International Journal of Medical Sciences最新文献

{"title":"Telomeres and telomerase in Sarcoma disease and therapy.","authors":"Jin Huang, Yan Feng, YangJing Shi, Weilin Shao, Genshan Li, Gangxian Chen, Ying Li, Zuozhang Yang, Zhihong Yao","doi":"10.7150/ijms.97485","DOIUrl":"10.7150/ijms.97485","url":null,"abstract":"<p><p>Sarcoma is a rare tumor derived from the mesenchymal tissue and mainly found in children and adolescents. The outcome for patients with sarcoma is relatively poor compared with that for many other solid malignant tumors. Sarcomas have a highly heterogeneous pathogenesis, histopathology and biological behavior. Dysregulated signaling pathways and various gene mutations are frequently observed in sarcomas. The telomere maintenance mechanism (TMM) has recently been considered as a prognostic factor for patients with sarcomas, and alternative lengthening of telomeres (ALT) positivity has been correlated with poor outcomes in patients with several types of sarcomas. Therefore, telomeres and telomerases may be useful targets for treating sarcomas. This review aims to provide an overview of telomere and telomerase biology in sarcomas.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel \"Endocrine Hormone\": The Diverse Role of Extracellular Vesicles in Multiorgan Insulin Resistance.","authors":"Fangzhi Xu, Lin Dou, Dongni Yu, Xi Wu, Longteng Liu, Yong Man, Xiuqing Huang","doi":"10.7150/ijms.97217","DOIUrl":"10.7150/ijms.97217","url":null,"abstract":"<p><p>Insulin resistance is the primary contributor to the disruption in glucose homeostasis in the body, playing a significant causative role in many metabolic diseases. Insulin resistance is characterized by compensatory insulin secretion and reduced insulin responsiveness in target organs. Dysregulation of the interaction between insulin-secreting cells and insulin-responsive target organs is an important factor driving the progression of insulin resistance. Circulating endocrine hormones are important mediators mediating the interaction between insulin-secreting cells and insulin-responsive target organs. In addition to the classical hormones secreted by endocrine glands and organ-specific hormones secreted by metabolism-related organs (adipose tissue, muscle, liver, etc.), extracellular vesicles have been recognized as a novel class of endocrine hormones with a complex composition. Extracellular vesicles can transport signaling molecules, such as miRNAs and LncRNAs, to vital organs related to insulin resistance, in a manner akin to conventional hormones. The significant role in regulating the development of insulin resistance underscores the increasing interest in extracellular vesicles as essential contributors to this process. In this review, we summarize the three types of hormones (classical hormones, organokines and extracellular vesicles) that play a regulatory role in insulin resistance, and focus on the novel endocrine hormones, extracellular vesicles, to elaborate the mechanism of extracellular vesicles' regulation of insulin resistance progress from two aspects: the impact on insulin-secreting cells and the influence on insulin-responsive target organs. In addition, this paper outlines the clinical applications of extracellular vesicles in insulin resistance. A comprehensive understanding of the regulatory mechanisms and diagnostic status of the inter-organ network in insulin resistance has great potential to advance targeted therapeutic interventions and diagnostic markers, thereby benefiting both the prevention and treatment of insulin resistance.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MS4A1-PTGS2 axis induces taurine metabolic reprogramming to exacerbate abdominal aortic aneurysm progression.","authors":"Xuejun Sun, Chaoxiang Du, Ye Chen, Zhibin Cai, Liangwan Chen","doi":"10.7150/ijms.99659","DOIUrl":"10.7150/ijms.99659","url":null,"abstract":"<p><p>This study unveils the pivotal roles of taurine metabolic reprogramming and its implications in the development and progression of Abdominal Aortic Aneurysm (AAA). Leveraging an integrated approach that combines single-cell RNA sequencing (scRNA-seq) and Weighted Gene Co-expression Network Analysis (WGCNA), our research investigates the intricate transcriptional and gene expression dynamics crucial to AAA. Our findings uniquely link metabolic shifts to the integrity of the extracellular matrix (ECM) and the functionality of smooth muscle cells (SMCs), key elements in the pathology of AAA. Utilizing scRNA-seq data from a mouse model (GSE152583 dataset), we identified critical alterations in cellular composition during AAA progression, particularly highlighting shifts in fibroblasts and inflammatory cells. Concurrently, WGCNA of human AAA tissue samples has outlined distinct gene expression patterns correlated with disease severity and progression, offering comprehensive insights into both molecular and cellular disease mechanisms. Moreover, this study introduces innovative metabolic profiling techniques to identify differential metabolites in AAA, integrating extensive metabolomic analyses with pathway enrichment strategies. This novel approach has pinpointed potential biomarkers and therapeutic targets, notably within taurine metabolism pathways, crucial for crafting non-surgical interventions. By merging state-of-the-art bioinformatics with thorough molecular analysis, our study not only enhances the understanding of AAA's complex pathophysiology but also catalyzes the development of targeted therapeutic strategies. This research represents a significant advancement in the molecular characterization of AAA, with substantial implications for its future diagnosis and treatment strategies.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aspirin Inhibits Colorectal Cancer via the TIGIT-BCL2-BAX pathway in T Cells.","authors":"Jiayu Liu, Qiunan Zhou, Kai Meng, Xiaojuan Yang, Bin Ma, Chunxia Su, Xiangguo Duan","doi":"10.7150/ijms.98343","DOIUrl":"10.7150/ijms.98343","url":null,"abstract":"<p><p>The T cell immunoglobulin and ITAM domain (TIGIT) is a recently discovered synergistic co-suppressor molecule that plays an important role in immune response and tumor immune escape in the context of cancer. Importantly, CD155 acts as a receptor for TIGIT, and CD155 signaling to immune cells is mediated through interactions with the co-stimulatory immune receptor CD226 (DNAM-1) and the inhibitory checkpoint receptors TIGIT and CD96. Aspirin (ASA) has been shown to reduce the growth and survival of colorectal cancer (CRC) cells, but the immunological mechanisms involved have not been sufficiently elucidated. In the present study the effects of aspirin on CRC in mice and on Jurkat cells were investigated. Aspirin may suppress the expression of TIGIT on T cells and Regulatory T cells (Tregs) and inhibit T cell viability, and therefore induce tumor cell apoptosis. TIGIT is expressed at higher levels on infiltrating lymphocytes within CRC tumor tissue than adjacent. Further, aspirin could inhibit Jurkat cell proliferation and induce apoptosis via downregulation of TIGIT expression and the anti-apoptosis B cell lymphoma 2 (BCL2) protein and upregulation of BCL2-associated X protein (BAX) expression. The present study suggests that aspirin can inhibit specific aspects of T cell function by reducing interleukin-10 and transforming growth factor-β1 secretion via the TIGIT-BCL2-BAX signaling pathway, resulting in improved effector T cell function that inhibits tumor progression.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous iron supplementation in pulmonary hypertension groups 1 to 4.","authors":"Leonie Biener, Josna Kohli, Vanessa Marggraf, Georg Nickenig, Dirk Skowasch, Carmen Pizarro","doi":"10.7150/ijms.92904","DOIUrl":"10.7150/ijms.92904","url":null,"abstract":"<p><p><b>Background:</b> Iron deficiency (ID) is common in patients with pulmonary arterial hypertension and has been associated with increased morbidity and mortality. We aimed to evaluate the therapeutic effects of iron supplementation in iron deficient patients with group 1 to 4 pulmonary hypertension (PH). <b>Methods:</b> A total of 85 PH patients (mean age 69.8 ± 12.0 years, 56.5% female) were included in this prospective trial. Patients were screened for ID at baseline. PH patients with ID received intravenous iron supplementation (500-1000 mg ferric carboxymaltose). PH patients without ID served as control group. At baseline and 16-week follow up, six-minute walk test (6MWT), laboratory testing and echocardiography were performed. Additionally, World Health Organization (WHO) functional class, fatigue score and quality of life (QoL) by the SF-36 questionnaire were assessed. <b>Results:</b> Overall, ID was present in 26.7% (n=8/30), 37.5% (n=9/24), 45.5% (n=10/22) and 44.4% (n=4/9) of patients in PH groups 1-4, respectively. In the total study population, iron restoration led to a significant mitigation of fatigue (p=0.01). However, 6MWT, WHO function class, NT-proBNP levels, QoL and right ventricular function did not change significantly. With regard to the underlying PH group, only PH group 3 patients experienced significant improvements in 6MWT distance (p=0.019), WHO functional class (p=0.017), fatigue (p=0.009) and some QoL domains, as compared to controls. <b>Conclusions:</b> ID was common in PH groups 1 to 4. Though intravenous iron supplementation adequately restored iron status and improved fatigue throughout all patients, in the underlying PH groups treatment was accompanied by improvements in exercise capacity, WHO function class and fatigue only in group 3 PH.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of long-term effects of pelvic radiotherapy on the function of bone marrow in recurrent cervical cancer patients.","authors":"Boer Deng, Weimin Kong, Chao Han, Chunxiao Zhou, Jing Li, Dan Song, Yuxuan Lin","doi":"10.7150/ijms.95900","DOIUrl":"10.7150/ijms.95900","url":null,"abstract":"<p><p><b>Purpose:</b> To study the effects of prior pelvic radiotherapy on bone marrow suppression in recurrent cervical cancer patients during chemotherapy. <b>Methods and materials:</b> The cases of 129 patients with recurrent cervical cancer were reviewed, of which 77 patients had pelvic radiotherapy history and another 52 patients with no pelvic radiotherapy history were used as control group. All patients received a chemotherapy regimen of paclitaxel combined with carboplatin (TC) per 21 days for 5-6 times. Hematologic toxicity, including count of red blood cell, white blood cell and neutrophil cell and platelet, was defined by using Common Terminology Criteria for Adverse Events (version 4.0). The relationship between age, body mass index, disease free survival, pathological types, FIGO stages, radiotherapy methods and the degree of bone marrow suppression during chemotherapy was statistically analyzed, respectively, for all recurrent cervical cancer patients. <b>Results:</b> Among 77 patients with previous radiotherapy history, 73 recurrent patients (94.8%) had bone marrow suppression followed by chemotherapy. Recurrent cervical cancer patients without prior radiotherapy (n=52) showed a lower risk of bone marrow suppression followed by chemotherapy (n=39, 75.0%, P < 0.05). The probability of severe bone marrow suppression (grade III-IV) after chemotherapy in recurrent cervical patients with or without history of radiotherapy was 41.6% and 13.5%, respectively (P < 0.05). In univariate analysis, radiotherapy methods were associated with the incidence of grade III-IV bone marrow suppression in recurrent cervical cancer patients (P=0.005). In multivariate analysis, radiotherapy methods and extended-field radiotherapy were the risk factor of grade III-IV bone marrow suppression (χ²=16.975, P=0.001). No significant differences in the counts of white blood cell, hemoglobin and platelet were observed before chemotherapy at relapse between patients with and without prior radiotherapy. Reduction of white blood cell counts, absolute value of neutrophil cell and platelet counts composited majority type of grade III and IV bone marrow suppression. <b>Conclusions:</b> The prior pelvic radiotherapy significantly increased the incidence of bone marrow suppression during chemotherapy in recurrent cervical cancer patients. When treating recurrent cervical cancer patients with chemotherapy who had prior radiotherapy, especially for those experienced external beam radiation therapy, essential attention and timely intervention are recommended to ensure completion of chemotherapy and clinical efficacy.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Common and Key Differential Pathogenic Pathways in Desminopathy and Titinopathy.","authors":"Qiuxiang Li, Liqun Xu, Huiqian Duan, Huan Yang, Yue-Bei Luo","doi":"10.7150/ijms.97797","DOIUrl":"10.7150/ijms.97797","url":null,"abstract":"<p><p>Myofibrillar myopathy (MFM) is a group of hereditary myopathies that mainly involves striated muscles. This study aimed to use tandem mass tag (TMT)-based proteomics to investigate the underlying pathomechanisms of two of the most common MFM subtypes, desminopathy and titinopathy. Muscles from 7 patients with desminopathy, 5 with titinopathy and 5 control individuals were included. Samples were labelled with TMT and then underwent high-resolution liquid chromatography-mass spectrometry analysis. Compared with control samples, there were 436 differentially abundant proteins (DAPs) in the desminopathy group and 269 in the titinopathy group. When comparing the desminopathy with the titinopathy group, there were 113 DAPs. In desminopathy, mitochondrial ATP production, muscle contraction, and cytoskeleton organization were significantly suppressed. Activated cellular components and pathways were mostly related to extracellular matrix (ECM). In titinopathy, mitochondrial-related pathways and the cellular component ECM were downregulated, while gluconeogenesis was activated. Direct comparison between desminopathy and titinopathy revealed hub genes that were all involved in glycolytic process. The disparity in glycolysis in the two MFM subtypes is likely due to fiber type switching. This study has revealed disorganization of cytoskeleton and mitochondrial dysfunction as the common pathophysiological processes in MFM, and glycolysis and ECM as the differential pathomechanism between desminopathy and titinopathy. This offers a future direction for targeted therapy for MFM.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effectiveness of Hyperbaric Oxygen Treatment in Patients with Complex Regional Pain Syndrome: A Retrospective Case series.","authors":"Michal Hájek, Dittmar Chmelař, Jakub Tlapák, Miloslav Klugar","doi":"10.7150/ijms.97513","DOIUrl":"10.7150/ijms.97513","url":null,"abstract":"<p><p><b>Background:</b> Complex regional pain syndrome (CRPS) presents as persistent regional pain, both spontaneous and triggered. The demand persists for innovative treatments that patients can endure with minimal adverse effects. Hyperbaric oxygen therapy (HBOT) emerges as a possible intervention in this regard. <b>Methods:</b> The main objective of this work is to retrospectively analyse a case series of patients diagnosed with CRPS treated in the Centre of Hyperbaric Medicine Ostrava over two years (period 2018-2019). The HBOT was applied at 2.0-2.4 absolute atmosphere (ATA) once a day. <b>Results:</b> A total of 83 patients with CRPS were treated with HBOT. 98% of cases reported pain, 92% reported limitation of movement of the affected limb, 87% had swelling of the limb, 41% had lividity and 70% had sensory problems. The mean number of HBOT exposures was 22.0 ± 7.1. At the end of HBOT treatment, 86% of cases had symptoms relief. The mean VAS value of pain at rest before the start of HBOT was 3.2±3.0, after treatment it was 1.6±1.9 (p<0.001). In a pain at activity it was 6.1±2.4 and 3.7±2.4 (p<0.001), respectively, at the end of HBOT. The value of the functional assessment of the limb was 7.0±2.0 and 4.3±2.4 (p<0.001), respectively, at the end of treatment. 79 cases were included in the end-of-treatment assessment. 23 cases (29%) were evaluated as large clinically significant response, 48 cases (61%) were evaluated as partial response with minimally important difference. The results showed larger clinical HBOT effect in cases of disease duration up to 3 and 6 months (p=0.029). <b>Conclusions:</b> The majority of patients improved pain and functional state of the affected limb. Our data also suggests the sooner after diagnosis of CRPS is HBOT started, the treatment has larger clinical effect. There was no serious HBOT-related complication or injury.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of different levels of physical activity on arterial stiffness and physical fitness performance in firefighters.","authors":"Chun-Hao Chang, Yi-Ju Hsu, Chih-Hsien Huang","doi":"10.7150/ijms.96269","DOIUrl":"10.7150/ijms.96269","url":null,"abstract":"<p><p><b>Background:</b> Firefighters have lower levels of physical activity while on call. It is critical to understand the impact of firefighters' physical activity on arterial stiffness. This study classified groups by physical activity level and combined peripheral vascular monitor measurement to explore the relationships between the level of physical activity and cardiovascular (CV) risk and physical fitness (PF) of firefighters, as well as the acute response to arterial stiffness (AS) following maximal aerobic exercise test (MAET) intervention. <b>Methods:</b> The International Physical Activity Questionnaire (IPAQ) was used to classify the participants into 3 groups: low, moderate, and high level of physical activity group, respectively. A total of 36 participants were recruited, 12 in each group. Participants were assessed for body composition, rest brachial-ankle pulse wave velocity (baPWV), handgrip strength (HGS), maximal oxygen uptake (V̇O_2max), and MAET baPWV. <b>Results:</b> In the three groups, significant differences were observed in V̇O_2max, HGS, relative fat mass (%FM), body mass index (BMI), muscle mass ratio (MMR), and Rest baPWV (<i>p</i> < 0.05). After maximal aerobic exercise, the MAET baPWV values decreased significantly in all groups (all <i>p</i> < 0.001). Rest baPWV was significantly correlated with firefighters' age, seniority, metabolic equivalents (METs), height and muscle mass (MM) (<i>p</i> < 0.05). <b>Conclusions:</b> Firefighters with high levels of physical activity had better body composition and physical fitness and lower Rest baPWV. In all three groups, baPWV was lower after the MAET than before it. Therefore, regardless of a firefighter's level of physical activity, high-intensity aerobic exercise may have a beneficial effect on arterial stiffness.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RBM15 activates glycolysis in M1-type macrophages to promote the progression of aortic aneurysm and dissection.","authors":"Mi Tang, Min Wang, Zhirong Wang, Bo Jiang","doi":"10.7150/ijms.97185","DOIUrl":"10.7150/ijms.97185","url":null,"abstract":"<p><p>Aortic aneurysm and dissection (AD) represent a critical cardiovascular emergency with an alarmingly high mortality rate. Recent research has spotlighted the overexpression of genes associated with the m6A modification in AD patients, linking them to the presence of inflammatory M1-type macrophages. Moreover, glycolysis is widely recognized as a key feature of inflammatory M1-type macrophages, but biomarkers linking glycolysis and macrophage function to promote disease progression in AD have not been reported. We conducted an analysis of aortic immune cell infiltration, macrophages, and m6A-related biomarkers in AD patients using bioinformatics techniques. Subsequently, we employed a combination of RT-PCR, WB, and immunofluorescence assays to elucidate the alterations in the expression of M1- and M2-type macrophages, as well as markers of glycolysis, following the overexpression of key biomarkers. These findings were further validated <i>in vivo</i> through the creation of a rat model of AD with knockdown of the aforementioned key biomarkers. The findings revealed that the m6A-modified related gene RBM15 exhibited heightened expression in AD samples and was correlated with macrophage polarization. Upon overexpression of RBM15 in macrophages, there was an observed increase in the expression of M1-type macrophage markers CXCL9 and CXCL10, alongside a decrease in the expression of M2-type macrophage markers CCL13 and MRC1. Furthermore, there was an elevation in the expression of glycolytic enzymes GLUT1 and Hexokinase, as well as HIF1α, GAPDH, and PFKFB3 after RBM15 overexpression. Moreover, <i>in vivo</i> knockdown of RBM15 led to an amelioration of aortic aneurysm in the rat AD model. This knockdown also resulted in a reduction of the M1-type macrophage marker iNOS, while significantly increasing the expression of the M2-type macrophage marker CD206. In conclusion, our findings demonstrate that RBM15 upregulates glycolysis in macrophages, thus contributing to the progression of AD through the promotion of M1-type macrophage polarization. Conversely, downregulation of RBM15 suppresses M1-type macrophage polarization, thereby decelerating the advancement of AD. These results unveil potential novel targets for the treatment of AD.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}