Evaluating the role of interleukin-2 and interleukin-12 in pediatric patients with concurrent Mycoplasma pneumoniae and Epstein-Barr virus infections

BACKGROUND Mycoplasma pneumoniae(MP)frequently causes respiratory infections in children,whereas Epstein-Barr virus(EBV)typically presents subclinical manifestations in immunocompetent pediatric populations.The incidence of MP and EBV coinfections is often overlooked clinically,with the contributory role of EBV in pulmonary infections alongside MP remaining unclear.AIM To evaluate the serum concentrations of interleukin-2(IL-2)and interleukin-12(IL-12)in pediatric patients with MP pneumonia co-infected with EBV and assess their prognostic implications.METHODS We retrospectively analyzed clinical data from patients diagnosed with MP and EBV co-infection,isolated MP infection,and a control group of healthy children,spanning from January 1,2018 to December 31,2021.Serum IL-2 and IL-12 levels were quantified using enzyme-linked immunosorbent assay.Logistic regression was employed to identify factors influencing poor prognosis,while receiver operating characteristic(ROC)curves evaluated the prognostic utility of serum IL-2 and IL-12 levels in co-infected patients.RESULTS The co-infection group exhibited elevated serum IL-2 and C-reactive protein(CRP)levels compared to both the MP-only and control groups,with a reverse trend observed for IL-12(P<0.05).In the poor prognosis cohort,elevated CRP and IL-2 levels,alongside prolonged fever duration,contrasted with reduced IL-12 levels(P<0.05).Logistic regression identified elevated IL-2 as an independent risk factor and high IL-12 as a protective factor for adverse outcomes(P<0.05).ROC analysis indicated that the area under the curves for IL-2,IL-12,and their combination in predicting poor prognosis were 0.815,0.895,and 0.915,respectively.CONCLUSION Elevated serum IL-2 and diminished IL-12 levels in pediatric patients with MP and EBV co-infection correlate with poorer prognosis,with combined IL-2 and IL-12 levels offering enhanced predictive accuracy.

Exploring the role of interleukin-6 receptor blockade in epilepsy and associated neuropsychiatric conditions through a mendelian randomization study

BACKGROUND The interplay between inflammation,immune dysregulation,and the onset of neurological disorders,including epilepsy,has become increasingly recognized.Interleukin(IL)-6,a pro-inflammatory cytokine,is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients.The role of IL-6 receptor(IL6R)blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes.neuropsychiatric conditions due to neuroinflammation.METHODS Mendelian randomization(MR)analysis employing single nucleotide poly-morphisms(SNPs)in the vicinity of the IL6R gene(total individuals=408225)was used to evaluate the putative causal relationship between IL6R blockade and epilepsy(total cases/controls=12891/312803),focal epilepsy(cases/controls=7526/399290),and generalized epilepsy(cases/controls=1413/399287).SNP weights were determined by their effect on C-reactive protein(CRP)levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects.To address potential outlier and pleiotropic influences,sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions.RESULTS The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk[inverse variance weighting:Odds ratio(OR):0.827;95%confidence interval(CI):0.685-1.000;P=0.05].Subtype analysis showed variability,with no significant effect observed in generalized,focal,or specific childhood and juvenile epilepsy forms.Beyond the primary inflammatory marker CRP,the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy,hinting at possible links to neuroinflammation,psychiatric symptoms,and associated mental disorders.CONCLUSION The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence,likely mediated via complex neuroinflammatory pathways.These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy.The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.

Exploring the therapeutic potential of precision T-Cell Receptors (TCRs) in targeting KRAS G12D cancer through in vitro development

Objectives:The Kirsten rat sarcoma virus(KRAS)G12D oncogenic mutation poses a significant challenge in treating solid tumors due to the lack of specific and effective therapeutic interventions.This study aims to explore innovative approaches in T cell receptor(TCR)engineering and characterization to target the KRAS G12D7-16 mutation,providing potential strategies for overcoming this therapeutic challenge.Methods:In this innovative study,we engineered and characterized two T cell receptors(TCRs),KDA11-01 and KDA11-02 with high affinity for the KRAS G12D7-16 mutation.These TCRs were isolated from tumor-infiltrating lymphocytes(TILs)derived from tumor tissues of patients with the KRAS G12D mutation.We assessed their specificity and anti-tumor activity in vitro using various cancer cell lines.Results:KDA11-01 and KDA11-02 demonstrated exceptional specificity for the HLA-A*11:01-restricted KRAS G12D7-16 epitope,significantly inducing IFN-γrelease and eliminating tumor cells without cross-reactivity or alloreactivity.Conclusions:The successful development of KDA11-01 and KDA11-02 introduces a novel and precise TCR-based therapeutic strategy against KRAS G12D mutation,showing potential for significant advancements in cancer immunotherapy.

趋化因子受体4及其配体12在下咽鳞状细胞癌中的表达及其临床意义

目的 探究趋化因子受体4(CXCR4)及趋化因子配体12(CXCL12)在下咽鳞状细胞癌(HSCC)中的表达及其临床意义。方法 以2017年1月—2022年11月收治的90例HSCC患者为研究对象,以HSCC患者手术切除的HSCC组织、癌旁组织为实验材料,采用免疫组织化学染色法检测HSCC组织和癌旁组织中CXCR4、CXCL12的表达情况;采用实时荧光定量PCR(qRT-PCR)法检测HSCC组织和癌旁组织中CXCR4 mRNA、CXCL12 mRNA水平;收集并记录HSCC患者临床病理特征,分析CXCR4、CXCL12表达水平与患者临床病理特征的关系;采用Pearson分析CXCR4与CXCL12水平相关性。结果 CXCR4在HSCC组织中的表达率为60.00%,明显高于癌旁组织的17.78%(P<0.05);CXCL12在HSCC组织中的表达率为57.78%,明显高于癌旁组织的24.44%(P<0.05)。HSCC组织中CXCR4、CXCL12水平均与淋巴结是否转移、TNM分期、分化程度有关(P<0.05)。与癌旁组织相比较,HSCC组织CXCR4、CXCL12水平均显著升高(P<0.05)。Pearson分析显示,HSCC患者中CXCR4水平与CXCL12水平呈正相关(r=0.538,P<0.05)。结论 CXCR4、CXCL12在HSCC组织中呈高表达,两者与HSCC淋巴结转移、分化程度、TNM分期有关。

肥胖型支气管哮喘患儿血清MMP12、CX3CR1水平与病情严重程度的相关性分析

目的探究血清基质金属蛋白酶12(MMP12)、趋化因子(C-X3-C基元)受体1(CX3CR1)与肥胖型(OB)支气管哮喘患儿病情严重程度的相关性。方法选取2020年9月至2023年5月在本院收治的200例支气管哮喘患儿作为研究对象,根据OB诊断标准将其分为OB组(100例)和非OB组(100例),比较两组血清MMP12、CX3CR1水平。比较不同肺功能分度、不同疾病严重程度患儿血清MMP12、CX3CR1水平。Pearson法分析血清MMP12、CX3CR1水平与肺功能分度、疾病严重程度的关系。结果OB组患儿血清MMP12、CX3CR1水平显著升高,差异有统计学意义(P<0.05)。不同肺功能分度患儿血清MMP12、CX3CR1水平比较差异具有统计学意义(P<0.05),随着肺功能分度的加重,患儿血清MMP12、CX3CR1水平逐渐上升,差异有统计学意义(P<0.05)。不同疾病严重程度患儿血清MMP12、CX3CR1水平比较差异具有统计学意义(P<0.05),随着患儿疾病严重程度的增加,患儿血清MMP12、CX3CR1水平依次升高,差异有统计学意义(P<0.05)。相关性分析显示,血清MMP12水平与肺功能分度、疾病严重程度呈正相关(r=0.502、0.517,P<0.05);血清CX3CR1与肺功能分度、疾病严重程度呈正相关(r=0.496、0.511,P<0.05)。结论OB支气管哮喘患儿血清MMP12、CX3CR1水平显著升高,且与患儿病情严重程度和肺功能密切相关。

Therapeutic strategies targeting the epidermal growth factor receptor signaling pathway in metastatic colorectal cancer

More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but second in mortality.More than half of the patients are in advanced stages at diagnosis.Treatment options are complex because of the heterogeneity of the patient population,including different molecular subtypes.Treatments have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,etc.In recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.

小胶质细胞P2Y_(12)受体在小鼠卒中后中枢痛中的作用和机制

目的探讨小胶质细胞P2Y_(12)受体在小鼠卒中后中枢痛中的作用及机制。方法选取无特定病原体(SPF)级雄性C57BL/6J小鼠32只,7~8周龄,体质量25~30 g,采用随机数字表法分为4组:假手术组(C组)、CPSP组、CPSP-M组(CPSP+P2Y_(12)受体拮抗剂MRS2395)、C-M组(假手术+P2Y_(12)受体拮抗剂MRS2395),每组8只。采用右侧丘脑腹后内侧核和腹后外侧核内注射10 nL 0.001 U/nLⅣ型胶原酶制备CPSP模型。CPSP-M组和C-M组在CPSP模型制备前30 min时腹腔注射MRS 2395(1.5 mg/kg),1次/d,连续注射5 d;C组和CPSP组给予等量生理盐水。造模前1 d(T_(0))和造模后1、3、5 d(T_(1)、T_(2)、T_(3))时测定热缩足潜伏期(TWL)、冷缩足潜伏期(CWL)和机械缩足反应频率(PWF)。随后处死小鼠取脑组织,采用免疫荧光法观察P2Y_(12)受体的表达部位,苏木精-伊红(HE)染色法观察脑组织病理改变,蛋白质印迹法检测脑组织P2Y_(12)受体、Toll样受体4(TLR4)、磷酸化核转录因子κB-p65(p-NF-κB p65)和NF-κB p65的表达水平。结果P2Y_(12)受体在CPSP组脑组织内只表达于小胶质细胞中,星形胶质细胞和神经元中未表达。与C组比较,CPSP组和CPSP-M组T_(1)~T_(3)时TWL、CWL缩短,PWF升高,脑组织损伤程度加重,P2Y_(12)受体、TLR4和p-NF-κB p65表达上调,C-M组T_(1)~T_(3)时以上各项指标与C组比较,差异无统计学意义(P>0.05);与CPSP组比较,CPSP-M组T_(1)~T_(3)时TWL、CWL延长,PWF降低,脑组织损伤程度减轻,P2Y_(12)受体、TLR4和p-NF-κB p65表达下调(P<0.05)。结论小胶质细胞P2Y_(12)受体可能通过激活TLR4/NF-κB信号通路参与小鼠CPSP的形成。

血清CXCL12和CXCR7在脑梗死后血管性认知功能障碍患者中的检测价值分析

目的探讨血清趋化因子配体12(CXCL12)和趋化因子受体7(CXCR7)在脑梗死后血管性认知功能障碍(VCI)患者中的检测价值。方法选取我院2021年2月至2023年2月收治的176例脑梗死患者作为研究组,根据有无发生VCI分为VCI组(47例)和非VCI组(129例),另选取同期在本院体检,且一般资料与研究组患者相匹配的176例健康者作为对照组。采用Spearman法分析脑梗死患者血清CXCL12、CXCR7表达水平与MoCA评分的相关性,Logistic回归分析影响脑梗死患者发生VCI的相关因素,受试者工作特征(ROC)曲线分析血清CXCL12和CXCR7对脑梗死后VCI的诊断价值。结果脑梗死患者血清CXCL12和CXCR7表达水平显著高于对照组,且VCI组二者表达水平均高于非VCI组(P<0.05);脑梗死患者血清CXCL12和CXCR7表达水平均与MoCA评分呈负相关(r=-0.857、-0.873,均P<0.05);VCI组和非VCI组年龄、临床类型比较,差异有统计学意义(P<0.05);年龄、临床类型、CXCL12、CXCR7为脑梗死患者发生VCI的危险因素(P<0.05);血清CXCL12和CXCR7单独检测诊断脑梗死后VCI的曲线下面积(AUC)分别为0.730、0.814,二者联合检测的AUC为0.871,优于单独检测(Z_(二者联合-CXCL12)=3.888、Z_(二者联合-CXCR7)=2.249,P=0.000、0.024)。结论血清CXCL12和CXCR7表达水平与脑梗死后VCI的发生密切相关,二者联合对脑梗死后VCI具有较高的诊断价值。

孕妇血清CXCL12和CXCR4水平检测联合多普勒超声检查在凶险性前置胎盘诊断中的应用价值研究

目的探讨孕妇血清CXC趋化因子配体12(CXC chemokine ligand 12,CXCL12)和CXC趋化因子受体4(CXC chemokine receptor 4,CXCR4)水平检测联合多普勒超声在凶险性前置胎盘诊断中的应用价值。方法收集2020年6月~2023年1月河北省沧州中西医结合医院收治的90例凶险性前置胎盘患者作为研究对象,根据产后病理结果分为胎盘植入组(n=38)和无胎盘植入组(n=52),另选取同期于河北省沧州中西医结合医院孕检且孕周与患者相匹配的健康孕妇(胎盘附着于子宫前壁)90例为对照组。比较各组血清CXCL12和CXCR4水平;ROC曲线分析血清CXCL12,CXCR4,多普勒超声对胎盘植入的诊断效能;以术后病理结果为金标准,四表格法计算血清CXCL12,CXCR4联合多普勒超声对发生胎盘植入的诊断效能。结果对照组、无胎盘植入组、胎盘植入组血清CXCL12(2.75±1.26 ng/ml,5.82±2.14 ng/ml,10.24±3.58 ng/ml),CXCR4(1.84±0.78 ng/ml,4.47±1.83 ng/ml,8.32±2.763 ng/ml)表达水平依次升高,差异具有统计学意义(F=158.998,199.141,均P<0.05)。CXCL12,CXCR4和多普勒超声联合检测诊断胎盘植入的AUC为0.948,敏感度和特异度分别为92.11%,86.54%,优于CXCL12,CXCR4,多普勒超声各自单独预测(Z=2.266,2.682,3.472,P=0.023,0.007,0.001)。结论凶险性前置胎盘患者血清CXCL12,CXCR4表达水平显著升高,血清CXCL12和CXCR4联合多普勒超声对凶险性前置胎盘患者胎盘植入的发生具有较好的诊断效能。

肝细胞肝癌中DDX24、TRIP12表达与上皮间质转化及临床预后的关系

目的探讨肝细胞肝癌(HCC)中DEAD盒解旋酶24(DDX24)、甲状腺激素受体相互作用因子12(TRIP12)表达,分析两者与上皮间质转化(EMT)及临床预后的关系。方法回顾性选取2019年2月—2021年1月中国人民解放军联勤保障部队第九四〇医院肝胆外科手术治疗的HCC患者96例。免疫组化检测癌组织和癌旁组织DDX24、TRIP12蛋白表达;采用实时荧光定量PCR检测DDX24、TRIP12和EMT指标[E-钙黏素(E-cad)、N-钙黏素(N-cad)及TWIST]表达;Pearson相关分析DDX24 mRNA、TRIP12 mRNA和EMT指标的相关性;绘制Kaplan-Meier曲线,Log-Rank检验分析DDX24 mRNA、TRIP12 mRNA高表达组和低表达组HCC患者预后的差异;多因素Cox比例风险模型分析影响HCC患者死亡预后的独立因素。结果HCC癌组织中DDX24、TRIP12阳性率显著高于癌旁组织(χ^(2)/P=109.714/<0.001,108.755/<0.001);与癌旁组织比较,HCC癌组织中DDX24、TRIP12、N-cad、TWIST mRNA表达较高,E-cad mRNA表达较低,差异均有统计学意义(t/P=35.810/<0.001,48.036/<0.001,25.015/<0.001,48.482/<0.001,38.069/<0.001)。HCC癌组织中DDX24 mRNA与TRIP12 mRNA表达呈正相关(r=0.701,P<0.001);DDX24 mRNA、TRIP12 mRNA均与N-cad mRNA、TWIST mRNA呈正相关,与E-cad mRNA呈负相关(r/P=0.723/<0.001,0.661/<0.001,0.706/<0.001,0.745/<0.001,-0.694/<0.001,-0.609/<0.001)。低分化程度、CNLC分期Ⅱ~Ⅲ期和有血管侵犯HCC患者癌组织中DDX24、TRIP12 mRNA高于高中分化程度、CNLC分期Ⅰ期和无血管侵犯者(DDX24:t/P=10.348/<0.001,18.474/<0.001,6.302/<0.001;TRIP12:t/P=25.661/<0.001,36.396/<0.001,14.928/<0.001)。DDX24 mRNA高表达组和低表达组3年总生存率分别为39.13%(18/46)、64.00%(32/50),2组生存曲线总体比较,差异具有统计学意义(Log rankχ^(2)=7.491,P=0.006);TRIP12 mRNA高表达组和低表达组3年总生存率分别为36.17%(17/47)、67.35%(33/49),2组生存曲线总体比较,差异有统计学意义(Log rankχ^(2)=8.146,P=0.004)。CNLC分期Ⅱ~Ⅲ期、低分化程度、血管侵犯、DDX24 mRNA高表达、TRIP12 mRNA高表达是影响HCC患者死亡预后的危险因素[HR(95%CI)=1.611(1.175~2.209),1.768(1.238~2.526),1.464(1.089~1.968),1.859(1.330~2.599),1.775(1.275~2.473)]。结论HCC癌组织中DDX24、TRIP12表达上调,与N-cad、TWIST呈正相关,与E-cad呈负相关,DDX24、TRIP12可能通过促进HCC肿瘤EMT的发生,促进HCC肿瘤的恶性进展,两者是影响HCC患者死亡预后的独立危险因素。

The in vitro Anti Hptocarcinoma Effects of Human Interleukin-12 from Transgenic Potato

[Objective]The aim was to examine the anti heptocarcinoma effects of human interleukin-12（hIL-12） from transgenic potatoes.[Method]Human heptocarcinoma cell line HepG22.2.15 was cocultured with human peripherial blood monocyte（PBMC）.Human IL-12 extracted from its transgenic patatoes was introduced to this coculture system.MTT method and laser confocal microscope were then employed to evaluate its survival rates and morphological changes of HepG22.2.15 cell line.[Result]The HepG22.2.15 survival rate of the plant produced hIL-12 treated group was significantly lower than that of the wild type control,while similar to that of commercial purified recombinant hIL-12 group.As indicated by AnnexinV/PI double staining laser confocal microscope,cocultured heptocarcinoma cells showed the typical early and final phase apoptotic morphological characteristics 48 hours after 2 × 10-4 mg/L potato secreted hIL-12 treatment.[Conclusion] These results demonstrated that Heptocarcinoma HepG22.2.15 cell growth could be actively inhibited by the transgenic potato expressed hIL-12 in vitro.

An effective vaccine against colon cancer in mice:Use of recombinant adenovirus interleukin-12 transduced dendritic cells

AIM： To investigate the effect of a vaccine with recombinant adenovirus interleukin-12 （AdVIL-12） transduced dendritic cells （DCs） against colon cancer in mice. METHODS： DCs and AdVIL-12 were incubated together at different time intervals and at different doses. Supernatant was collected and tested for IL-12 by enzyme-linked immunosorbent assay （ELISA）. In order to determine whether tumor cell lysate-pulsed （TP） AdVIL-12/DCs enhance therapeutic potential in the established tumor model, CT26 colon tumor cells were implanted subcutaneously （s.c.） in the midflank of naive BALB/c mice. Tumor-bearing mice were injected with a vaccination of CT26 TP AdVIL-12/DCs on d 3 and 10. As a protective colon tumor model, naive BALB/c mice were immunized s.c. in their abdomens with CT26 TP AdVIL-12/DCs twice at seven day intervals. After the immunization on d 7, the mice were challenged with a lethal dose of CT26 tumor cells and survival times were evaluated. Subsequently, cytotoxic T lymphocyte （CTL） activity and interferon gamma （IFNy） secretion was evaluated in the immunized mice, and assayed CTL ex vivo. RESULTS： Murine DCs were retrovirally transduced with AdVIL-12 efficiency, and the AdVIL-12 transduced DCs secreted a high level of IL-12 （AdVIL-12/DCs, 615.27 ± 42.3 pg/mL vs DCs, 46.32 ± 7.29 pg/mL, P 〈 0.05）. Vaccination with CT26 TP AdVIL-12/DCs could enhance anti-tumor immunity against CT26 colon tumor in murine therapeutic models （tumor volume on d 19：CT26 TP AdVIL-12/DCs 107 ± 42 mm^3 vs CT26 TP DCs 383± 65 mm^3, P 〈 0.05） and protective models. Moreover, the CT26 TP AdVIL-12/DC vaccination enhances tumor-specific CTL activity, producing high levels of IFN7 in immunized mice. Ex vivo primed T cells with AdVIL-12/DCs were able to induce more effective CTL activity than in primed T cells with CT26 TP/DCs （E：T = 100：1, 69.49% ± 6.11% specific lysis vs 37.44% ＋ 4.32% specific lysis, P 〈 0.05）.CONCLUSION： Vaccination with recombinant AdVIL-12 transduced DC pulsed tumor cell lysate enhance antitumor immunity specific to colon cancer in mice.

Expression and significance of intratumoral interleukin-12 and interleukin-18 in human gastric carcinoma

AIM: To explore the effect of intratumoral expressions of interleukin-12 (IL-12) and interleukin-18 (IL-18) on clinical features, angiogenesis and prognosis of gastric carcinoma. METHODS: The expressions of IL-12 and IL-18 from 50 samples of gastric cancer tissue were analyzed by immunohistochemistry, and microvessel density (MVD) was determined with microscopic imaging analysis system. RESULTS: The positive expression rates of IL-12 and IL-18 were 44% (22/50) and 26% (13/50), respectively. IL-12 was significantly associated with pathologic differentiation, depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, and IL-18 was closely related to distant metastasis. Intratumoral IL-12 and IL-18 expressions were not statistically related to MVD scoring. IL-12-positive patients survived significantly longer than those with IL-12-negative tumors, but there was no significant difference between IL-18-positive patients and IL-18-negative ones. The multivariate analysis with Cox proportional hazard model revealed IL-12, MVD and T stage were independent prognostic factors. CONCLUSION: The positive expressions of IL-12 and IL-18 can play an important role in progression and metastasis of gastric cancer, and IL-12 might be an independent factor of poor prognosis in gastric carcinoma.

Lactobacilli inhibit interleukin-8 production induced by Helicobacter pylori lipopolysaccharide-activated Toll-like receptor 4

AIM： To investigate the effect of Lactobacillus bulgaricus （LBG） on the Toll-like receptor 4 （TLR4） pathway and interleukin-8 （IL-8） production in SGC-7901 cells treated with Helicobacter pyloriSydney strain 1 lipopolysaccharide （HpyloriSS1-LPS）. METHODS： SGC-7901 cells were treated with HpyloriSS1-LPS in the presence or absence of pretreatment for 1 h with viable LBG or supernatant recovered from LBG culture MRS broth （LBG-s）. Cellular lysates were prepared for Western blot with anti-TLR4, anti-transforming growth factor β-activated kinase 1 （TAK1）, anti-phospho-TAK1, anti-nuclear factor κB （NF-κB）, anti-p38 mitogen-activated protein kinase （p38MAPK）, and anti-phospho-p38MAPK antibodies. The amount of IL-8 in cell culture medium was measured by ELISA. RESULTS： H pyloriSS1-LPS up-regulated the expression of TLR4, stimulated the phosphorylation of TAKI, subsequently enhanced the activation of NF- κB and the phosphorylation of p38MAPK in a time- dependent manner, leading to augmentation of IL-8 production in SGC-7901 cells. Viable LBG or LBG-s pretreatment attenuated the expression of TLR4, inhibited the phosphorylation of TAK1 and p38MAPK, prevented the activation of NF-κB, and consequently blocked IL-8 production.CONCLUSION： H py/oriSS1-LPS induces IL-8 production through activating TLR4 signaling in SGC-7901 cells and viable LBG or LBG-s prevents H pyloriSS1-LPS-mediated IL-8 production via inhibition of the TLR4 pathway.

Interleukin-22 receptor 1 is expressed in multinucleated giant cells:A study on intestinal tuberculosis and Crohn’s disease

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.

Microwave Exposure Impairs Synaptic Plasticity in the Rat Hippocampus and PC12 Cells through Over-activation of the NMDA Receptor Signaling Pathway

Objective The aim of this study is to investigate whether microwave exposure would affect the N-methyI-D-aspartate receptor （NMDAR） signaling pathway to establish whether this plays a role in synaptic plasticity impairment. Methods 48 male Wistar rats were exposed to 30 mW/cm^2 microwave for 10 min every other day for three times. Hippocampal structure was observed through H＆E staining and transmission electron microscope. PC12 cells were exposed to 30 mW/cm^2 microwave for 5 min and the synapse morphology was visualized with scanning electron microscope and atomic force microscope. The release of amino acid neurotransmitters and calcium influx were detected. The expressions of several key NMDAR signaling molecules were evaluated. Results Microwave exposure caused injury in rat hippocampal structure and PC12 cells, especially the structure and quantity of synapses. The ratio of glutamic acid and gamma-aminobutyric acid neurotransmitters was increased and the intracellular calcium level was elevated in PC12 cells. A significant change in NMDAR subunits （NR1, NR2A, and NR2B） and related signaling molecules （CaZ＋/calmodulin-dependent kinase II gamma and phosphorylated cAMP-response element binding protein） were examined. Conclusion 30 mW/cm^2 microwave exposure resulted in alterations of synaptic structure, amino acid neurotransmitter release and calcium influx. NMDAR signaling molecules were closely associated with impaired synaptic plasticity.

Interleukin-12 and Th1 immune response in Crohn’s disease: Pathogenetic relevance and therapeutic inplication

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract that share clinical and pathological characteristics. The most accredited hypothesis is that both CD and UC result from a deregulated mucosal immune response to normal constituents of the gut microflora. Evidence, however, indicates that the main pathological processes in these two diseases are distinct. In CD, the tissue- damaging inflammatory reaction is driven by activated type 1 helper T-cell (Th1), whereas a humoral response predominates in UC. Consistently, a marked accumulation of macrophages making interleukin (IL)-12, the major Th1-inducing factor, is seen in CD but not in UC mucosa. Preliminary studies also indicate that administration of a monoclonal antibody blocking the IL-12/p40 subunit can be useful to induce and maintain clinical remission in CD patients. Notably, the recently described IL-23 shares the p40 subunit with IL-12, raising the possibility that the clinical benefit of the anti-IL-12/p40 antibody in CD may also be due to the neutralization of IL-23 activity. This review summarizes the current information on the expression and functional role of IL-12 and IL- 12-associated signaling pathways both in patients with CD and experimental models of colitis, thus emphasizing major differences between IL-12 and IL-23 activity on the development of intestinal inflammation.

Serum soluble interleukin-2 receptor levels in patients with chronic hepatitis B virus infection and its relation with antiHBc

AIM： To investigate the relationship between serum soluble interleukin-2 receptor （sIL-2R） level and anti-HBc in patients with chronic hepatitis B virus （HBV） infection. METHODS： Sera from 100 patients with chronic HBV infection and 30 healthy controls were included in this study. The patients were divided into group A [HBsAg （＋）, HBeAg （＋） and anti-HBc （＋）, n = 50] and group B [HBsAg （＋）, HBeAg （＋） and anti-HBc （-）, n = 50]. sIL-2R levels were determined using ELISA. HBV DNA and alanine aminotransferase （ALT） were also detected. RESULTS： Serum sIL-2R levels were significantly higher in patients with chronic HBV infection than in healthy controls. Moreover, serum sIL-2R levels were significantly higher in patients with HBsAg （＋）, HBeAg （＋） and antiHBc （＋） （976.56±213.51×10^3 U/L） than in patients with HBsAg （＋）, HBeAg （＋） and anti-HBc （-） （393.41±189.54 ×10^3 U/L, P〈 0.01）. A significant relationship was found between serum sIL-2R and ALT levels （P〈 0.01） in patients with chronic HBV infection, but there was no correlation between sIL-2R and HBV DNA levels. The anti-HBc status was significantly related to the age of patients （P〈 0.01）. CONCLUSION： The high sIL-2R level is related to positive anti-HBc in chronic hepatitis B patients. Positive anti-HBc may be related to T-lymphocyte activation and negative anti-HBc may imply immune tolerance in these patients.

Changes in soluble interleukin-2 receptor level in serum and Na^+ -K^+ -exchanging ATPase activity in semen of infertile men caused by antisperm antibody

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.

Study of recombinant human interleukin-12 for treatment of complications after radiotherapy for tumor patients

AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.