Current medicinal chemistry最新文献

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Elemene Injection Suppresses Pancreatic Cancer Progress through Regulating Cell Adhesion: A Research Based upon Network Pharmacology and Verification Test. 榄香烯注射液通过调节细胞粘附抑制胰腺癌进展:基于网络药理学和验证试验的研究。
IF 3.5 4区 医学
Current medicinal chemistry Pub Date : 2025-01-20 DOI: 10.2174/0109298673351591241114101143
Jiangang Zhao, Fenglin Zhang, Ping Li
{"title":"Elemene Injection Suppresses Pancreatic Cancer Progress through Regulating Cell Adhesion: A Research Based upon Network Pharmacology and Verification Test.","authors":"Jiangang Zhao, Fenglin Zhang, Ping Li","doi":"10.2174/0109298673351591241114101143","DOIUrl":"https://doi.org/10.2174/0109298673351591241114101143","url":null,"abstract":"<p><strong>Background: </strong>This study investigates the potential effects of elemene injection on pancreatic cancer using network pharmacology and experimental validation.</p><p><strong>Methods: </strong>GEO database were used to acquire genes which are differentially expressed between pancreatic cancer tissue and normal tissue. The vigorous energetic ingredients were identified in research and the object genes were obtained from BATMAN-TCM. The key targets and signaling pathways of elemene injection were identified using compound- target network analysis, protein-protein interaction network analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. in vitro experiments were carried out to confirm the accuracy of the network pharmacology predictions.</p><p><strong>Results: </strong>Two hundred and eleven target genes that may be involved in Elemene's impact on pancreatic cancer were identified. Bioinformatics analysis was conducted to determine the two active mixtures and one key target. GO and KEGG enrichment analyses indicated that elemene injection exerts therapeutic effects on pancreatic cancer, regulating the cell adhesion by ECM-receptor interaction pathway. The experiments verified that elemene injection suppressed the growth and movement of pancreatic cancer cell lines Panc02 and MiaPaca-2 and the mechanism is related to regulating ECM-receptor interaction pathway-related genes. FN1 was identified as core targets by bioinformatics analysis. The FN1 was downregulated by elemene injection and was validated by QPCR and Western Blot.</p><p><strong>Conclusion: </strong>The findings of the current study emphasized that elemene injection might control cell attachment, decrease metastasis, and suppresses pancreatic cancer progress. FN1 might be a therapeutic target for pancreatic cancer.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001788","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}
引用次数: 0
The Expression of the LDLR, LDLRAP1, and PCSK9 Genes has Prognostic Significance in Triple-negative Breast Cancer. LDLR、LDLRAP1和PCSK9基因表达在三阴性乳腺癌中的预后意义
IF 3.5 4区 医学
Current medicinal chemistry Pub Date : 2025-01-20 DOI: 10.2174/0109298673291217241219055416
Ivan Denisovich Antipenko, Darya Mikhailovna Olkhovik, Olga Nikolaevna Solopova, Gulfia Amirovna Khayretdinova, Olga Sergeevna Kalacheva, Julia Alekseevna Makarova, Maxim Yurievich Shkurnikov
{"title":"The Expression of the LDLR, LDLRAP1, and PCSK9 Genes has Prognostic Significance in Triple-negative Breast Cancer.","authors":"Ivan Denisovich Antipenko, Darya Mikhailovna Olkhovik, Olga Nikolaevna Solopova, Gulfia Amirovna Khayretdinova, Olga Sergeevna Kalacheva, Julia Alekseevna Makarova, Maxim Yurievich Shkurnikov","doi":"10.2174/0109298673291217241219055416","DOIUrl":"https://doi.org/10.2174/0109298673291217241219055416","url":null,"abstract":"<p><strong>Aims: </strong>The purpose of this study was to investigate the prognostic significance of cholesterol uptake genes in predicting the survival of breast cancer patients.</p><p><strong>Background: </strong>Cholesterol plays a crucial role in the homeostasis of tumor cells. It is known that cholesterol levels can influence important parameters of the disease, such as sensitivity to therapy, progression, and metastasis of cancer. Previous studies suggest that breast cancer subtypes exhibit differences in metabolism.</p><p><strong>Objective: </strong>The objectives of this study were to determine whether cholesterol uptake genes have prognostic significance for overall survival in breast cancer patients, evaluate if this prognostic significance varies between breast cancer subtypes, and identify differences in the expression of cholesterol uptake genes among these subtypes.</p><p><strong>Methods: </strong>Data from mRNA sequencing of tumors from the Cancer Genome Atlas (TCGA) portal were analyzed. Tumors were classified into molecular subtypes, and the prognostic significance of cholesterol uptake gene expression levels was evaluated for each subtype. DESeq2 and Fisher's test were used to assess differences in gene expression.</p><p><strong>Results: </strong>High expression levels of genes involved in de novo cholesterol synthesis were associated with poor prognosis for the Basal-like and Luminal A breast cancer subtypes. The prognostic significance of low-density lipoprotein receptor (LDLR), LDLR adapter protein 1 (LDLRAP1), and proprotein convertase subtilisin/kexin type 9 (PCSK9), which are responsible for exogenous cholesterol uptake, varied across subtypes. Specifically, low expression of LDLR was associated with a favorable prognosis for the luminal A (OR = 2.17; FDR = 0.0048) and luminal B (OR = 2.21; FDR = 0.015) subtypes but indicated poor prognosis in the basal-like subtype (OR = 0.48; FDR = 0.05). No genes were significant for prognosis prediction in the HER2-positive subtype. The HER2+ subtype exhibited higher expression of cholesterol uptake genes compared to the basal-like subtype based on the analysis of tumor mRNA sequencing (OR = 6.45, p-value = 3.07E-05). This finding was also confirmed through the study of publicly available single-cell sequencing data (OR = 40.3, p-value = 2.19e-07), which may contribute to the differences in their prognostic significance.</p><p><strong>Conclusion: </strong>The prognostic significance of cholesterol uptake gene expression varies among breast cancer subtypes. Precise fitting of biomarkers into breast cancer subtypes may aid in more accurate patient stratification and improve treatment approaches.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001817","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}
引用次数: 0
Exploring PANoptosis Related Novel Diagnostic Biomarkers and Potential Drugs for Sarcopenia based on Machine Learning and Experimental Validation. 基于机器学习和实验验证的PANoptosis相关新诊断生物标志物和潜在药物的探索。
IF 3.5 4区 医学
Current medicinal chemistry Pub Date : 2025-01-20 DOI: 10.2174/0109298673341863241210112605
Zhibo Deng, Chao Song, Rongsheng Zhang, Yu Xiu, Linhai Yang, Hanhao Dai, Jun Luo, Jie Xu
{"title":"Exploring PANoptosis Related Novel Diagnostic Biomarkers and Potential Drugs for Sarcopenia based on Machine Learning and Experimental Validation.","authors":"Zhibo Deng, Chao Song, Rongsheng Zhang, Yu Xiu, Linhai Yang, Hanhao Dai, Jun Luo, Jie Xu","doi":"10.2174/0109298673341863241210112605","DOIUrl":"https://doi.org/10.2174/0109298673341863241210112605","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia, an aseptic chronic inflammatory disease, is a complex and debilitating disease characterized by the progressive degeneration of skeletal muscle. PANoptosis, a novel proinflammatory programmed cell death pathway, has been linked to various diseases. However, the precise role of PANoptosis-related features in sarcopenia remains uncertain.</p><p><strong>Methods: </strong>According to the intersection of differentially expressed genes (DEGs) in the sarcopenia dataset GSE167186 and the PANoptosis gene set, we classified patients into PANoptosis-related subtypes (PANRS) using consensus clustering. The DEGs of PANRS were intersected with weighted gene co-expression network analysis (WGCNA). Proteinprotein interaction network and cytoHubba algorithms were employed to further identify potential genes related to PANoptosis. The most characteristic genes were selected using LASSO regression and validated by ROC curve analysis, followed by relevant immune infiltration analysis. Additionally, small-molecule drug screening was performed using Cmap. The relative expression levels of hub genes in sarcopenia were confirmed by PCR. Finally, single-cell analysis and GSEA were used to examine the distribution and function of hub genes.</p><p><strong>Results: </strong>Thirty-five candidate genes were identified through WGCNA and PANRS. Machine learning and ROC curve analysis revealed three core genes: LTBP2, ETS2, and H3.3B, all of which were up-regulated in patients with sarcopenia (p<0.01). Immune infiltration analysis indicated that these three diagnostic genes were linked to the activation of NK cells and macrophages. Single-cell analysis demonstrated that LTBP2 was mainly localized in fibroblasts, while ETS2 and H3.3B exhibited a uniform distribution. Enrichment analysis indicated that the three hub genes were predominantly associated with the inhibition of energy metabolism.</p><p><strong>Conclusion: </strong>In this study, the hub genes LTBP2, ETS2, and H3.3B associated with PANoptosis in sarcopenia were successfully identified through a combination of bioinformatics and experimental verification methods. This establishes a foundation for new candidate diagnostic and therapeutic targets for sarcopenia.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001792","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}
引用次数: 0
LGALS3BP: A Potential Prognostic Biomarker Influencing Antitumor Immunity in Triple-negative Breast Cancer. LGALS3BP:影响三阴性乳腺癌抗肿瘤免疫的潜在预后生物标志物
IF 3.5 4区 医学
Current medicinal chemistry Pub Date : 2025-01-20 DOI: 10.2174/0109298673367980250101053748
Anqi Hu, Shuaikang Pan, Yuan He, XueRu Wang, Dong Qian, Xiaoyang Li
{"title":"LGALS3BP: A Potential Prognostic Biomarker Influencing Antitumor Immunity in Triple-negative Breast Cancer.","authors":"Anqi Hu, Shuaikang Pan, Yuan He, XueRu Wang, Dong Qian, Xiaoyang Li","doi":"10.2174/0109298673367980250101053748","DOIUrl":"https://doi.org/10.2174/0109298673367980250101053748","url":null,"abstract":"<p><strong>Objective: </strong>LGALS3BP exhibits differential expression in various types of tumors. This study aimed to analyze its potential diagnostic and prognostic value in Triple- negative Breast Cancer (TNBC).</p><p><strong>Methods: </strong>We conducted a comprehensive analysis of LGALS3BP's differential expression and its association with patient survival outcomes using data from public databases. To further validate these findings, Immunohistochemistry (IHC) experiments were performed to confirm the differential expression of LGALS3BP protein in TNBC. Additionally, we also investigated the relationship among LGALS3BP, tumor immune infiltration, and drug sensitivity.</p><p><strong>Results: </strong>Results indicated LGALS3BP to be significantly upregulated in TNBC, with its high expression correlating with improved survival outcomes. Furthermore, LGALS3BP expression correlated with immune cell infiltration. Notably, high LGALS3BP expression may confer a greater likelihood of benefiting from immunotherapy.</p><p><strong>Conclusion: </strong>LGALS3BP may serve as a diagnostic and prognostic biomarker for TNBC.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001753","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}
引用次数: 0
Delineating the Potential Therapeutic Effects of Lobaric Acid as a Novel Strategy in the Treatment of Melanoma. 描述四叶酸作为一种治疗黑色素瘤的新策略的潜在治疗效果。
IF 3.5 4区 医学
Current medicinal chemistry Pub Date : 2025-01-20 DOI: 10.2174/0109298673322435240913095954
Huda Abdirizak Jama, Mine Ensoy, Açelya Yılmazer, Demet Cansaran-Duman
{"title":"Delineating the Potential Therapeutic Effects of Lobaric Acid as a Novel Strategy in the Treatment of Melanoma.","authors":"Huda Abdirizak Jama, Mine Ensoy, Açelya Yılmazer, Demet Cansaran-Duman","doi":"10.2174/0109298673322435240913095954","DOIUrl":"https://doi.org/10.2174/0109298673322435240913095954","url":null,"abstract":"<p><strong>Introduction: </strong>Melanoma is one of the most dangerous and common types of cancer in humans. In order to minimize the toxicity and side effects of melanoma treatment, it is important to identify drug candidates that have strong anti-cancer activity and fewer side effects. Lobaric acid is a small molecule that has been found to have significant anti-cancer effects on various types of cancer cells.</p><p><strong>Methods: </strong>The study aimed to investigate the effects of lobaric acid on human melanoma cell lines (A-375, MDA-MB-435, G-361, and WM-115) and normal human epidermal melanocyte cells. The study also examined the regulation of cell cycle and apoptosis, as well as the gene expression level of apoptosis-related genes and regulatory proteins to induce apoptosis in melanoma cells.</p><p><strong>Results: </strong>The study suggests that lobaric acid may have an effect on the proliferation of A-375 melanoma cells, with results indicating a dose- and time-dependent manner. Additionally, the study found that the expression levels of 70 target genes out of 88 apoptosis- related genes in the primary apoptosis library panel were obtained. Out of these, 54 genes showed an increase in expression levels, while 16 genes showed a decrease. Moreover, it has been determined that the levels of apoptosis-related proteins, such as Casp3, Casp7, Casp9, and PARP, were increased. The results suggest that lobaric acid induces apoptosis through the extrinsic pathway by upregulating the expression of Caspases and PARP.</p><p><strong>Conclusion: </strong>The findings of this study provided a strong basis for the use of lobaric acid as a potential therapeutic agent in the treatment of melanoma.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001786","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}
引用次数: 0
A Review on the Potential Effects of Curcumin in the Treatment of Neuroblastoma and its Underlying Mechanisms. 姜黄素治疗神经母细胞瘤的潜在作用及其机制综述。
IF 3.5 4区 医学
Current medicinal chemistry Pub Date : 2025-01-17 DOI: 10.2174/0109298673345693241218070409
Sayeh Shaban, Tayebeh Chahkandi, Amir Masoud Jafari-Nozad, Tahereh Farkhondeh, Saeed Samarghandian
{"title":"A Review on the Potential Effects of Curcumin in the Treatment of Neuroblastoma and its Underlying Mechanisms.","authors":"Sayeh Shaban, Tayebeh Chahkandi, Amir Masoud Jafari-Nozad, Tahereh Farkhondeh, Saeed Samarghandian","doi":"10.2174/0109298673345693241218070409","DOIUrl":"https://doi.org/10.2174/0109298673345693241218070409","url":null,"abstract":"<p><p>Neuroblastoma (NB) is a rare embryonal neuroendocrine tumor that primarily affects children aged 5 years old or younger. In advanced stages, NB requires a multifaceted treatment approach, including a combination of surgery, chemo, and radiation therapy. However, high-risk NB is still associated with poor prognosis, long-term side effects, and a high chance of relapse. To counter the drawbacks of conventional treatments, the antitumor properties of natural substances have been extensively studied in recent years. Curcumin (CUR) is a polyphenol of the plants of the Curcuma longa species and is well-known for its potent biological activities, such as antioxidant, anti-inflammatory, and anticancer properties. CUR may function as a potential therapeutic compound in NB cells by decreasing cell viability, proliferation, and migration, while inducing oxidative stress and apoptosis in cancer cells. Different molecular pathways have been suggested for this anti-cancer activity of CUR, such as caspase-3 activation, p53 and Bcl-2 signaling pathways, inhibition of AKT and FOXO3 nuclear translocation, and regulation of the chaperoning system proteins. Despite its favorable effects, CUR faces several challenges in treating cancer, such as low bioavailability and bioactivity. Consequently, recent studies have focused on the development of CUR nanoformulations and new drug delivery systems, aiming to overcome these barriers. This review provides an updated summary of the recent literature regarding CUR's protective role in NB and the potential underlying mechanisms. In conclusion, CUR and its nanoformulations show great potential for NB management, and we suggest additional well-designed basic and preclinical studies to explore CUR's efficiency in detail, especially its therapeutic effectiveness in humans.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001766","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}
引用次数: 0
The [18F] F-PSMA Probe: Chemical Perspectives. [18F] F-PSMA探针:化学视角。
IF 3.5 4区 医学
Current medicinal chemistry Pub Date : 2025-01-17 DOI: 10.2174/0109298673333642250102080759
Isabelle Xavier de-Britto, Stephanie Nascimento Neves-da-Silva, Luciana Magalhaes Rebelo Alencar, Pierre Basilio Almeida Fechine, Ralph Santos-Oliveira
{"title":"The [18F] F-PSMA Probe: Chemical Perspectives.","authors":"Isabelle Xavier de-Britto, Stephanie Nascimento Neves-da-Silva, Luciana Magalhaes Rebelo Alencar, Pierre Basilio Almeida Fechine, Ralph Santos-Oliveira","doi":"10.2174/0109298673333642250102080759","DOIUrl":"https://doi.org/10.2174/0109298673333642250102080759","url":null,"abstract":"<p><p>This study discusses the chemical perspectives of the [18F]F-PSMA probe, a pivotal tool in prostate cancer imaging. [18F]Fluorine, a positron emitter with a half-life of 109.8 minutes, is produced in a cyclotron by bombarding [18O]-enriched targets with protons. The chemistry of this isotope parallels that of stable fluorine, facilitating its use in positron emission tomography (PET). The synthesis of [18F]F-PSMA involves a nucleophilic substitution (SN1) reaction, where [18F]fluoride ion replaces a leaving group in the precursor molecule. Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells, making it a crucial target for imaging. PSMA-targeted radioligands, such as [68Ga]Ga-PSMA-11, [18F]F-DCFPyL, and [99mTc]Tc-PSMA-I&S, bind to the extracellular domain of PSMA, enabling precise imaging. The design of PSMA radiotracers incorporates specific targeting moieties, functional groups for radiolabeling, and linkers to maintain binding affinity and pharmacokinetics. Common linkers include aliphatic, aromatic, peptide-based, and polyethylene glycol structures, while functional groups like tosylate and PyTFP are used for efficient [18F]fluorination. This review aims to elucidate the main linker and reactions in order to optimize these components to improve imaging sensitivity and specificity in detecting prostate cancer.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001811","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}
引用次数: 0
Mendelian Randomization and Transcriptome Data Analysis Reveal Bidirectional Causal Relationships and Mechanisms Between Type 2 Diabetes and Gastric Cancer. 孟德尔随机化和转录组数据分析揭示2型糖尿病与胃癌的双向因果关系和机制
IF 3.5 4区 医学
Current medicinal chemistry Pub Date : 2025-01-17 DOI: 10.2174/0109298673348645241226091059
Junyang Ma, Yuan Gao, Shufu Hou, Shichang Cui, Jiankang Zhu
{"title":"Mendelian Randomization and Transcriptome Data Analysis Reveal Bidirectional Causal Relationships and Mechanisms Between Type 2 Diabetes and Gastric Cancer.","authors":"Junyang Ma, Yuan Gao, Shufu Hou, Shichang Cui, Jiankang Zhu","doi":"10.2174/0109298673348645241226091059","DOIUrl":"https://doi.org/10.2174/0109298673348645241226091059","url":null,"abstract":"<p><strong>Introduction: </strong>Gastric cancer (GC) is the fifth most common cancer globally, and the relationship between type 2 diabetes mellitus (T2DM) and cancer risk remains controversial.</p><p><strong>Methods: </strong>We performed Mendelian randomization (MR) analysis using publicly available GWAS data to assess the causal relationship between T2DM and GC, validated by heterogeneity and pleiotropy analyses. Transcriptomic data from TCGA and GEO were analyzed to identify common differentially expressed genes (DEGs). Weighted gene co-- expression network analysis (WGCNA) was used to construct a prognostic risk model. Drug sensitivity and immune infiltration were evaluated using GDSC and ImmuCellAI, respectively. Additionally, gene mutation analysis was conducted using TCGA data.</p><p><strong>Results: </strong>The Mendelian randomization analysis revealed a causal relationship between T2DM and GC at the genetic level. Specifically, the causal effect of T2DM on GC was estimated with an odds ratio (OR) of 1.32 (95% CI: 1.12-1.56), while the reverse causal effect of GC on T2DM was estimated at an OR of 0.78 (95% CI: 0.67-0.91). Sensitivity analyses, including Cochran's Q test and the leave-one-out test, confirmed the robustness of these findings. We constructed a prognostic risk score consisting of three T2DM-related genes (CST2, PSAPL1, and C4orf48) based on transcriptome data analysis. Patients with high-risk scores exhibited significantly worse overall survival (OS) (p < 0.05). Cox regression analysis further confirmed the independent predictive value of the risk score for GC prognosis. Our predictive model demonstrated good performance, with an AUC of 0.786 in the training set and 0.757 in the validation set. Gene enrichment analysis indicated that the genes shared between T2DM and GC were associated with inflammatory response, immune response, and metabolic pathways. Tumor immune microenvironment analysis suggested that immune evasion mechanisms may play a key role in developing GC in patients with coexisting T2DM.</p><p><strong>Conclusion: </strong>T2DM is associated with reduced GC risk. The risk score and model may help guide GC prognosis and management.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001755","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}
引用次数: 0
Computational Approaches for Multitarget Drug Design in Alzheimer's Disease: A Comprehensive Review. 阿尔茨海默病多靶点药物设计的计算方法:综述
IF 3.5 4区 医学
Current medicinal chemistry Pub Date : 2025-01-16 DOI: 10.2174/0109298673320300240930064551
Fatima Zahra Guerguer, Meriem Khedraoui, Abdelouahid Samadi, Samir Chtita
{"title":"Computational Approaches for Multitarget Drug Design in Alzheimer's Disease: A Comprehensive Review.","authors":"Fatima Zahra Guerguer, Meriem Khedraoui, Abdelouahid Samadi, Samir Chtita","doi":"10.2174/0109298673320300240930064551","DOIUrl":"https://doi.org/10.2174/0109298673320300240930064551","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a chronic and progressive neurodegenerative brain disorder, primarily affecting the elderly. Its socio-economic impact and mortality rate are alarming, necessitating innovative approaches to drug discovery. Unlike single-target diseases, Alzheimer's multifactorial nature makes single-target approaches less effective. To address this challenge, researchers are turning to drug design strategies targeting multiple disease pathways simultaneously. This approach has led to the promising identification of dual or multiple-target inhibitors, offering new perspectives for improving disease management. Computer-Aided Drug Design (CADD) such as virtual screening, docking, QSAR, molecular dynamics, ADMET prediction, etc., are valuable tools for designing and identifying new multi target directed ligands (MTDLs). These methods enable efficient screening of extensive compound libraries and accurate prediction of pharmacokinetic profiles, optimizing development costs and time. Challenges such as model accuracy, simulation complexity, and data integration persist. Addressing these issues requires advances in in silico modeling, high-performance computing, and experimental validation. In this regard, this review highlights recent advances using various computational methods to screen and identify new candidate compounds containing different heterocyclic motifs that could serve as potential bases for designing ligands targeting multiple targets for Alzheimer's disease.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001770","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}
引用次数: 0
Advanced Targeted Therapy for Colorectal Cancer with Lipid Nanoparticles. 脂质纳米颗粒用于结直肠癌的先进靶向治疗。
IF 3.5 4区 医学
Current medicinal chemistry Pub Date : 2025-01-16 DOI: 10.2174/0109298673327576241201145252
Pawan Kedar, Sankha Bhattacharya, Preeti Sakore, Bhupendra G Prajapati
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