IL-13Rα2在胃癌及癌前病变中的表达及其临床意义

目的:长期的炎症微环境促进胃上皮的萎缩、肠上皮化生、异型增生以及胃癌的发生,但目前其中机制尚不清楚。本研究旨在检测白细胞介素13受体α2(interleukin-13 receptorα2,IL-13Rα2)在胃癌及癌前病变中的表达情况,并探讨其临床意义。方法:210例活检组织分为慢性非萎缩性胃炎组(CNAG组,n=30)、慢性萎缩性胃炎伴肠上皮化生组(CAG/IM组,n=50)、胃黏膜低级别异型增生组(LGD组,n=30)、胃黏膜高级别异型增生组(HGD组,n=30)和胃癌组(GC组,n=70),采用免疫组织化学EnVision两步法检测上述各组中IL-13Rα2蛋白的表达。另外,再检测120例胃癌根治性组织中IL-13Rα2蛋白的表达,分析IL-13Rα2蛋白的表达与胃癌临床病理特征的关系。结果:CNAG组、CAG/IM组、LGD组、HGD组和GC组中IL-13Rα2的阳性率分别为3.3%、42.0%、13.3%、6.7%、84.3%;与CNAG组比较,CAG/IM组的IL-13Rα2阳性表达率升高(P<0.05);与CAG/IM组比较,LGD和HGD组的IL-13Rα2阳性表达率均降低(均P<0.05),GC组的IL-13Rα2阳性表达率升高(P<0.001)。在根治性标本中,与癌旁组织相比,胃癌组织中IL-13Rα2的阳性表达率显著升高(P<0.001);临床病理分析显示:胃癌组织中IL-13Rα2阳性表达与Lauren分型有关[其在肠型胃癌中表达高于弥漫型、实性型和混合型胃癌,差异均有统计学意义(均P<0.001)];而与患者的年龄、性别、幽门螺杆菌感染状态、临床分期和淋巴结转移情况无明显相关性(均P>0.05)。结论:IL-13Rα2在胃肠上皮化生中呈弱阳性表达,在胃癌中呈强阳性表达。IL-13Rα2在胃癌尤其是肠型胃癌中呈特异性高表达,有望成为胃癌治疗的新靶点。

嗅觉受体家族13亚家族C成员2在肝细胞癌中的表达及临床病理意义

目的探讨嗅觉受体家族13亚家族C成员2(olfactory receptor family 13 subfamily C member 2,OR13C2)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及临床病理意义。方法收集2017年8月至2022年3月于右江民族医学院附属医院进行手术切除治疗的HCC患者为研究对象,取石蜡包埋的癌组织及癌旁非癌肝组织适量,采用免疫组化染色EnVision二步法检测OR13C2在上述组织中的表达情况,通过Logistic回归模型分析OR13C2的表达与HCC组织学分级、癌旁肝纤维化等临床病理特征的相关性。结果OR13C2在HCC癌组织中的表达明显低于癌旁肝组织,差异具有统计学意义(P<0.05);HCC肿瘤组织中OR13C2的表达与HCC组织学分级差异有统计学意义(P<0.05),HCC中OR13C2的表达与HCC的组织学分级呈负相关(r=-0.213,P<0.05),OR13C2表达下调为肿瘤去分化风险因子(风险值为3.914,P<0.05);OR13C2在癌组织中的表达与HCC的发病年龄、性别、包膜侵犯、临床分期、乙型肝炎病毒感染、术前血清甲胎蛋白及微血管侵犯以及癌组织中Glypican-3、Arginase-1表达的差异均无统计学意义(P>0.05),OR13C2在癌旁肝组织中的表达与肝纤维化分期、慢性肝炎分级差异无统计学意义(P>0.05)。结论HCC癌组织中OR13C2表达水平下调,这种下调与肿瘤的组织学分级负相关,是一个肿瘤去分化的风险因子。这些结果提示OR13C2表达失调在HCC发生中可能起一定的促进作用。

血清FGF-21 IL-13 sVEGFR-2与急性心力衰竭患者短期预后的关系

目的 探讨血清成纤维细胞生长因子-21(FGF-21)、白细胞介素-13(IL-13)、可溶性血管内皮生长因子受体-2(sVEGFR-2)水平与急性心力衰竭患者短期预后的相关性。方法 选取2019年1月至2020年12月在我院接受治疗的急性心力衰竭患者136例作为心力衰竭组。选取同期在我院健康体检者80例作为健康对照组。采用ELISA法检测血清FGF-21、IL-13、sVEGFR-2水平。随访1年,根据急性心力衰竭患者有无不良心血管事件发生分为预后良好组和预后不良组,并分析影响患者1年内临床结局的危险因素。采用ROC曲线,分析FGF-21、IL-13、sVEGFR-2对急性心力衰竭患者预后不良的诊断效能。结果 心力衰竭组血清FGF-21、IL-13高于健康对照组[FGF-21(pg/mL):74.81±16.29 vs. 19.37±5.11, IL-13(pg/mL):5.14±1.23 vs.1.62±0.54,P<0.001]、sVEGFR-2低于健康对照组(ng/mL:6.30±1.57 vs.15.18±4.29,P<0.05)。预后不良组血清FGF-21、IL-13、NT-proBNP分别高于预后良好组[FGF(pg/mL):92.31±20.84 vs.67.52±13.70, IL-13(pg/mL):6.94±1.75 vs.4.39±1.18, NT-proBNP(ng/L):4689.16±132.50 vs.2120.59±51.48],LVEF值、血清sVEGFR-2低于预后良好组[LVEF(%):45.27±6.13 vs.53.95±7.80, sVEGFR(ng/mL):4.85±1.24 vs.6.98±2.31,P<0.05]。多因素Logistic回归分析结果显示,LVEF(95%CI 0.265~0.840,P<0.001)及血清NT-proBNP(95%CI 1.002~2.317,P=0.015)、FGF-21(95%CI 1.438~5.019,P<0.001)、IL-13(95%CI 1.027~3.165,P=0.006)、sVEGFR-2(95%CI 1.190~4.283,P=0.002)是影响急性心力衰竭患者不良预后的独立危险因素。ROC曲线结果显示,血清FGF-21、IL-13、sVEGFR-2及三项联合检测预测急性心力衰竭患者不良预后的曲线下面积分别为0.810、0.775、0.821、0.918。结论 血清FGF-21、IL-13、sVEGFR-2水平与急性心力衰竭患者NYHA分级及临床预后密切相关,联合检测血清FGF-21、IL-13、sVEGFR-2对评估患者不良预后有较高参考价值。

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.

Fluence of Glucosidorum Tripterygii Totorum on joint and serum soluble interleukin-2 receptor in patients with ankylosing spondylitis

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.

Study of the Effect of Leeching on Plasma Endothelin and Soluble Interleukin-2 Receptor in Patients with Systemic Lupus Erythematosus

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.

Elevated pancreatic enzymes, IgM, soluble interleukin-2 receptor in anti-GADab(+) type 1 diabetes

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.

Effects of Aprotinin on Serum Interleukin-2 and Soluble Interleukin-2 Receptor during Cardiopulmonary Bypass

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.

Glycosylation-independent binding to extracellular domains 11-13 of mannose-6-phosphate/insulin-like growth factor-2 receptor mediates the effects of soluble CREG on the phenotypic proliferation of vascular smooth muscle cells

Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was～25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from～30 kD to～25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.

Expression of estrogen receptor alpha,nerve growth factor,interleukin-2,and androgen receptor in the cerebellum of ovariectomized rats following soybean isoflavone treatment

BACKGROUND： Studies have shown that estrogen receptor alpha （ERα）, nerve growth factor （NGF）, interleukin-2 （IL-2）, and androgen receptor （AR） expression in the cerebellum decreases when estrogen levels decrease in vivo. Soybean isoflavone, a type of non-steroid estrogen with similar molecular structure and function to estradiol, exhibits estrogen-like characteristics. OBJECTIVE： To investigate the effects of various doses of soybean isoflavone on expression of ERa, NGF, IL-2, and AR in the cerebellum of ovariectomized rat, and to determine whether there is a dose-dependent effect.DESIGN, TIME AND SETTING： Controlled trial at the cellular and molecular level. The study was performed at the Experimental Animal Engineering Center, College of Veterinary Medicine, Sichuan Agricultural University from July 2006 to May 2008. MATERIALS： Soybean isoflavone, comprised of daidzin, genistein and isoflavone, was provided by Taiyuan Yuantai Biochemical Industry, China. The ERα, NGF, IL-2, and AR in situ hybridization kit, rabbit anti-rat ERa, NGF, IL-2, and AR monoclonal antibodies, and SABC kit were purchased from Wuhan Boster Biological Technology, China. METHODS： A total of 50 female, Sprague Dawley rats, aged 3 months, were randomly assigned to 5 groups, with 10 animals in each group. With the exception of the sham-operation group （abdominal cavity opening alone）, all rats underwent bilateral ovariectomy. At 14 days after surgery, rats in the high-, middle-, and low-dose soybean isoflavone groups were subcutaneously injected with 1.5, 1.0, and 0.5 mg/kg soybean isoflavone, respectively, every 2 days for 6 consecutive weeks. Rats in the sham-operation and ovariectomized groups were subcutaneously injected with absolute alcohol （0.5 mL/kg）. MAIN OUTCOME MEASURES： Expression levels and distribution of ERα, NGF, IL-2, and AR in the cerebellum were detected by immunohistochemistry and in situ hybridization. RESULTS： Compared with the sham-operation group, immunoreactive products and hybridization signals of ERa, NGF, IL-2, and AR were significantly decreased in the cerebellar cortex and nuclei of ovariectomized rats （P 〈 0.05 or P 〈 0.01）, but increased following soybean isoflavone treatment. In particular, levels of the high-dose soybean isoflavone group were almost restored to levels of the sham-operation group （P 〉 0.05）. The immunoreactive products were primarily located in the cytoplasm and neurites, and rarely in the cell membrane and nuclei. However, the hybridization signals were predominantly located in the nuclei, but rarely in the cytoplasm, cell membrane, or neurites. CONCLUSION： Soybean isoflavone upregulated ERα, NGF, IL-2, and AR protein and gene expression in a dose-dependent manner, and played an important role in sustaining and protecting structure and function of cerebellar neurons. Moreover, the similarity of expression patterns of these molecules indicated that they were mutually interactive during the regulation of soybean isoflavone to the cerebellum.

INTERLEUKIN-2 (IL-2) PRODUCTION AND INTERLEUKIN-2 RECEPTOR EXPRESSION IN PATIENTS WITH APLASTIC ANEMIA

IL-2 production and IL-2 receptor (Tac antigen) of the peripheral blood mononuclear cells in 30 patients with aplastic anemic (AA) were studied. We found that mononuclear cells from patients produce spontaneously IL-2 in the absence of exogenous lee-tin stimulation, the proportion of Tac+ cells in mononuclear cells increased. The release of IL-2 and or Tac antigen expression were elevated in almost every patient with AA. The plasma from patients stimulate mitogen-induced blastogenesis and Tac antigen expression of normal human lymphocytes. Immunological 1 abnormalities of patients with AA possibly might represents secondary response to bone marrow depression.

CHANGES ON RECEPTOR EXPRESSIONAND PRODUCTION OF INTERLEUKIN-2 IN CIRCULATING LYMPHOCYTE POPULATION AFTER OPEN HEART SURGERY

To evaluate the change of perioperative cell mediated immunity after cardiac operation with cardiopul-monary bypass (CPB), so as to provide some information for timely prevention and treatment against post-operative immunological disorder, 40 patients were studied. By searching for the effects of CPB and anes-thesia, interleukln-2 receptor (IL-2R) expression upon the surface of peripheral blood mononuclear cells(PBMC), as well as interleukin-2 (IL-2) production in vitro was traced 55 min after anesthesia, at end ofCPB, on postoperative 1, 7, and 14 day versus preanesthesia control. Our data demonstrated that expres-sion of IL-2R on PBMC was significantly suppressed in all comparing with the baseline value, meanwhile,IL-2 production in vitro also statistically dropped. However,no statistical difference was found on perioper-ative IL 2R expression and IL-2 synthesis in the cholecystectomy group. We conclude that postoperativeimmunological disorder seems to be the main factor, which could be denoted as reduced IL 2R expressionon PBMC and lL-2 synthesis in vitro for sepsis, even multiple system organ failure developed after cardiacsurgery.

MEK/ERK和PI3K/Akt通路对大鼠脉络膜新生血管中DDR2和MMP-13表达的调控作用

背景 研究表明盘状结构域受体2（DDR2）和基质金属蛋白酶-13（MMP-13）在肿瘤新生血管发生中具有重要作用,是相关疾病治疗的关键靶点,但DDR2和MMP-13在脉络膜新生血管（CNV）发生中的作用尚不清楚.目的 探讨DDR2和MMP-13在大鼠CNV中的表达特点以及MEK/ERK和PI3 K/Akt通路对DDR2及MMP-13表达的调控作用.方法 采用532 nm倍频激光视网膜光凝法制备棕色挪威（BN）大鼠CNV模型,将78只BN模型鼠按照随机数字表法分为正常对照组（n=7）、模型对照组（n=39）、PD98059（MEK1抑制剂）组（n=16）和LY294002（PI3K抑制剂）组（n=16）,PD98059组和LY294002组大鼠分别于光凝后1d、7d玻璃体内注射5 mmol/L PD98059 3μl或5 mmol/L LY294002 3μl.分别于光凝前和光凝后1、3、7、14 d用过量麻醉法处死动物并制备样本和切片,采用Western blot法检测各组大鼠眼杯中ERK、p-ERK、Akt和p-Akt蛋白的表达变化,采用逆转录PCR（RT-PCR）法检测各组大鼠眼杯中DDR2 mRNA和MMP-13 mRNA的表达变化,采用组织病理学方法测定各组大鼠CNV厚度,采用免疫组织化学和免疫荧光染色法分别定位和测定大鼠CNV区域DDR2和MMP-13的表达.结果 光凝后3d,光凝局部细胞增生,光凝后7 d CNV形成,至光凝后14 d CNV趋于稳定.免疫组织化学染色结果显示,DDR2在正常大鼠视网膜血管内皮细胞层、视网膜神经节细胞（RGCs）层和内核层细胞中呈弱表达,但在CNV中呈强阳性表达;MMP-13在正常对照组大鼠视网膜内界膜层、光感受器层和巩膜层均呈强阳性表达,在模型对照组中呈强阳性表达.免疫荧光结果显示,CNV组织中DDR2和MMP-13共表达.RT-PCR结果显示,模型对照组光凝后1、3、7、14 d DDR2 mRNA相对表达水平分别为55.22±4.03、47.74±2.23、14.82±4.56和5.59±2.47,MMP-13 mRNA相对表达水平分别为25.54±3.83、43.51±4.36、10.90±4.00和5.23±3.23,与正常对照组相比,差异均有统计学意义（均P＜0.05）.免疫荧光结果显示,模型对照组光凝后3、7、14 d大鼠CNV区DDR2相对荧光密度单位（RFU）值分别为2.73±0.53、5.21±0.31和3.22±0.33,MMP-13 RFU值分别为1.66±0.17、3.57±0.44和2.67±0.21,组间总体比较差异均有统计学意义（F=81.01,P＜0.05;F=40.31,P＜0.01）;PD98059组和LY294002组光凝后14 d CNV区DDR2 RFU值分别为1.14±0.19和1.03±0.14,与模型对照组比较,差异均有统计学意义（均P＜0.05）,MMP-13RFU值分别为1.37±0.25和1.24±0.20,与模型对照组比较,差异均有统计学意义（均P＜0.05）.Western blot结果显示,模型对照组光凝后7d眼杯中p-ERK和p-Akt水平升高,与正常对照组大鼠相比差异均有统计学意义（均P＜0.05）;至光凝后14 d恢复至近正常水平,与正常对照组比较差异均无统计学意义（均P＞0.05）.PD98058组大鼠眼杯p-ERK水平明显下降,注射后7d、14 d PD98058组大鼠眼杯中p-ERK表达的抑制率分别为71.58％和65.21％,PD98058组7d与模型对照组7d比较、PD98058组14 d与模型对照组14 d比较,差异均有统计学意义（均P＜0.05）.LY294002组大鼠眼杯中p-Akt表达水平明显下降,LY294002注射后7d、14d大鼠眼杯中p-Akt表达的抑制率分别为65.62％和67.04％,LY294002组7d与模型对照组7d比较、LY294002组14d与模型对照组14 d比较,差异均有统计学意义（均P＜0.05）.各组眼杯中ERK和Akt的表达水平总体比较差异均无统计学意义（F=0.62,P＞0.05;F=0.81,P＞0.05）.模型对照组、PD98059组和LY294002组光凝后14 d大鼠CNV厚度分别为（119.19±18.03）、（51.00±11.29）和（59.18±9.00） μm,总体比较差异有统计学意义（F=29.376,P＜0.05）,与模型对照组比较,PD98059和LY294002注射后CNV厚度分别减少57.21％和50.34％,差异均有统计学意义（均P＜0.05）.结论 DDR2和MMP-13在大鼠CNV中表达上调,参与CNV的形成;MEK/ERK和PI3K/Akt通路通过参与调控DDR2和MMP-13在CNV局部的表达而抑制CNV的发生和进展.

乙型病毒性肝炎患者血清IL-2、slL-2R、IL-13及PDGF测定的意义

目的:探讨乙型肝炎患者血清IL-2、sIL-2R、IL-13及PDGF水平的变化及测定的临床意义。方法:150例乙型肝炎患者分为3组(急性肝炎组20例、慢性肝炎组90例和重型肝炎组40例);设健康人45名作为对照组。前2项血清标志物均采用放射免疫分析;后2项血清指标则采用酶联免疫吸附试验测定。将测定结果进行统计分析。结果:本文测定数值显示,血清IL-2水平急性肝炎患者组水平与对照组比较略有降低,但无统计学意义(P>0.05);慢性肝炎和重型肝炎2组患者该指标水平则均显著低于对照组(P均<0.05)。sIL-2R水平显示急性、慢性及重型肝炎3组患者均非常显著地高于对照组(P均<0.01),且发现其递增规律与肝炎病情的严重程度呈明显的平行关系。IL-13水平测定结果也显示3组患者均显著高于对照组(P均<0.05)。PDGF测定值显示,急性肝炎组水平显著高于对照组(P<0.05),慢性肝炎和重型肝炎2组水平则较对照组升高更为显著(P均<0.01)。其水平的递增关系也与病情的严重程度相一致。结论:本文患者4项血清指标水平的变化与乙型肝炎的发病及病情进展有关;其测定有助于了解本病的发生机制和预后评估。

IL-13Rα2在脑胶质瘤中的表达及其临床诊断意义

目的探讨白细胞介素13受体α2(IL-13Rα2)在脑胶质瘤中的表达及其与肿瘤恶性程度的关系。方法免疫组化染色检测59例脑胶质瘤、3例脑膜瘤、3例癫痫病灶组织、5例正常脑组织及U251细胞中IL-13Rα2蛋白的表达,分析其与肿瘤恶性程度的关系。结果正常脑组织、脑膜瘤及癫痫病灶中均无IL-13Rα2的表达;而59例胶质瘤组织中33例IL-13Rα2表达阳性,阳性率55.9%;胶质瘤组织IL-13Rα2阳性表达率显著高于非胶质瘤组织(P<0.05)。高级别胶质瘤(Ⅲ、Ⅳ级)IL-13Rα2阳性表达率为78.1%(25/32),低级别(Ⅰ、Ⅱ级)胶质瘤为29.6%(8/27),两者相较差异显著(P<0.05)。U251细胞IL-13Rα2表达阳性。结论本结果提示胶质瘤中IL-13Rα2蛋白表达与其恶性程度有关。

IL-13 Rα2作为功能受体介导信号转导的研究进展

IL-13主要是由活化T 细胞产生的12 kD 的多效性细胞因子。IL-13和IL-4蛋白在氨基酸序列上有30％的同一性［1］，前者可在B 淋巴细胞、内皮细胞、单核细胞等诸多细胞中通过由IL-4Rα、IL-13Rα1和IL-13Rα2组成的复杂受体系统发挥效应。IL-13Rα1单独和IL-13结合能力很弱，但与IL-4Rα形成异源二聚体后却可形成高亲和力的IL-13受体复合物，并激活Janus 蛋白激酶／信号转导子及转录激活子（Janus kinase ／signal transducers and activators oftranscription， JAK／STAT）信号通路发挥功能。目前已证实IL-13与多种疾病如肿瘤、纤维化密切相关［2］。IL-13Rα2比IL-13Rα1更易与IL-13结合，所以它能与IL-13Rα1竞争IL-13并阻断JAK／STAT 通路介导的纤维化过程，又由于胞浆尾很短而被视为 诱饵受体＂。最近研究［3］表明在相关模型中其可以通过AP-1／TGF-β等通路发挥信号功能并最终导致纤维化。此外，IL-13Rα2在肿瘤细胞中高表达，因此，很有可能以IL-13Rα2为特异性的靶向受体来探索肿瘤治疗新方法。

Role of P2X_7 receptors in the development of diabetic retinopathy

The P2X7 receptor is one of the members of the family of purinoceptors which are ligand-gated membrane ion channels activated by extracellular adenosine 5'-triphosphate. A unique feature of the P2X7 receptor is that its activation can result in the formation of large plasma membrane pores that allow not only the flux of ions but also of hydrophilic molecules of up to 900 Da. Recent studies indicate that P2X7-mediated signaling can trigger apoptotic cell death after ischemia and during the course of certain neurodegenerative disorders. Expression of the P2X7 receptor has been demonstrated in most types of cells in the retina. This purinoceptor mediates the contraction of pericytes and regulates the spatial and temporal dynamics of the vasomotor response through cell-to-cell electrotonic transmission within the microvascular networks. Of potential clinical significance, investigators have found that diabetes markedly boosts the vulnerability of retinal microvessels to the lethal effect of P2X7 receptor activation. This purinergic vasotoxicity may result in reduced retinal blood flow and disrupted vascular function in the diabetic retina. With recent reports indicating an association between P2X7 receptor activation and inflammatory cytokine expression in the retina, this receptor may also exacerbate the development of diabetic retinopathy by a mechanism involving inflammation.

Severe acute respiratory syndrome coronavirus 2 infection: Role of interleukin-6 and the inflammatory cascade

Since December 2019,a novel coronavirus that represents a serious threat to human lives has emerged.There is still no definite treatment for severe cases of the disease caused by this virus,named coronavirus disease 2019(COVID-19).One of the most considered treatment strategies targets the exaggerated immune regulator,and interleukin(IL)-6 is a crucial pro-inflammatory mediator.Severe acute respiratory syndrome coronavirus 2(SARSCoV-2)cases show an elevated level of IL-6 related to disease severity.IL-6 activity can be inhibited by the following:IL-6 itself,IL-6 signaling pathways such as Janus kinase and signal transducer and activator of transcription(JAK-STAT),gp130,IL-6R,and downstream activated ILs,such as IL-17 and IL-6 cytokine.Currently,according to these studies and their results,IL-6 blockade with anti-IL-6 or its receptor antibodies such as tocilizumab in COVID-19 is beneficial in severe cases and may reduce the mortality rate.JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-αand IL-6 and have shown various results in clinical trials.IL-6 induces IL-17 secretion,and IL-17 is involved in the pathogenesis of inflammatory processes.Clinical trials of anti-IL-17 drugs are currently recruiting,and anti-gp130 antibody is preclinical.However,this agent has shown positive effects in inflammatory bowel disease clinical trials and could be tested for SARS-CoV-2.This study aimed to review the role of IL-6 in the cytokine storm and studies regarding IL-6 and blockade of its inflammatory pathways in COVID-19 to determine if any of these agents are beneficial for COVID-19 patients.

Argon preconditioning protects neuronal cells with a Toll-like receptor-mediated effect

The noble gas argon has the potential to protect neuronal cells from cell death.So far,this effect has been studied in treatment after acute damage.Preconditioning using argon has not yet been investigated.In this study,human neuroblastoma SH-SY5Y cells were treated with different concentrations of argon(25%,50%,and 74%;21%O_(2),5%CO_(2),balance nitrogen)at different time intervals before inflicting damage with rotenone(20μM,4 hours).Apoptosis was determined by flow cytometry after annexin V and propidium iodide staining.Surface expressions of Toll-like receptors 2 and 4 were also examined.Cells were also processed for analysis by western blot and qPCR to determine the expression of apoptotic and inflammatory proteins,such as extracellular-signal regulated kinase(ERK1/2),nuclear transcription factor-κB(NF-κB),protein kinase B(Akt),caspase-3,Bax,Bcl-2,interleukin-8,and heat shock proteins.Immunohistochemical staining was performed for TLR2 and 4 and interleukin-8.Cells were also pretreated with OxPAPC,an antagonist of TLR2 and 4 to elucidate the molecular mechanism.Results showed that argon preconditioning before rotenone application caused a dose-dependent but not a time-dependent reduction in the number of apoptotic cells.Preconditioning with 74%argon for 2 hours was used for further experiments showing the most promising results.Argon decreased the surface expression of TLR2 and 4,whereas OxPAPC treatment partially abolished the protective effect of argon.Argon increased phosphorylation of ERK1/2 but decreased NF-κB and Akt.Preconditioning inhibited mitochondrial apoptosis and the heat shock response.Argon also suppressed the expression of the pro-inflammatory cytokine interleukin-8.Immunohistochemistry confirmed the alteration of TLRs and interleukin-8.OxPAPC reversed the argon effect on ERK1/2,Bax,Bcl-2,caspase-3,and interleukin-8 expression,but not on NF-κB and the heat shock proteins.Taken together,argon preconditioning protects against apoptosis of neuronal cells and mediates its action via Toll-like receptors.Argon may represent a promising therapeutic alternative in various clinical settings,such as the treatment of stroke.