Endocrine, metabolic & immune disorders drug targets最新文献

{"title":"Immunocytes Play a Crucial Role as Mediators in the Protective Effects of D-β-Hydroxybutyrate Dehydrogenase 1 against Type 2 Diabetes Mellitus: A Mendelian Randomization Study.","authors":"Yi-Ying Liu, Yue-Yang Zhang, Qin Wan","doi":"10.2174/0118715303380282250225071730","DOIUrl":"https://doi.org/10.2174/0118715303380282250225071730","url":null,"abstract":"<p><strong>Background: </strong>Observational studies suggest an association between the immune system and type 2 diabetes. The present study sought to ascertain the causal relationship between BDH1 and type 2 diabetes and investigate whether immunocytes mediate this relationship.</p><p><strong>Methods: </strong>Appropriate single nucleotide polymorphisms (SNPs) were carefully selected from publicly available GWAS databases based on rigorous criteria to ensure the validity of the Mendelian randomization (MR) analysis. Inverse variance weighting (IVW) was employed as the primary approach for assessing effect sizes, supplemented by four sensitivity analysis techniques: weighted median, simple mode, weighted mode, and MR-Egger regression tests, all aimed at ensuring the robustness and reliability of the IVW results. Reverse MR was conducted to confirm the feasibility of the mediation analysis. Lastly, Cochran's Q test, MR Egger intercept regression, and MR-PRESSO analysis were utilized to examine heterogeneity and horizontal pleiotropy.</p><p><strong>Results: </strong>The expression of BDH1 is inversely associated with the risk of type 2 diabetes, with an odds ratio of 0.97 (95% CI: 0.95-0.99). IgD+ CD38+ B cell absolute count (20.7%), HLA DR on dendritic cell (18.7%), BAFF-R on CD20- CD38- B cell (9.5%), CD25 on IgD+ CD24+ B cell (4.1%), and BAFF-R on IgD+ B cell (3.4%), all exhibit certain mediating effects, whereas IgD+ CD38+ B cell absolute count, activated and resting CD4 regulatory T cell %, CD4+ T cell, transitional B cell absolute count, CD28- CD8 dim T cell absolute count, CD45 on HLA DR+ CD8+ T cell, FSC-A on HLA DR+ natural killer, and SSC-A on plasmacytoid dendritic cell exert masking effects.</p><p><strong>Conclusion: </strong>The findings indicate that immunocytes could serve as a crucial mediating mechanism through which BDH1 exerts its protective effect against type 2 diabetes, offering novel insights for the prevention and therapeutic management of the disease.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of Nitrogen Metabolism-Related Prognostic Signatures for Forecasting Bladder Cancer Prognosis.","authors":"Hongtao Cheng, Yuhong Li, Shuyu Shen","doi":"10.2174/0118715303371907250514054016","DOIUrl":"https://doi.org/10.2174/0118715303371907250514054016","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer is one of the major health threats worldwide, and aberrant regulation of nitrogen metabolism is closely related to its development. Understanding the role of nitrogen metabolism-related genes in BC is pivotal for the development of new therapeutic strategies and prognostic assessment.</p><p><strong>Aim and objectives: </strong>This study aimed to explore the prognostic factors associated with nitrogen metabolism in bladder cancer (BC) and to construct a prognostic model.</p><p><strong>Methods: </strong>Differential expression gene analysis was performed to identify genes associated with nitrogen metabolism by analyzing mRNA expression data from BC patients. The prognostic relationship between these genes and BC patients was analyzed using univariate Cox regression. One hundred one combinatorial machine learning methods were applied for feature selection, and key prognostic genes were identified based on the method with the highest combined score. Immunocyte infiltration analysis was carried out to assess the tumor microenvironmental characteristics of patients in different risk groups.</p><p><strong>Results: </strong>Twenty-five genes significantly associated with prognosis were identified from nitrogen metabolism-related genes. Twenty-three most prognostically predictive signature genes were screened under feature screening with multiple machine-learning models. Immune cell infiltration analysis showed that patients in the high-risk group had significantly different immune cell infiltration, suggesting that these genes may influence BC progression by regulating immune escape mechanisms. These results provide new biomarkers and potential therapeutic targets for precision treatment and prognostic assessment of BC.</p><p><strong>Conclusion: </strong>The expression patterns of nitrogen metabolism-related genes identified can be used as effective biomarkers for bladder cancer prognosis, providing a scientific basis for personalized treatment. Future studies can further explore the specific biological functions and mechanisms of action of these genes to promote more effective clinical applications.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on Immune Characteristics and Gene Polymorphisms of Hypertension Patients.","authors":"Xin Wei, Zhongxin Wang, Yigui Tang, Lu Tian, Yuanhong Xu, Meijuan Zheng","doi":"10.2174/0118715303365110250209092351","DOIUrl":"https://doi.org/10.2174/0118715303365110250209092351","url":null,"abstract":"<p><strong>Objective: </strong>Hypertension seriously endangers the health of patients. We studied the immune characteristics and gene polymorphisms of hypertension patients.</p><p><strong>Methods: </strong>Forty-six hypertension patients (including 19 isolated hypertension patients without other diseases (IHP) and 27 complicated hypertension patients with related complications (CHP) and 28 healthy individuals (HCs) were recruited in this study. Immune cells and cytokines were detected by flow cytometry, immunoglobulins (Ig) were detected by immunoturbidimetry, and hormones were detected by chemiluminescence. Besides, gene polymorphisms were detected by PCR.</p><p><strong>Results: </strong>Compared with HCs, the frequency and counts of circulating B cells increased significantly, while CD56dim natural killer (NK) cells decreased significantly in hypertension patients. The frequency and counts of circulating double positive T (DPT) cells increased significantly in IHP patients, while double negative T (DNT) cells decreased significantly in CHP patients as compared with HCs. Hormones and cytokines expression in hypertension patients increased significantly as compared with HCs. B cells were positively correlated with ACTH expression and strongly associated with hypertension. However, high ACTH levels can inhibit IgM expression in CHP patients. Besides, some CHP patients had gene polymorphisms in statins and antihypertensive drug metabolism, which may require individualized adjustments to drug use.</p><p><strong>Conclusion: </strong>This study found the immune characteristics and gene polymorphisms of hypertension patients, which may provide new ideas and a theoretical basis for the prevention and treatment of hypertension.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Serum Osteocalcin and Cardiometabolic Risk Factors in Latent Autoimmune Diabetes in Adults: Insights from Glutamic Acid Decarboxylase Subgroup Analysis.","authors":"Xiuli Fu, Zihui Xu, Jinlin Xu, Qin Tan, Zhongjing Wang","doi":"10.2174/0118715303364381250428100830","DOIUrl":"https://doi.org/10.2174/0118715303364381250428100830","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to explore the association between serum osteocalcin and cardiometabolic risk factors in latent autoimmune diabetes in adults (LADA).</p><p><strong>Background: </strong>Patients with LADA tend to experience poorer glycaemic control, placing them at a higher risk of cardiovascular disease.</p><p><strong>Objective: </strong>This study aimed to explore the relationship between osteocalcin levels and cardiometabolic risk factors, such as HbA1c, lipids, insulin resistance and obesity, in patients with LADA.</p><p><strong>Method: </strong>This retrospective study included 110 patients suffering from LADA with high glutamic acid decarboxylase (GAD) levels (≥180 IU/ml) and 286 with low GAD levels (<180 IU/ml) between January 2018 and December 2021. All participants were aged ≥30 years. Blood samples, collected after 8 hours of fasting, were analysed for osteocalcin and other biomarkers using chemiluminescence immunoassay. Logistic regression analysis assessed the relationship between osteocalcin and cardiometabolic risk factors.</p><p><strong>Results: </strong>The LADA^high group had a lower body mass index (19.5 vs 23.4 kg/m², p = 0.014) and a lower proportion of obesity (19.1% vs 25.2%, p = 0.001) compared with the LADA^low group. Participants in the LADA^high group were slightly older (58.7 vs 58.3 years, p = 0.641). Fasting blood glucose was higher (8.9 vs 8.4 mmol/l, p = 0.068), and C-peptide was lower (1.0 vs 1.8 ng/ml, p = 0.024). Osteocalcin levels were significantly lower in the LADA^high group (12.19 vs 13.96 ng/ml, p = 0.004). Subgroup analyses revealed significant correlations, such as those between osteocalcin and HbA1c in the LADA^low group and an inverse relationship with triglyceride in men from the LADA^high group. Logistic regression analysis indicated that lower osteocalcin levels were significantly associated with a higher risk of poor glycaemic control and increased obesity.</p><p><strong>Conclusion: </strong>Lower osteocalcin levels in patients with LADA with high GAD are associated with worse cardiometabolic parameters and increased cardiovascular risk. Osteocalcin may be a potential marker for assessing cardiometabolic risk in patients with LADA.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EphrinB2 Ameliorates Renal Fibrosis by Inhibiting the TGF-β/Smad3 Signaling Pathway and the Inflammation Response.","authors":"Cheng Yuan, Qiuyuan Zhou, Feng Chen, Xueyun Gao, Ayinigaer Yusufu, Xiaoyan Wu, Lihua Ni","doi":"10.2174/0118715303366454250507042518","DOIUrl":"https://doi.org/10.2174/0118715303366454250507042518","url":null,"abstract":"<p><strong>Background: </strong>EphrinB2 is known to play a variety of roles in the pathological process of fibrosis in the heart, skin, and retina, according to current research. However, the role of Ephrin- B2 in renal fibrosis remains to be clarified.</p><p><strong>Objective: </strong>We aimed to investigate the role of EphrinB2 in the renal fibrosis model and its underlying mechanisms.</p><p><strong>Materials and methods: </strong>Unilateral ureteral obstruction (UUO) models and TGF-β-treated renal tubular epithelial cells (HK2) were adopted in this study to determine if EphrinB2 could lead to renal fibrosis.</p><p><strong>Results: </strong>EphrinB2 was highly expressed in renal tubular cells in UUO mice. Using adeno-associated virus (AAV)-mediated EphrinB2 overexpression, we observed significant improvements in renal function and injury, as well as a marked reduction in fibrosis. For example, EphrinB2 overexpression decreased the expression of fibrosis markers such as Fibronectin and α-SMA by approximately 40%. In vitro, EphrinB2 also significantly reduced extracellular matrix (ECM) deposition and cellular fibrosis under TGF-β stimulation. Mechanistically, EphrinB2 inhibited TGF-β/Smad3 signaling by approximately 40%, and reduced inflammatory markers such as MCP1 and IL-1β by approximately 60% and 35%, respectively.</p><p><strong>Conclusions: </strong>This study uncovered a previously unrecognized anti-fibrotic role of EphrinB2 in renal fibrosis, which is achieved through the prevention TGF-β/Smad3 signaling and inflammation response. It seemed that EphrinB2 might be a promising therapeutic target in the treatment of fibrotic diseases and kidney failure.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA Sequencing Analysis Reveals the Regulatory Functions of Copines Family Genes in Testicular Cancer Progression.","authors":"Nan Li, Kai Yu, Delun Huang, Xuehong Zhu, Zhong Lin","doi":"10.2174/0118715303375462250430055914","DOIUrl":"https://doi.org/10.2174/0118715303375462250430055914","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The aim of this study is to investigate the expression patterns and regulatory functions of Copines family genes in different cellular subpopulations in testicular cancer based on single-cell data and to analyze the regulatory mechanism of Copines family genes in cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Testicular cancer is a frequently diagnosed male tumor. Emerging evidence suggests that Copines family genes are implicated in a variety of cancer phenotypes and cancer progression. Analyzing the expression pattern of Copines family genes in testicular cancer may help improve the treatment efficacy of the cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study sought to characterize the expression profiles of Copines family genes in the cellular subpopulations of testicular cancer and to identify key signaling pathways through which they regulate cancer progression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Based on single-cell transcriptomic data of testicular cancer, we classified testicular cancer cell subpopulations and analyzed the expressions of Copines family genes in each subpopulation. Cell subpopulations were grouped according to the expression levels of Copines family genes, and differentially expressed Copines family genes between the groups were screened by differential expression analysis. Functional enrichment analysis on the differentially expressed genes (DEGs) was performed with a clusterprofiler package. Functional pathways enriched by the Copines family genes were calculated by AUCell enrichment score. Copy number variation (CNV) analysis was performed using inferCNV to analyze gene mutation patterns across cellular subpopulations, and pseudotime analysis was conducted using Monocle to infer cellular differentiation pathways of cellular subpopulations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Single-cell clustering identified four major cell subpopulations, namely, NK/T cells, tumor cells, B cells, and macrophages. Notably, the control samples had a relatively small proportion of tumor cells. Further clustering of the tumor cells identified six cell subpopulations, among which multiple Copines genes, especially CPNE1 and CPNE3, showed a high expression. The testicular cancer samples were grouped by the expression patterns of Copines genes, and the DEGs between groups included GNLY, MGP1, GFD2, CCL21, SPARCL13 as well as some other genes involved in the malignant progression of cancer. Pseudotime analysis showed that the upregulated genes were enriched in cell migration and PI3K-Akt pathway, while the downregulated genes were related to immunity. This indicated that the Copines genes regulated the cellular heterogeneity and malignant transformation in testicular cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study revealed the potential molecular mechanism through which Copines family genes drove the progression of testicular cancer through regulating PI3K-Akt signaling pathway and cell cycle, providing a new target for the development of pr","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge Gaps in Patients Undergoing Thyroid Fine-Needle Aspiration Biopsy.","authors":"Mustafa C Şenoymak, Nisa Babacanlar, Nuriye H Erbatur, Ferrat Deniz, Arif Yönem","doi":"10.2174/0118715303364657250415115259","DOIUrl":"https://doi.org/10.2174/0118715303364657250415115259","url":null,"abstract":"<p><strong>Background: </strong>Fine-needle Aspiration Biopsy (FNAB) is the most accurate diagnostic method to assess the malignancy risk of thyroid nodules. This study aims to assess the level of knowledge among patients regarding thyroid FNAB and its outcomes and to explore how this knowledge correlates with their sociodemographic and clinical characteristics.</p><p><strong>Methods: </strong>In a cross-sectional study at a tertiary healthcare facility's endocrinology and metabolism outpatient clinic, participants who had undergone their first thyroid FNAB and attended the clinic to review their results were included. Data collection encompassed demographic information, clinical history, and sonographic features of thyroid nodules. Patient knowledge was assessed using a 6-item questionnaire that evaluated awareness of the indications for thyroid FNAB, potential diagnostic outcomes, and the likelihood of a repeat biopsy.</p><p><strong>Results: </strong>A total of 423 patients participated in this study, with the majority being female (83.7%). The median age was 54 years. The indication for the biopsy was correctly identified by 68.5% of participants. Awareness of the potential for benign (85.1%) and malignant (84.6%) results was high. However, only 20.4% were informed about non-diagnostic outcomes and 16.6% about indeterminate results. Furthermore, 34.1% understood the need for a repeat biopsy. Participants under 65 years of age demonstrated significantly higher knowledge regarding the reason for the biopsy and the potential for benign or malignant results (p < 0.001). Participants with at least a high school education (38.1%) were more knowledgeable about all aspects of FNAB compared to those with lower educational levels (p < 0.05). Patients with a history of non-thyroidal malignancy (5.7%) demonstrated significantly greater understanding of non-diagnostic and indeterminate results (p < 0.001).</p><p><strong>Conclusion: </strong>The study reveals substantial knowledge gaps, particularly in understanding thyroid FNAB and its outcomes. Thus, targeted educational interventions are necessary to enhance patient comprehension and improve clinical outcomes.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Stigma Toward Fatty Liver Disease.","authors":"Yasser Fouad, Alaa M Mostafa, Ziyan Pan, Shaymaa Nafady, Hany Samir Rasmy, Shaker Wagih Shaltout, Dalia Hassan, Mohamed Alboraie, Mohammed Eslam","doi":"10.2174/0118715303359141250420070406","DOIUrl":"https://doi.org/10.2174/0118715303359141250420070406","url":null,"abstract":"<p><strong>Background and aims: </strong>A recent Delphi statement proposed an adapted term from metabolic dysfunction-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD), substituting \"fatty\" with \"steatotic\", as the former was claimed to be stigmatizing. In this cross-sectional study, we aimed to investigate this and understand stigma and awareness among fatty liver disease patients.</p><p><strong>Methods: </strong>A semi-structured interview consisting of questions was carried out with patients to get an understanding of their knowledge of fatty liver disease and their opinions on the terminology used for its diagnosis.</p><p><strong>Results: </strong>Surveys were completed by 222 fatty liver disease patients in a written questionnaire. Out of the participants, only 84 (37.8%) and 37 (16.7%) of patients believed that cirrhosis or hepatocellular carcinoma might result from fatty liver disease, while 82 (36.9%), 87 (39.2%), and 52 (23.4%) of patients thought fatty liver was connected to diabetes or cardiovascular disease. 189 individuals (85.1%) said that including the word \"alcohol\" in the name of a condition carries a stigma. Conversely, 177 (79.7%) of participants said that they do not consider the term \"fatty\" to be stigmatizing. Additionally, the degree of awareness of the disease's consequences seems very low. 159 (71.9%) and 180 (81.1%) participant expressed their lack of knowledge on how the disease can be diagnosed or treated, respectively, and 146 (65.8%) of the participants showed a desire to acquire knowledge about the impact of fatty liver disease on their well-being and health.</p><p><strong>Conclusions: </strong>A part of our concern about fatty liver disease awareness without trivialization. The use of the word \"fat\" in the nomenclature of fatty liver disease linked with metabolic dysfunction is not perceived to be stigmatizing. The suggested change to MASLD does not seem warranted, at least if the stigma is the main concern.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD27 and GZMK as Co-Biomarkers in Rheumatoid Arthritis and Crohn's disease and Mediate Immune Imbalance.","authors":"Li Zheng, Yong Zeng, Miao Fang, Hongquan Heng, Ying Luo, Jie Zhong","doi":"10.2174/0118715303372365250421114853","DOIUrl":"https://doi.org/10.2174/0118715303372365250421114853","url":null,"abstract":"<p><strong>Background: </strong>Studies have found similar immune responses, genetic susceptibility, and inflammatory mediators between Rheumatoid arthritis (RA) and Crohn's disease (CD), but these findings are controversial.</p><p><strong>Methods: </strong>The Gene Expression Omnibus (GEO) was utilized to get microarray data. Differentially expressed genes (DEGs) in individuals with CD and RA were identified. Weighted gene co-expression network analysis (WGCNA) was used to identify key modular genes in CD and RA. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to identify hub genes. The correlation between immune cell infiltration and common biomarkers was examined by utilizing the GSEA and ssGSEA.</p><p><strong>Results: </strong>CD27 and GZMK were recognized as co-biomarkers in RA and CD. The analysis of immune infiltration revealed a significant relationship between a range of immune cells, including CD8 T cell, MDSC, and natural killer T cell, and both RA and CD.</p><p><strong>Conclusion: </strong>CD27 and GZMK are biomarkers shared by CD and RA and are potential diagnostic and therapeutic targets for them, especially in patients with CD combined with RA. CD and RA are highly associated with dysregulation of the acquired immune response system and imbalance of the innate immune system.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Esketamine Reduces Lung Injury Caused by Limb Ischemia-Reperfusion by Regulating Oxidative Stress <i>via</i> the TLR4/NF-κB/NLRP3 Pathway.","authors":"Meng Wang, Qian Ma, Wenjuan Wang, Jiawei Cun, Heng Wen","doi":"10.2174/0118715303393744250423100211","DOIUrl":"https://doi.org/10.2174/0118715303393744250423100211","url":null,"abstract":"<p><strong>Background: </strong>Esketamine has shown promise in mitigating tissue damage caused by ischemia- reperfusion injury, making it a potential therapeutic candidate for acute lung injury (ALI) induced by limb ischemia-reperfusion (LIR-ALI).</p><p><strong>Objective: </strong>This study sought to explore the role and mechanism of esketamine in the LIR-ALI rat model.</p><p><strong>Methods: </strong>The effects of esketamine on the LIR-ALI rats model were evaluated through histopathological examination, assessment of pulmonary edema, measurement of MDA and SOD levels, and analysis of inflammatory cytokine levels (IL-1β, etc.) in the bronchoalveolar fluid (BALF) and serum. Western blot analysis was used to assess the expressions of TLR4, NF-κB, and NLRP3. TLR4 agonist, LPS, was used to validate the role of NF-κB/NLRP3 pathway in LIRALI.</p><p><strong>Results: </strong>Esketamine significantly alleviated LIR-induced ALI by reducing pulmonary edema, inflammatory cell infiltration, and oxidative stress. Elevated MDA content and suppressed SOD activity were significantly reversed by esketamine, along with inactivity of the TLR4/NF-κB/NLRP3 pathway. Esketamine treatment reduced inflammatory response in BALF and serum. TLR4 activation by LPS reversed the ameliorative effects of esketamine on LIR-ALI.</p><p><strong>Conclusion: </strong>Esketamine protected against LIR-induced ALI by mitigating oxidative stress and suppressing the TLR4/NF-κB/NLRP3 axis. These findings highlight the potential therapeutic value of esketamine for ALI.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}