{"title":"High Glycolysis and Lipid Metabolism Status Predicts Poor Prognosis in Colorectal Cancer Patients.","authors":"Meng Li, Maoyi Yue, Yao Chen, Gang Zhao","doi":"10.2174/0115665240369037250319000043","DOIUrl":"https://doi.org/10.2174/0115665240369037250319000043","url":null,"abstract":"<p><strong>Background: </strong>The prognosis of patients with stage III colorectal cancer (CRC) shows significant variations. The purpose of this study was to investigate the role of key regulatory proteins in glycolysis and lipid metabolism for the prognostic evaluation of stage III CRC patients.</p><p><strong>Methods: </strong>Utilizing the Cancer Genome Atlas (TCGA) database, we analyzed the expression of various key regulatory genes in glycolysis and lipid metabolism pathways in CRC, as well as the relationship between gene expression levels and overall survival. We selected the top two key genes exhibiting differential expression patterns in glycolysis and lipid metabolism, namely, glucose transporter type 1 (GLUT1), pyruvate kinase M2 (PKM2), fatty acid synthase (FASN), and stearoyl-CoA desaturase 1 (SCD1), as targets for subsequent exploration. We analyzed the effects of GLUT1, PKM2, FASN, and SCD1 on the proliferation, migration, and drug sensitivity of CRC cells in vitro. These proteins were detected by immunohistochemistry (IHC) in the clinical tissues of stage III CRC patients. Based on the intensity of IHC staining for GLUT1, PKM2, FASN and SCD1, the cumulative score from these 4 target proteins for each sample was calculated (score range from 0 to 8). The relationships between high (scores of 6-8) or low (scores of 0-5) expression of glycolysis and lipid metabolism molecules and the clinicopathological characteristics, and survival of patients were analyzed.</p><p><strong>Results: </strong>The expression disparities of the GLUT1, PKM2, FASN, and SCD1 genes were the most prominent between tumor and normal tissues. Overexpression of GLUT1, PKM2, FASN, or SCD1 significantly promoted CRC cell growth and migration, as evidenced by CCK-8, colony formation, and Transwell assays. Exogenous introduction of GLUT1, PKM2, FASN, or SCD1 increased oxaliplatin IC50 values, enhanced cell survival, and reduced early apoptosis in CRC cells exposed to oxaliplatin. High glycolysis and lipid metabolism status were associated with poor tumor differentiation, vascular or nerve invasion, and shorter overall survival. The status of glycolysis and lipid metabolism was an independent prognostic factor for stage III CRC patients.</p><p><strong>Conclusion: </strong>High glycolysis and lipid metabolism status are correlated with a poor prognosis in patients with stage III colorectal cancer.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718273","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}
Mohammad Amin Momeni-Moghaddam, Gholamreza Asadikaram, Mohammad Masoumi, Mohammad Kazemi Arababadi, Erfan Sadeghi, Mohammad Khaksari, Hamed Akbari
{"title":"Potential Effects of Opium on Pro-Inflammatory Cytokines in Coronary Artery Disease by Interfering with Anti-inflammatory Drugs.","authors":"Mohammad Amin Momeni-Moghaddam, Gholamreza Asadikaram, Mohammad Masoumi, Mohammad Kazemi Arababadi, Erfan Sadeghi, Mohammad Khaksari, Hamed Akbari","doi":"10.2174/0115665240353642250306032936","DOIUrl":"https://doi.org/10.2174/0115665240353642250306032936","url":null,"abstract":"<p><strong>Background: </strong>Opium is one of the factors that may interfere with Coronary Artery Disease (CAD). This study aimed to investigate the role of opium in certain pro-inflammatory and anti-inflammatory cytokines in CAD patients with and without opium dependence on regular prescription medicines.</p><p><strong>Methods: </strong>Seventy-seven patients with suspected CAD were selected as candidates for coronary angiography in this case-control study. They were categorized into three groups:1) CAD opiumaddicted (CAD+OA, n=30); 2) CAD non-opium-addicted (CAD, n=30); and 3) non-opium-addicted with no CAD individuals as a control group (Ctrl, n=17). Routine medications, including aspirin, atorvastatin, bisoprolol, valsartan, losartan, clopidogrel, metoprolol, isosorbide, trinitrate glyceryl, captopril, and carvedilol, were administered to these patients. ELISA was performed to quantify plasma levels of interleukin-23 (IL-23), IL-17, IL-1β, transforming growth factor beta (TGF-β), and IL-10.</p><p><strong>Results: </strong>A significantly higher level of IL-23 was found in the CAD+OA group than in the CAD and control groups. In addition, in the CAD+OA group, the mean difference in TGF-β levels was significantly lower than that in CAD patients, whereas no significant difference was found between the Ctrl group and the CAD+OA and CAD groups. No significant differences were observed in the mean levels of IL-17, IL-1β, or IL-10 among the groups.</p><p><strong>Conclusion: </strong>Opium was found to contribute to the induction of inflammation by interfering with cardiovascular medications, resulting in deterioration of CAD complications. Additionally, certain medications, including aspirin, glyceryl trinitrate, atorvastatin, and clopidogrel, played a significant role in regulating the expression of cytokines.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604099","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}
Wen-Hui Tang, Dong-Mei Wang, Zi'e Zhan, Da-Hai Kang, Tai Wan, Zhuo-Fan Liu
{"title":"Proteomic Analysis of Molecular Mechanisms Involved in TGF-β-Induced Epithelial-Mesenchymal Transition in Human Lung Adenocarcinoma A549 Cells.","authors":"Wen-Hui Tang, Dong-Mei Wang, Zi'e Zhan, Da-Hai Kang, Tai Wan, Zhuo-Fan Liu","doi":"10.2174/0115665240356010250304053147","DOIUrl":"https://doi.org/10.2174/0115665240356010250304053147","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to examine the molecular mechanisms involved in transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT) in human lung adenocarcinoma (LUAD) A549 cells.</p><p><strong>Methods: </strong>Proteins were extracted from cultured human LUAD A549 cells cultured under two conditions: untreated and treated with TGF-β (5 ng/ml) for 48 hours. The expression levels of EMT-related proteins, including E-cadherin, Vimentin, and α- smooth muscle actin, were assessed using western blotting. Proteomic analysis was performed using isobaric tags for relative and absolute quantification combined with two-dimensional liquid chromatography-tandem mass spectrometry. Differentially expressed proteins were subjected to bioinformatics analysis, including functional annotation and interaction network studies.</p><p><strong>Results: </strong>A total of 122 proteins were identified as differentially expressed between the untreated and TGF-β-treated A549 cells. Of these, 55 proteins were upregulated, while 67 were downregulated following TGF-β treatment. Bioinformatics and interaction network analyses highlighted six proteins-GAPDH, TP53, MAPK1, IGF1, SRC, and MYC-as being closely associated with the EMT in human LUAD.</p><p><strong>Conclusion: </strong>This study provides new insights into the processes of invasion and metastasis in LUAD by examining the molecular mechanisms underlying TGF-β- induced EMT in A549 cells.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585004","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":"ESM-1 Promotes the Process of Diabetic Nephropathy by Promoting the Expression of CXCL3.","authors":"Ping Zhao, Tingting Deng, Jialing Zeng","doi":"10.2174/0115665240304670250108055944","DOIUrl":"https://doi.org/10.2174/0115665240304670250108055944","url":null,"abstract":"<p><strong>Background: </strong>The analysis of diabetic nephropathy (DN)-related gene dataset demonstrated that C-X-C motif chemokine ligand 3 (CXCL3) is highly expressed in DN. Exploring the impact of CXCL3 in the course of DN is the core goal of this study.</p><p><strong>Methods: </strong>The cell model used in this study was CIHP-1 cells induced by high glucose (HG). qRT-PCR and western blot analysis were carried out to determine the expression difference of CXCL3. After down-regulating the CXCL3 level, we analyzed HG-induced CIHP-1 cell viability by MTT assay, proliferation by EdU staining, apoptosis by flow cytometry, and changes in related protein expression by western blot. In order to analyze the possible regulatory relationship between endothelial cellspecific molecule 1 (ESM-1) and CXCL3 in DN, we constructed an over-expressed ESM-1 plasmid and carried out a rescue experiment.</p><p><strong>Results: </strong>CXCL3 and ESM-1 were highly expressed in HG-induced podocytes (p<0.05). Silenced CXCL3 (siCXCL3) increased the viability and proliferation of CIHP- 1 cells induced by HG, reduced the proportion of apoptosis, and produced corresponding protein changes (p<0.01). After the overexpression of ESM-1, the effects of siCXCL3 were partially offset (p<0.05).</p><p><strong>Conclusion: </strong>In this study, ESM-1 increased HG-induced podocyte damage by promoting CXCL3 expression.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566605","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}
Sergey V Silkin, Stanislav I Pekov, Konstantin V Bocharov, Igor A Popov
{"title":"Recent Accomplishments in Exhaled Breath Condensate Analysis - Molecular Aspects.","authors":"Sergey V Silkin, Stanislav I Pekov, Konstantin V Bocharov, Igor A Popov","doi":"10.2174/0115665240352590250217110256","DOIUrl":"https://doi.org/10.2174/0115665240352590250217110256","url":null,"abstract":"<p><p>Nowadays, the research of exhaled breath condensate (EBC) analysis is widely discussed in the scientific community. The growing interest in EBC analysis results is related to the ample advantages of non-invasive techniques in healthcare and related fields. In particular, EBC analysis can be used to diagnose respiratory diseases, monitor the disease's course during therapy, and monitor drug intake and metabolism. This review aims to systematize the accumulated knowledge on EBC collection, concentration, storage, and analysis methods and compare them with similar procedures for exhaled breath (EB). We proposed a generalized chemical classification of EBC compounds that are biomarkers for various diseases. The potential transformation of substances during EB condensation was considered, and EBC analysis methods were systematically categorized based on this classification. Methods for EBC analysis using chromatographic separation with mass spectrometric detection (hyphenated methods) were separately discussed as the most promising methods for future research applications.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467256","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":"Aptamers for Brain Tumors: A Therapeutic Agent for Effectively Crossing the Blood-Brain Barrier.","authors":"Thangavel Lakshmipriya, Subash C B Gopinath","doi":"10.2174/0115665240364882250217114939","DOIUrl":"https://doi.org/10.2174/0115665240364882250217114939","url":null,"abstract":"","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457158","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 Molecular Mechanism of a Complex1-Induced Apoptosis in Cancer Cells of the Esophagus.","authors":"Zhi-Qiang Liu, Jun-Rui Luo, Xin Yao, Zhen-Hui Wang, Shuang-Ying Hao, Ming-Xue Li, Hong Zhang","doi":"10.2174/0115665240358914250217052433","DOIUrl":"https://doi.org/10.2174/0115665240358914250217052433","url":null,"abstract":"<p><strong>Background: </strong>Esophageal Cancer (EC) is a commonly occurring cancer of the digestive tract. The bismuth compounds from thiosemicarbazones have been observed to be active against cancer cells. However, a synthetic nine-coordinate bismuth (III) complex (complex 1) has never been assessed so far for its anticancer in the esophageal squamous cell carcinoma cell line (EC109).</p><p><strong>Objective: </strong>This study aimed to investigate the apoptosis effect of a complex1 in the EC109 cells.</p><p><strong>Methods: </strong>EC109 cells were treated with complex1. The MTT assay was employed to assess the viability of EC109 cells; the changes in apoptotic and morphological characteristics, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP) were examined. The expression levels of proteins associated with apoptosis were assessed using western blotting.</p><p><strong>Results: </strong>Complex1 was found to inhibit the growth of EC109 cells, exhibiting an IC50 of 0.654 μM through apoptosis depends upon complexation with bismuth(III). In addition, cells exposed to complex1 exhibited a significant increase in the level of intracellular ROS through the suppression of the antioxidant system and caused a reduction in mitochondrial membrane potential(MMP). Co-treatment with N-acetyl-Lcysteine( NAC), an antioxidant agent prevented accumulation of ROS and cell death. Complex1 also led to enhanced Bax expression, and reduced Bcl-2 expression in EC109 cells, thereby enhancing caspase-3/9 activity.</p><p><strong>Conclusion: </strong>Our study confirmed that complex1 induced apoptosis via enhancing the generation of ROS along with a decline in levels of antioxidant enzymes, subsequently causing MMP loss.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467258","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}
Mahrokh Abouali Gale Dari, Farhoodeh Ghaedrahmati, Arash Moalemnia, Mitra Ansari Dezfouli, Feryal Savari, Amir Mohammad Zamani, Behnam Ahmadi, Mohammad Nazarbeigi, Maryam Farzaneh, Mojtaba Zehtabi
{"title":"Exploring the Gut Microbiota as a Promising Target for Breast Cancer Treatment.","authors":"Mahrokh Abouali Gale Dari, Farhoodeh Ghaedrahmati, Arash Moalemnia, Mitra Ansari Dezfouli, Feryal Savari, Amir Mohammad Zamani, Behnam Ahmadi, Mohammad Nazarbeigi, Maryam Farzaneh, Mojtaba Zehtabi","doi":"10.2174/0115665240351595250213103451","DOIUrl":"https://doi.org/10.2174/0115665240351595250213103451","url":null,"abstract":"<p><p>Breast cancer is a heterogeneous disease and highly prevalent malignancy affecting women globally. Breast cancer treatments have been demonstrated to elicit significant and long-lasting effects on various aspects of a patient's life, including physical, emotional, social, and financial, highlighting the need for comprehensive cancer care. Recent research suggests that the composition and activity of the gut microbiota may play a crucial role in anticancer responses. Various compositional features of the gut microbial population have been found to influence both the clinical and biological aspects of breast cancer. Notably, the dominance of specific microbial populations in the human intestine may significantly impact the effectiveness of cancer treatment strategies. Therefore, the manipulation of the microbiota to improve the anticancer effects of conventional tumor treatments represents a promising strategy for enhancing the efficacy of cancer therapy. Emerging evidence indicates that alterations in the gut microbiota composition and activity have the potential to impact breast cancer risk and treatment outcomes. In this paper, we conduct a comprehensive investigation of various databases and published articles to explore the impact of gut microbial composition on both the molecular and clinical aspects of breast cancer. We also discuss the implications of our findings for future research directions and clinical strategies.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432665","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}
Yue Zhang, Dongmei Su, Zhaoyi Sun, Yanjiang Fu, Xiaoya Chen, Yuzhu Hu, Xiao Zhang, Shunfei Zheng, Xu Ma, Shanshan Hu
{"title":"EGCG Mitigates Apoptosis of Lens Epithelial Cells in Age-Related Cataract via the PAK1/Cleaved Caspase-3 Pathway.","authors":"Yue Zhang, Dongmei Su, Zhaoyi Sun, Yanjiang Fu, Xiaoya Chen, Yuzhu Hu, Xiao Zhang, Shunfei Zheng, Xu Ma, Shanshan Hu","doi":"10.2174/0115665240334265250213064823","DOIUrl":"https://doi.org/10.2174/0115665240334265250213064823","url":null,"abstract":"<p><strong>Background: </strong>Oxidative damage and apoptosis of lens epithelial cells (LECs) are the primary factors contributing to the development of age-related cataracts (ARC). The potential protective effects of epigallocatechin gallate (EGCG) on LECs remain unclear despite its remarkable antioxidant and anti-apoptotic properties. The aim of this study was to explore the role of serine/threonine-protein kinase (PAK1) in EGCG-mediated attenuation of H2O2-induced apoptosis of LECs in vivo and in vitro.</p><p><strong>Methods: </strong>PAK1 expression was assessed in the anterior capsule of the lens from mice and patients with and without ARC using western blotting and immunohistochemistry. Human lens epithelial B3 (HLE-B3) cells were pre-treated with EGCG+H2O2 or H2O2 only, and PAK1 expression was determined using qRT-PCR and western blotting. Apoptosis (following PAK1 overexpression or silencing) and cell survival were assessed using Hoechst 33342 staining and a cell counting Kit-8 assay, respectively. Cleaved caspase-3 was measured in transected cells, aged/young mice, and mice treated with EGCG via western blotting.</p><p><strong>Results: </strong>PAK1 expression was significantly lower in ARC LECs than in control LECs. In HLE-B3 cells, EGCG+H2O2 treatment upregulated PAK1 mRNA and protein expression when compared with H2O2 alone. PAK1 overexpression alleviated H2O2- induced apoptosis in LECs, while low expression weakened EGCG's protective effects. PAK1 overexpression reduced cleaved caspase-3 expression in H2O2-treated cells, whereas PAK1 silencing increased its expression in EGCG+H2O2-treated cells. EGCG decreased cleaved caspase-3 expression in H2O2-treated cells. These results suggest that PAK1 inhibits cleaved caspase-3 expression, thereby enhancing EGCG's attenuation of H2O2-induced LEC apoptosis.</p><p><strong>Conclusion: </strong>The PAK1/cleaved caspase-3 pathway plays a key role in EGCG's protective effects on the development of ARC. This provides a new therapeutic target for the use of EGCG in preventing and treating ARC.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413678","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}