Jianghong Wang, Xiaoyuan Wang, Yanru Song, Zilin Huang, Han Wu, Liang Chang, Bingjie Huo, Guanwei Fan
{"title":"Huopuxialing Decoction: A Promising Candidate for Precancerous Lesions of Gastric Cancer Treatment Based on Bioinformatics and Experimental Verification","authors":"Jianghong Wang, Xiaoyuan Wang, Yanru Song, Zilin Huang, Han Wu, Liang Chang, Bingjie Huo, Guanwei Fan","doi":"10.2174/0113862073325718240827073225","DOIUrl":"https://doi.org/10.2174/0113862073325718240827073225","url":null,"abstract":"Background: The Precancerous Lesion of Gastric Cancer (PLGC) is an early stage in the development of gastric cancer. The clinical application of HPXLD has been found to be effective in treating PLGC, but the mechanism of how HPXLD acts on PLGC is still unclear. Objective: The objectives of this study were to reveal the molecular mechanism of how HPXLD can be used to treat PLGC and investigate this mechanism through bioinformatics and experimental validation. Methods: PLGC-associated target genes were identified through bioinformatics analysis. A rat model of PLGC was induced using N-methyl-N'-nitro-N-nitrosoquanidine (MNNG) in combination with ranitidine, hot saline, ethanol, and intermittent fasting, with interventions by HPXLD. The pathological alterations in gastric mucosa were assessed through Hematoxylin-eosin staining (HE). Immunohistochemistry (IHC) and Western blot analyses were employed to evaluate the changes in expression levels of inflammation-related proteins. Results: After conducting bioinformatics analysis, it was found that there were 23 HPXLDPLGC crossover genes, which were significantly enriched in the IL-17 signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway. The results of HE showed that HPXLD was effective in improving gastric mucosal histopathological changes. Additionally, the IHC results demonstrated that HPXLD was able to downregulate the expression of IL-6, COX-2, MCP- 1, and MMP-9. Furthermore, Western blot analysis revealed that HPXLD was able to downregulate the expressions of IL-6, IL-17RA, ACT1, NF-κB, and TNF-α. Conclusion: HPXLD has been shown to improve PLGC by reducing the expression of inflammation- related proteins. This suggests that HPXLD may potentially be a treatment option for PLGC.","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":"204 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258710","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 Potential Role of Sophora alopecuroides L. in Inflammation of Bovine Mammary Epithelial Cells Induced by Lipoteichoic Acid Based on Network Pharmacology and Experimental Validation","authors":"Ziwen Yuan, Fang Li, Wenfei Zhang, Yanming Wei, Yongli Hua","doi":"10.2174/0113862073313036240829070704","DOIUrl":"https://doi.org/10.2174/0113862073313036240829070704","url":null,"abstract":"Aim: This study aimed to investigate the anti-inflammatory effect and mechanism of Sophora alopecuroides L. (KDZ) on lipoteichoic acid (LTA)-induced inflammation in Bovine Mammary Epithelial Cells (BMEC). Method: The KDZ active ingredient database was established by using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to detect the chemical components of KDZ and combine it with the TCMSP database. Furthermore, potential targets of KDZ active ingredients were collected through the UniProt database, and mastitis-related targets were screened through the OMIM, Genecard, and DisGeNET databases. Furthermore, common targets were identified between ingredient targets and disease targets, and protein-protein interaction analysis was performed on them using the STRING platform. Furthermore, the protein interaction network was constructed using Cytoscape software. Core targets were screened through network topology analysis. On this basis, GO and KEGG enrichment analyses were performed on the common target, and molecular simulation docking analysis was conducted on the main active ingredients and core targets. Finally, the accuracy of the network analysis results was validated using in vitro cell experiments. Result: The results of UPLC-QTOF-MS detection and network pharmacology analysis showed that KDZ could intervene in signaling pathways, such as the IL-17 signaling pathway, TNF signaling pathway, MAPK signaling pathway, etc., by acting on 80 common targets through 15 potential active ingredients, thereby regulating biological processes, such as positive regulation of peptidyl serine physiology, apoptotic process, and inflammatory response, to treat mastitis. Besides, molecular simulation docking analysis also showed that the main active ingredients in KDZ, such as quercetin, matrine, calycosin, etc., can form stable bindings with 11 core targets (TNF-α, IL-6, IL-1β, etc.) through hydrogen bonding. Further in vitro validation experiments confirmed that KDZ intervention could inhibit the IL-17 signaling pathway by inhibiting the expression of GSK3β and subsequently inhibiting the production of downstream inflammatory cytokines IL-8, IL-6, IL-1β, and TNF-α, thereby alleviating LTA-induced BMEC inflammatory damage. Conclusion: KDZ can alleviate LTA-induced BMEC inflammatory damage by inhibiting the IL- 17 signaling pathway. This study can provide a scientific basis for the clinical application of KDZ and lay the foundation for the development of new therapeutic drugs for mastitis.","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":"86 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258714","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 Mitochondrial Autophagy Dysregulation in Osteosarcoma: Its Implications for Prognosis and Targeted Therapy.","authors":"Xiangpan Kong, Dawei He, Quan Wang","doi":"10.2174/0113862073314265240828170126","DOIUrl":"https://doi.org/10.2174/0113862073314265240828170126","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the differential expression of mitophagyrelated genes in osteosarcoma patients with distinct prognostic outcomes and explore potential molecular regulatory mechanisms.</p><p><strong>Methods: </strong>We analyzed microarray data from metastatic and nonmetastatic osteosarcoma patients using the UCSC dataset. Differential gene screening and intersection of mitophagy-related genes were performed using NetworkAnalyst. Random forest and LASSO regression were employed to screen selected genes and establish a risk prediction model. Functional enrichment analysis, protein- protein interaction (PPI) networks, immunoassays, and in vitro experiments were conducted to validate the findings.</p><p><strong>Results: </strong>Seven differentially expressed genes were identified, and a robust risk prediction model was developed (AUC=0.886). PPI and functional enrichment analyses provided insights into relevant molecules and regulatory pathways. The immunoassay results revealed differences in the immune environment between the metastatic and nonmetastatic groups. Immunohistochemistry demonstrated significant downregulation of EPHA3 expression in the metastatic group, and in vitro experiments indicated that inhibiting EPHA3 increased the proliferative activity and migration ability of osteosarcoma cells.</p><p><strong>Conclusion: </strong>Our study suggests that the downregulation of EPHA3 may contribute to mitochondrial autophagy dysfunction, thereby increasing the risk of osteosarcoma metastasis.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281495","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":"Using a Dual-Disease Target Mapping Network Pharmacology Approach, Verbascoside Ameliorates Osteoporosis by Activating Estrogen Signaling to Alleviate Oxidative Stress.","authors":"Peitong Wu, Qingguo Lv, Shuo Wang, Xueqin Feng, Kaiyue Zhang, Chunnan Li, Yishan Li, Xiaochen Gao, Jiaming Sun","doi":"10.2174/0113862073312956240826053228","DOIUrl":"https://doi.org/10.2174/0113862073312956240826053228","url":null,"abstract":"<p><strong>Background: </strong>Verbascoside, a compound classified as a phenylethanol glycoside in Dihuang, has been the subject of modern pharmacological investigations. These studies have revealed its noteworthy antioxidant, anti-inflammatory, memory-enhancing, neuroprotective, antitumor, and various other pharmacological properties. While verbascoside exhibits favorable antioxidant effects, its precise mechanism of action in ameliorating osteoporosis through the treatment of oxidative stress remains unclear.</p><p><strong>Methods: </strong>This study employed CCK8, ALP, ELISA, and ROS staining techniques to examine the osteoporotic effects of verbascoside on zebrafish and MC3T3-E1 cells. Additionally, this study aimed to investigate the molecular mechanism by which verbascoside improves osteoporosis by mitigating oxidative stress. To identify the common targets of verbascoside in relation to oxidative stress and osteoporosis, network pharmacology and molecular dynamics simulation were employed. The construction of the verbascoside - oxidative stress - osteoporosis - potential target gene network aimed to identify the core targets, while the mechanism of action was elucidated through KEGG analysis, and the accuracy was confirmed by assessing the mRNA expression of the targets.</p><p><strong>Results: </strong>In vivo experiments demonstrated that verbascoside exhibited therapeutic effects on osteoporosis and reduced ROS production in zebrafish. In vitro experiments further revealed that verbascoside enhanced the proliferation and differentiation of MC3T3-E1 cells, thereby improving the oxidative stress status of osteoblasts. Thirteen core targets and estrogen signaling pathways were identified through the application of network pharmacology. The pivotal role of the estrogen signaling pathway in facilitating the ability of verbascoside to mitigate oxidative stressinduced osteoporosis was substantiated by the modulation of target protein mRNA expression.</p><p><strong>Conclusion: </strong>The findings underscore the considerable therapeutic potential of verbascoside in ameliorating osteoporosis through the alleviation of oxidative stress, thus establishing it as a promising compound for the treatment of this condition.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153315","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}
Pengyan Shi, Xiaoying Chen, Jiangtao Cao, Zhe Feng, Boyu Xue
{"title":"Exploring the Mechanism of Modified Zexie Decoction Against Metabolic Associated Fatty Liver Disease Based on Network Pharmacology and Experimental Validation.","authors":"Pengyan Shi, Xiaoying Chen, Jiangtao Cao, Zhe Feng, Boyu Xue","doi":"10.2174/0113862073344422240906051007","DOIUrl":"https://doi.org/10.2174/0113862073344422240906051007","url":null,"abstract":"<p><strong>Introduction/objective: </strong>The incidence of metabolic-associated fatty liver disease (MAFLD) increases annually. Modified Zexie Decoction (MZXD) can treat this disease; however, their mechanisms of action are uncertain. This study evaluated the mechanisms of MZXD against MAFLD based on network pharmacology, molecular docking, and in vivo experiments.</p><p><strong>Methods: </strong>The main active compounds, targets and signaling pathways of MZXD against MAFLD were obtained using network pharmacological analysis. Underlying mechanisms were validated by molecular docking and in vivo assays.</p><p><strong>Results: </strong>Forty-one active ingredients and 197 intersection targets were identified. The main active ingredients include quercetin, luteolin, isorhamnetin, 3-methylhexane, and 3β- acetoxyatractylone. The main targets were TP53, JUN, HSP90AA1, MAPK1, MAPK3, AKT1, NF-κB p65, TNF, ESR1, FOS, and IL-6. The pathway enrichment analysis indicated that MZXD was related to the IL-17, TNF, and PI3K-AKT signaling pathways. Molecular docking suggested that these active ingredients bound strongly to TNF, IL-6, and NF-κB p65, which are integral components of the TNF pathway. In the rat MAFLD model, MZXD attenuated high-fat diet( HFD)-induced liver injury and lipid accumulation, decreased the serum levels of the inflammatory mediators TNF-α, IL6, and IL-1β, and inhibited the protein expression of TNF-α, IL6, p- IKB-α and p-NF-κB p65. Furthermore, immunohistochemistry results showed that MZXD attenuated the F4/80 staining intensity of the liver compared with the model group.</p><p><strong>Conclusion: </strong>Collectively, our results suggested that MZXD could improve MAFLD by downregulating TNF/NF-κB signaling mediated macrophage activation.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153314","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}
Yuanxia Yang, Miaoting Yang, Lijuan Wang, Liufang He, Tao Shi
{"title":"Establishment of LC-MS/MS Methodology for the Determination of Rapamycin Concentration in Rat Whole Blood.","authors":"Yuanxia Yang, Miaoting Yang, Lijuan Wang, Liufang He, Tao Shi","doi":"10.2174/0113862073291189240819115228","DOIUrl":"https://doi.org/10.2174/0113862073291189240819115228","url":null,"abstract":"<p><strong>Background: </strong>The establishment and validation of methods for testing biological samples are crucial steps in pharmacokinetic studies. Currently, several methodological reports have been published on the detection of rapamycin plasma concentrations.</p><p><strong>Objective: </strong>The objective of this study was to explore an effective method for detecting rapamycin in rat whole blood biological samples.</p><p><strong>Method: </strong>In this study, we designed a rapid, sensitive, and specific liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS) methodology for detecting rapamycin in rat whole blood biological samples. We comprehensively validated the specificity, linear range, lower limit of quantification (LLOQ), precision, accuracy, recovery, and stability of this method.</p><p><strong>Results: </strong>The findings of this study confirmed the successful implementation of LC-MS/MS for the detection of rapamycin, demonstrating its sensitivity, specificity, and reliability in quantitative analysis. This method ensures the accuracy and reliability of subsequent study data through our validated LC-MS/MS approach.</p><p><strong>Conclusion: </strong>The results demonstrated the successful implementation of an LC-MS/MS method for sensitive, specific, and reliable quantitative analysis of rapamycin in rat whole blood samples. This method ensures the accuracy and reliability of subsequent study data.</p><p><strong>Significance: </strong>The importance of this study lies in the successful establishment of a rapid, sensitive, and specific LC-MS/MS method for detecting rapamycin concentration in rat whole blood, ensuring the accuracy and reliability of subsequent research data. This provides a crucial tool and foundation for further understanding the metabolism and pharmacological effects of rapamycin in vivo, aiding in the advancement of drug research and clinical applications in related fields.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125072","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}
Yang Huang, Lili Zhong, Jing Yang, Qiaomei Dai, Li Zhao, Mengdi Zhang, Hong Liu
{"title":"Zuogui Pills Improve the Learning and Memory Ability of Brain-Aging Mice through the Estrogen Receptor ERα Methylation Pathway.","authors":"Yang Huang, Lili Zhong, Jing Yang, Qiaomei Dai, Li Zhao, Mengdi Zhang, Hong Liu","doi":"10.2174/0113862073306093240820113714","DOIUrl":"https://doi.org/10.2174/0113862073306093240820113714","url":null,"abstract":"<p><strong>Introduction: </strong>Sex hormones are important factors in maintaining brain function and acting as brain protectors. Recent research suggests that neuronal damage in brain aging may be linked to the methylation of the estrogen receptor α (ERα). However, the mechanism of Zuogui Pills (ZGW) in brain-aging ERα DNA methylation and neuronal repair remains unknown.</p><p><strong>Materials and methods: </strong>D-galactose-induced ovary removal mice were used as a model of aging. Changes in estrous cycle were detected in mice by vaginal cell smear. Animal behavior tests, including the Morris water maze (MWM) and new object recognition (NOR) test, were conducted. Hematoxylin-eosin (HE) and Nissl-staining were carried out to assess hippocampal neurogenesis. Enzyme-linked immunosorbent assay (ELISA) was performed for 5- methylcytosine methylation levels, and immunohistochemistry (IHC) and western blotting (WB) experiments were performed to assess ERα/DNA methyltransferase 1 (DNMT1) expression after ZGW treatment. Finally, bisulfite sequencing PCR (BSP) analysis was performed to identify methylated differentially expressed estrogen receptor 1 (ESR1) gene in D-gal-induced senescent neurons before and after ZGW treatment.</p><p><strong>Results: </strong>We found that ERα methylation was involved in the delayed brain ageing process of ZGW. Mechanistically, ZGW can improve the learning and memory ability of brain-aging mice, reduce the expression of 5-methylcytosine (5-mc) in serum, increase the amount of ERα, inhibit the expression of DNMT1, and significantly reduce methylated expression of the ESRI gene.</p><p><strong>Conclusion: </strong>Our data suggested that ZGW slowed down D-gal-induced brain aging in mice, and these results showed that ZGW is beneficial for aging. It may be used for neuronal protection in aging.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125073","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 Molecular Docking and Molecular Dynamics Analysis of Antimicrobial Triazole Derivatives: Insights from Synthesis, Computational and In Vitro Studies.","authors":"Shikha Sharma, Naveen Kumawat, Suraj N Mali, Monika Meghani, Nitin Kumar, Bijo Mathew, Sunil Kumar","doi":"10.2174/0113862073314430240730095615","DOIUrl":"https://doi.org/10.2174/0113862073314430240730095615","url":null,"abstract":"<p><strong>Introduction: </strong>In the ongoing fight against bacterial resistance to antibiotics, this study focuses on synthesizing and evaluating 1,2,4-triazole derivatives to explore their potential as new antibacterial agents. 1,2,4-Triazole compounds are promising drug candidates with a wide range of therapeutic effects, including pain relief, antiseptic, antimicrobial, antioxidant, antiurease, anti-inflammatory, diuretic, anticancer, anticonvulsant, antidiabetic, and antimigraine properties.</p><p><strong>Method: </strong>The structures of all the synthesized compounds were identified using their physicochemical properties and spectral techniques, such as IR and NMR. These compounds were then evaluated in molecular docking studies against antimicrobial activity in vitro and further supported by molecular dynamics studies.</p><p><strong>Result: </strong>Compound 7, featuring a 6-chloro group on the phenyl ring, emerged as the most effective against Gram-positive S. aureus compared to the standard antibiotic ciprofloxacin. Docking studies revealed high and comparable affinities for all ten ligands, with compounds 4 and 6 showing the best-docked activity against Penicillin Acylase mutants. Further, compounds 6 and 10 displayed significant affinity against D-alanine-D-alanine ligase (DDL) from Yersinia pestis during 100 ns MD simulation.</p><p><strong>Conclusion: </strong>Notably, compound 7 demonstrated the highest binding score to the 5C1P protein, suggesting its potential as a lead molecule for the development of potent and safer antimicrobial agents. This research contributes valuable insights into addressing the escalating challenge of bacterial resistance.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105080","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}
Jun Cao, Shijia Zhang, Kehui Zhou, Xiaochun Mao, Ming Zhao, Jinbiao Shang, Xiabin Lan
{"title":"A Novel Cuproptosis-Related Gene Signature Predicts Prognosis in Papillary Thyroid Carcinoma Patients","authors":"Jun Cao, Shijia Zhang, Kehui Zhou, Xiaochun Mao, Ming Zhao, Jinbiao Shang, Xiabin Lan","doi":"10.2174/0113862073333880240819105537","DOIUrl":"https://doi.org/10.2174/0113862073333880240819105537","url":null,"abstract":"background: Cuproptosis is a novel type of cell death mediated by protein lipoylation,and is closely related to mitochondrial metabolism. Clinical association of cuproptosis-related genes(CRGs)in thyroid cancer, however, remains unclear. In this study, we systematically evaluated the differential expression and genetic alterations of CRGs in papillary thyroid cancer (PTC) and constructed a CRG signature to predict the prognosis of PTC patients. method: We integrated the data of The Cancer Genome Atlas (TCGA) database and analyzed the expression of 10 CRGs in PTC. CRG signature was constructed by univariate Cox analysis and selection operator (LASSO) Cox regression. In addition, the signature-related molecular features were validated by a combination of functional enrichment, Cox regression, and immune infiltration analysis. Independent validation cohort data and quantitative real-time polymerase chain reaction (qRT-PCR) were used to validate the expression of differentially expressed CRG (CDKN2A). result: Thyroid cancer patients could be divided into two subtypes (low and high CRG score groups) and we found that overall survival (OS) of patients was lower in high CRG score group (HCSG) than in low CRG score group (LCSG) (p &amp;amp;lt; 0.001). And the area under the curve (AUC) values for 3 years, 5 years, and 8 years were 0.872, 0.941, and 0.976, respectively. Cox regression analysis showed that the CRG score could be used as an independent prognostic indicator for PTC. Functional enrichment analysis indicated that the CRG prognostic signature was also associated with the tumor immune microenvironment. In HCSG, the immune suppression type cell score is significantly higher than in LCSG. In addition, we identified the expression of CRG (CDKN2A) by qRT-PCR, and the results were consistent with the TCGA database. conclusion: Our CRG signature has a good predictive ability for the prognosis of PTC patients. CRGs may play an important role in tumorigenesis and could be used to predict immunotherapy efficacy of PTC.","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":"8 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142176454","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}
Menghai Wu, Huaxin Qi, Jun Li, Periyannan Velu, Xia Han
{"title":"Rosmanol Alleviates Myocardial Ischemia-Reperfusion Injury by Enhancing the Myocardial miR-126/VEGF/PI3K/AKT Signaling in STZ-Induced Diabetic Rats.","authors":"Menghai Wu, Huaxin Qi, Jun Li, Periyannan Velu, Xia Han","doi":"10.2174/0113862073285839240808113152","DOIUrl":"https://doi.org/10.2174/0113862073285839240808113152","url":null,"abstract":"<p><strong>Background: </strong>A major factor in type 1 diabetes mortality is Ischemic Heart Disease (IHD). In order to treat IHD, blood flow must be restored to the heart, which results in myocardial ischemia-reperfusion (MI/R) damage. While rosmanol inhibits MI/R damage, its role in diabetic- MI/R (D-MI/R) injury remains unclear. Both microRNA (miR) 126 and the PI3K/AKT signaling pathway have been linked to preventing MI/R damage.</p><p><strong>Objective: </strong>The objective of the present study was to investigate whether rosmanol inhibits DMI/ R-injury in diabetic rats and whether miR-126-phosphatidylinositol 3-kinase (PI3K)/ protein kinase B axis (miR-126-PI3K/AKT) is implicated in this protective effect.</p><p><strong>Methods: </strong>For 30 days, diabetic rats received either distilled water or the drug rosmanol (40 mg/kg, orally) before being subjected to MI/R.</p><p><strong>Results: </strong>The findings from the current study demonstrated how rosmanol reduced MI/R damage in rats with diabetes caused by streptozotocin (STZ). Using spectrophotometry, it was possible to measure the decrease in myocardial enzyme levels, the rise in cardiac viability, the inhibition of myocardial oxidative stress, the increase in cardiac function, and the detection of these changes using a hemodynamic monitoring system. In addition, rosmanol augmented the miR- 126-PI3K/AKT in the hearts of ischemic rats. After stimulating the myocardial miR-126- PI3K/AKT axis, our results showed that rosmanol protected the heart against MI/R in STZinduced diabetic rats.</p><p><strong>Conclusion: </strong>According to the most recent research, rosmanol may be a useful tool in the therapy of diabetic IHD since it is an effective agent against D-MI/R damage.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079516","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}