aspects of some important plants of the genus Salvia.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562837","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":"Exploring the Mechanism of Shen Qi Gui Oral Liquid against Chemotherapy-Induced Myelosuppression in Cancer Patients Based on Network Pharmacology and Molecular Docking.","authors":"Feng Wan, Qiao Zheng, Tiecheng Zhou, Hang Zhou, Fu Peng, Dejiao Yao, Cheng Peng","doi":"10.2174/0113862073316774240708110250","DOIUrl":"https://doi.org/10.2174/0113862073316774240708110250","url":null,"abstract":"<p><strong>Background: </strong>Shen Qi Gui oral liquid (SQG) may be beneficial for chemotherapyinduced myelosuppression (CIM). However, the underlying mechanism of CIM treated with SQG is still lacking.</p><p><strong>Methods: </strong>A total of 27 blood samples from cancer patients were selected to perform RNA-seq to obtain the Differentially Expressed Genes (DEGs). Then, the active components and target genes of SQG were acquired. Next, the drug targets and DEGs were intersected to obtain the intersection genes, followed by functional enrichment analysis and construction of a drug-compoundgene- disease network. Subsequently, core genes were selected. Then, immune cell infiltration, molecular docking, pharmacokinetic and toxicity prediction, and RT-qPCR were performed.</p><p><strong>Results: </strong>A total of 1,341 DEGs, 51 active compounds, and 264 target genes were identified. Then, 30 intersection genes were acquired. Next, a drug-compound-gene-disease network was constructed, and 7 core genes were acquired. Immune infiltration analysis exhibited that only T follicular helper cells were significantly increased in the CIM group, which was significantly negatively correlated with MAPK1, MAPK14, MCL1, PTEN, and PTGS2. The luteolin, quercetin, and beta-sitosterol showed better affinity with core genes. Luteolin and quercetin, which satisfied Lipinski's rule of five, were likely absorbed by the gastrointestinal system. Toxicity predictions showed that neither luteolin nor quercetin exhibited carcinogenicity or hepatotoxicity.</p><p><strong>Conclusion: </strong>PTEN, PTGS2, CCL2, FOS, MCL1, MAPK1, and MAPK14 were identified as the core genes in CIM patients, which were involved in the MAPK and PI3K-Akt signaling pathways. Luteolin and quercetin may be the promising drugs against CIM.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562838","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":"The Neuro-Healing Frontier: Alpha-Mangostin's Potential in Alzheimer's and Parkinson's Treatment.","authors":"Ahsas Goyal, Nandini Agrawal, Neetu Agrawal, Aanchal Verma, Kunal Solanki, Harlokesh Narayan Yadav","doi":"10.2174/0113862073311357240626103752","DOIUrl":"https://doi.org/10.2174/0113862073311357240626103752","url":null,"abstract":"<p><p>Neurodegenerative disorders represent a set of advancing, severe, and incapacitating conditions impacting millions globally, with a rising prevalence. Despite concerted efforts and an enhanced understanding of the intricate pathophysiology of neurodegeneration, the quest for effective treatments remains unfulfilled. Consequently, there exists a pressing clinical necessity for the exploration of innovative therapeutic approaches. Alpha-mangostin has exhibited beneficial effects in alleviating the severity of neurodegenerative disorders, primarily attributed to its antioxidant properties. Alpha-mangostin showcases diverse pharmacological effects, encompassing anti-inflammatory, anti-tumour, and antioxidant effects. Consequently, it has surfaced as a promising remedy with both prophylactic and restorative impacts on various neurodegenerative ailments. Recent research has illuminated the therapeutic targets of alpha-mangostin, suggesting its potential utility in addressing neurodegeneration. This review showcases the neuroprotective effects of alpha-mangostin. Drawing from numerous preliminary studies and taking into account the compound's remedial effects, the primary focus is on its role as a health-giving compound for the therapy of diseases associated with the degeneration of the nervous system. Given the substantial evidence supporting its efficacy in various experimental models, this review advocates for further investigations, with a special highlight on elucidating neuroprotective mechanisms and conducting clinical trials to validate its effectiveness in managing Alzheimer's disease as well as Parkinson's disease.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562840","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":"Study on Pharmacological Activities and Mechanisms of the Essential Oil of the Flowers of Hemerocallis citrina Baroni (EOFHCB) in the Treatment of Anxiety Disorders by GC-MS, Network Pharmacology, and Molecular Docking.","authors":"Tao Lu, Ziyi Liu, Huaxiang Zhao, Xuan Zhou, Qiong Wang, Xiaoning Jiao, Zhen Lu","doi":"10.2174/0113862073309835240611075049","DOIUrl":"https://doi.org/10.2174/0113862073309835240611075049","url":null,"abstract":"<p><strong>Background: </strong>Hemerocallis citrina Baroni (Huanghuacai), a plant of the genus Hemerocallis in the family Asphodelaceae, is widely planted in China. Based on our survey results, the chemical compounds in the essential oil of the flowers of Hemerocallis citrina Baroni (EOFHCB) and relevant pharmacological activities have never been studied systematically.</p><p><strong>Objective: </strong>To preliminarily decipher the pharmacological activities and mechanisms of EOFHCB in the treatment of anxiety disorders by GC-MS, Network Pharmacology, and Molecular docking.</p><p><strong>Methods: </strong>EOFHCB compositions were identified using GC-MS, and their targets were predicted using Swiss Target Prediction databases. The targets of anxiety disorders were obtained by GeneCards, DisGeNET, and OMIM databases. The STRING database was used to construct the protein-protein interaction networks, and the DAVID database was used to carry out GO enrichment and KEGG pathway enrichment analysis. The EOFHCB-components-targetspathways- anxiety disorders network was constructed by Cytoscape software (Version 3.10.0). Finally, the result was verified by molecular docking.</p><p><strong>Results: </strong>28 chemical components were identified by GC-MS, including 3-furanmethanol (28.43%), 2-methyl-1-butanol (27.13%), nerolidol (10.62%), and so on, which correspond to 241 potential targets. Several 2440 biological processes, 187 cellular compositions, and 311 molecular functions were enriched by GO enrichment analysis and 174 pathways by KEGG enrichment analysis. The key targets are PTGS 2, SRC, DRD 2, ESR 1, MAOB, and SLC6A4. The most important pathway is the neuroactive ligand-receptor interaction.</p><p><strong>Conclusion: </strong>EOFHCB exerts its therapeutic effects on anxiety disorders through multicomponents, multi-targets, and multi-pathways, which provided new ideas and methods for the in-depth research of aromatic Chinese medicine in the treatment of anxiety disorders.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562839","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":"SLC16A3 is a Prognostic Marker and Affects Immune Regulation in Bladder Cancer.","authors":"Chengjun Li, Guangdi Chu, Guofeng Ma, Xinlei Chen, Xiaocheng Ma, Haitao Niu","doi":"10.2174/0113862073278304240614064748","DOIUrl":"https://doi.org/10.2174/0113862073278304240614064748","url":null,"abstract":"<p><strong>Background: </strong>Overexpression of SLC16A3 can contribute to the development of various tumors by regulating metabolism, but a systematic analysis of SLC16A3 in bladder cancer (BC) has been rarely reported.</p><p><strong>Methods: </strong>We used the BC datasets from public databases to investigate SLC16A3 expression in BC. We first analysed the relationship between SLC16A3 expression and clinical characteristics of 412 bladder cancer patients. After that, gene function analyses and immunocorrelation analyses of SLC16A3 were conducted with the R package. For immunotherapy effect and drug sensitivity analysis, we also used the R package. We also analysed the relation between SLC16A3 expression and 20 m6A modification key genes. Finally, we determined the expression localization of SLC16A3 in bladder cancer by single-cell sequencing analysis using 3,115 BC cells. We further detected the expression of SLC16A3/MCT4 on BC samples by reversed transcriptionquantitative polymerase chain reaction and immunohistochemistry.</p><p><strong>Results: </strong>The SLC16A3 was overexpressed in BC cells, including epithelial cells (p＜0.001). The high SLC16A3 expression level of patients with BC was significantly related to poor prognosis (p＝0.044), and we established a reliable prognosis model for BC patients. Statistically significant associations between SLC16A3 and m6A modification (ALKBH5) gene (p＜0.001), key genes in aerobic glycolysis, M2 macrophage infiltration (p＝0.0058), and immune checkpoint regulation were observed.</p><p><strong>Conclusion: </strong>Overexpression of SLC16A3 is an independent prognostic factor in patients with BC. SLC16A3 may influence the immune infiltration of BC by regulating BC metabolism and m6A methylation, which ultimately can lead to the progress of BC. For the detection and therapy of BC, SLC16A3 may be a potent therapeutic target for BC.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491168","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":"Relationships Among Serological Indicators and In Vitro High-Throughput Drug Sensitivity Screening Results in Patients with Hepatocellular Carcinoma.","authors":"Xu Feng, Guo-Ying Feng, Jie Tao, Yu-Pei Ao, Xin-Hua Wu, Shi-Guai Qi, Zheng-Rong Shi, Ling-Yun Gao","doi":"10.2174/0113862073305230240611091708","DOIUrl":"https://doi.org/10.2174/0113862073305230240611091708","url":null,"abstract":"<p><strong>Aim: </strong>The purpose of this study was to analyze the relationship between serum indicators and high-throughput drug screening (HDS) results, aiming to achieve specific therapy for hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>This study recruited patients with HCC who underwent surgical resection at the Hepatobiliary Surgery Center of the First Affiliated Hospital of Chongqing Medical University from December 2019 to December 2021. HCC tissues were obtained from patients during surgery and subjected to in vitro cell culture, and then HDS testing was performed on the cultured tissue samples. We used Spearman's correlation analysis to examine the relationships between drug sensitivity results for anti-hepatocellular carcinoma drugs, other antitumor drugs, and serological indicators, the Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Systemic Immune Inflammatory Index (SII), Systemic Inflammatory Response Index (SIRI), Prognostic Nutritional Index (PNI), and Lymphocyte Monocyte Ratio (LMR). A significant correlation was considered when P<0.05 and |r|>0.40. Furthermore, linear regression analysis was conducted to elucidate the relationship between serological indicators and drug susceptibility, with significant results indicated by P<0.05 and R²≥0.50.</p><p><strong>Results: </strong>In this study, 82 patients with HCC who had undergone hepatectomy and completed in vitro cell culture and HDS testing were evaluated. Using Spearman's correlation with a significance threshold of P<0.05 and |r|>0.40, we identified significant associations between serological indicators and specific drug regimens: NLR correlated with 5-Fluorouracil, 5- Fluorouracil+Calcium folinate (FOLFOX4), and Capecitabine + Cisplatin (XP); PLR with FOLFOX4; SII with XP, FOLFOX4, Doxorubicin + Oxaliplatin (ADM+L-OHP); and SIRI with XP and FOLFOX4. No correlations were found between PNI or LMR and any drug inhibition rates. A comprehensive evaluation using linear regression analysis-which included variables such as sex, age, hepatitis B virus and liver cirrhosis status, size and number of lesions, alphafetoprotein, total bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, and prothrombin time, alongside NLR, PLR, SII, and SIRI was conducted in relation to drug regimens. This analysis revealed that NLR, SII, and SIRI are significant predictors of FOLFOX4 inhibition rate, while NLR predicts the inhibition rate of XP effectively. However, no significant links were established between molecular targeted drugs, other antitumor drugs, and serological indicators.</p><p><strong>Conclusions: </strong>NLR, SII, and SIRI were correlated with FOLFOX4, and the higher the values of NLR, SII, and SIRI, the higher the in vitro inhibition of FOLFOX. Also, NLR was correlated with XP, and the higher the value of NLR, the higher the in vitro inhibition of XP.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455735","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}