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
Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that ...Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.展开更多
目的探究视黄酸相关孤儿受体(RORγt)白细胞介素23(IL-23)通路调节辅助性T细胞17(Th17)在老年盐敏感性高血压发病中的作用。方法对内蒙古自治区的村民进行调查,2021年1月至2022年1月选取289例老年高血压患者作为研究对象,采用Sullivan...目的探究视黄酸相关孤儿受体(RORγt)白细胞介素23(IL-23)通路调节辅助性T细胞17(Th17)在老年盐敏感性高血压发病中的作用。方法对内蒙古自治区的村民进行调查,2021年1月至2022年1月选取289例老年高血压患者作为研究对象,采用Sullivan盐负荷试验将患者进行分组,盐敏感高血压患者103例作为研究组,非盐敏感高血压患者186例作为对照组,给予慢性盐负荷试验。结果研究组收缩压、舒张压、MAP、心率在D10、D17均显著高于对照组(P<0.01)。2组尿量、尿钠、尿钾、尿肌酐水平在基线D3比较无显著差异(P>0.05),D10与对照组比较,研究组尿钠[(315.32±57.21)mmol/24 h vs(226.64±58.53)mmol/24 h,P=0.000]、尿肌酐[(12.46±1.64)mmol/24 h vs(10.12±1.17)mmol/24 h,P=0.000]显著增高。2组Th17比例、IL-17A水平在D4、D5、D10逐渐上升,在D17下降,且研究组Th17比例、IL-17A水平在D4、D5、D10、D17均显著高于对照组(P<0.01)。结论Th17参与了盐敏感性高血压的发生,RORγt-IL-23受体信号通路可诱导Th17细胞分化。展开更多
AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD gene...AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed <19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS: The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced signifi cantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.展开更多
BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in ge...BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)- 23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS We analysed 133 patients with intestinal tuberculosis, 128 with Crohn’s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.展开更多
Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPas...Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPase activi-ty in semen by phosphorus (Pi) assay. Results: The slL-2R level in serum was significantly higher and the Na^+ -K^+ -exchanging ATPase activity in semen significantly lower in AsAb positive infertile men when compared with thecontrols. Conclusion: The AsAb titer varies with the slL-2R level in serum. A decrease in Na^+ -K^+ -exchangingATPase activity in semen may play a role in male infertility caused by AsAb.展开更多
AIM:To elucidate the effect of rapamycin on regulating the production of interleukin(IL)-1β in Aspergillus fumigatus(A.fumigatus)-induced keratitis and to verify whether the expression of IL-1β in A.fumigatus k...AIM:To elucidate the effect of rapamycin on regulating the production of interleukin(IL)-1β in Aspergillus fumigatus(A.fumigatus)-induced keratitis and to verify whether the expression of IL-1β in A.fumigatus keratitis is associated with the mammalian target of rapamycin(mT OR)/Toll-like receptor 4(TLR4) signaling pathway.METHODS:Fungal keratitis mouse models of susceptible C57 BL/6 mice were established using A.fumigatus.The mice were subsequently treated with rapamycin.The protein levels of p-mT OR,TLR4,and IL-1β in normal and infected corneal tissue were measured by Western blot.The TLR4 and IL-1β m RNA levels were determined by real-time polymerase chain reaction(PCR).RESULTS:In C57 BL/6 mice,rapamycin treatment decreased the clinical scores and production of the pro-inflammatory cytokine,IL-1β.The expression of TLR4,stimulated by A.fumigatus,was reduced as well when the mT OR signaling pathway was suppressed by rapamycin.CONCLUSION:Rapamycin is beneficial for the outcome of fungal keratitis and has an inhibitory effect expression of the inflammatory cytokine IL-1β.The inhibitory effect on IL-1β expression can be associated with the mT OR/TLR4 signaling pathway in A.fumigatus infection in mice.展开更多
Interleukin-34(IL-34)is a novel cytokine that plays an important role in innate immunity and inflammatory processes by binding to the colonystimulating factor-1 receptor(CSF-1R).However,information on the function of ...Interleukin-34(IL-34)is a novel cytokine that plays an important role in innate immunity and inflammatory processes by binding to the colonystimulating factor-1 receptor(CSF-1R).However,information on the function of IL-34 in fish remains limited.In the present study,we identified an IL-34 homolog from mudskippers(Boleophthalmus pectinirostris).In silico analysis showed that the mudskipper IL-34(BpIL-34)was similar to other known IL-34 variants in sequence and structure and was most closely related to an orange-spotted grouper(Epinephelus coioides)homolog.BpIL-34 transcripts were constitutively expressed in various tissues,with the highest level of expression found in the brain.Edwardsiella tarda infection significantly up-regulated the mRNA expression of BpIL-34 in the mudskipper tissues.The recombinant mature BpIL-34 peptide(rBpIL-34)was purified and used to produce anti-rBpIL-34 IgG.Western blot analysis combined with PNGase F digestion revealed that native BpIL-34 in monocytes/macrophages(MOs/MФs)was N-glycosylated.In vitro,rBpIL-34 treatment enhanced the phagocytotic and bactericidal activity of mudskipper MOs/MФs,as well as the mRNA expression of pro-inflammatory cytokines like tumor necrosis factorα(BpTNF-α)and BpIL-1βin these cells.Furthermore,the knockdown of mudskipper CSF-1R1(BpCSF-1R1),but not mudskipper BpCSF-1R2,significantly inhibited the rBpIL-34-mediated enhanced effect on MO/MФfunction.In conclusion,our results indicate that mudskipper BpIL-34 modulates the functions of MOs/MФs via BpCSF-1R1.展开更多
AIM:To investigate the effect of Tenascin C(TNC)on the expression of pro-inflammatory cytokines and matrixmetalloproteinases in human cardiac myofibroblasts(CMF).METHODS:CMF were isolated and cultured from patients un...AIM:To investigate the effect of Tenascin C(TNC)on the expression of pro-inflammatory cytokines and matrixmetalloproteinases in human cardiac myofibroblasts(CMF).METHODS:CMF were isolated and cultured from patients undergoing coronary artery bypass grafting.Cultured cells were treated with either TNC(0.1μmol/L,24 h)or a recombinant protein corresponding to different domains of the TNC protein;fibrinogen-like globe(FBG)and fibronectin typeⅢ-like repeats(TNⅢ5-7)(both 1μmol/L,24 h).The expression of the proinflammatory cytokines;interleukin(IL)-6,IL-1β,TNFαand the matrix metalloproteinases;MMPs(MMP1,2,3,9,10,MT1-MMP)was assessed using real time RT-PCR and western blot analysis.RESULTS:TNC increased both IL-6 and MMP3(P<0.01)mR NA levels in cultured human CMF but had no significant effect on the other markers studied.The increase in IL-6 mR NA expression was mirrored by an increase in protein secretion as assessed by enzymelinked immunosorbant assay(P<0.01).Treating CMF with the recombinant protein FBG increased IL-6mR NA and protein(P<0.01)whereas the recombinant protein TNⅢ5-7 had no effect.Neither FBG nor TNⅢ5-7 had any significant effect on MMP3 expression.The expression of toll-like receptor 4(TLR4)in human CMF was confirmed by real time RT-PCR,western blot and immunohistochemistry.Pre-incubation of cells with TLR4neutralising antisera attenuated the effect of both TNC and FBG on IL-6 mR NA and protein expression.CONCLUSION:TNC up-regulates IL-6 expression in human CMF,an effect mediated through the FBG domain of TNC and via the TLR4 receptor.展开更多
AIM: To study the efficacy of marrow mesenchymal stem cells (MSCs) transplantation combined with interleukin-1 receptor antagonist (IL-1Ra) for acute liver failure (ALF). METHODS: Chinese experimental miniature swine ...AIM: To study the efficacy of marrow mesenchymal stem cells (MSCs) transplantation combined with interleukin-1 receptor antagonist (IL-1Ra) for acute liver failure (ALF). METHODS: Chinese experimental miniature swine were randomly divided into four groups (n = 7), and all animals were given D-galactosamine (D-gal) to induce ALF. Group A animals were then injected with 40 mL saline via the portal vein 24 h after D-gal induction;Group B animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h, 2 d and 4 d after D-gal induction; Group C received approximately 1 × 108 green fluorescence protein (GFP)-labeled MSCs (GFP-MSCs) suspended in 40 mL normal saline via the portal vein 24 h after D-gal induction; Group D animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h after D-gal induction, MSCs transplantation was then carried out at 24 h after D-gal induction, and finally 2 mg/kg IL-1Ra was injected via the ear vein 1 d and 3 d after surgery as before. Liver function, serum inflammatory parameters and pathological changes were measured and the fate of MSCs was determined.RESULTS: The optimal efficiency of transfection (97%) was achieved at an multiplicity of infection of 80, as observed by fluorescence microscopy and flow cytometry (FCM). Over 90% of GFP-MSCs were identified as CD44+ CD90+ CD45-MSCs by FCM, which indicated that most GFP-MSCs retained MSCs characteristics. Biochemical assays, the levels of serum inflammatory parameters and histological results in Group D all showed a significant improvement in liver injury compared with the other groups (P < 0.05). The number of GFP-MSCs in Group D was also greater than that in Group B, and the long-term cell proliferation rate was also better in Group D than in the other groups.CONCLUSION: MSCs transplantation is useful in ALF, IL-1Ra plays an important role in alleviating the inflammatory condition, and combination therapy with MSCs transplantation and IL-1Ra is a promising treatment for ALF.展开更多
Objective The current study was designed to find out the effect of Glucosidorum Tripterygii Totorum (GTT) on the serum level of soluble interleukin-2 receptor (sIL-2R) in patient with ankylosing spondylitis (AS). Meth...Objective The current study was designed to find out the effect of Glucosidorum Tripterygii Totorum (GTT) on the serum level of soluble interleukin-2 receptor (sIL-2R) in patient with ankylosing spondylitis (AS). Method 29 patients with active AS were selected to take GTT (1mg per kg) three times a day for one year. After that, its curative effect was evaluated. The serum level of sIL-2R of these patients was measured by sandwich ELISA method and was compared with that of normal subjects. Result The serum level of sIL-2R in active AS patients was obviously higher than that of the non-active AS patients. (P<0.01). The total effective rate of GTT on AS was 89.6%, while clinical relief rate 27.6%, obvious effective rate 44.8%, effective rate 17.2% and non-effective rate 10.4%. The patients’ serum level of sIL-2R after therapy was significantly lower than that before therapy except patients with no effect. (P<0.05). Conclusion GTT has positive curative effect on active AS patients and could cause obvious decrease of the serum level of sIL-2R. The serum level of sIL-2R can be used as an important index of activity of AS and as a guide of therapy.展开更多
Objective: to explore the mechanism of leeching in treating systemic lupus erythematosus (SLE). Methods: Forty-four patients with SLE were randomly divided into conventional corticosteroid treated group (control group...Objective: to explore the mechanism of leeching in treating systemic lupus erythematosus (SLE). Methods: Forty-four patients with SLE were randomly divided into conventional corticosteroid treated group (control group, n =20) and conventional treatment group with leeching intervention added (leeching group, n =24). Before and after treatment the concentration of plasma endothelin (ET) and soluble interleukin-2 receptor (sIL-2R) were determined. Results: Before treatment the level of plasma ET and sIL-2R in the SLE patients were all higher than those in the normal healthy group, ( P <0.01). But after treatment the level of these in both groups were significantly improved than those of before treatment ( P <0.05), and comparison between these two treated groups showed that the difference between them was significant ( P <0.05). Conclusion: Leeching added to conventional treatment of SLE could be more effective in improving the level of plasma ET and sIL-2R, and ameliorating the impairment of renal tissues.展开更多
Summary: Human interleukin-15 (hIL-15) is an important cytokine to activate endothelial cells and can be regulated by many other cytokines. The aim of this study is to examine the ability of interferon-γ (IFN-γ...Summary: Human interleukin-15 (hIL-15) is an important cytokine to activate endothelial cells and can be regulated by many other cytokines. The aim of this study is to examine the ability of interferon-γ (IFN-γ), and tumor necrosis factor-or (TNF-α to induce the production of human interleukin-15 (hIL-15) and IL-15 receptor (IL-15Rα by human umbilical vein endothelial cells (HUVECs). The data are summarized as follows: 1. Northern blot revealed that IL-15 mRNA was up-regulated by IFN-γ and TNF-α 2. Intracellular IL-15 protein was visualized by fluorescence microscopy, whereas the expression of IL-15 on the surface of HUVECs was detected by fluorescence activated cell sorting (FACS), and no detectable IL-15 in the medium was verified by ELISA. 3. IL-15Rα was detected on the surface of HUVECs by FACS after IFN-α and TNF-α stimulation, whereas Western blotting revealed that the elevated expression on surface IL-15Rα was not due to the increased protein expression. The conclusion demonstrated from our results is that IFN-α and TNF-α play an important role in regulating the expression of IL-15 and IL-15Rα on the surface of HUVECs.展开更多
It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5-hydroxytryptamine (HT)2c receptor functioning. The a...It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5-hydroxytryptamine (HT)2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were.investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes (Cys/Cys) is significantly lower (22.6s; 95% CI 18.3-27.8s) than in male homozygous mutants (Ser/Ser) (40.4s; 95% CI 20.3-80.4s) (P = 0.03). It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.展开更多
Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effec...Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effects of aprotinin on them were observed. Twenty patients undergoing heart valve (s) replacement were randomly divided into two groups: control group (n=10) and apro- tinin group (n=10). In aprotinin group, 1 000 000 KIU aprotinin was given by vein injection and then 2 000 000 KIU was given as a bolus in prime. Blood samples were collected before CPB, right after CPB and on the 1st, 3rd and 7th postoperative day (POD) for serum IL-2 and sIL-2R determination. Results showed that after CPB, IL-2 was reduced and slL-2R increased. Meanwhile, serum IL-2R was lower in aprotinin group than that of control. It is concluded that the immunity depression after CPB is associated with low level of IL-2 and high level of sIL-2R and aprotinin can ameliorate the situation.展开更多
Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the pres...Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the presence of the anti-glutamic acid decarboxylase antibody (anti-GADab). Fulminant type 1 diabetes is classified as type 1B diabetes, and characterized by the absence of anti-GADab, flu-like symptoms, and elevated serum exocrine pancreatic enzymes. We report a type 1 diabetic patient who showed flu-like symptoms, elevated serum exocrine pancreatic enzymes, and an extremely high-titer of anti-GADab, manifesting the characteristics of both type 1A and fulminant type 1 diabetes.展开更多
Objective: Recent studies have shown that the local expression of soluble interleukin (IL) -1 receptor type Ⅱ (slL-1 R Ⅱ ) in endometrial tissue of women with endometriosis is decreased, and the depression of I...Objective: Recent studies have shown that the local expression of soluble interleukin (IL) -1 receptor type Ⅱ (slL-1 R Ⅱ ) in endometrial tissue of women with endometriosis is decreased, and the depression of IL-1 R Ⅱ was more significant in infertile women than that in fertile women with endometriosis. In this research, we investigated the remedial effect of slL-1-R Ⅱ administration on endometriosis in the nude mouse model. Methods: Nineteen nude model mice with endometriosis were randomly divided into three groups: group A was treated by intraperitoneal administration with only slL-1 R Ⅱ for two weeks, group B was similarly treated with only IL- 1, and group C (control) was administered saline. After 2 weeks, the size of the ectopic endometrial lesions was calculated, and the expression of vascular endothelial growth factor (VEGF) and B-cell lymphoma leukemia-2 (Bcl- 2) were detected by immunohistochemistry. The IL-8 and VEGF levels in the peritoneal fluid (PF) and serum were also measured by enzyme-linked immunosorbent assay (ELISA). Results: The mean size of ectopic endometrial lesion did not differ between the three groups (P 〉 0.05). Compared with the control, the expression of VEGF and Bcl-2 was significantly lower in group A, and higher in group B. In the three groups, the levels of IL-8 in the PF and serum were highest in group A, and lowest in group B. Conclusion: slL-1 R Ⅱ may suppresse hyperplasia of ectopic endometriosis, perhaps by reducing the expression of certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new clinical strategy for the treatment of endometriosis.展开更多
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National Key R&D Program of China,Nos.2019YFA0110300 (to LZ),2021YFA1201400 (to LZ)Natural Science Foundation of Shanghai,No.21ZR1468600 (to LZ)Open Fund of the Key Laboratory of Cellular Physiology (Shanxi Medical University),Ministry of Education,No.KLMEC/SXMU-201910 (to XJ)。
文摘Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.
文摘目的探究视黄酸相关孤儿受体(RORγt)白细胞介素23(IL-23)通路调节辅助性T细胞17(Th17)在老年盐敏感性高血压发病中的作用。方法对内蒙古自治区的村民进行调查,2021年1月至2022年1月选取289例老年高血压患者作为研究对象,采用Sullivan盐负荷试验将患者进行分组,盐敏感高血压患者103例作为研究组,非盐敏感高血压患者186例作为对照组,给予慢性盐负荷试验。结果研究组收缩压、舒张压、MAP、心率在D10、D17均显著高于对照组(P<0.01)。2组尿量、尿钠、尿钾、尿肌酐水平在基线D3比较无显著差异(P>0.05),D10与对照组比较,研究组尿钠[(315.32±57.21)mmol/24 h vs(226.64±58.53)mmol/24 h,P=0.000]、尿肌酐[(12.46±1.64)mmol/24 h vs(10.12±1.17)mmol/24 h,P=0.000]显著增高。2组Th17比例、IL-17A水平在D4、D5、D10逐渐上升,在D17下降,且研究组Th17比例、IL-17A水平在D4、D5、D10、D17均显著高于对照组(P<0.01)。结论Th17参与了盐敏感性高血压的发生,RORγt-IL-23受体信号通路可诱导Th17细胞分化。
基金The National Minister of Health grant, No. RC0702GA35
文摘AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed <19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS: The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced signifi cantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.
基金Supported by Key R&D Plan of Science and Technology Department of Jiangxi Province,No.20171BBG70087
文摘BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)- 23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS We analysed 133 patients with intestinal tuberculosis, 128 with Crohn’s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.
文摘Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPase activi-ty in semen by phosphorus (Pi) assay. Results: The slL-2R level in serum was significantly higher and the Na^+ -K^+ -exchanging ATPase activity in semen significantly lower in AsAb positive infertile men when compared with thecontrols. Conclusion: The AsAb titer varies with the slL-2R level in serum. A decrease in Na^+ -K^+ -exchangingATPase activity in semen may play a role in male infertility caused by AsAb.
基金Supported by the National Natural Science Foundation of China(No.81470609No.81500695)
文摘AIM:To elucidate the effect of rapamycin on regulating the production of interleukin(IL)-1β in Aspergillus fumigatus(A.fumigatus)-induced keratitis and to verify whether the expression of IL-1β in A.fumigatus keratitis is associated with the mammalian target of rapamycin(mT OR)/Toll-like receptor 4(TLR4) signaling pathway.METHODS:Fungal keratitis mouse models of susceptible C57 BL/6 mice were established using A.fumigatus.The mice were subsequently treated with rapamycin.The protein levels of p-mT OR,TLR4,and IL-1β in normal and infected corneal tissue were measured by Western blot.The TLR4 and IL-1β m RNA levels were determined by real-time polymerase chain reaction(PCR).RESULTS:In C57 BL/6 mice,rapamycin treatment decreased the clinical scores and production of the pro-inflammatory cytokine,IL-1β.The expression of TLR4,stimulated by A.fumigatus,was reduced as well when the mT OR signaling pathway was suppressed by rapamycin.CONCLUSION:Rapamycin is beneficial for the outcome of fungal keratitis and has an inhibitory effect expression of the inflammatory cytokine IL-1β.The inhibitory effect on IL-1β expression can be associated with the mT OR/TLR4 signaling pathway in A.fumigatus infection in mice.
基金supported by the National Natural Science Foundation of China(3197282131772876)+3 种基金the Program of Zhejiang Provincial Natural Science Foundation of China(LZ18C190001)Science and Technology Department of Zhejiang Province(LGN18C180002)Natural Science Foundation of Ningbo City(2018A610342)the K.C.Wong Magna Fund in Ningbo University。
文摘Interleukin-34(IL-34)is a novel cytokine that plays an important role in innate immunity and inflammatory processes by binding to the colonystimulating factor-1 receptor(CSF-1R).However,information on the function of IL-34 in fish remains limited.In the present study,we identified an IL-34 homolog from mudskippers(Boleophthalmus pectinirostris).In silico analysis showed that the mudskipper IL-34(BpIL-34)was similar to other known IL-34 variants in sequence and structure and was most closely related to an orange-spotted grouper(Epinephelus coioides)homolog.BpIL-34 transcripts were constitutively expressed in various tissues,with the highest level of expression found in the brain.Edwardsiella tarda infection significantly up-regulated the mRNA expression of BpIL-34 in the mudskipper tissues.The recombinant mature BpIL-34 peptide(rBpIL-34)was purified and used to produce anti-rBpIL-34 IgG.Western blot analysis combined with PNGase F digestion revealed that native BpIL-34 in monocytes/macrophages(MOs/MФs)was N-glycosylated.In vitro,rBpIL-34 treatment enhanced the phagocytotic and bactericidal activity of mudskipper MOs/MФs,as well as the mRNA expression of pro-inflammatory cytokines like tumor necrosis factorα(BpTNF-α)and BpIL-1βin these cells.Furthermore,the knockdown of mudskipper CSF-1R1(BpCSF-1R1),but not mudskipper BpCSF-1R2,significantly inhibited the rBpIL-34-mediated enhanced effect on MO/MФfunction.In conclusion,our results indicate that mudskipper BpIL-34 modulates the functions of MOs/MФs via BpCSF-1R1.
文摘AIM:To investigate the effect of Tenascin C(TNC)on the expression of pro-inflammatory cytokines and matrixmetalloproteinases in human cardiac myofibroblasts(CMF).METHODS:CMF were isolated and cultured from patients undergoing coronary artery bypass grafting.Cultured cells were treated with either TNC(0.1μmol/L,24 h)or a recombinant protein corresponding to different domains of the TNC protein;fibrinogen-like globe(FBG)and fibronectin typeⅢ-like repeats(TNⅢ5-7)(both 1μmol/L,24 h).The expression of the proinflammatory cytokines;interleukin(IL)-6,IL-1β,TNFαand the matrix metalloproteinases;MMPs(MMP1,2,3,9,10,MT1-MMP)was assessed using real time RT-PCR and western blot analysis.RESULTS:TNC increased both IL-6 and MMP3(P<0.01)mR NA levels in cultured human CMF but had no significant effect on the other markers studied.The increase in IL-6 mR NA expression was mirrored by an increase in protein secretion as assessed by enzymelinked immunosorbant assay(P<0.01).Treating CMF with the recombinant protein FBG increased IL-6mR NA and protein(P<0.01)whereas the recombinant protein TNⅢ5-7 had no effect.Neither FBG nor TNⅢ5-7 had any significant effect on MMP3 expression.The expression of toll-like receptor 4(TLR4)in human CMF was confirmed by real time RT-PCR,western blot and immunohistochemistry.Pre-incubation of cells with TLR4neutralising antisera attenuated the effect of both TNC and FBG on IL-6 mR NA and protein expression.CONCLUSION:TNC up-regulates IL-6 expression in human CMF,an effect mediated through the FBG domain of TNC and via the TLR4 receptor.
基金Supported by National Natural Science Foundation of China,No. 30901431
文摘AIM: To study the efficacy of marrow mesenchymal stem cells (MSCs) transplantation combined with interleukin-1 receptor antagonist (IL-1Ra) for acute liver failure (ALF). METHODS: Chinese experimental miniature swine were randomly divided into four groups (n = 7), and all animals were given D-galactosamine (D-gal) to induce ALF. Group A animals were then injected with 40 mL saline via the portal vein 24 h after D-gal induction;Group B animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h, 2 d and 4 d after D-gal induction; Group C received approximately 1 × 108 green fluorescence protein (GFP)-labeled MSCs (GFP-MSCs) suspended in 40 mL normal saline via the portal vein 24 h after D-gal induction; Group D animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h after D-gal induction, MSCs transplantation was then carried out at 24 h after D-gal induction, and finally 2 mg/kg IL-1Ra was injected via the ear vein 1 d and 3 d after surgery as before. Liver function, serum inflammatory parameters and pathological changes were measured and the fate of MSCs was determined.RESULTS: The optimal efficiency of transfection (97%) was achieved at an multiplicity of infection of 80, as observed by fluorescence microscopy and flow cytometry (FCM). Over 90% of GFP-MSCs were identified as CD44+ CD90+ CD45-MSCs by FCM, which indicated that most GFP-MSCs retained MSCs characteristics. Biochemical assays, the levels of serum inflammatory parameters and histological results in Group D all showed a significant improvement in liver injury compared with the other groups (P < 0.05). The number of GFP-MSCs in Group D was also greater than that in Group B, and the long-term cell proliferation rate was also better in Group D than in the other groups.CONCLUSION: MSCs transplantation is useful in ALF, IL-1Ra plays an important role in alleviating the inflammatory condition, and combination therapy with MSCs transplantation and IL-1Ra is a promising treatment for ALF.
文摘Objective The current study was designed to find out the effect of Glucosidorum Tripterygii Totorum (GTT) on the serum level of soluble interleukin-2 receptor (sIL-2R) in patient with ankylosing spondylitis (AS). Method 29 patients with active AS were selected to take GTT (1mg per kg) three times a day for one year. After that, its curative effect was evaluated. The serum level of sIL-2R of these patients was measured by sandwich ELISA method and was compared with that of normal subjects. Result The serum level of sIL-2R in active AS patients was obviously higher than that of the non-active AS patients. (P<0.01). The total effective rate of GTT on AS was 89.6%, while clinical relief rate 27.6%, obvious effective rate 44.8%, effective rate 17.2% and non-effective rate 10.4%. The patients’ serum level of sIL-2R after therapy was significantly lower than that before therapy except patients with no effect. (P<0.05). Conclusion GTT has positive curative effect on active AS patients and could cause obvious decrease of the serum level of sIL-2R. The serum level of sIL-2R can be used as an important index of activity of AS and as a guide of therapy.
文摘Objective: to explore the mechanism of leeching in treating systemic lupus erythematosus (SLE). Methods: Forty-four patients with SLE were randomly divided into conventional corticosteroid treated group (control group, n =20) and conventional treatment group with leeching intervention added (leeching group, n =24). Before and after treatment the concentration of plasma endothelin (ET) and soluble interleukin-2 receptor (sIL-2R) were determined. Results: Before treatment the level of plasma ET and sIL-2R in the SLE patients were all higher than those in the normal healthy group, ( P <0.01). But after treatment the level of these in both groups were significantly improved than those of before treatment ( P <0.05), and comparison between these two treated groups showed that the difference between them was significant ( P <0.05). Conclusion: Leeching added to conventional treatment of SLE could be more effective in improving the level of plasma ET and sIL-2R, and ameliorating the impairment of renal tissues.
文摘Summary: Human interleukin-15 (hIL-15) is an important cytokine to activate endothelial cells and can be regulated by many other cytokines. The aim of this study is to examine the ability of interferon-γ (IFN-γ), and tumor necrosis factor-or (TNF-α to induce the production of human interleukin-15 (hIL-15) and IL-15 receptor (IL-15Rα by human umbilical vein endothelial cells (HUVECs). The data are summarized as follows: 1. Northern blot revealed that IL-15 mRNA was up-regulated by IFN-γ and TNF-α 2. Intracellular IL-15 protein was visualized by fluorescence microscopy, whereas the expression of IL-15 on the surface of HUVECs was detected by fluorescence activated cell sorting (FACS), and no detectable IL-15 in the medium was verified by ELISA. 3. IL-15Rα was detected on the surface of HUVECs by FACS after IFN-α and TNF-α stimulation, whereas Western blotting revealed that the elevated expression on surface IL-15Rα was not due to the increased protein expression. The conclusion demonstrated from our results is that IFN-α and TNF-α play an important role in regulating the expression of IL-15 and IL-15Rα on the surface of HUVECs.
文摘It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5-hydroxytryptamine (HT)2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were.investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes (Cys/Cys) is significantly lower (22.6s; 95% CI 18.3-27.8s) than in male homozygous mutants (Ser/Ser) (40.4s; 95% CI 20.3-80.4s) (P = 0.03). It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.
基金a grant from the NationalNatural Science Foundation of China (No. 39270658).
文摘Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effects of aprotinin on them were observed. Twenty patients undergoing heart valve (s) replacement were randomly divided into two groups: control group (n=10) and apro- tinin group (n=10). In aprotinin group, 1 000 000 KIU aprotinin was given by vein injection and then 2 000 000 KIU was given as a bolus in prime. Blood samples were collected before CPB, right after CPB and on the 1st, 3rd and 7th postoperative day (POD) for serum IL-2 and sIL-2R determination. Results showed that after CPB, IL-2 was reduced and slL-2R increased. Meanwhile, serum IL-2R was lower in aprotinin group than that of control. It is concluded that the immunity depression after CPB is associated with low level of IL-2 and high level of sIL-2R and aprotinin can ameliorate the situation.
文摘Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the presence of the anti-glutamic acid decarboxylase antibody (anti-GADab). Fulminant type 1 diabetes is classified as type 1B diabetes, and characterized by the absence of anti-GADab, flu-like symptoms, and elevated serum exocrine pancreatic enzymes. We report a type 1 diabetic patient who showed flu-like symptoms, elevated serum exocrine pancreatic enzymes, and an extremely high-titer of anti-GADab, manifesting the characteristics of both type 1A and fulminant type 1 diabetes.
基金supported by funding from Innovative Research Team in Nanjing Medical University(IRT0631)the collaborating Grants(30611120524)
文摘Objective: Recent studies have shown that the local expression of soluble interleukin (IL) -1 receptor type Ⅱ (slL-1 R Ⅱ ) in endometrial tissue of women with endometriosis is decreased, and the depression of IL-1 R Ⅱ was more significant in infertile women than that in fertile women with endometriosis. In this research, we investigated the remedial effect of slL-1-R Ⅱ administration on endometriosis in the nude mouse model. Methods: Nineteen nude model mice with endometriosis were randomly divided into three groups: group A was treated by intraperitoneal administration with only slL-1 R Ⅱ for two weeks, group B was similarly treated with only IL- 1, and group C (control) was administered saline. After 2 weeks, the size of the ectopic endometrial lesions was calculated, and the expression of vascular endothelial growth factor (VEGF) and B-cell lymphoma leukemia-2 (Bcl- 2) were detected by immunohistochemistry. The IL-8 and VEGF levels in the peritoneal fluid (PF) and serum were also measured by enzyme-linked immunosorbent assay (ELISA). Results: The mean size of ectopic endometrial lesion did not differ between the three groups (P 〉 0.05). Compared with the control, the expression of VEGF and Bcl-2 was significantly lower in group A, and higher in group B. In the three groups, the levels of IL-8 in the PF and serum were highest in group A, and lowest in group B. Conclusion: slL-1 R Ⅱ may suppresse hyperplasia of ectopic endometriosis, perhaps by reducing the expression of certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new clinical strategy for the treatment of endometriosis.