Current molecular medicine最新文献

{"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}

{"title":"Experimental Evidence of the Benefits of Acupuncture/Electroacupuncture for Acute Lung Injury/ Acute Respiratory Distress Syndrome: A Literature Review of Rodent Studies.","authors":"Lin Zeng, Jiangtian Yan","doi":"10.2174/0115665240334516241123130753","DOIUrl":"https://doi.org/10.2174/0115665240334516241123130753","url":null,"abstract":"<p><p>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) encompass various etiologies and are distinguished by the onset of acute pulmonary inflammation and heightened permeability of the pulmonary vasculature, often leading to substantial morbidity and frequent mortality. There is a scarcity of viable approaches for treating effectively. In recent decades, acupuncture has been proven to be antiinflammatory. This review aims to provide a comprehensive summary of the previously documented mechanisms underlying the beneficial effects of acupuncture in ALI/ARDS, including inhibiting excessive oxidative stress, alleviating pulmonary inflammatory response, suppressing programmed cell death, and protecting the alveolar-capillary membrane. Collectively, these findings indicate that acupuncture yields therapeutic benefits for ALI/ARDS.</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":"143001649","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":"Mechanisms Underlying the Anti-Atherosclerotic Effects of EGCG.","authors":"Lili Wang, Chunlian Tang, Qun Pan","doi":"10.2174/0115665240354839241113044604","DOIUrl":"https://doi.org/10.2174/0115665240354839241113044604","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a chronic inflammatory vascular disease and the primary pathological basis of cardiovascular diseases. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol compound in green tea, has garnered significant attention in recent years for its protective effects against AS. EGCG possesses properties that lower lipid levels, exhibit antioxidant and anti-inflammatory activities, enhance plaque stability, and promote the recovery of endothelial function. The regulatory mechanisms of EGCG in AS primarily involve inhibiting apoptosis, modulating autophagy, improving gut microbiota, and regulating the Nrf2 and inflammatory signaling pathways. This review summarizes the role of EGCG in the prevention and treatment of AS and its potential mechanisms, providing a scientific basis for future research directions and therapeutic applications.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Overview of Invasive Ductal Carcinoma (IDC) in Women's Breast Cancer.","authors":"Adriana E Gallas, Grace O Morenikeji, Raven E King, Muyiwa S Adegbaju, Adeola Ayoola, Godstime Taiwo, Olanrewaju B Morenikeji","doi":"10.2174/0115665240349468241113065031","DOIUrl":"https://doi.org/10.2174/0115665240349468241113065031","url":null,"abstract":"<p><p>Invasive ductal carcinoma (IDC) is the most common type of breast cancer, primarily affecting women in the United States and across the world. This review summarizes key concepts related to IDC causes, treatment approaches, and the identification of biological markers for specific prognoses. Furthermore, we reviewed many studies, including those involving patients with IDC and ductal carcinoma in situ (DCIS) that progressed to IDC. We reported various studies on the causes of IDC, including mutations on BRCA1 and BRCA2, different levels of expression of specific genes in signaling pathways, menopause status, alcohol consumption, aging, and hormone imbalances that cause IDC while p-SMAD4 expressions, DNA methylation, regulations of hub genes, and underestimation of IDC affecting prognoses. Prompt IDC diagnosis and early intervention have been reported to demonstrate a greater probability of eradicating IDC and preventing further recurrence in the future. It is crucial for physicians and researchers to equip patients with the best information possible to proactively manage their health, whether it be for IDC prevention or treatment. Overall, our review provided a comprehensive understanding of IDC that enables patients to grasp the nature of the disease with the hope of mitigating IDC risk, decrease the anxiety of a cancer diagnosis, and encourage patients to become more involved in making informed decisions for their healthcare.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977983","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":"KDM4A Silencing Reverses Cisplatin Resistance in Ovarian Cancer Cells by Reducing Mitophagy via SNCA Transcriptional Inactivation.","authors":"Yan Xing, Meiya Mao, Tianhong Zhu, Hongyan Shi, Huiqing Ding","doi":"10.2174/0115665240281083241112053145","DOIUrl":"https://doi.org/10.2174/0115665240281083241112053145","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer is one of the deadliest gynecologic cancers, with chemotherapy resistance as the greatest clinical challenge. Autophagy occurrence is associated with cisplatin (DDP)-resistant ovarian cancer cells. Herein, the role and mechanism of alpha-synuclein (SNCA), the autophagy-related gene, in DDP resistance of ovarian cancer cells are explored.</p><p><strong>Methods: </strong>Differentially expressed genes in DDP resistance of ovarian cancer cells were analyzed by GEO2R tools. DDP-resistant ovarian cancer cells (A2780/DDP) were transfected and treated with 2.5 μg/mL DDP for 72 h, followed by the determination of cell viability, proliferation, apoptosis, and expressions of SNCA, lysine demethylase 4A (KDM4A), histone H3 lysine 9 trimethylation (H3K9me3), and mitophagy-related proteins. The H3K9me3 demethylation of SNCA by KDM4A was confirmed by chromatin immunoprecipitation.</p><p><strong>Results: </strong>SNCA and KDM4A were highly expressed in DDP-resistant ovarian cancer cells and their parental cells. KDM4A knockdown diminished expressions of KDM4A and SNCA and elevated H3K9me3 expression and H3K9me3 enrichment on SNCA promoter in A2780/DDP cells. SNCA or KDM4A knockdown inhibited cell viability, proliferation, and levels of LC3-II/LC3-I and Parkin while inducing cell apoptosis and upregulating Cyt-C expression of A2780/DDP cells with/without DDP treatment; however, SNCA overexpression not only did conversely but also reversed the effects of KDM4A knockdown on DDP-treated A2780/DDP cells and vice versa.</p><p><strong>Conclusion: </strong>Silencing of KDM4A-mediated transcription inactivation of SNCA reduces mitophagy, thus inhibiting the resistance of ovarian cancer cells to cisplatin. KDM4A may be a promising drug target for DDP-resistant ovarian cancer cells.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945967","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":"Cancer Stem Cell and Tumor Immune Microenvironment (TIME): Dangerous Crosstalk.","authors":"Salim Moussa","doi":"10.2174/0115665240345875241105053103","DOIUrl":"https://doi.org/10.2174/0115665240345875241105053103","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) are the key drivers of tumorigenesis and relapse. A growing body of evidence reveals the tremendous power of CSCs to directly resist innate and adaptive anti-tumor immune responses. The immunomodulatory property gives CSCs the ability to control the tumor immune microenvironment (TIME). CSCs hijack the anti-tumor capacity of immune cells to provide self-protection from immune attack and enhance the pro-tumor immune cell infiltration and activity. To date, cancer immunotherapy strategies have largely been designed without taking into account the immunosuppressive properties of CSCs. As a result, the clinical efficacy of cancer immunotherapy is altered, perpetuating tumor progression and relapse. Therefore, targeting the signals underlying CSC immune evasion is essential to improve immunotherapy efficacy and reduce tumor relapse. The aim of this mini-view is to comprehensively summarize the key immune escape mechanisms adopted by CSCs. This will provide necessary clues for the development of more effective cancer immunotherapy strategies.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946013","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":"Macrophages and Pulmonary Fibrosis.","authors":"Shengjun Chen, Xiaodong Song, Changjun Lv","doi":"10.2174/0115665240286046240112112310","DOIUrl":"https://doi.org/10.2174/0115665240286046240112112310","url":null,"abstract":"<p><p>Most chronic respiratory diseases often lead to the clinical manifestation of pulmonary fibrosis. Inflammation and immune disorders are widely recognized as primary contributors to the onset of pulmonary fibrosis. Given that macrophages are predominantly responsible for inflammation and immune disorders, in this review, we first focused on the role of different subpopulations of macrophages in the lung and discussed the crosstalk between macrophages and other immune cells, such as neutrophils, regulatory T cells, NKT cells, and B lymphocytes during pulmonary fibrogenesis. Subsequently, we analyzed the interaction between macrophages and fibroblasts as a possible new research direction. Finally, we proposed that exosomes, which function as a means of communication between macrophages and target cells to maintain cellular homeostasis, are a strategy for targeting lung drugs in the future. By comprehending the mechanisms underlying the interplay between macrophages and other lung cells, we aim to enhance our understanding of pulmonary fibrosis, leading to improved diagnostics, preventative measures, and the potential development of macrophage-based therapeutics.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945969","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":"Predictive Value and Potential of Targeting Complement Factor C3 in Patients with Renal Injury in Preeclampsia.","authors":"Chengxiang Ni, Sen Zhang, Wenpei Bai","doi":"10.2174/0115665240302343240801105324","DOIUrl":"https://doi.org/10.2174/0115665240302343240801105324","url":null,"abstract":"<p><strong>Aim: </strong>The activation of the complement system is accompanied by the occurrence and development of preeclampsia, as well as kidney diseases. Here, the role of complement C3 [C3] in renal injury in preeclampsia was explored, and its potential application as an early diagnostic biomarker or drug target to ameliorate kidney injury induced by preeclampsia was preliminarily evaluated.</p><p><strong>Method: </strong>A total of 48 subjects were included in the present study, and the complement C3 levels and renal function were analyzed.</p><p><strong>Results: </strong>Patients with preeclampsia with severe features [sPe] had poorer renal function compared with the patients with preeclampsia. Urinary C3 levels could be used to distinguish between healthy controls, patients with preeclampsia, and patients with sPe. Increased renal inflammation and oxidative stress were notably increased in the preeclampsia mice with impaired renal function and attenuation of C3 activity using a C3 receptor antagonist, which reduced Pe-like symptoms and renal impairment, decreased serum blood urea nitrogen, creatinine, and urinary albumin levels, and decreased expression of the oxidative stress marker malondialdehyde, whilst increasing superoxide dismutase activity. In addition, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 ([HO-1) pathway was involved in the inhibition of complement C3 in the kidney.</p><p><strong>Conclusion: </strong>Higher urinary C3 levels could be used to predict kidney damage as it was found that the activation of the Nrf2/HO-1 pathway attenuated C3 levels, and this resulted in increased renal impairment in preeclampsia.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946016","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}