Current molecular medicine最新文献

{"title":"Elucidating the Causal Dynamics between Inflammatory Proteins and Atrial Fibrillation Risk Through Bidirectional Mendelian Randomization.","authors":"Yuan Lv, Bin Huang, Liyin Xu, Xianjun Wu","doi":"10.2174/0115665240347233250119190837","DOIUrl":"https://doi.org/10.2174/0115665240347233250119190837","url":null,"abstract":"<p><strong>Background: </strong>Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with significant morbidity and mortality. Inflammation has been implicated in the pathogenesis of AF, but the causal relationship between specific inflammatory proteins and AF risk is not well established. This study aims to clarify this relationship using a bidirectional two-sample Mendelian Randomization (TSMR) approach.</p><p><strong>Methods: </strong>Employing a bidirectional Mendelian Randomization (MR) method, we analyzed genetic variants as instrumental variables (IVs) to investigate the influence of 91 circulating inflammatory proteins on AF risk. This approach allowed us to assess the potential causal effects of inflammatory proteins on AF and vice versa, thus providing a comprehensive understanding of the bidirectional nature of their relationship.</p><p><strong>Results: </strong>Seven inflammatory proteins were significantly associated with AF risk. Three proteins increased the risk: Fibroblast Growth Factor 5 (FGF-5) with an odds ratio (OR) of 1.0743 (95% CI: 1.0466-1.1027, p=7.41E-08), Tumor Necrosis Factor (TNF) with an OR of 1.0832 (95% CI: 1.0261-1.1434, p=0.0038), and Interleukin-2 Receptor Subunit Beta (IL-2RB) with an OR of 1.0814 (95% CI: 1.0151-1.1519, p=0.0153). Four proteins showed a protective effect: CD40 Ligand Receptor (CD40) with an OR of 0.9671 (95% CI: 0.9392-0.9959, p=0.0254), Fms-related Tyrosine Kinase 3 Ligand (FIt3L) with an OR of 0.9553 (95% CI: 0.9173-0.9949, p=0.0274), Leukemia Inhibitory Factor Receptor (LIF-R) with an OR of 0.9254 (95% CI: 0.8678- 0.9868, p=0.0181), and Sulfotransferase 1A1 (ST1A1) with an OR of 0.9461 (95% CI: 0.9097-0.9839, p=0.0056). The reverse MR analysis revealed no significant effects of AF on the levels of these inflammatory proteins, suggesting a unidirectional causality from proteins to AF.</p><p><strong>Conclusion: </strong>This bidirectional MR study provides robust evidence for a causal relationship between specific inflammatory proteins and AF risk. The identified proteins could serve as potential biomarkers for AF risk stratification and targets for therapeutic intervention, offering new insights into the pathophysiology of AF and avenues for future research.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001679","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 the AP1 Transcription Factor FOSL1 to Assess the Exacerbation of Psoriasis.","authors":"Vladimir Sobolev, Anna Soboleva, Ksenia Katkova, Elena Denisova, Olga Zhukova, Nikolay Potekaev, Luiza Sakanyia, Irina Korsunskaya, Alexandre Mezentsev","doi":"10.2174/0115665240343441241231102305","DOIUrl":"https://doi.org/10.2174/0115665240343441241231102305","url":null,"abstract":"<p><strong>Background: </strong>The transcription factor AP1 plays a crucial role in the proliferation, apoptosis, and terminal differentiation of epidermal keratinocytes.</p><p><strong>Objective: </strong>This study aimed to clarify whether the subunit of AP1, FOSL1 protein, can be used to assess the exacerbation of psoriasis by evaluating its changes in protein and mRNA levels in cultured epidermal keratinocytes and skin specimens of the patients prescribed with bathwater PUVA (Psoralen and UVA) therapy. This study aimed to investigate FOSL1, a subunit of the transcription factor AP-1, as a potential biomarker for psoriasis by examining its protein and mRNA expression in skin specimens from patients undergoing bathwater PUVA (Psoralen and UVA) therapy and cultured epidermal keratinocytes.</p><p><strong>Methods: </strong>The distribution of FOSL1 in patients' skin was explored by immunohistochemistry. Changes in gene and protein expression were quantitatively assessed by qPCR and ELISA, respectively.</p><p><strong>Results: </strong>Immunohistochemistry analysis revealed that FOSL1 accumulated in lesional skin. The expression of FOSL1 significantly increased during disease flare-ups but decreased following the treatment with bathwater PUVA therapy. Furthermore, silencing FOSL1 led to a marked reduction in the expression of ten FOSL1 target genes associated with the disease.</p><p><strong>Conclusion: </strong>Our study suggests that FOSL1 shows potential as a biomarker for psoriasis. This is supported by two key findings: first, the expression of FOSL1 correlates with disease activity, and second, its expression is linked to changes in the expression of genes previously implicated in the pathogenesis of psoriasis, namely MMP1, MMP9, IVL, CCNA2, CCL2, HMOX1, PLAU, PLAUR, and THBD.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001701","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":"Association between Sputum Culture Conversion and Body Mass Index among Multidrug-Resistant Tuberculosis Patients in Punjab, Pakistan: A Multicenter Retrospective Study.","authors":"Abdul Majeed Akhtar, Iqra Hamid Khan, Fatima Iftikhar Shah, Shamsa Kanwal, Sufia Majeed, Najeeb Ullah, Somia Shehzadi, Asmat Ullah","doi":"10.2174/0115665240342370241230194338","DOIUrl":"https://doi.org/10.2174/0115665240342370241230194338","url":null,"abstract":"<p><strong>Background: </strong>The global challenge of Multidrug-resistant Tuberculosis (MDR-TB) presents a substantial public health concern, requiring extended and complex treatment regimens. Understanding the factors impacting treatment results, particularly sputum culture conversion and Body Mass Index (BMI), is crucial. This retrospective cohort investigation conducted in Punjab, Pakistan, sought to explore the correlation between BMI and sputum culture conversion in individuals diagnosed with MDR-TB.</p><p><strong>Material and methodology: </strong>Data from 2663 confirmed MDR-TB patients across multiple Programmatic Management of Drug-Resistant Tuberculosis PMDT sites in Punjab, Pakistan, were retrospectively analyzed. Demographic and clinical characteristics, BMI, comorbidities, previous TB treatments, and drug resistance were evaluated. Cox proportional hazards regression models were employed to assess the association between time to sputum culture conversion and patient characteristics.</p><p><strong>Results: </strong>The study compared MDR-TB treatment outcomes based on BMI categories (≥18.5 vs. <18.5 Kg/m^2). It involved 1626 employed patients, with a mean age of 33 ± 15 years, displaying baseline body weights averaging 48±7 kg (normal weight) and 37±6 kg (underweight). On average, sputum culture conversion occurred at four months, with approximately 37% achieving conversion within this period. Among several factors studied, the univariate analysis identified BMI <18.5 Kg/m^2, prior firstline drug treatment, and comorbidities as significantly associated with failure to achieve sputum culture conversion within 6 months. In multivariate analysis, the inability to achieve conversion was notably linked to BMI <18.5 Kg/m^2, previous first-line drug treatment, and resistance to fluoroquinolone drugs.</p><p><strong>Conclusion: </strong>This study provided valuable insights into sputum culture conversion, BMI, and drug resistance among MDR-TB patients. While around half of the patients achieved sputum culture conversion within six months, factors, such as comorbidities, previous TB treatment, and drug resistance, significantly influenced treatment outcomes.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001675","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":"MicroRNA-130b Is a Unique Autophagy-Related Epigenetic Predictor of FLOT-Chemotherapy in Gastric Cancers.","authors":"Liudmila V Spirina, Alina B Zinnurova, Olga V Bakina, Alexandra V Avgustinovich, Sergey G Afanas'ev, Maxim Yu Volkov, Tatyana S Klyushina, Alexandr M Volkov, Natalia V Tarasenko, Nadezhda V Masunova","doi":"10.2174/0115665240336458241217161009","DOIUrl":"https://doi.org/10.2174/0115665240336458241217161009","url":null,"abstract":"<p><strong>Introduction: </strong>Liquid biopsies have great potential for precision medicine as they provide information about primary and metastatic tumors using minimally invasive techniques. MicroRNAs (miRNAs) are promising biomarkers for detecting gastric cancer (GC). The aim of the study was to identify miR molecules associated with autophagy in gastric cancer (GC) cells, determine their expression levels in GC and FLOT-treated patients, and assess the efficacy of FLOT therapy in GC patients.</p><p><strong>Methods: </strong>Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathways were used to analyze cellular pathways. MicroRNAs were isolated from the tissues.</p><p><strong>Results: </strong>The study found a connection between the expression of the let-7a-5p gene and the size of primary tumors. Bioinformatics analysis identified multiple targets and signaling pathways associated with this phenomenon. We observed an increase in the levels of miR-21-3p and hsa-miR-130b-3p with lymph node involvement. miR-21-3p is associated with the activation of molecular pathways induced by H. pylori in cases of coinfection. Patients with complete regression had higher levels of expression of hsamir- 130b-3p.</p><p><strong>Conclusion: </strong>The bioinformatics analysis allowed us to identify the most significant targets among microRNAs. Based on the presented data, it becomes clear that GC is heterogeneous and that the process of autophagy is complex. The association between hsa-miR-130b-3p and tumor response to therapy is particularly interesting.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001658","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":"LncRNA-DANCR: A Key Player in Colorectal Cancer Development and Progression.","authors":"Omid Anbiyaee, Farhoodeh Ghaedrahmati, Shirin Azizidoost, Safa Radmehr, Maryam Farzaneh, Abdolah Mousavi Salehi","doi":"10.2174/0115665240339328241217184041","DOIUrl":"https://doi.org/10.2174/0115665240339328241217184041","url":null,"abstract":"<p><p>Colorectal Cancer (CRC) is a significant global health issue, being the third most common cancer worldwide and the second most frequent cause of cancerrelated deaths. It occurs when cells in the colon or rectum grow uncontrollably, often developing from precancerous polyps. Genetic predisposition and environmental factors, such as diet and lifestyle, contribute to the disease. Recent research has focused on molecular targeted therapies and non-coding RNAs, particularly long noncoding RNAs (lncRNAs), which play a critical role in regulating CRC development and progression. DANCR interacts with microRNAs, proteins, and mRNAs, influencing gene expression and stability. DANCR functions as a promoter of tumor growth, invasion, metastasis, proliferation, migration, apoptosis, disease progression, and prognosis in various cancers. In CRC, DANCR influences both progression and clinical outcomes. This review aims to comprehensively explore the current knowledge regarding DANCR in CRC, including its molecular characteristics, expression patterns, and involvement in regulatory mechanisms, as well as its potential use as a diagnostic, prognostic, and therapeutic tool.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001652","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":"Thymoquinone-PLGA-PF68 Nanoparticles Induce S Phase Cell Cycle Arrest and Apoptosis, Leading to the Inhibition of Migration and Colony Formation in Tamoxifen-Resistant Breast Cancer Cells.","authors":"Nurul Shahfiza Noor, Shahrul Bariyah Sahul Hamid","doi":"10.2174/0115665240347014241203065055","DOIUrl":"https://doi.org/10.2174/0115665240347014241203065055","url":null,"abstract":"<p><strong>Background: </strong>A biocompatible polymeric nanoparticle, TQ-PLGA-PF68, was developed through the interaction of the phytochemical thymoquinone (TQ) encapsulated in poly(L-lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-PEG) with Pluronics F68. So far, this combination has not been assessed on breast cancer cells resistant to anti-cancer drugs. Therefore, this study aimed to assess the cell death caused by TQ-PLGA-PF68 nanoparticles, particularly in resistant breast cancer cell lines expressing estrogen receptor (ER) positivity, such as TamR MCF-7.</p><p><strong>Methods: </strong>The antiproliferative activity of TQ-PLGA-PF68 nanoparticles was measured using the MTS assay. The cytotoxic effects were further evaluated through colony formation assay and scratch-wound healing assay. Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assay was performed to determine the characteristics of the apoptosis as well as cell cycle arrest induced by TQ-PLGA-PF68 nanoparticles. The localization of these nanoparticles in the cells was examined using Transmission Electron Microscopy (TEM).</p><p><strong>Results: </strong>With a TQ concentration of 58.5 μM encapsulated within the nanoparticles, cytotoxicity analysis revealed a significant inhibition of cell proliferation (p<0.05). This finding was corroborated by the results of the colony formation assay. Treatment with TQ-PLGA-PF68 nanoparticles significantly decreased the number of surviving TamR MCF-7 cells by 35% (p<0.001) compared to untreated TamR MCF-7 cells. Concurrently, the scratch-wound healing assay indicated a closure rate of 50% versus >80% (p<0.05) in untreated TamR MCF-7 cells at 12 hours post-wounding. The TUNEL assay successfully confirmed the apoptosis characteristics associated with cell cycle arrest. TEM observation confirmed the cellular internalization of these nanoparticles, suggesting the in vitro therapeutic potential of the formulation.</p><p><strong>Conclusion: </strong>In this study, a significant functional change in TamR MCF-7 cells induced by the TQ nanoparticles was observed. The unique incorporation of TQ into the PLGA-PEG and Pluronics F68 formulation preserved its bioactivity, thereby reducing the migratory and proliferative traits of drug-resistant cells. This discovery may pave the way for exploring the application of biocompatible polymeric TQ nanoparticles as a novel therapeutic approach in future studies pertaining to resistant breast cancer.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001695","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":"Reversal of Mucin 1 Reduction-Induced Enterocyte Apoptosis by Retinoic Acid through the PI3K/AKT Signaling Pathway in an In vitro Model of Necrotizing Enterocolitis.","authors":"Qian Su, Li Chen, Yanzhen Xu, Jinxing Feng, Jialin Yu, Zhaoxia Zhang, Zhangbin Yu, Dong Liu","doi":"10.2174/0115665240337176241204070150","DOIUrl":"https://doi.org/10.2174/0115665240337176241204070150","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the roles of Mucin 1 (MUC1), the PI3K/AKT pathway, and enterocyte apoptosis in Necrotizing Enterocolitis (NEC).</p><p><strong>Methods: </strong>Using an NEC Caco-2 cell model, retinoic acid treatment and MUC1 gene silencing were employed. Flow cytometry was used to assess apoptosis, while quantitative PCR and western blot analyses were conducted to evaluate the gene and protein expressions of MUC1, PI3K, Akt, and factors related to apoptotic modulation.</p><p><strong>Results: </strong>In comparison to the control group, NEC induction resulted in a significant reduction in MUC1 expression, accompanied by an elevation in enterocyte apoptosis. In NEC and Si-MUC1 Caco-2 cells, downregulation of PI3K/AKT signals and Bcl-2 was observed, while upregulation of Bax, CytoC, and Caspase 3 at both mRNA and protein levels was prominent. Retinoic acid supplementation exhibited a noteworthy increase in MUC1, AKT, and Bcl-2 mRNA and protein expressions, coupled with a decrease in Bax, CytoC, and Caspase 3, thereby mitigating apoptosis in NEC.</p><p><strong>Conclusion: </strong>Our findings suggested that reduced MUC1 expression in NEC contributes to the upregulation of enterocyte mitochondrial apoptosis through the PI3K/AKT signaling pathway. Retinoic acid supplementation emerges as a potential therapeutic strategy for NEC, demonstrating its ability to upregulate MUC1 expression and attenuate apoptosis via the PI3K/AKT signaling pathway.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Analysis of the Role of PAX9 in Head and Neck Squamous Cell Carcinoma.","authors":"Lang Zeng, Wenjing Yun, Wen-Long Luo","doi":"10.2174/0115665240328109241205084841","DOIUrl":"https://doi.org/10.2174/0115665240328109241205084841","url":null,"abstract":"<p><strong>Background: </strong>Paired box 9 (PAX9) has been linked to several human disorders; however, its relevance in Head And Neck Squamous Cell Carcinoma (HNSCC) remains unknown.</p><p><strong>Methods: </strong>The difference in PAX9 mRNA expression in pan-cancer was analyzed utilizing The Cancer Genome Atlas (TCGA), and the level of PAX9 protein expression across various types of cancer was assessed utilizing the Human Protein Atlas (HPA) and UALCAN databases, as well as the cellular localization of PAX9. UALCAN studied the methylation levels of PAX9 in pan-cancer. The predictive significance of PAX9 in pan-cancer was assessed utilizing the Kaplan-Meier Plotter website. Functional enrichment analysis was carried out with the \"cluster Profiler\" program. By employing CCK8 and colony formation methods, the influence of PAX9 on the growth of HNSCC cells was evaluated. By conducting a transwell experiment, we assessed the influence of PAX9 on the migration of HNSCC cells. Western blotting was used to determine the levels of Bax and Bcl-2, two proteins involved in the regulation of apoptosis. A nude mouse model was established to study the impact of PAX9 overexpression on the growth of subcutaneous HNSCC tumors.</p><p><strong>Results: </strong>In HNSCC, the expression of PAX9 was found to be low, while levels of promoter methylation rose considerably. Low PAX9 expression has been linked to a decrease in overall survival (OS) rates among individuals with HNSCC. Furthermore, overexpressing the PAX9 gene decreased HNSCC cell proliferation, migration, and invasion while boosting apoptosis rates.</p><p><strong>Conclusion: </strong>The abnormal expression of PAX9 is linked to various cancers. In HNSCC, PAX9 is a potential tumor suppressor, inhibiting tumor invasion and migration. The results reveal a potentially significant new therapeutic target for HNSCC.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001588","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":"Ag85B-Induced M1 Macrophage Polarization via the TLR4/TRAF6/NF-κB Axis Leading to Bronchial Epithelial Cell Damage and TH17/Treg Imbalance.","authors":"Lei Zhou, Li Luo, Linzi Luo, Hailong Luo, Yan Ding, Zhibin Lu, Yangbao Xiao","doi":"10.2174/0115665240319773241204073135","DOIUrl":"https://doi.org/10.2174/0115665240319773241204073135","url":null,"abstract":"<p><strong>Background: </strong>Antigen 85B (Ag85B) is a signature antigen of Mycobacterium tuberculosis (MTB). In this study, we aimed to investigate the impact of macrophages stimulated with Ag85B on bronchial epithelial cells and T cells, as well as the underlying mechanisms involved.</p><p><strong>Methods: </strong>We used Ag85B to stimulate macrophage and investigated the impact of Ag85B on macrophage polarization. We assessed the impact of TLR4 on Ag85Bmediated macrophage polarization by silencing TLR4. Additionally, the regulatory role of TLR4 on the TRAF6/NF-κB pathway was evaluated through immunoblotting. Activated macrophages with Ag85B were co-cultured with bronchial epithelial cells and T cells, respectively. Through immunoblotting quantification, biochemical methods, and flow cytometry, we explored the effects and molecular mechanisms of Ag85B-induced macrophage activation on bronchial epithelial cell damage and T-cell transformation.</p><p><strong>Results: </strong>In macrophages stimulated with Ag85B, levels of M1 polarization-related genes (CXCL9, CXCL10, and iNOS) and cytokines (IL-6, TNF-α, IL-1β, and IL-12) were increased, and the M1/M2 ratio was elevated. TLR4 silence inhibited the effects of Ag85B on macrophages and decreased TRAF6 and p-NF-κB/NF-κB levels. TRAF6 overexpression reversed the inhibitory effect of TLR4 on macrophage stimulation with Ag85B. After co-culturing with macrophages induced by Ag85B, MBEC cell proliferation was inhibited, apoptosis was promoted, and the TH17/Treg ratio of T cells was increased. Silencing TLR4 reversed the impact of Ag85B-induced macrophage polarization on bronchial epithelial cells and T cells, which was further reversed by TRAF6 overexpression.</p><p><strong>Conclusion: </strong>Ag85B promoted M1 polarization in macrophages through the TLR4/TRAF6/NF-κB axis, resulting in bronchial epithelial cell damage and an imbalance in TH17/Treg cells.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001589","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":"Morphine-Induced Elevation of Reactive Oxygen Species Attenuates Chemotherapy Efficacy in Diverse Cancer Cell Types.","authors":"Gong Chen, Si Zeng, Bin Wang, Daguo Wang, Jie Ding, Tao Feng","doi":"10.2174/0115665240314564241129044548","DOIUrl":"https://doi.org/10.2174/0115665240314564241129044548","url":null,"abstract":"<p><strong>Background: </strong>Morphine, a mu-opioid receptor (MOR) agonist commonly utilized in clinical settings alongside chemotherapy to manage chronic pain in cancer patients, has exhibited contradictory effects on cancer, displaying specificity toward certain cancer types and doses.</p><p><strong>Objective: </strong>The aim of this study was to conduct a systematic assessment and comparison of the impacts of morphine on three distinct cancer models in a preclinical setting.</p><p><strong>Methods: </strong>Viability and apoptosis assays were conducted on a panel of cancer cell lines following treatment with morphine, chemotherapy drugs alone, or their combination. Oxidative stress levels, along with the activities of superoxide dismutase and catalase, were measured. Rescue studies were also carried out using antioxidant reagents.</p><p><strong>Results: </strong>Morphine induces resistance to conventional chemotherapeutic agents. It was observed that while morphine affected cell viability differently among ovarian cancer, anaplastic thyroid cancer, and oral squamous cell carcinoma, at concentrations that did not directly impact cancer cell viability, it significantly mitigated the inhibitory effects of chemotherapeutic agents across all tested cancer cells. This phenomenon persisted irrespective of the chemotherapeutic agent used, including cisplatin, doxorubicin, and 5-FU. It remained unaffected by adding naloxone, the MOR receptor antagonist, indicating that morphine's mechanism is independent of the μ- opioid receptor. Moreover, it was demonstrated that morphine heightened cellular reactive oxygen species (ROS) levels and suppressed the activities of superoxide dismutase and catalase. Rescue studies revealed that the addition of antioxidant reversed the protective impact of morphine on cancer cells against chemotherapy.</p><p><strong>Conclusion: </strong>These findings hold promise in potentially guiding the clinical application of morphine for cancer patients undergoing chemotherapy.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001684","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}