AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response media...AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response mediators. METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 ageand sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH) 2 -Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PⅢNP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PⅢNP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PⅢNP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PⅢNP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PⅢNP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCVinduced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated. CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PⅢNP highlight their involvement in the immune response in patients with HCV-4related liver diseases in Egypt.展开更多
Objective: To investigate the effect of interleukin-23 (IL-23) on myocardial ischemia-reperfusion (I/R) injury.Methods: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO) group, ischemia a...Objective: To investigate the effect of interleukin-23 (IL-23) on myocardial ischemia-reperfusion (I/R) injury.Methods: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO) group, ischemia and reperfusion (I/R) group, (IL-23 + I/R) group and (anti-IL-23 + I/R) group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH), creatine kinase (CK) and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-α and IL-6 were detected by Elisa. Results: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK. Meanwhile, IL-23 significantly increased the expression of eIL-17A, TNF-α and IL-6 and enhanced both the increase of the MDA level and the decrease of the SOD level induced by I/R. IL-23 had no effect on the expression of HMGB1. All these effects were abolished by anti-IL-23 administration. Conclusion: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction.展开更多
In order to investigate the mRNA expression and function of interleukin-23 （p 19/p40） and interleukin-12 （p35/p40） in the psoriatic lesion, no-lesion and normal human skin, reverse transcriptase-polymerase chain r...In order to investigate the mRNA expression and function of interleukin-23 （p 19/p40） and interleukin-12 （p35/p40） in the psoriatic lesion, no-lesion and normal human skin, reverse transcriptase-polymerase chain reaction （RT-PCR） was used to detect the expression of IL-23 （p19/p40） and IL-12 （p35/p40）. The results showed that the expression of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic lesion than those of non-lesional skin and normal skin. The levels of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic non-lesional skin than normal skin. However, no significant difference was found in the level of IL-12p35 mRNA among the psoriatic lesional skin, nonesional skin and normal skin. It was suggested that IL-23 might be more important in the pathogenesis of psoriasis than IL- 12.展开更多
The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multi...The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.展开更多
Objective：The interleukin-23 receptor （IL-23R） has been shown to be associated with autoimmune diseases in many different populations.This study aimed to investigate the association between IL-23R gene polymorphism...Objective：The interleukin-23 receptor （IL-23R） has been shown to be associated with autoimmune diseases in many different populations.This study aimed to investigate the association between IL-23R gene polymorphism and susceptibility to Hashimoto＇s thyroiditis （HT） in Chinese Han population of Shandong.Methods：A case-control cohort study was performed in 145 HT patients from First People＇s Hospital of Jining between February 2010 to October 2013 and 150 healthy controls.Two single nucleotide polymorphisms located in the promoter region ofIL-23R gene （rs 17375018 and rs7517847） were examined by polymerase chain reaction-restriction fragment length polymorphism analysis.Hardy-Weinberg equilibrium was performed using the Chi-square test.Genotype frequencies were estimated by direct counting,and allele and genotype frequencies between patients and controls were analyzed by the Chi-square test.Results：The rs 17375018 GG genotype and the G allele were significantly increased in HT patients compared with healthy controls （P =0.034 and P =0.013,respectively）.No association was identified between HT patients and healthy controls in rs7517847.Conclusion：The study demonstrated that polymorphism of IL-23R gene rs17375018 is highly associated with HT in Chinese Han population of Shandong,suggesting that IL-23R gene polymorphism （rs 17375018 G） may play a critical role in susceptibility to HT.展开更多
Background Interleukin-23 （IL-23） is a pro-inflammatory cytokine that is thought to be central to the development of autoimmune diseases. This study was conducted to determine whether or not the serum concentration ...Background Interleukin-23 （IL-23） is a pro-inflammatory cytokine that is thought to be central to the development of autoimmune diseases. This study was conducted to determine whether or not the serum concentration of IL-23 is elevated in patients with rheumatoid arthritis （RA）, and to determine the relationship between the IL-23 level and disease activity in RA patients. Methods Serum samples were obtained from 59 patients with RA and 30 healthy controls. The clinical parameters of disease activity were determined, including the 28-joint disease activity score （DAS28）, C-reactive protein （CRP）, rheumatoid factor （RF） levels, and the degree of bony erosions based on X-rays. The levels of IL-23 and IL-17 were determined by enzyme-linked immunosorbent assay （ELISA）. The correlations between the serum levels of IL-23 and disease activity parameters of patients with RA were determined. Results The serum IL-23 level was significantly elevated in patients with RA compared to healthy controls. The serum IL-23 levels in the RA patients correlated with IL-17 and CRP levels, and the DAS28. The levels of IL-23 based on X-ray classification phase I, II, III, and IV were gradually elevated in RA patients. Conclusions The levels of serum IL-23 in RA patients were higher than in healthy controls. Thus, elevated serum IL-23 levels may be useful markers to detect active RA. In addition, IL-23 is involved in disease progression and bony erosions in patients with RA.展开更多
Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The...Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.展开更多
The dendritic cell vaccine is a treatment vaccine with potent clinical applications.Functional cytokines can enhance dendritic cell anti-tumor immune responses.This experiment was conducted to study the effects of bon...The dendritic cell vaccine is a treatment vaccine with potent clinical applications.Functional cytokines can enhance dendritic cell anti-tumor immune responses.This experiment was conducted to study the effects of bone marrow-derived dendritic cells(BM-DCs)modified with genes encoding murine interleukin-23(IL-23)on murine pancreatic carcinoma,and effects of the treatment of pancreatic carcinoma with β-elemene combined with IL-23-modified dendritic cell vaccine.The murine IL-23 cDNA was sub-cloned into a dual-expression vector.DCs were pulsed with tumor cell lysate after being modified wth IL-23.Mice were divided into groups which were injected with IL-23-transduced DC vaccine,non-transduced DC vaccine and sodium respectively.The preventive immune and immunotherapeutic effects of DC vaccines on mice and cytokine release in vivo were then assessed.Results showed inhibitory effects on tumor cells and increased survival time in the experimental group treated with the vaccine combined with β-elemene.The IL-23 protein apparently increases the antigen presenting ability of DCs.After injection with DC vaccines,IFN-γ production in the treatment group was significantly increased as compared with that in the control group(P<0.01),and IL-4 production was decreased as compared with that in the control group(P<0.05).Tumor size was obviously reduced,and survival time clearly prolonged in the group with β-elemene combined with DC vaccine,in comparison to the other treatment groups and the control(P<0.01).IL-23-modified dendritic cell vaccines enhance specific Th1-type and cytotoxic T lymphocyte(CTL)responses against pancreatic carcinoma cells,and induce not only auto-immune ability but also preventive immunity against pancreatic carcinoma implanted in mice.β-elemene has great anti-tumor collaborative functions.展开更多
目的观察咳喘镇定汤在小儿咳嗽变异性哮喘治疗中的作用及对患儿嗜酸性粒细胞计数(eosinophil count,EOS)、白介素-23(interleukin-23,IL-23)/辅助性T细胞17(helper T cells17,Th17)轴的影响。方法选取2020年8月—2023年2月收治的小儿咳...目的观察咳喘镇定汤在小儿咳嗽变异性哮喘治疗中的作用及对患儿嗜酸性粒细胞计数(eosinophil count,EOS)、白介素-23(interleukin-23,IL-23)/辅助性T细胞17(helper T cells17,Th17)轴的影响。方法选取2020年8月—2023年2月收治的小儿咳嗽变异性哮喘患儿104例,将患儿采用简单随机法分为两组。常规组给予止咳化痰、抗炎、平喘等常规治疗,咳喘镇定汤组在常规组基础上采用咳喘镇定汤辅助治疗。检测组间及组内T淋巴亚群、EOS、巨噬细胞炎症蛋白-1α(macrophage inflammatory protein-1α,MIP-1α)、Clara细胞分泌蛋白16(clara cell secreted protein 16,CC-16)、嗜酸细胞活化趋化因子(Eotaxin)、IL-23/Th17轴、小气道功能水平。评估组间及组内咳嗽症状评分、中医证候评分差异。统计组间疗效和不良反应。结果治疗前T淋巴亚群、CC-16、Eotaxin等差异无统计学意义(P>0.05)。两组治疗后CD_(8)^(+)、EOS、MIP-1α、Eotaxin降低,CC-16、CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+)升高,咳喘镇定汤组治疗后CD_(8)^(+)、EOS、MIP-1α、Eotaxin低于常规组,CC-16、CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+)高于常规组(P<0.05)。治疗前比较IL-23/Th17轴差异无统计学意义(P>0.05)。两组治疗后IL-23、Th17、白介素-17(interleukin-17,IL-17)降低,咳喘镇定汤组治疗后IL-23/Th17轴低于常规组(P<0.05)。治疗前相关评分无差异(P>0.05)。两组治疗后咳嗽症状评分、中医证候评分降低,咳喘镇定汤组治疗后咳嗽症状评分、中医症候评分低于常规组(P<0.05)。治疗前小气道功能无差异(P>0.05)。两组治疗后小气道功能升高,咳喘镇定汤组治疗后小气道功能高于常规组(P<0.05)。咳喘镇定汤组治愈13例,显效和有效共35例,总有效率92.31%高于常规组,差异有统计学意义(P<0.05)。结论咳喘镇定汤可通过调控小儿咳嗽变异性哮喘患儿IL-23/Th17轴,改善T淋巴亚群和小气道功能,减轻咳嗽症状,提高疗效。展开更多
文摘AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response mediators. METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 ageand sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH) 2 -Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PⅢNP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PⅢNP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PⅢNP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PⅢNP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PⅢNP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCVinduced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated. CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PⅢNP highlight their involvement in the immune response in patients with HCV-4related liver diseases in Egypt.
基金Hubei Natural Science Foundation of China(2015CFB701).
文摘Objective: To investigate the effect of interleukin-23 (IL-23) on myocardial ischemia-reperfusion (I/R) injury.Methods: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO) group, ischemia and reperfusion (I/R) group, (IL-23 + I/R) group and (anti-IL-23 + I/R) group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH), creatine kinase (CK) and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-α and IL-6 were detected by Elisa. Results: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK. Meanwhile, IL-23 significantly increased the expression of eIL-17A, TNF-α and IL-6 and enhanced both the increase of the MDA level and the decrease of the SOD level induced by I/R. IL-23 had no effect on the expression of HMGB1. All these effects were abolished by anti-IL-23 administration. Conclusion: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction.
文摘In order to investigate the mRNA expression and function of interleukin-23 （p 19/p40） and interleukin-12 （p35/p40） in the psoriatic lesion, no-lesion and normal human skin, reverse transcriptase-polymerase chain reaction （RT-PCR） was used to detect the expression of IL-23 （p19/p40） and IL-12 （p35/p40）. The results showed that the expression of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic lesion than those of non-lesional skin and normal skin. The levels of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic non-lesional skin than normal skin. However, no significant difference was found in the level of IL-12p35 mRNA among the psoriatic lesional skin, nonesional skin and normal skin. It was suggested that IL-23 might be more important in the pathogenesis of psoriasis than IL- 12.
基金supported by the National Natural Science Foundational of China(Key Program),No.U24A20692(to CJZ)the National Natural Science Foundational of China,Nos.82101414(to MLJ),82371355(to CJZ)+4 种基金the National Natural Science Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovation and Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’s Hospital,No.30420230005(to CJZ)Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(to CJZ)。
文摘The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.
文摘Objective：The interleukin-23 receptor （IL-23R） has been shown to be associated with autoimmune diseases in many different populations.This study aimed to investigate the association between IL-23R gene polymorphism and susceptibility to Hashimoto＇s thyroiditis （HT） in Chinese Han population of Shandong.Methods：A case-control cohort study was performed in 145 HT patients from First People＇s Hospital of Jining between February 2010 to October 2013 and 150 healthy controls.Two single nucleotide polymorphisms located in the promoter region ofIL-23R gene （rs 17375018 and rs7517847） were examined by polymerase chain reaction-restriction fragment length polymorphism analysis.Hardy-Weinberg equilibrium was performed using the Chi-square test.Genotype frequencies were estimated by direct counting,and allele and genotype frequencies between patients and controls were analyzed by the Chi-square test.Results：The rs 17375018 GG genotype and the G allele were significantly increased in HT patients compared with healthy controls （P =0.034 and P =0.013,respectively）.No association was identified between HT patients and healthy controls in rs7517847.Conclusion：The study demonstrated that polymorphism of IL-23R gene rs17375018 is highly associated with HT in Chinese Han population of Shandong,suggesting that IL-23R gene polymorphism （rs 17375018 G） may play a critical role in susceptibility to HT.
基金This research was supported by a grant from the National Natural Science Foundation of China （No. 81072450）
文摘Background Interleukin-23 （IL-23） is a pro-inflammatory cytokine that is thought to be central to the development of autoimmune diseases. This study was conducted to determine whether or not the serum concentration of IL-23 is elevated in patients with rheumatoid arthritis （RA）, and to determine the relationship between the IL-23 level and disease activity in RA patients. Methods Serum samples were obtained from 59 patients with RA and 30 healthy controls. The clinical parameters of disease activity were determined, including the 28-joint disease activity score （DAS28）, C-reactive protein （CRP）, rheumatoid factor （RF） levels, and the degree of bony erosions based on X-rays. The levels of IL-23 and IL-17 were determined by enzyme-linked immunosorbent assay （ELISA）. The correlations between the serum levels of IL-23 and disease activity parameters of patients with RA were determined. Results The serum IL-23 level was significantly elevated in patients with RA compared to healthy controls. The serum IL-23 levels in the RA patients correlated with IL-17 and CRP levels, and the DAS28. The levels of IL-23 based on X-ray classification phase I, II, III, and IV were gradually elevated in RA patients. Conclusions The levels of serum IL-23 in RA patients were higher than in healthy controls. Thus, elevated serum IL-23 levels may be useful markers to detect active RA. In addition, IL-23 is involved in disease progression and bony erosions in patients with RA.
基金supported by the National Natural Science Foundation of China,Nos. 82173806 and U1803281Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science,Nos. 2021-I2M-1-030 and 2022-I2M-2-002Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-JKCS-08 (all to RL)。
文摘Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
文摘The dendritic cell vaccine is a treatment vaccine with potent clinical applications.Functional cytokines can enhance dendritic cell anti-tumor immune responses.This experiment was conducted to study the effects of bone marrow-derived dendritic cells(BM-DCs)modified with genes encoding murine interleukin-23(IL-23)on murine pancreatic carcinoma,and effects of the treatment of pancreatic carcinoma with β-elemene combined with IL-23-modified dendritic cell vaccine.The murine IL-23 cDNA was sub-cloned into a dual-expression vector.DCs were pulsed with tumor cell lysate after being modified wth IL-23.Mice were divided into groups which were injected with IL-23-transduced DC vaccine,non-transduced DC vaccine and sodium respectively.The preventive immune and immunotherapeutic effects of DC vaccines on mice and cytokine release in vivo were then assessed.Results showed inhibitory effects on tumor cells and increased survival time in the experimental group treated with the vaccine combined with β-elemene.The IL-23 protein apparently increases the antigen presenting ability of DCs.After injection with DC vaccines,IFN-γ production in the treatment group was significantly increased as compared with that in the control group(P<0.01),and IL-4 production was decreased as compared with that in the control group(P<0.05).Tumor size was obviously reduced,and survival time clearly prolonged in the group with β-elemene combined with DC vaccine,in comparison to the other treatment groups and the control(P<0.01).IL-23-modified dendritic cell vaccines enhance specific Th1-type and cytotoxic T lymphocyte(CTL)responses against pancreatic carcinoma cells,and induce not only auto-immune ability but also preventive immunity against pancreatic carcinoma implanted in mice.β-elemene has great anti-tumor collaborative functions.
文摘目的观察咳喘镇定汤在小儿咳嗽变异性哮喘治疗中的作用及对患儿嗜酸性粒细胞计数(eosinophil count,EOS)、白介素-23(interleukin-23,IL-23)/辅助性T细胞17(helper T cells17,Th17)轴的影响。方法选取2020年8月—2023年2月收治的小儿咳嗽变异性哮喘患儿104例,将患儿采用简单随机法分为两组。常规组给予止咳化痰、抗炎、平喘等常规治疗,咳喘镇定汤组在常规组基础上采用咳喘镇定汤辅助治疗。检测组间及组内T淋巴亚群、EOS、巨噬细胞炎症蛋白-1α(macrophage inflammatory protein-1α,MIP-1α)、Clara细胞分泌蛋白16(clara cell secreted protein 16,CC-16)、嗜酸细胞活化趋化因子(Eotaxin)、IL-23/Th17轴、小气道功能水平。评估组间及组内咳嗽症状评分、中医证候评分差异。统计组间疗效和不良反应。结果治疗前T淋巴亚群、CC-16、Eotaxin等差异无统计学意义(P>0.05)。两组治疗后CD_(8)^(+)、EOS、MIP-1α、Eotaxin降低,CC-16、CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+)升高,咳喘镇定汤组治疗后CD_(8)^(+)、EOS、MIP-1α、Eotaxin低于常规组,CC-16、CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+)高于常规组(P<0.05)。治疗前比较IL-23/Th17轴差异无统计学意义(P>0.05)。两组治疗后IL-23、Th17、白介素-17(interleukin-17,IL-17)降低,咳喘镇定汤组治疗后IL-23/Th17轴低于常规组(P<0.05)。治疗前相关评分无差异(P>0.05)。两组治疗后咳嗽症状评分、中医证候评分降低,咳喘镇定汤组治疗后咳嗽症状评分、中医症候评分低于常规组(P<0.05)。治疗前小气道功能无差异(P>0.05)。两组治疗后小气道功能升高,咳喘镇定汤组治疗后小气道功能高于常规组(P<0.05)。咳喘镇定汤组治愈13例,显效和有效共35例,总有效率92.31%高于常规组,差异有统计学意义(P<0.05)。结论咳喘镇定汤可通过调控小儿咳嗽变异性哮喘患儿IL-23/Th17轴,改善T淋巴亚群和小气道功能,减轻咳嗽症状,提高疗效。
