JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"The combination of FLCWK with 5-FU inhibits colon cancer and multidrug resistance by activating PXR to suppress the IL-6/STAT3 pathway","authors":"Lifan Zhong,&nbsp;Qianru Wang,&nbsp;Zhixiong Kou,&nbsp;Lianfang Gan,&nbsp;Zhaoxin Yang,&nbsp;Junhua Pan,&nbsp;Ling Huang,&nbsp;Yunqiang Chen","doi":"10.1111/jcmm.70185","DOIUrl":"10.1111/jcmm.70185","url":null,"abstract":"<p>5-fluorouracil (5-FU) is a preferred chemotherapeutic agent for the treatment of colon cancer. Nonetheless, its clinical effectiveness is frequently hampered by suboptimal therapeutic outcomes and the emergence of drug resistance. Therefore, there exists a pressing demand for novel therapeutic agents to circumvent chemoresistance. The pregnane X receptor (PXR) exerts a pivotal regulatory influence on the proliferation, invasion, and chemoresistance mechanisms in colon cancer. Activation of PXR drives up the transcription of the multidrug resistance gene (MDR1), thus prompting the expression of P-glycoprotein (P-gp) responsible for conferring tumour resistance. This study scrutinized the potential of Fengliao Changweikang (FLCWK) in augmenting the efficacy of 5-FU in the management of colon cancer. To this end, we engineered colon cancer cells with varied levels of PXR expression via lentiviral transfection, subsequently validating the findings in nude mice. By means of MTT assays, flow cytometry apoptosis analysis, Western blotting and immunofluorescence, we probed into the prospective impacts of FLCWK and 5-FU on cellular viability and resistance. Our results revealed that while upregulation of PXR amplified the therapeutic benefits in colon cancer treatment, it concurrently heightened resistance levels. FLCWK demonstrated a capacity to reduce P-gp expression, with the combined administration of FLCWK and 5-FU effectively reversing resistance mechanisms. Furthermore, activation of PXR was found to impede the IL-6/STAT3 signalling pathway. In an effort to mimic the development of colon cancer, we established an azomethane oxide (AOM)/ dextran sodium sulfate (DSS) mouse model, showing that FLCWK bolstered the inhibitory effects of 5-FU, impeding the progression of colon cancer. In summation, our findings point towards the potential of FLCWK in the treatment of colon cancer, particularly in strengthening the therapeutic efficacy of 5-FU in the prevention and control of the disease.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 21","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal miR-155-5p promote the occurrence of carotid atherosclerosis","authors":"Wen-Wen Yang,&nbsp;Qing-Xiang Li,&nbsp;Fei Wang,&nbsp;Xin-Ran Zhang,&nbsp;Xian-Li Zhang,&nbsp;Meng Wang,&nbsp;Dong Xue,&nbsp;Ying Zhao,&nbsp;Lu Tang","doi":"10.1111/jcmm.70187","DOIUrl":"10.1111/jcmm.70187","url":null,"abstract":"<p>Periodontitis is a significant independent risk factor for atherosclerosis. Yet, the exact mechanism of action is still not fully understood. In this study, we investigated the effect of exosomes-miR-155-5p derived from periodontal endothelial cells on atherosclerosis in vitro and in vivo. Higher expression of miR-155-5p was detected in the plasma exosomes of patients with chronic periodontitis (CP) and carotid atherosclerosis (CAS) compared to patients with CP. Also, the expression level of miR-155-5p was associated with the severity of CP. miR-155-5p-enriched exosomes from HUVECs increased the angiogenesis and permeability of HAECs and promoted the expression of angiogenesis, permeability, and inflammation genes. Along with the overexpression or inhibition of miR-155-5p, the biological effect of HUVECs-derived exosomes on HAECs changed correspondingly. In ApoE−/− mouse models, miR-155-5p-enriched exosomes promoted the occurrence of carotid atherosclerosis by increasing permeable and angiogenic activity. Collectively, these findings highlight a molecular mechanism of periodontitis in CAS, uncovering exosomal miR-155-5p derived periodontitis affecting carotid endothelial cells in an ‘exosomecrine’ manner. Exosomal miR-155-5p may be used as a biomarker and target for clinical intervention to control this intractable disease in future, and the graphic abstract was shown in Figure S1.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 21","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CARD9 protein SUMOylation regulates HOXB5 nuclear translocation and Parkin-mediated mitophagy in myocardial I/R injury","authors":"Yuanbin Li,&nbsp;Yuting Tang,&nbsp;Xu Yan,&nbsp;Hui Lin,&nbsp;Wanjin Jiang,&nbsp;Luwei Zhang,&nbsp;Hu Zhao,&nbsp;Zhuang Chen","doi":"10.1111/jcmm.70195","DOIUrl":"10.1111/jcmm.70195","url":null,"abstract":"<p>Myocardial injury induced by ischemia–reperfusion (I/R) remains a difficult clinical problem. However, the exact mechanisms underlying I/R-induced have yet to be clarified. CARD9 is an important cytoplasmic-binding protein. In this study, an immunocoprecipitation assay showed that SUMOylation of the CARD9 protein promoted the binding of CARD9 to HOXB5, but hindered the O-GlcNAc glycosylation of HOXB5, a predicted transcription factor of Parkin and a key factor in mitophagy. O-GlcNAc glycosylation is an important signal for translocation of proteins from the cytoplasm to the nucleus. CARD9 protein SUMOylation is regulated by PIAS3, which is related to I/R-induced myocardial injury. Therefore, we propose that knockdown of PIAS3 inhibits SUMOylation of the CARD9 protein, facilitates the dissociation of CARD9 and HOXB5, which increases the O-GlcNAc-mediated glycosylation of HOXB5, while the resulting HOXB5 nuclear translocation promotes Parkin-induced mitophagy and alleviates myocardial I/R injury.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 21","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibiting YAP1 reduced abdominal aortic aneurysm formation by suppressing adventitial fibroblast phenotype transformation and migration","authors":"Cuiping Xie,&nbsp;Yanting Hu,&nbsp;Zhehui Yin","doi":"10.1111/jcmm.70159","DOIUrl":"10.1111/jcmm.70159","url":null,"abstract":"<p>The adventitial fibroblast (AF) is the most abundant cell in the vascular adventitia, a few studies had confirmed that AF contributed to abdominal aortic aneurysm (AAA) development; YAP1 involved in several vascular diseases by promoting AF transformed to myofibroblast, the role of YAP1 in AAA is not clear yet. This study aims to determine whether YAP1 play a role in AAA process by regulating AF function. We found the expression of YAP1was significantly increased in aneurysm tissues of AAA patients compared to normal adjacent vascular tissues and mainly in adventitia. YAP1 also upregulated in elastase-induced and CaCl₂-induced mice AAA model. Suppressed YAP1 function with YAP1 inhibitor-Verteporfin declined AAA incident rate remarkably in mice, and the collagen deposition in the adventitia was alleviated obviously. Afterwards, we studied the effect of YAP1 on the function of AF, Verteporfin was used to block YAP1 in vitro, the process of AF transforming to myofibroblast and migration were almost completely eliminated after inhibiting YAP1 expression. This study demonstrated that YAP1 may play a key role in AAA development, inhibiting YAP1 significantly reduced AAA formation through suppressed the process of AF transformed to myofibroblast and migration.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 21","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Up-regulation of HOXA-AS2 and MEG3 long non-coding RNAs acts as a potential peripheral biomarker for bipolar disorder","authors":"Maryam Hosseini,&nbsp;Mohammad Javad Mokhtari","doi":"10.1111/jcmm.70150","DOIUrl":"10.1111/jcmm.70150","url":null,"abstract":"<p>Bipolar disorder (BD) is a psychiatric condition that is frequently misdiagnosed and linked to inadequate treatment. Long non-coding RNAs (lncRNAs) have lately gained recognition as crucial genetic elements and are now regarded as regulatory mechanisms in the neurological system. Our objective was to measure the quantities of HOXA-AS2 and MEG3 ncRNA transcripts. HOXA-AS2 and MEG3 ncRNA levels were checked in the peripheral blood of 50 type I BD and 50 control samples by real-time PCR. Furthermore, we conducted ROC curve analysis and correlation analysis to examine the association between gene expression and specific clinical characteristics in instances with BD. Additionally, a computational study was performed to investigate the binding sites of miRNAs on the HOXA-AS2 and MEG3 lncRNAs. BD subjects showed a significant increase in the expression of HOXA-AS2 and MEG3 compared to controls. The lncRNAs HOXA-AS2 and MEG3 have an area under the ROC curve (AUC) values of 0.70 and 0.71, respectively. There was a significant correlation between the expression levels of ncRNAs HOXA-AS2 and MEG3 in the peripheral blood of patients with BD and occupation scores. The data presented indicate a potential correlation between the expression of HOXA-AS2 and MEG3 lncRNAs with an elevated risk of BD. Furthermore, these lncRNAs may be linked to several molecular pathways. Our findings indicate that the amounts of lncRNAs HOXA-AS2 and MEG3 in transcripts might be a promising potential biomarker for patients with BD.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 21","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “The marine-derived furanone reduces intracellular lipid accumulation in vitro by targeting LXRα and PPARα”","authors":"","doi":"10.1111/jcmm.70108","DOIUrl":"10.1111/jcmm.70108","url":null,"abstract":"<p>Li T, Hu SM, Pang XY, et al. The marine-derived furanone reduces intracellular lipid accumulation in vitro by targeting LXRα and PPARα. <i>J Cell Mol Med</i>. 2020;24:3384-3398. doi:10.1111/JCMM.15012</p><p>In Ting Li et al., several incorrect images were used in Figure 3B. The correct figure is shown below. The related fluorescent images were shown in the Supporting Information. The authors confirm all results and conclusions of this article remain unchanged.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 21","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NAT10-mediated RNA ac4C acetylation contributes to the myocardial infarction-induced cardiac fibrosis","authors":"Jun Li,&nbsp;Feierkaiti Yushanjiang,&nbsp;Zhao Fang,&nbsp;Wan-li Liu","doi":"10.1111/jcmm.70141","DOIUrl":"10.1111/jcmm.70141","url":null,"abstract":"<p>Cardiac fibrosis is featured cardiac fibroblast activation and extracellular matrix accumulation. Ac4C acetylation is an important epigenetic regulation of RNAs that has been recently discovered, and it is solely carried out by NAT10, the exclusive enzyme used for the modification. However, the potential regulatory mechanisms of ac4C acetylation in myocardial fibrosis following myocardial infarction remain poorly understood. In our study, we activated fibroblasts in vitro using TGF-β1 (20 ng/mL), followed by establishing a myocardial infarction mouse model to evaluate the impact of NAT10 on collagen synthesis and cardiac fibroblast proliferation. We utilized a NAT10 inhibitor, Remodelin, to attenuate the acetylation capacity of NAT10. In the cardiac fibrosis tissues of chronic myocardial infarction mice and cultured cardiac fibroblasts (CFs) in response to TGF-β1 treatment, there was an elevation in the levels of NAT10 expression. This increase facilitated proliferation, the accumulation of collagens, as well as fibroblast-to-myofibroblast transition. Through the administration of Remodelin, we effectively reduced cardiac fibrosis in myocardial infarction mice by inhibiting NAT10's ability to acetylate mRNA. Inhibition of NAT10 resulted in changes in collagen-related gene expression and ac4C acetylation levels. Mechanistically, we found that NAT10 upregulates the acetylation modification of BCL-XL mRNA and enhances the stability of BCL-XL mRNA, thereby upregulating its protein expression, inhibiting the activation of Caspase3 and blocking the apoptosis of CFs. Therefore, the crucial involvement of NAT10-mediated ac4C acetylation is significant in the cardiac fibrosis progression, affording promising molecular targets for the treatment of fibrosis and relevant cardiac diseases.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 21","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal effect of gut microbiota on juvenile idiopathic arthritis: A two-sample Mendelian a randomization study","authors":"Lian Zhang,&nbsp;Zhihua Yang,&nbsp;LuLu Zhang,&nbsp;Yanwen Wei,&nbsp;Lisheng Wan","doi":"10.1111/jcmm.70183","DOIUrl":"https://doi.org/10.1111/jcmm.70183","url":null,"abstract":"<p>There is increasing evidence of a significant association between the gut microbiome and juvenile idiopathic arthritis (JIA). However, whether this association is causal remains to be determined. This study was a two-sample Mendelian randomization (MR) study using publicly available genome-wide association study (GWAS) summary data to investigate the causal relationship between the gut microbiome and JIA. We used summary data on gut flora and JIA obtained from genome-wide association studies (GWAS) from MiBioGen and NHGRI-EBI, using inverse variance weighting as the main method to analyse causality in the TSMR causality analysis. To check the stability of the TSMR results, we performed several sensitivity analyses and assessed the presence of reverse causality through a reverse TSMR analysis. We calculated the degree of sample overlap where applicable. The current TSMR analyses identified four bacterial taxa associated with JIA. Specifically, two bacteria, Catenibacterium (<i>p</i> = 2 × 10–2) and Holdemania (<i>p</i> = 4 × 10–2), were negatively associated with the risk of developing JIA, suggesting a protective effect, while Olsenella (<i>p</i> = 1 × 10–2) and Rikenellaceae (RC9gutgroup) (<i>p</i> = 1 × 10–2) were positively associated with the risk of JIA, suggesting that these two bacteria may be risk factors for JIA. However, the results for Catenibacterium and Holdemania should be interpreted with caution due to instability observed in ‘leave-one-out’ sensitivity analyses. Reverse TSMR analyses found no evidence of reverse causality between JIA and gut flora. Our confirmation of a causal relationship between gut flora and JIA provides an innovative perspective for the study of JIA: targeting and modulating dysregulation of specific bacterial taxa to prevent and treat JIA.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 20","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pairwise analysis of gene expression for oral squamous cell carcinoma via a large-scale transcriptome integration","authors":"Nan Li,&nbsp;Zunkai Hu,&nbsp;Ning Zhang,&nbsp;Yining Liang,&nbsp;Yating Feng,&nbsp;Wanfu Ding,&nbsp;Lixin Cheng,&nbsp;Yuyan Zheng","doi":"10.1111/jcmm.70153","DOIUrl":"10.1111/jcmm.70153","url":null,"abstract":"<p>Among all cancers occurring in the head and neck region, oral squamous cell carcinoma (OSCC) is the most common oral malignant tumours characterized by its aggressiveness and metastasis. The development of transcriptomics technology has greatly facilitated the diagnosis of various cancers. However, identifying genetic biomarkers is limited by data from a single batch of OSCC samples, and integrating analysis across different platforms remains a great challenge. In this study, we integrated five OSCC transcriptome datasets using an innovative strategy capable of mitigating batch effect, and extracting information from different datasets based on changes in the relative expression of gene pairs. By leveraging a machine learning method, we developed a prediction model including 27 differential gene pairs (DGPs) to discriminate OSCC from control samples, achieving an area under the receiver operating characteristic curve (AUC) of 0.8987 for the training set. Moreover, the model demonstrated commendable performance in four external validation sets, with AUCs of 0.9926, 0.9688, 0.8052 and 0.8565, respectively. Subsequently, a prognostic model was constructed based on six key gene pairs through univariate and multivariate Cox regression analysis. The AUCs of the model at 1-year and 3-year overall survival time prediction were 0.717 and 0.779 in an independent dataset. Our result demonstrates the effectiveness of this new method of integrating data and identifying DGPs. Using DGPs can significantly improve the performance of both diagnostic and prognostic models.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 20","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal association of circulating inflammatory proteins on neurodegenerative diseases: Insights from a mendelian randomization study","authors":"Wenwen Lin,&nbsp;Xuewei Wu,&nbsp;Guanyong Ou","doi":"10.1111/jcmm.70176","DOIUrl":"10.1111/jcmm.70176","url":null,"abstract":"<p>Neuroinflammation is increasingly recognized as a pivotal factor in the development and progression of neurodegenerative disorders. While correlations between inflammatory cytokines and these diseases are documented, the definitive causal dynamics remain to be elucidated. We explored the causal association between 91 circulating inflammatory cytokines and Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Parkinson's disease (PD) through Mendelian randomization analysis. Leveraging genetic variants from the most comprehensive genome-wide association studies (GWAS) available for these cytokines, AD, ALS, MS and PD, we sought to uncover the causality. Our study validated a causal influence of genetically determined cytokine levels on the susceptibility to AD, with notable cytokines including C-X-C motif chemokine 1 (OR = 0.9993, <i>p</i> = 0.0424), Interleukin-18 (OR = 0.9994, <i>p</i> = 0.0186), Leukaemia inhibitory factor receptor (OR = 0.9993, <i>p</i> = 0.0122) and Monocyte chemoattractant protein-1 (OR = 0.9992, <i>p</i> = 0.0026) in risk attenuation. Additionally, a positive causal relationship was identified between two cytokines—C-C motif chemokine 19 (OR = 1.0005, <i>p</i> = 0.0478) and Fms-related tyrosine kinase 3 ligand (OR = 1.0005, <i>p</i> = 0.0210)—and AD incidence. Conversely, transforming growth factor-alpha (OR = 0.8630, <i>p</i> = 0.0298), CD40L receptor (OR = 0.7737, <i>p</i> = 1.1265E-09) and Interleukin-12 subunit beta (OR = 0.8987, <i>p</i> = 0.0333) showed inverse associations with ALS, MS and PD, respectively. The consistency observed in various MR analyses, alongside sensitivity analysis, underscored the absence of horizontal pleiotropy, thus supporting our causal findings. This study reveals, for the first time, a genetically anchored causal nexus between levels of circulating inflammatory cytokines and the risk of neurodegenerative diseases.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 20","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}