There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,...There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence.The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities.IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory proce-sses associated with epilepsy.Furthermore,IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy,highlighting its involvement in neuropsychiatric comorbidities.In summary,IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications.Future resear-ch should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes,stages and neuropsychiatric comorbidities of epilepsy,with the aim of developing more precise and effective interventions.Furthermore,the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epile-psy warrants further investigation.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in th...BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.展开更多
冠状动脉性心脏病(coronary artery disease, CAD)显著影响着我国居民的健康,也给全球医疗带来巨大的经济负担。动脉粥样硬化(atherosclerosis, AS)是CAD的病理基础。胆固醇-25-羟化酶(cholesterol 25-hydroxylase, CH25H)是一种参与脂...冠状动脉性心脏病(coronary artery disease, CAD)显著影响着我国居民的健康,也给全球医疗带来巨大的经济负担。动脉粥样硬化(atherosclerosis, AS)是CAD的病理基础。胆固醇-25-羟化酶(cholesterol 25-hydroxylase, CH25H)是一种参与脂质代谢的酶,它可以将胆固醇催化生成25-羟基胆固醇(25-hydroxycholesterol, 25-HC),而25-HC是众所周知的胆固醇的氧化产物,即氧甾醇。既往的研究表明CH25H和25-HC在调节胆固醇的代谢、炎症反应、AS以及免疫反应和抗病毒感染等方面发挥多种作用。近年来越来越多的研究聚焦于CH25H和25-HC与AS和CAD的相关性。因此本文就CH25H和25-HC在AS和CAD中已知的作用机制简单作一综述。Coronary artery disease (CAD) significantly affects the health of Chinese residents and imposes a huge economic burden on global healthcare. Atherosclerosis (AS) is the pathological basis of CAD. Cholesterol 25 hydroxylase (CH25H) is an enzyme involved in lipid metabolism. It catalyzes the conversion of cholesterol into 25-hydroxycholesterol (25-HC), which is a well-known oxidation product of cholesterol. Previous studies have shown that CH25H and 25-HC play multiple roles in regulating cholesterol metabolism, inflammatory response, AS, immune response, and antiviral infection. In recent years, more and more research has focused on the correlation between CH25H and 25-HC with AS and CAD. Therefore, this article provides a brief overview of the known mechanisms of action of CH25H and 25-HC in AS and CAD.展开更多
Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory resp...Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.展开更多
文摘There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence.The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities.IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory proce-sses associated with epilepsy.Furthermore,IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy,highlighting its involvement in neuropsychiatric comorbidities.In summary,IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications.Future resear-ch should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes,stages and neuropsychiatric comorbidities of epilepsy,with the aim of developing more precise and effective interventions.Furthermore,the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epile-psy warrants further investigation.
基金Supported by the Natural Science Foundation of Gansu Province,No.21JR7RA373 and No.24JRRA295.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.
文摘冠状动脉性心脏病(coronary artery disease, CAD)显著影响着我国居民的健康,也给全球医疗带来巨大的经济负担。动脉粥样硬化(atherosclerosis, AS)是CAD的病理基础。胆固醇-25-羟化酶(cholesterol 25-hydroxylase, CH25H)是一种参与脂质代谢的酶,它可以将胆固醇催化生成25-羟基胆固醇(25-hydroxycholesterol, 25-HC),而25-HC是众所周知的胆固醇的氧化产物,即氧甾醇。既往的研究表明CH25H和25-HC在调节胆固醇的代谢、炎症反应、AS以及免疫反应和抗病毒感染等方面发挥多种作用。近年来越来越多的研究聚焦于CH25H和25-HC与AS和CAD的相关性。因此本文就CH25H和25-HC在AS和CAD中已知的作用机制简单作一综述。Coronary artery disease (CAD) significantly affects the health of Chinese residents and imposes a huge economic burden on global healthcare. Atherosclerosis (AS) is the pathological basis of CAD. Cholesterol 25 hydroxylase (CH25H) is an enzyme involved in lipid metabolism. It catalyzes the conversion of cholesterol into 25-hydroxycholesterol (25-HC), which is a well-known oxidation product of cholesterol. Previous studies have shown that CH25H and 25-HC play multiple roles in regulating cholesterol metabolism, inflammatory response, AS, immune response, and antiviral infection. In recent years, more and more research has focused on the correlation between CH25H and 25-HC with AS and CAD. Therefore, this article provides a brief overview of the known mechanisms of action of CH25H and 25-HC in AS and CAD.
文摘Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.
