Pub Date : 2025-04-23DOI: 10.1016/j.cyto.2025.156946
Wenqiang Li , Shijie Li , Weijing Sun, Dezhi Han
This study explored the mechanism by which glucose transporter type 1 (GLUT1) promotes neutrophil extracellular trap (NET)-mediated macrophage phenotype conversion in a high-glucose environment, based on the interaction between fibroblasts and macrophages. We demonstrated that GLUT1 plays an important role in immune cell–fibroblast crosstalk. High glucose induces GLUT1 to upregulate high mobility group box 1 (HMGB1) levels, thereby promoting NET release and macrophage M1 polarization. Addition of a NET inhibitor promoted macrophage M2 polarization and alleviated the impaired macrophage phenotype conversion. Additionally, overexpression of Glut1 enhanced the expression of inflammatory factors tumor necrosis factor alpha (TNF-α) and interleukin beta (IL-1β), leading to inflammatory damage to fibroblasts, which was reversed significantly by inhibiting NETs . The results indicated that GLUT1 mediates the crosstalk between NETs, macrophage phenotype conversion impairment, and inflammatory damage in fibroblasts. This study emphasizes the importance of GLUT1 in the interaction between immune cells and fibroblasts, and its regulatory role in the impairment of NET-mediated macrophage phenotype conversion. These findings suggest that the regulatory mechanisms between HMGB1 and NETs in a high-glucose environment might provide potential therapeutic targets to treat diabetic wounds.
{"title":"The mechanism of action of GLUT1 in promoting NETs-mediated impairment of macrophage phenotypic switching based on macrophage-fibroblast interplay","authors":"Wenqiang Li , Shijie Li , Weijing Sun, Dezhi Han","doi":"10.1016/j.cyto.2025.156946","DOIUrl":"10.1016/j.cyto.2025.156946","url":null,"abstract":"<div><div>This study explored the mechanism by which glucose transporter type 1 (GLUT1) promotes neutrophil extracellular trap (NET)-mediated macrophage phenotype conversion in a high-glucose environment, based on the interaction between fibroblasts and macrophages. We demonstrated that GLUT1 plays an important role in immune cell–fibroblast crosstalk. High glucose induces GLUT1 to upregulate high mobility group box 1 (HMGB1) levels, thereby promoting NET release and macrophage M1 polarization. Addition of a NET inhibitor promoted macrophage M2 polarization and alleviated the impaired macrophage phenotype conversion. Additionally, overexpression of <em>Glut1</em> enhanced the expression of inflammatory factors tumor necrosis factor alpha (TNF-α) and interleukin beta (IL-1β), leading to inflammatory damage to fibroblasts, which was reversed significantly by inhibiting NETs . The results indicated that GLUT1 mediates the crosstalk between NETs, macrophage phenotype conversion impairment, and inflammatory damage in fibroblasts. This study emphasizes the importance of GLUT1 in the interaction between immune cells and fibroblasts, and its regulatory role in the impairment of NET-mediated macrophage phenotype conversion. These findings suggest that the regulatory mechanisms between HMGB1 and NETs in a high-glucose environment might provide potential therapeutic targets to treat diabetic wounds.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156946"},"PeriodicalIF":3.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-20DOI: 10.1016/j.cyto.2025.156941
Bo He , Yingjie Li , Ning Zhou
Background
The link between oxidative stress and lipid metabolism is widely studied, but their causal relationship in the general population remains unclear.
Methods
We utilized weighted regression and propensity score matching (PSM) models to investigate the relationship between endogenous oxidative stress markers (serum bilirubin and uric acid) and lipid metabolism in 11,087 participants of European ancestry from the National Health and Nutrition Examination Survey (NHANES) during the period from 2005 to 2018. Additionally, we performed a bidirectional two-sample Mendelian randomization (MR) analysis using Genome-Wide Association Study (GWAS) summary statistics from individuals of European ancestry (n = 997 to 575,531) to explore the genetic causal relationship between oxidative stress markers and lipid metabolism profiles (n = 20,430).
Results
Weighted regression showed that serum uric acid significantly increased high cholesterol (OR = 1.11, 95 % CI = 1.06–1.15, P < 0.001) and high triglycerides (OR = 1.25, 95 % CI = 1.20–1.30, P < 0.001). PSM analysis confirmed that serum uric acid increased the incidence of high triglycerides (OR = 1.57, 95 % CI = 1.35–1.82, P < 0.001). Additionally, a strong bidirectional genetic relationship was found between oxidative stress markers and lipid metabolism. For example, serum uric acid increased serum triglycerides (β = 0.1904, Se = 0.05, P < 0.001) and decreased total cholesterol in very large HDL (β = −0.1298, Se = 0.039, P < 0.001). Conversely, total cholesterol reduced direct bilirubin levels (β = −0.1707, Se = 0.018, P < 0.001). No significant horizontal pleiotropy was detected by MR-Egger intercept.
Conclusion
Our findings demonstrate a robust genetic and population-based association between oxidative stress markers and lipid metabolism, suggesting potential therapeutic targets for lipid disorders based on endogenous oxidative stressors.
{"title":"From genes to clinic: Genomic and cross-sectional cohort analysis of oxidative stressors and lipid metabolism in European ancestry","authors":"Bo He , Yingjie Li , Ning Zhou","doi":"10.1016/j.cyto.2025.156941","DOIUrl":"10.1016/j.cyto.2025.156941","url":null,"abstract":"<div><h3>Background</h3><div>The link between oxidative stress and lipid metabolism is widely studied, but their causal relationship in the general population remains unclear.</div></div><div><h3>Methods</h3><div>We utilized weighted regression and propensity score matching (PSM) models to investigate the relationship between endogenous oxidative stress markers (serum bilirubin and uric acid) and lipid metabolism in 11,087 participants of European ancestry from the National Health and Nutrition Examination Survey (NHANES) during the period from 2005 to 2018. Additionally, we performed a bidirectional two-sample Mendelian randomization (MR) analysis using Genome-Wide Association Study (GWAS) summary statistics from individuals of European ancestry (<em>n</em> = 997 to 575,531) to explore the genetic causal relationship between oxidative stress markers and lipid metabolism profiles (<em>n</em> = 20,430).</div></div><div><h3>Results</h3><div>Weighted regression showed that serum uric acid significantly increased high cholesterol (OR = 1.11, 95 % CI = 1.06–1.15, <em>P</em> < 0.001) and high triglycerides (OR = 1.25, 95 % CI = 1.20–1.30, <em>P</em> < 0.001). PSM analysis confirmed that serum uric acid increased the incidence of high triglycerides (OR = 1.57, 95 % CI = 1.35–1.82, P < 0.001). Additionally, a strong bidirectional genetic relationship was found between oxidative stress markers and lipid metabolism. For example, serum uric acid increased serum triglycerides (β = 0.1904, Se = 0.05, <em>P</em> < 0.001) and decreased total cholesterol in very large HDL (β = −0.1298, Se = 0.039, <em>P</em> < 0.001). Conversely, total cholesterol reduced direct bilirubin levels (β = −0.1707, Se = 0.018, P < 0.001). No significant horizontal pleiotropy was detected by MR-Egger intercept.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate a robust genetic and population-based association between oxidative stress markers and lipid metabolism, suggesting potential therapeutic targets for lipid disorders based on endogenous oxidative stressors.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156941"},"PeriodicalIF":3.7,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-19DOI: 10.1016/j.cyto.2025.156942
Yunfei Ma , Qiang He , Yan Su , Wen Zhao , Cheng Huang , Jing Qin , Shengjie You , Yan Hu , Xin Ni
Objective
To elucidate the causal relationship between immune cells and neuroblastoma, we conducted a two-sample Mendelian randomization (MR) analysis.
Materials and methods
The exposure and outcome data for the genome-wide association study (GWAS) used in this research were sourced from an open-access database. The study utilized two-sample MR analysis to evaluate the causal relationship between 731 immune cell features and neuroblastoma. The main approach to explore this relationship is to apply the inverse variance weighting (IVW) method. In addition, sensitivity analyses including leave-one-out analysis, Cochran's Q test, Mendelian randomization Egger method (MR-Egger) intercept test and Mendelian randomization pleiotropy residual sum and outlier test (MR-PRESSO) were performed to verify the reliability of the MR results.
Results
The study identifies five immune cell traits as causally contributing to neuroblastoma risk, including CD3− lymphocyte (% of leukocytes) (IVW: OR[95 % CI] 0.65[0.42–0.99], P = 0.0469), CD86 on granulocyte (IVW: OR[95 % CI] 0.61[0.41–0.92], P = 0.0167), FSC-A on granulocyte(IVW: OR[95 % CI] 0.73[0.57–0.93], P = 0.0117), HLA DR+ CD8+ T cell Absolute Count(IVW: OR[95 % CI]: 1.38[1.01–1.88], P = 0.0408), IgD− CD38+ B cell Absolute Count(IVW: OR[95 % CI] 0.42[0.27–0.66], P = 0.0002). The results of sensitivity analyses were consistent with the main findings.
Conclusion
We demonstrated a close causal relationship between specific types of immune cells and neuroblastoma by genetic methods, offering valuable guidance for future clinical studies.
{"title":"Genetic insights into neuroblastoma: the role of immune cell features","authors":"Yunfei Ma , Qiang He , Yan Su , Wen Zhao , Cheng Huang , Jing Qin , Shengjie You , Yan Hu , Xin Ni","doi":"10.1016/j.cyto.2025.156942","DOIUrl":"10.1016/j.cyto.2025.156942","url":null,"abstract":"<div><h3>Objective</h3><div>To elucidate the causal relationship between immune cells and neuroblastoma, we conducted a two-sample Mendelian randomization (MR) analysis.</div></div><div><h3>Materials and methods</h3><div>The exposure and outcome data for the genome-wide association study (GWAS) used in this research were sourced from an open-access database. The study utilized two-sample MR analysis to evaluate the causal relationship between 731 immune cell features and neuroblastoma. The main approach to explore this relationship is to apply the inverse variance weighting (IVW) method. In addition, sensitivity analyses including leave-one-out analysis, Cochran's Q test, Mendelian randomization Egger method (MR-Egger) intercept test and Mendelian randomization pleiotropy residual sum and outlier test (MR-PRESSO) were performed to verify the reliability of the MR results.</div></div><div><h3>Results</h3><div>The study identifies five immune cell traits as causally contributing to neuroblastoma risk, including CD3<sup>−</sup> lymphocyte (% of leukocytes) (IVW: OR[95 % CI] 0.65[0.42–0.99], <em>P</em> = 0.0469), CD86 on granulocyte (IVW: OR[95 % CI] 0.61[0.41–0.92], <em>P</em> = 0.0167), FSC-A on granulocyte(IVW: OR[95 % CI] 0.73[0.57–0.93], <em>P</em> = 0.0117), HLA DR+ CD8+ T cell Absolute Count(IVW: OR[95 % CI]: 1.38[1.01–1.88], <em>P</em> = 0.0408), IgD− CD38+ B cell Absolute Count(IVW: OR[95 % CI] 0.42[0.27–0.66], <em>P</em> = 0.0002). The results of sensitivity analyses were consistent with the main findings.</div></div><div><h3>Conclusion</h3><div>We demonstrated a close causal relationship between specific types of immune cells and neuroblastoma by genetic methods, offering valuable guidance for future clinical studies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156942"},"PeriodicalIF":3.7,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-19DOI: 10.1016/j.cyto.2025.156943
Cheng Zhang , Xuelei Yin , Jun Jiang , Peng Wang , Yirong Wang
Objective
To explore the role of GFPT2 in the sensitivity of STK11/KRAS lung cancer cells to cisplatin chemotherapy, and its underlying mechanism.
Materials & methods
A549 and H460 cells were used to analyze the effect of GFPT2 on cisplatin chemotherapy sensitivity, as both carry KRAS mutations and H460 has LKB1 inactivation mutations, meeting the requirements of a KRAS/LKB1 co mutant tumor model. The levels of UDP-GlcNAc, OGT, OGA, and O-GlcNAc in the HBP pathway were also determined. To verify the potential role of HBP, we added OGT inhibitors. In vivo, we constructed a nude mouse model bearing A549 tumor to further validate the results of in vitro cell experiments.
Results
GFPT2 silencing can significantly inhibit cell proliferation, invasion, and migration, promote cell apoptosis, and enhance the effect of cisplatin (p < 0.05). After OSMI-1 processing, GFPT2 enhances O-GlcNAc modification levels via the OGT-mediated HBP, thereby decreasing the sensitivity of STK11/KRAS mutant cells to cisplatin chemotherapy. In addition, GFPT2 silencing enhances the chemotherapy sensitivity of cisplatin and inhibits tumor growth, while overexpression of GFPT2 weakens this effect (p < 0.05). The above results provide new targets and combination therapy options for the clinical treatment of KRAS/LKB1 mutant lung cancer.
Conclusion
Our study found that inhibiting GFPT2 can enhance the chemotherapy sensitivity of cisplatin to STK11/KRAS/LKB1 mutant NSCLCs cells through the OGT mediated HBP pathway, filling a key gap in the chemotherapy resistance mechanism of KRAS/LKB1 mutant lung cancer.
{"title":"Downregulation of GFPT2 enhances cisplatin chemotherapy sensitivity in STK11/KRAS mutant non-small cell lung cancer by regulating the hexosamine biosynthesis pathway, resisting tumor growth","authors":"Cheng Zhang , Xuelei Yin , Jun Jiang , Peng Wang , Yirong Wang","doi":"10.1016/j.cyto.2025.156943","DOIUrl":"10.1016/j.cyto.2025.156943","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the role of GFPT2 in the sensitivity of STK11/KRAS lung cancer cells to cisplatin chemotherapy, and its underlying mechanism.</div></div><div><h3>Materials & methods</h3><div>A549 and H460 cells were used to analyze the effect of GFPT2 on cisplatin chemotherapy sensitivity, as both carry KRAS mutations and H460 has LKB1 inactivation mutations, meeting the requirements of a KRAS/LKB1 co mutant tumor model. The levels of UDP-GlcNAc, OGT, OGA, and O-GlcNAc in the HBP pathway were also determined. To verify the potential role of HBP, we added OGT inhibitors. In vivo, we constructed a nude mouse model bearing A549 tumor to further validate the results of in vitro cell experiments.</div></div><div><h3>Results</h3><div>GFPT2 silencing can significantly inhibit cell proliferation, invasion, and migration, promote cell apoptosis, and enhance the effect of cisplatin (<em>p</em> < 0.05). After OSMI-1 processing, GFPT2 enhances O-GlcNAc modification levels via the OGT-mediated HBP, thereby decreasing the sensitivity of STK11/KRAS mutant cells to cisplatin chemotherapy. In addition, GFPT2 silencing enhances the chemotherapy sensitivity of cisplatin and inhibits tumor growth, while overexpression of GFPT2 weakens this effect (<em>p</em> < 0.05). The above results provide new targets and combination therapy options for the clinical treatment of KRAS/LKB1 mutant lung cancer.</div></div><div><h3>Conclusion</h3><div>Our study found that inhibiting GFPT2 can enhance the chemotherapy sensitivity of cisplatin to STK11/KRAS/LKB1 mutant NSCLCs cells through the OGT mediated HBP pathway, filling a key gap in the chemotherapy resistance mechanism of KRAS/LKB1 mutant lung cancer.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156943"},"PeriodicalIF":3.7,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-14DOI: 10.1016/j.cyto.2025.156938
Bo Zhou , Lu Gan , Pimo Zhou , Tai Yang , Fang Tang , Peng Jin , Ping Jin , Jiulin Chen
Background
Atherosclerosis (AS) is a disease that occurs in the great arteries and is the main cause of cardiovascular disease and death.
Objective
To investigate the clinical significance of LINC00426 in AS and to investigate that LINC00426 regulates PDGF-BB-induced proliferation, migration, invasion and inflammatory response of vascular smooth muscle cells (VSMCs) by modulating miR-873-5p/SRRM2 axis.
Methods
The expression of LINC00426 was detected using RT-qPCR. The diagnostic role of LINC00426 in AS was analyzed with ROC curves. CCK-8 assay was used to measure cell proliferation, and transwell assay was used to measure cell migration and invasion ability. The targeted binding relationship between LINC00426 and miR-873-5p, miR-873-5p and SRRM2 was detected using dual-luciferase reporter gene assay. The concentration of proinflammatory factors was detected by using ELISA kit.
Result
The expression of LINC00426 was increased in patients with AS, and LINC00426 had a diagnostic role in AS. In addition, LINC00426 regulated PDGF-BB-induced proliferation, migration, invasion, and inflammation of VSMCs by regulating miR-873-5p/SRRM2 axis.
Conclusion
LINC00426 may function as a biomarker for the diagnosis and treatment of AS.
{"title":"LINC00426 promotes the progression of atherosclerosis by regulating miR-873-5p/SRRM2 axis","authors":"Bo Zhou , Lu Gan , Pimo Zhou , Tai Yang , Fang Tang , Peng Jin , Ping Jin , Jiulin Chen","doi":"10.1016/j.cyto.2025.156938","DOIUrl":"10.1016/j.cyto.2025.156938","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerosis (AS) is a disease that occurs in the great arteries and is the main cause of cardiovascular disease and death.</div></div><div><h3>Objective</h3><div>To investigate the clinical significance of LINC00426 in AS and to investigate that LINC00426 regulates PDGF-BB-induced proliferation, migration, invasion and inflammatory response of vascular smooth muscle cells (VSMCs) by modulating miR-873-5p/SRRM2 axis.</div></div><div><h3>Methods</h3><div>The expression of LINC00426 was detected using RT-qPCR. The diagnostic role of LINC00426 in AS was analyzed with ROC curves. CCK-8 assay was used to measure cell proliferation, and transwell assay was used to measure cell migration and invasion ability. The targeted binding relationship between LINC00426 and miR-873-5p, miR-873-5p and SRRM2 was detected using dual-luciferase reporter gene assay. The concentration of proinflammatory factors was detected by using ELISA kit.</div></div><div><h3>Result</h3><div>The expression of LINC00426 was increased in patients with AS, and LINC00426 had a diagnostic role in AS. In addition, LINC00426 regulated PDGF-BB-induced proliferation, migration, invasion, and inflammation of VSMCs by regulating miR-873-5p/SRRM2 axis.</div></div><div><h3>Conclusion</h3><div>LINC00426 may function as a biomarker for the diagnosis and treatment of AS.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156938"},"PeriodicalIF":3.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-13DOI: 10.1016/j.cyto.2025.156939
Min Zhou , Wenhui Zhao , Xiaobo Zhang , Ye Cheng , Mengxiang Wang , Yan Chen , Lingrui Zhao
In this study, we utilized the public database along with single-cell genomics techniques to systematically analyze the expression patterns and clinical significance of key genes in the nicotinamide metabolism pathway in liver cancer samples. The findings indicate that differential nicotinamide metabolism-related key genes are expressed in liver cancer samples. The liver cancer samples were put into separate subgroups using consistency clustering analysis based on differential gene expression levels observed. Additionally, immune infiltration and drug sensitivity analysis also revealed differences between the two subgroups. Survival analysis suggested that the key genes were associated with prognosis. Finally, a prognostic model was established using the key genes, offering a fresh viewpoint on the molecular mechanism investigating liver cancer. This study demonstrated the significant correlation between key genes in the nicotinamide metabolism pathway and the occurrence and progression of liver cancer and indicated that these key genes could serve as prognostic markers and tailored treatment targets for liver cancer.
{"title":"Nicotinamide metabolism affects the prognosis of hepatocellular carcinoma by influencing the tumor microenvironment","authors":"Min Zhou , Wenhui Zhao , Xiaobo Zhang , Ye Cheng , Mengxiang Wang , Yan Chen , Lingrui Zhao","doi":"10.1016/j.cyto.2025.156939","DOIUrl":"10.1016/j.cyto.2025.156939","url":null,"abstract":"<div><div>In this study, we utilized the public database along with single-cell genomics techniques to systematically analyze the expression patterns and clinical significance of key genes in the nicotinamide metabolism pathway in liver cancer samples. The findings indicate that differential nicotinamide metabolism-related key genes are expressed in liver cancer samples. The liver cancer samples were put into separate subgroups using consistency clustering analysis based on differential gene expression levels observed. Additionally, immune infiltration and drug sensitivity analysis also revealed differences between the two subgroups. Survival analysis suggested that the key genes were associated with prognosis. Finally, a prognostic model was established using the key genes, offering a fresh viewpoint on the molecular mechanism investigating liver cancer. This study demonstrated the significant correlation between key genes in the nicotinamide metabolism pathway and the occurrence and progression of liver cancer and indicated that these key genes could serve as prognostic markers and tailored treatment targets for liver cancer.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156939"},"PeriodicalIF":3.7,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-08DOI: 10.1016/j.cyto.2025.156936
Ahmed A. Morsi , Ezat A. Mersal , Marwa Omar Abdel All , Alshaymaa M. Abdelmenem , Amal F. Dawood , Atheer Alanazi , Norah Mahdi , Mohamed S. Salim
Angiotensin-converting enzyme 2 (ACE2) is a critical component in the renin-angiotensin system. A Disintegrin And Metalloprotease 17 (ADAM17) is the first identified sheddase for common inflammatory cytokines. Changes in ACE2 expression and its biological activity facilitated by ADAM17 are involved in several diseases including neurodegenerative disorders. Herein, the study investigated an innovative viewpoint on cadmium (Cd)-induced neurotoxicity and explored whether ADAM17/ACE2 interplay mediated the Cd-induced brain injury and neuroinflammation. For this aim, 32 adult male Wistar rats were included and randomly grouped. Eight rats served as a control group and the remaining 24 experimental rats were exposed to Cd (5 mg/kg/day, orally, 21 days); assigned as either Cd-alone (Cd group), received ADAM17 inhibitor [TAPI-1, 10 mg/kg, intraperitoneal] (Cd/TAPI-1 group), or received vitamin E, 100 mg/kg/d, orally (Cd/vit E group). Ultimately, the brains were harvested and exposed to biochemical, histological, and immunohistochemical (IHC) studies for measuring oxidative stress and inflammatory markers, histopathological examination, and for IHC identification of ADAM17, ACE2, and glial fibrillary acidic protein (GFAP). Cd resulted in biochemical disturbances in the inflammatory and oxidative stress markers, degenerative histopathological changes in the cerebral cortex and hippocampus, and enhanced ADAM17 and GFAP expression, meanwhile downregulated ACE2 expression. Vitamin E showed a superior effect in maintaining the oxidative/antioxidant-balanced defense system. However, the biochemical and histological changes in the brain were more effectively alleviated by TAPI-1 administration than by the partial improvement made by vitamin E therapy. These observations suggested that oxidative stress was involved in Cd-mediated upregulation of ADAM17 and ACE2 shedding. It was concluded that oxidative stress, at least in part, resulted in ADAM17-mediated ACE2 cleavage in the current Cd-induced brain damage.
{"title":"ADAM17/ACE2 interaction mediates cadmium-induced brain damage and neuroinflammation in Wistar rats","authors":"Ahmed A. Morsi , Ezat A. Mersal , Marwa Omar Abdel All , Alshaymaa M. Abdelmenem , Amal F. Dawood , Atheer Alanazi , Norah Mahdi , Mohamed S. Salim","doi":"10.1016/j.cyto.2025.156936","DOIUrl":"10.1016/j.cyto.2025.156936","url":null,"abstract":"<div><div>Angiotensin-converting enzyme 2 (ACE2) is a critical component in the renin-angiotensin system. A Disintegrin And Metalloprotease 17 (ADAM17) is the first identified sheddase for common inflammatory cytokines. Changes in ACE2 expression and its biological activity facilitated by ADAM17 are involved in several diseases including neurodegenerative disorders. Herein, the study investigated an innovative viewpoint on cadmium (Cd)-induced neurotoxicity and explored whether ADAM17/ACE2 interplay mediated the Cd-induced brain injury and neuroinflammation. For this aim, 32 adult male Wistar rats were included and randomly grouped. Eight rats served as a control group and the remaining 24 experimental rats were exposed to Cd (5 mg/kg/day, orally, 21 days); assigned as either Cd-alone (Cd group), received ADAM17 inhibitor [TAPI-1, 10 mg/kg, intraperitoneal] (Cd/TAPI-1 group), or received vitamin E, 100 mg/kg/d, orally (Cd/vit E group). Ultimately, the brains were harvested and exposed to biochemical, histological, and immunohistochemical (IHC) studies for measuring oxidative stress and inflammatory markers, histopathological examination, and for IHC identification of ADAM17, ACE2, and glial fibrillary acidic protein (GFAP). Cd resulted in biochemical disturbances in the inflammatory and oxidative stress markers, degenerative histopathological changes in the cerebral cortex and hippocampus, and enhanced ADAM17 and GFAP expression, meanwhile downregulated ACE2 expression. Vitamin E showed a superior effect in maintaining the oxidative/antioxidant-balanced defense system. However, the biochemical and histological changes in the brain were more effectively alleviated by TAPI-1 administration than by the partial improvement made by vitamin E therapy. These observations suggested that oxidative stress was involved in Cd-mediated upregulation of ADAM17 and ACE2 shedding. It was concluded that oxidative stress, at least in part, resulted in ADAM17-mediated ACE2 cleavage in the current Cd-induced brain damage.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156936"},"PeriodicalIF":3.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Knee osteoarthritis (KOA) is a multifactorial condition affected by genetic and environmental factors. Studies have explored the relationship between IL-16 genetic polymorphisms and KOA risk, but findings have been inconclusive. This meta-analysis seeks to assess the association between IL-16 polymorphisms and KOA risk.
Methods
A systematic literature search was conducted in several databases, including PubMed, Web of Science, EMBASE, SciELO, and CNKI, for studies published until June 1, 2024. Two independent researchers identified peer-reviewed articles in English, Portuguese, and Chinese using keywords related to “Knee Osteoarthritis” and “Interleukin 16.” Relevant references were also manually reviewed for additional studies. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to assess the association strength. Additionally, minor allele frequencies (MAFs), Hardy-Weinberg equilibrium (HWE) data, heterogeneity, publication bias, and Newcastle-Ottawa scores (NOS) were evaluated.
Results
This analysis included 15 case-control studies, encompassing 1747 individuals with KOA and 1627 healthy controls. Within these studies, five investigated the genetic variations rs11556218 (584 cases, 542 controls), rs4778889 (583 cases, 543 controls), and rs4072111 (580 cases, 542 controls). The findings suggest that the IL-16 variants rs11556218 and rs4072111 may offer protection against KOA development, while no link exists between the rs4778889 variant and KOA susceptibility. The variability in IL-16 polymorphisms, particularly in Asian and Chinese populations, indicates different genetic associations with KOA risk. Strong results, supported by sensitivity analyses and the absence of significant publication bias, emphasize the influence of study methods on the relationship between these polymorphisms and KOA risk.
Conclusions
The analysis of three polymorphisms—rs11556218, rs4778889, and rs4072111—shows varying associations with KOA. Rs11556218 and rs4072111 offer protective effects in non-Asian populations, while rs4778889 shows no significant association across cohorts. Notably, rs11556218 and rs4072111 do not correlate with KOA susceptibility in Asian and Chinese populations, suggesting ethnic differences in genetic influences on KOA.
{"title":"A thorough analysis of data on the correlation between IL-16 polymorphisms and the susceptibility to knee osteoarthritis: A meta-analysis","authors":"Amirhossein Omidi , Mohammad Bahrami , Seyed Alireza Dastgheib , Ahmadreza Golshan-Tafti , Ali Masoudi , Amirmasoud Shiri , Maryam Aghasipour , Amirhossein Shahbazi , Kazem Aghili , Hossein Neamatzadeh","doi":"10.1016/j.cyto.2025.156929","DOIUrl":"10.1016/j.cyto.2025.156929","url":null,"abstract":"<div><h3>Background</h3><div>Knee osteoarthritis (KOA) is a multifactorial condition affected by genetic and environmental factors. Studies have explored the relationship between IL-16 genetic polymorphisms and KOA risk, but findings have been inconclusive. This meta-analysis seeks to assess the association between IL-16 polymorphisms and KOA risk.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted in several databases, including PubMed, Web of Science, EMBASE, SciELO, and CNKI, for studies published until June 1, 2024. Two independent researchers identified peer-reviewed articles in English, Portuguese, and Chinese using keywords related to “Knee Osteoarthritis” and “Interleukin 16.” Relevant references were also manually reviewed for additional studies. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to assess the association strength. Additionally, minor allele frequencies (MAFs), Hardy-Weinberg equilibrium (HWE) data, heterogeneity, publication bias, and Newcastle-Ottawa scores (NOS) were evaluated.</div></div><div><h3>Results</h3><div>This analysis included 15 case-control studies, encompassing 1747 individuals with KOA and 1627 healthy controls. Within these studies, five investigated the genetic variations rs11556218 (584 cases, 542 controls), rs4778889 (583 cases, 543 controls), and rs4072111 (580 cases, 542 controls). The findings suggest that the IL-16 variants rs11556218 and rs4072111 may offer protection against KOA development, while no link exists between the rs4778889 variant and KOA susceptibility. The variability in IL-16 polymorphisms, particularly in Asian and Chinese populations, indicates different genetic associations with KOA risk. Strong results, supported by sensitivity analyses and the absence of significant publication bias, emphasize the influence of study methods on the relationship between these polymorphisms and KOA risk.</div></div><div><h3>Conclusions</h3><div>The analysis of three polymorphisms—rs11556218, rs4778889, and rs4072111—shows varying associations with KOA. Rs11556218 and rs4072111 offer protective effects in non-Asian populations, while rs4778889 shows no significant association across cohorts. Notably, rs11556218 and rs4072111 do not correlate with KOA susceptibility in Asian and Chinese populations, suggesting ethnic differences in genetic influences on KOA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-05DOI: 10.1016/j.cyto.2025.156930
Ji Ren , Luhong Xie , Xiaoyu Zhu , Xiuying Chen , Lin Wei , Dianqin Xu , Kun Qiao , Shaoju Min , Yan Ding , Yujie Tan
Epigenetic modification can be a key weapon employed by both sides of the battle between Cervical Cancer progression due to persistent high-risk papillomavirus (hr-HPV) infection and the development of anti-cancer modalities. Alongside the overactivated Wnt/β-catenin activity, reduced TET1 expression and ratio of 5-hydroxymethylcytosine (5hmC) to 5-methylcytosine (5mC) were found in cervical cancer, which was correlated with lymph node metastasis. After treating cervical cancer cells with Resveratrol (RES), we found that TET1 expression was elevated and Wnt/β-catenin pathway activity was suppressed. Therefore, the aim of this study is to investigate the influence of resveratrol on the TET1 and Wnt/β-catenin pathways, and to elucidate the molecular mechanisms involved in this process, thereby clarifying the potential value of RES in the treatment of cervical cancer. Our data illustrate the TET1-mediated epigenetic modulation was an integral part of the effects of RES on the Wnt/β-catenin pathway in cervical cancer.
{"title":"Resveratrol interrupts Wnt/β-catenin signalling in cervical cancer by activating ten-eleven translocation 5-methylcytosine dioxygenase 1","authors":"Ji Ren , Luhong Xie , Xiaoyu Zhu , Xiuying Chen , Lin Wei , Dianqin Xu , Kun Qiao , Shaoju Min , Yan Ding , Yujie Tan","doi":"10.1016/j.cyto.2025.156930","DOIUrl":"10.1016/j.cyto.2025.156930","url":null,"abstract":"<div><div>Epigenetic modification can be a key weapon employed by both sides of the battle between Cervical Cancer progression due to persistent high-risk papillomavirus (hr-HPV) infection and the development of anti-cancer modalities. Alongside the overactivated Wnt/β-catenin activity, reduced TET1 expression and ratio of 5-hydroxymethylcytosine (5hmC) to 5-methylcytosine (5mC) were found in cervical cancer, which was correlated with lymph node metastasis. After treating cervical cancer cells with Resveratrol (RES), we found that TET1 expression was elevated and Wnt/β-catenin pathway activity was suppressed. Therefore, the aim of this study is to investigate the influence of resveratrol on the TET1 and Wnt/β-catenin pathways, and to elucidate the molecular mechanisms involved in this process, thereby clarifying the potential value of RES in the treatment of cervical cancer. Our data illustrate the TET1-mediated epigenetic modulation was an integral part of the effects of RES on the Wnt/β-catenin pathway in cervical cancer.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156930"},"PeriodicalIF":3.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adipocytokines, including leptin, adiponectin, and resistin, are key mediators linking adiposity, insulin resistance, and inflammation. We present the first genome-wide association study (GWAS; N = 5258) and exome-wide association study (ExWAS; N = 4578) on leptin, adiponectin, and resistin in South Asian population. We identified novel associations in genes ZNF467, and LEPREL2 for leptin; ZNF467, LEPREL2, CRLF3, ZNF732, SOX30, XIRP1, ATP8B3, SPATA2L, TMCO4, TLN2, ABCA12, and SHB for adiponectin; and D2HGDH for resistin. Additionally, we confirmed known associations of FTO, MC4R, and HOXB3 with leptin and ADIPOQ with adiponectin. Notably, ADIPOQ variants were consistently significant across GWAS, ExWAS, and gene-based analyses, reinforcing their central role in regulating adiponectin levels. Most of these novel associations identified were population-specific, highlighting the importance of studying diverse populations to uncover unique genetic signals. After adjusting for BMI, the associations with adiponectin and resistin remained significant, whereas most associations for leptin weakened in both effect size and significance. Functional annotation revealed that the identified variants were enriched for expression in adipose tissue, the brain (cerebellar hemisphere and cerebral cortex), and the pituitary gland. These variants act as eQTLs and splice-QTLs in adipose, brain, and pancreas, suggesting cross-tissue regulatory mechanisms. ExWAS further implicated rare variant burden in genes such as LONP1, ZNF335, and TTC16 for adiponectin and resistin. These findings enhance our understanding of adipocytokine biology, emphasises the need for population-specific genetic research, and lays foundation for future functional studies.
{"title":"Novel genetic associations with childhood adipocytokines in Indian adolescents","authors":"Janaki M. Nair , Ganesh Chauhan , Gauri Prasad , Shraddha Chakraborty , Khushdeep Bandesh , Anil K. Giri , Raman K. Marwaha , Analabha Basu , Nikhil Tandon , Dwaipayan Bharadwaj","doi":"10.1016/j.cyto.2025.156935","DOIUrl":"10.1016/j.cyto.2025.156935","url":null,"abstract":"<div><div>Adipocytokines, including leptin, adiponectin, and resistin, are key mediators linking adiposity, insulin resistance, and inflammation. We present the first genome-wide association study (GWAS; <em>N</em> = 5258) and exome-wide association study (ExWAS; <em>N</em> = 4578) on leptin, adiponectin, and resistin in South Asian population. We identified novel associations in genes <em>ZNF467</em>, and <em>LEPREL2</em> for leptin; <em>ZNF467, LEPREL2, CRLF3, ZNF732, SOX30, XIRP1, ATP8B3, SPATA2L, TMCO4, TLN2, ABCA12</em>, and <em>SHB</em> for adiponectin; and <em>D2HGDH</em> for resistin. Additionally, we confirmed known associations of <em>FTO, MC4R</em>, and <em>HOXB3</em> with leptin and <em>ADIPOQ</em> with adiponectin. Notably, <em>ADIPOQ</em> variants were consistently significant across GWAS, ExWAS, and gene-based analyses, reinforcing their central role in regulating adiponectin levels. Most of these novel associations identified were population-specific, highlighting the importance of studying diverse populations to uncover unique genetic signals. After adjusting for BMI, the associations with adiponectin and resistin remained significant, whereas most associations for leptin weakened in both effect size and significance. Functional annotation revealed that the identified variants were enriched for expression in adipose tissue, the brain (cerebellar hemisphere and cerebral cortex), and the pituitary gland. These variants act as eQTLs and splice-QTLs in adipose, brain, and pancreas, suggesting cross-tissue regulatory mechanisms. ExWAS further implicated rare variant burden in genes such as <em>LONP1, ZNF335,</em> and <em>TTC16</em> for adiponectin and resistin. These findings enhance our understanding of adipocytokine biology, emphasises the need for population-specific genetic research, and lays foundation for future functional studies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156935"},"PeriodicalIF":3.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号