Higher production of tumor necrosis factor alpha in hemozoin-fed human adherent monocytes is dependent on lipidic component of malarial pigment:new evidences on cytokine regulation in Plasmodium falciparum malaria

Objective:To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment.Methods:Adherent human monocytes were fed for 3 hours with different meals(native hemozoin;lipid free hemozoin;and control latex particles),then tumor necrosis factor alpha was monitored in cell supernatants up to 48 hours through western blotting or specific enzyme-linked immunoadsorbent assay.In selected experiments,unfed monocytes were treated with different doses of 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid or 4-hydroxynonenal instead of phagocytosis.Results:Hemozoin-fed monocytes produced higher levels of tumor necrosis factor alpha than unstimulated and latex-fed cells, while lipid-free hemozoin did not reproduce these results.Additionally,hemozoin effects were mimicked dose-dependently by 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid,but not by 4-hydroxynonenal.Conclusions:Present data suggest an essential role for lipids in hemozoindependent enhanced release of tumor necrosis factor alpha from monocytes,and 15(S,R)hydroxy -6,8,11,13-eicosatetraenoic acid could be one possible specific mediator.

Inhibition of telomerase with human telomerase reverse transcriptase antisense increases the sensitivity of tumor necrosis factor-α-induced apoptosis in prostate cancer cells

Aim： To investigate the effect of inhibition of telomerase with human telomerase reverse transcriptase （hTERT） antisense on tumor necrosis factor-α （TNF-α-induced apoptosis in prostate cancer cells （PC3）. Methods： Antisense phosphorothioate oligodeoxynucleotide （AS PS-ODN） was synthesized and purified. Telomerase activity was measured using the telomeric repeat amplification protocol （TRAP） and polymerase chain reaction enzyme-linked immunoassay （PCR-ELISA）. hTERT mRNA was measured by reverse transcription PCR （RT-PCR） assay and gel-image system, hTERT protein was detected by immunochemistry and flow cytometry. Cell viability was detected by 3-（4, 5-dimethylthiazol-2-yl）-2,5-Diphenyltetrazolium （MTT） assay. Cell apoptosis was observed by morphological method and determined by flow cytometry. Results： The telomerase activity decreased with time after hTERT AS PS-ODN treatment. The levels of hTERT mRNA decreased with time after hTERT AS PS-ODN treatment, which appeared before the decline of the telomerase activity. The percentage of positive cells of hTERT protein declined with time after hTERT AS PS-ODN treatment, which appeared after the decline of hTERT mRNA. There was no difference in telomerase activity, hTERT mRNA and protein levels between hTERT sense phosphorothioate oligodeoxynucleotide （S PS-ODN） and the control group. The cell viability decreased with time after hTERT AS PS-ODN combined with TNF-α treatment. The percentage of apoptosis increased with time after hTERT AS PS-ODN combined with TNF-α treatment. There was no difference in cell viability and the percentage of apoptosis between hTERT S PS-ODN and the control group. Conclusion： hTERT AS PS-ODN can significantly inhibit telomerase activity by downregulating the hTERT mRNA and protein expression, and inhibition of telomerase with hTERT antisense can enhance TNF-α- induced apoptosis of PC3 cells.

Antitumor effect of tumor necrosis factor-related apoptosis inducing ligand combined with mevastatin on a human glioma cell line SWO-38

BACKGROUND： Previous studies have reported that statins are less toxic to the human body and have greater antitumor activity; however, few studies have addressed the antitumor effect of statins combined with tumor necrosis factor-related apoptosis inducing ligand （TRAIL）. OBJECTIVE： To explore the effect of TRAIL combined with mevastatin on the proliferation and apoptotic cell death of a human glioma cell line SWO-38, and to study its mechanism of action. DESIGN, TIME AND SETTING： An in vitro control experiment was performed at the Central Laboratory of the Third Hospital Affiliated to Sun Yat-sen University, between January and April 2009. MATERIALS： The human SWO-38 cell line was provided by Cell Research, Department of Animal Experimental Center of Sun Yat-sen University; human recombinant soluble TRAIL by R＆D, USA; and mevastatin by Sigma, USA. METHODS： SWO-38 cells were separately incubated in TRAIL （100, 200, 300, 400, and 500 tJg/L） and mevastatin （5, 10, 20, 30, and 40 pmol/L） for 72 hours. In addition, SWO-38 cells were incubated in TRAIL （300 μg/L）, mevastatin （30 μmol/L）, and a solution containing both TRAIL and mevastatin for 12, 24, 48 and 72 hours. MAIN OUTCOME MEASURES： Cell proliferation was detected using methyl thiazolyl tetrazolium assay; cell apoptosis was observed using Hoechst 33258 staining and fluorescence microscopy and was measured using Annexin V/propidium iodide flow cytometry; TRAIL R1/DR4 and TRAIL R2/DR5 protein expressions levels were measured using indirect immunofluorescence staining combined with flow cytometry in the recombinant soluble TRAIL （rsTRAIL, 300 tJg/L）, mevastatin （30 IJmol/L） and combination groups; TRAIL R1/DR4 and TRAIL R2/DR5 mRNA expression was detected using real-time polymerase chain reaction. RESULTS： rsTRAIL, mevastatin and their combination inhibited tumor proliferation in a time- and dose-dependent manner. The proliferation inhibitory rate and apoptosis rate of human SWO-38 cells in the combined group were significantly greater than the rsTRAIL or mevastatin alone group （P 〈 0.01）. TRAIL R1/DR4 and TRAIL R2/DR5 protein and mRNA expressions were increased in the combination group compared with mevastatin or rsTRAIL alone after 72 hours （P 〈 0.01）. CONCLUSION： Both rsTRAIL and mevastatin inhibit the proliferation and apoptosis of the human glioma cell line SWO-38, while their combination enhances the anti-tumor effect. The mechanism of action possibly correlates to the upregulation of TRAIL R1/DR4 and TRAIL R2/DR5 mRNA expression by mevastatin, thereby enhancing the cell sensitivity to rsTRAIL.

Upregulation of stromal cell-derived factor-1 alpha/CXCR4 axis-induced migration of human neural progenitors by tumor necrosis factor-alpha and interleukin-8

BACKGROUND： Studies of several animal models of central nervous system diseases have shown that neural progenitor cells （NPCs） can migrate to injured tissues. Stromal cell-derived factor 1 alpha （SDF-la）, and its primary physiological receptor CXCR4, have been shown to contribute to this process. OBJECTIVE： To investigate migration efficacy of human NPCs toward a SDF-1α gradient, and the regulatory roles of tumor necrosis factor-α （TNF-α） and interleukin-8 （IL-8） in SDF-1α/CXCR4 axis-induced migration of NPCs. DESIGN, TIME AND SETTING： An in vitro, randomized, controlled, cellular and molecular biology study was performed at the Laboratory of Department of Cell Biology, Medical College of Soochow University between October 2005 and November 2007. MATERIALS： SDF-1α and mouse anti-human CXCR4 fusion antibody were purchased from R＆D Systems, USA. TNF-αwas purchased from Biomyx Technology, USA and IL-8 was kindly provided by the Biotechnology Research Institute of Soochow University. METHODS： NPCs isolated from forebrain tissue of 9 to 10-week-old human fetuses were cultured in vitro. The cells were incubated with 0, 20, and 40 ng/mL TNF-α, or 0, 20, and 40 ng/mL IL-8, for 48 hours prior to migration assay. For antibody-blocking experiments, cells were further pretreated with 0, 20, and 40 μg/mL mouse anti-human CXCR4 fusion antibody for 2 hours. Subsequently, the transwell assay and CXCR4 blockade experiments were performed to evaluate migration of human NPCs toward a SDF-1α gradient. Serum-free culture medium without SDF-1α served as the negative control. MAIN OUTCOME MEASURES： The transwell assay was performed to evaluate migration of human NPCs toward a SDF-1α gradient, which was blocked by fusion antibody against CXCR4. In addition, CXCR4 expression in human NPCs stimulated by TNF-α and IL-8 was measured by flow cytometry. RESULTS： Results from the transwell assay demonstrated that SDF-1α was a strong chemoattractant for human NPCs （P 〈 0.01）, and 20 ng/mL produced the highest levels of migration. Anti-human CXCR4 fusion antibody significantly blocked the chemotactic effect （P 〈 0.05）. Flow cytometry results showed that treatment with TNF-α and IL-8 resulted in increased CXCR4 expression and greater chemotaxis efficiency of NPCs towards SDF-1α（P 〈 0.01）. CONCLUSION： These results demonstrated that SDF-la significantly attracted NPCs in vitro, and neutralizing anti-CXCR4 antibody could block part of this chemotactic function. TNF-α and IL-8 increased chemotaxis efficiency of NPCs towards the SDF-1αgradient by upregulating CXCR4 expression in NPCs.

Correlation of tumor necrosis factor receptor superfamily 13B variation with sporadic intracranial aneurysm and clinical characteristics in Han Chinese populations

BACKGROUND： Inflammatory reaction correlates with sporadic intracranial aneurysm （IA）. Variation of tumor necrosis factor receptor superfamily 13B （TNFRSF13B）, an inflammatory mediator receptor, may associate with IA. OBJECTIVE： To explore the relationship between TNFRSF13B gene and sporadic IA, as well as the clinical characteristics of sporadic IA. DESIGN, TIME AND SETTING： Case-control study of genetic association was performed at the Experimental Technology Center of China Medical University from November 2006 to January 2008. PARTICIPANTS： A total of 367 patients with IA, confirmed by three-dimensional computed tomography angiography, magnetic resonance angiography, digital subtraction angiography, and neuro surgery, were admitted to the Department of Neurosurgery, First Affiliated Hospital of China Medical University from 2006 to 2007, and were selected as the case group. All patients were Han, with no family history of IA. In addition, a total of 396 non-lA patients were selected as control subjects. METHODS： Peripheral vein blood was harvested to extract whole blood genomic DNA. Genotyping and TNFRSF13B single nucleotide polymorphism （SNP） rs11078355 G〉A allele polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism. The relationship of TNFRSF13B SNP rs11078355 G〉A polymorphisms to IA and IA clinical characteristics were analyzed using the chi-square and two-sided test. MAIN OUTCOME MEASURES： TNFRSF13B SNP rs11078355 G〉A genotype distribution. RESULTS： In the IA patients, TNFRSF13B SNP rs11078355 G〉A genotype frequency was significantly increased （X2 = 16.306, odds ratio = 1.881,95% confidence interval = 1.382 2.560, P 〈 0.001）. In IA patients aged 〉 65 years, the frequency of TNFRSF13B SNP rs11078355 GA ＋ AA genotype was significantly greater than the GG genotype （X2 = 26.604, odds ratio = 5.248, 95% confidence interval = 2.662 10.345, P 〈 0.001）. CONCLUSION： The TNFRSF13B gene may associate with sporadic IA in Han Chinese populations In elderly patients, allele A may be an independent risk factor for IA, in addition to senile diseases, such as hypertension and diabetes mellitus.

Tumor necrosis family receptor superfamily member 9/tumor necrosis factor receptor-associated f

Hepatitis C virus(HCV)infection is an excellent immunological model for understanding the mechanisms developed by non-cytopathic viruses and tumors to evade the adaptative immune response.The antigen-specific cytotoxic T cell response is essential for keeping HCV under control,but during persistent infection,these cells become exhausted or even deleted.The exhaustion process is progressive and depends on the infection duration and level of antigenemia.During high antigenic load and long duration of infection,T cells become extremely exhausted and ultimately disappear due to apoptosis.The development of exhaustion involves the impairment of positive co-stimulation induced by regulatory cytokines,such as transforming growth factor beta 1.This cytokine downregulates tumor necrosis factor receptor(TNFR)-associated factor 1(TRAF1),the signal transducer of the T cell co-stimulatory molecule TNFR superfamily member 9(known as 4-1BB).This impairment correlates with the low reactivity of T cells and an exhaustion phenotype.Treatment with interleukin-7 in vitro restores TRAF1 expression and rescues T cell effector function.The process of TRAF1 loss and its in vitro recovery is hierarchical,and more affected by severe disease progression.In conclusion,TRAF1 dynamics on T cells define a new pathogenic model that describes some aspects of the natural history of HCV,and sheds light on novel immunotherapy strategies for chronic viral infections and cancer.

Tumor necrosis factor-αinhibition restores matrix formation by human adipose-derived stem cells in the late stage of chondrogenic differentiation

BACKGROUND Cartilage tissue engineering is a promising strategy for treating cartilage damage.Matrix formation by adipose-derived stem cells(ADSCs),which are one type of seed cell used for cartilage tissue engineering,decreases in the late stage of induced chondrogenic differentiation in vitro,which seriously limits research on ADSCs and their application.AIM To improve the chondrogenic differentiation efficiency of ADSCs in vitro,and optimize the existing chondrogenic induction protocol.METHODS Tumor necrosis factor-alpha(TNF-α)inhibitor was added to chondrogenic culture medium,and then Western blotting,enzyme linked immunosorbent assay,immunofluorescence and toluidine blue staining were used to detect the cartilage matrix secretion and the expression of key proteins of nuclear factor kappa-B(NF-κB)signaling pathway.RESULTS In this study,we found that the levels of TNF-αand matrix metalloproteinase 3 were increased during the chondrogenic differentiation of ADSCs.TNF-αthen bound to its receptor and activated the NF-κB pathway,leading to a decrease in cartilage matrix synthesis and secretion.Blocking TNF-αwith its inhibitors etanercept(1μg/mL)or infliximab(10μg/mL)significantly restored matrix formation.CONCLUSION Therefore,this study developed a combination of ADSC therapy and targeted anti-inflammatory drugs to optimize the chondrogenesis of ADSCs,and this approach could be very beneficial for translating ADSC-based approaches to treat cartilage damage.

Controlling malignant pericardial effusion by intrapericardial administration of recombinant mutant human tumor necrosis factor in patients with carcinoma

Objective: To evaluate the therapeutic efficacy of injecting recombinant mutant human tumor necrosis factor (rmhTNF) into pericardial cavity of carcinoma patients with malignant pericardial effusion. Methods: In 20 cases of malignant pericardial effusion, the intrapericardial catheter was inserted into pericardial cavity, and then rmhTNF of 1.5 × 107 U was infused. The infusion was repeated every 5-7 days with the total 4-6 times. If the effusion disappeared, rmhTNF was then used 2 more times and then the intrapericardial catheter was pulled out. Results: Of 20 patients, 14 were complete response (CR), 4 were partial response (PR) and 2 no change (NC). The disappearance of effusion in 6 cases lasted for more than 6 months. Conclusion: Injecting rmhTNF into pericardial cavity may be a better way to control malignant pericardial effusion and has mild side effects.

Effects of increased human tumor necrosis factor-like molecule 1A expression in peripheral blood of children with acute Guillain-Barre syndrome on interferon-gamma secretion

BACKGROUND： Human tumor necrosis factor-like molecule 1A （hTL1A） is a strong T helper cell type 1 （Thl） co-stimulator. Guillain-Barre syndrome （GBS） is an autoimmune disorder of the nervous system, which is mediated by Thl cells. OBJECTIVE： To determine hTL1A expression in peripheral blood T lymphocytes of acute GBS children and the effects of hTL1A on secretion of interferon-γ. DESIGN, TIME AND SETTING： A randomized, controlled, neuroimmunological in vitro study was performed at the Central Laboratory of First Hospital of Jilin University, China from November 2005 to November 2007. MATERIALS： Venous blood samples were obtained from 6 healthy donors, aged 6-12 years （all routine blood examination items were normal）, and 6 additional children with acute GBS, aged 6-12 years. The GBS children fell ill within 1 week and were not treated with hormones or immunoglobulin Purified recombinant human soluble tumor necrosis factor-like molecule 1A （rhsTL1A, 1 mg/mL, relative molecular mass 22 000, 6× His tag, soluble form） was supplied by the Central Laboratory of First Hospital of Jilin University, China. METHODS： Peripheral blood mononuclear cells were isolated from healthy donors using the standard Ficoll gradient centrifugation and were incubated in 96-well culture plates. The cells were assigned to the following groups： control （2 μg/mL phytohemagglutinin）, 2μg/mL phytohemagglutinin ＋ 25, 100 and 400 ng/mL rhsTL1A. T cell proliferation was quantified using the tritiated thymidine （3H-TdR） method. Serum interferon-γ levels in acute GBS children were detected by enzyme-linked immunosorbent assay （ELISA）. The ratio of hTL1A-positive T cells to CD3-positive T cells in peripheral blood of acute GBS children was determined using flow cytometry. Following in vitro pre-activation of peripheral blood mononuclear cells by 2 μg/mL phytohemagglutinin, the peripheral blood mononuclear cells were treated with 400 ng/mL exogenous rhsTLIA. Finally, peripheral blood mononuclear cell-secreted interferon-γlevels were measured by ELISA. MAIN OUTCOME MEASURES： The following parameters were measured： rhsTLIA stimulation index to stimulate proliferation of T cells; the serum interferon-γ levels in acute GBS children; the ratio of hTL1A-positive cells to CD3-positive cells; the levels of interferon-γ secreted by peripheral blood mononuclear cells in acute GBS children, as well as rhsTL1A-stimulated interferon-γ levels. RESULTS： T cell proliferation assay revealed that the stimulation index in each rhsTL1A group was greater than the control group. The stimulation index of the 400 ng/mL rhsTL1A group was the greatest. Serum interferon-γ levels in acute GBS children were significantly greater than the control group （P 〈 0.05）. The ratio of hTLIA＋ CD3＋ T cells to CD3＋ T cells in acute GBS children was significantly greater than the control group （P 〈 0.01 ）. Phytohemagglutinin stimulated peripheral blood mononuclear cells to a greater extent than 400 ng/mL rhsTL1A in the acute GBS group, and the secreted interferon-γ levels were significantly increased （P 〈 0.05）. CONCLUSION： In T cells pre-activated with 2 μg/mL phytohemagglutinin, proliferation was effectively increased with 400 ng/mL rhsTL1A treatment. Expression of hTLIA was increased in activated T cells from peripheral blood of acute GBS children, followed by increased interferon-γ secretion. These mechanisms are considered to be part of the pathological process that induces the secretion of inflammatory cytokines in GBS syndrome.

Effect of tumor necrosis factor-α on ventricular arrhythmias in rats with acute myocardial infarction in vivo

Acute myocardial infarction （AMI） is an acute cardiovascular emergency. This study was undertaken to assess the effect of tumor necrosis factor-a （TNF-a） on ventricular arrhythmias induced byAMI in rats in vivo. Two hundred and forty male Wistar rats were randomized into a sham- operation group, an AMI group, and a recombinant human tumor necrosis factor receptor：Fc fusion protein（rhTNFR：Fc） group. Acute anterior wall myocardial infarction was produced in the AMI group by ligating the left anterior descending coronary artery （LAD）, and there was no ligation but operation in the sham-operation group. The rhTNFR：Fc group was treated with rhTNFR：Fc（10 mg/kg）, a TNF-a antagonist, 24 hours before LAD ligation. The spontaneous and induced programmed electrical stimulation ventricular arrhythmias were recorded at baseline and 10 minutes, 20 minutes, 30 minutes, 60 minutes, 3 hours, 6 hours and 12 hours after ligation. At the same time the protein and mRNA expression levels of TNF-a among different groups were detected by histochemistry and real-time fluorescent quantitative PCR. Expression of TNF-a increased markedly from 10 minutes after infarction, peaked at 20-30 minutes, and returned to baseline gradually in the AMI group and rhTNFR：Fc group. The time- windows of spontaneous and induced ventricular arrhythmias were similar. Compared with the AMI group, the rhTNFR：Fc group showed a lesser expression of TNF-a protein and a lower incidence of ventricular arrhythmias （P〈0.05）. There was no obvious change in the sham-operation group. The expression of TNF-a induced by AMI could contribute to the onset of ventricular arrhythmias.

Protective effect of curcumin on tumor necrosis factor-alpha-induced neuronal damage in the rat hippocampus A relationship to the inhibition of neuronal Ca^(2+) influx

BACKGROUND： Previous studies of curcumin have focused mainly on its cytotoxic properties for antitumor therapy. There are few studies addressing the application of curcumin in the prevention and treatment of nervous system diseases. OBJECTIVE： To observe the protective effect of curcumin against tumor necrosis factor-alpha （TNF-α）-induced neuronal damage in the rat hippocampus and to explore the intervention effect of curcumin on Ca^2＋ influx following neuronal damage. DESIGN, TIME AND SETTING： A cell morphological and physiological study was performed at the Institute of Brain Research, Medical College of Jinan University, China, from December 2006 to June 2007. MATERIALS： Curcumin （Sigma, USA） and TNF-α （Sigma, USA） were used in this study. METHODS： Hippocampal neurons were isolated from one-day neonatal rats and primarily cultured for 5 days. Following this they received 1 pmol/L curcumin and 100 ng/mL TNF-a pre-treatment. Dynamic morphological changes were observed for 1 hour by inverted microscopy. At 48 hours post-treatment, static morphological characteristics of the neurons were observed using inverted microscopy. Subsequently, hippocampal neurons were primarily cultured for 7 days, after receiving 1 pmol/L curcumJn and 4.5 ng/mL TNF-a pre-treatment. Intracellular free Ca^2＋ was measured using Fluo 3/acetoxymethyl ester. MAIN OUTCOME MEASURES： Effects of curcumin on TNF-a-induced neuronal damage and Ca^2＋ influx in the rat hippocampus were measured. RESULTS： Following curcumin treatment, TNF-a-induced neurons grew as normal. TNF-a induced a rapid Ca^2＋ influx into the neuronal cytoplasm; however, Ca2＋ fluorescence intensity only slightly increased when neurons were co-perfused with curcumin and TNF-α. CONCLUSION： Curcumin has a protective effect on rat hippocampal neurons possibly by reducing the TNF-α-induced rapid Ca^2＋ influx into neuronal cytoplasm and by maintaining the Ca^2＋ homeostasis.

Morphological Study on the Mechanism of Tumor-selective Cytocidal Action of Tumor Necrosis Factor

Using light microscopy and electron microscopy, we observed the morphological changes inheuman hepatocellular carcinoma cell line (SMMC-7721) treated with tumor necrosis tumor necrosis factor (TNF)and the cytocidal effect of TNF on the heterotransplanted human hepatocellular carcinoma. It wasfound that the changes of the injury occurred earlier in the cell membranes than in the nuclei duringthe course of TNF killing of SMMC-7721 cells and there were similar lesions around the necroticarea in the heterotransplanted human hepatocellular carcinoma in the nude mice as compared withthose produced in SMMC-7721 cells. In addition, the determination of the DNA content in TNF-treated SMMC-7721 cells and controls revealed no significant difference between them. On the basisof these results and Darzynkiewicz’s proposals, it is suggested that TNF exerts its tumor-selectivekilling effect by binding to a specific to a specific plasma membrane receptor to disturb synthesis or assembly ofcell membrane components, thus causing the plasma membrane injury and finally cell lysis.

TNFSF15基因多态性与溃疡性结肠炎相关性的meta分析

目的系统评价人类肿瘤坏死因子超家族成员15(TNFSF15)基因在rs3810936位点的C/T多态性与溃疡性结肠炎(UC)的相关性。方法通过计算机检索EMbase、PubMed、Ovid、Springer、中国知网、万方医学网、维普资讯中文期刊服务平台等数据库,搜索关于TNFSF15基因在rs3810936位点C/T多态性与UC相关性的病例对照研究,检索时限为建库至2024年2月。由2位研究者独立进行文献筛选、资料提取及纳入研究偏倚风险评价后使用Review Manager 5.3、Stata 12.0软件进行meta分析。结果最终纳入9项病例对照研究,共2173例UC患者(病例组)和2744例健康者(对照组)。TNFSF15基因在rs3810936位点C/T多态性与UC发病风险具有相关性,携带CC+CT、CC基因型者UC发病风险均高于TT基因型,携带CT+TT基因型者UC发病风险低于CC基因型,携带C等位基因者UC发病风险高于T等位基因,差异均有统计学意义(优势比=1.25、1.41、0.82、1.17,95%可信区间1.06~1.46、1.17~1.71、0.71~0.93、1.08~1.27,P=0.006、<0.001、0.003、<0.001)。结论TNFSF15基因在rs3810936位点C/T多态性与UC发病有关,携带等位基因C会增加UC的发病风险。但受纳入研究数量和质量限制,该结论仍需开展大样本、高质量的研究进行验证。

应用ROC曲线分析外周血可溶性TNF受体、IL-15评估肺结核的预后价值

目的:分析外周血可溶性肿瘤坏死因子受体(sTNFR)、白细胞介素-15(IL-15)评估肺结核的预后价值。方法:选定枣庄市胸科医院2022年1月至2023年8月就诊的150例肺结核患者,比较预后良好组与不良组的血清sTNFR-55、sTNFR-75、IL-15水平,多因素logistic回归分析肺结核患者预后不良的危险因素,并绘制受试者工作曲线,计算曲线下面积,分析血清sTNFR-55、sTNFR-75、IL-15对肺结核预后不良的预测效能。结果:预后不良组的血清sTNFR-55、sTNFR-75水平均低于预后良好组,血清IL-15水平高于预后良好组(P<0.05)。logistic回归分析,年龄、病变范围、血清sTNFR-55、sTNFR-75、IL-15是肺结核患者预后不良的危险因素(P<0.05)。血清sTNFR-55、sTNFR-75、IL-15联合检测灵敏度均高于单一检测(P<0.05),血清sTNFR-55、sTNFR-75、IL-15联合检测特异度与单一检测比较无差异(P>0.05)。结论:肺结核患者的血清sTNFR-55、sTNFR-75表达量较低,血清IL-15表达量较高,联合检测血清sTNFR-55、sTNFR-75、IL-15,可提高对患者预后的预测效能,具有一定的参考价值。

人工肝支持系统治疗对重型肝炎患者血清TNF-α、IL-2、IL-10和IL-15水平的影响

目的 探讨重型肝炎患者人工肝支持系统 (ALSS)治疗前后外周血中肿瘤坏死因子 α(TNF α)、白细胞介素 2 (IL 2 )、白细胞介素 10 (IL 10 )、白细胞介素 15 (IL 15 )水平的变化。方法 应用血浆置换技术治疗重型肝炎患者 5 9例 ,采用ELISA法于每次治疗前后检测TNF α、IL 2、IL 10、IL 15水平 ,并观察其动态变化。结果 重型肝炎患者血清TNF α水平明显高于对照组 ,IL 2水平明显低于对照组 ,ALSS治疗后TNF α水平明显下降 ,而IL 2、IL 10则呈上升趋势 ,治疗前后IL 15水平无明显变化。结论 ALSS治疗能降低重型肝炎患者TNF α含量 ,并升高IL 2和IL 10水平 ,从而抑制炎性介质的产生 ,减轻免疫反应对肝细胞的损伤 。

血清HER-2/neu、TPS、CA15-3和TSGF联合检测在乳腺癌诊断中的价值

目的:探究乳腺癌患者血清中人表皮生长因子受体2(HER-2/neu)、组织多肽特异性抗原(TPS)、糖类抗原15-3(CA15-3)和肿瘤特异性生长因子(TSGF)联合检测在乳腺癌诊断中的价值。方法 :采用化学发光免疫分析法检测48例乳腺癌患者、46例良性乳腺疾病患者以及50例健康女性血清中HER-2/neu、TPS、CA15-3和TSGF水平。结果 :乳腺癌组HER-2/neu、TPS、CA15-3及TSGF水平均显著高于良性疾病组及健康对照组(P<0.01),而良性乳腺疾病组4项肿瘤标志物浓度水平与健康对照组比较均无统计学差异(P>0.05);HER-2/neu、TPS、CA15-3和TSGF联合检测灵敏度明显高于各单项检测灵敏度。结论:单项肿瘤标志物检测在乳腺癌诊断中的应用价值不高,而HER-2/neu、TPS、CA15-3和TSGF联合检测有助于提高乳腺癌的诊断灵敏度,对乳腺癌具有较高的诊断价值。

热休克反应和热休克转录因子1对LPS诱导的TNF-α和IL-15表达的影响

【目的】观察热休克反应 (HSR)以及热休克转录因子 1(HSF1)对LPS诱导的TNF α和IL 15表达的影响。【方法】用 2 0 0ng/mlLPS处理热休克或未热休克的小鼠RAW 2 6 4 .7巨噬细胞 ,抽提细胞的总RNA进行RT PCR实验 ,观察TNF α和IL 15mRNA表达的情况 ;采用HSF1基因敲除小鼠经腹腔内注射LPS复制内毒素血症模型 ,抽提HSF1基因敲除小鼠 (HSF1-/ -)和野生型小鼠 (HSF1+ / + )肺组织的总RNA进行RT PCR实验 ,观察TNF α和IL 15mRNA表达的情况。用TESS分析IL 15的启动子 ,寻找热休克元件(Heatshockelement,HSE)。【结果】小鼠RAW 2 6 4 .7巨噬细胞受LPS刺激后 ,TNF α和IL 15mRNA的水平明显增加 ,而热休克抑制了LPS诱导的TNF α和IL 15mRNA的表达 ;腹腔注射LPS后 ,HSF1-/ -小鼠和HSF1+ / + 小鼠的肺组织中TNF α和IL 15mRNA的水平明显增加 ,HSF1-/ -小鼠的肺组织中TNF α和IL 15mRNA水平的增加明显高于HSF1+ / + 小鼠。经TESS软件分析发现IL 15的启动子区含有 2个HSE。【结论】HSR、HSF1抑制了LPS诱导的TNF α和IL 15的表达 ;HSF1可能通过与IL 15启动子区的HSE结合抑制LPS诱导的IL 15的表达。

恩替卡韦联合乳果糖治疗乙型肝炎后肝硬化的临床效果及对血清HBV-DNA、KLF2和TNFSF15的影响

目的探讨恩替卡韦联合乳果糖治疗乙型肝炎后肝硬化的临床效果及对血清乙型肝炎病毒(HBV)-DNA、锌指样转录因子2(krüppel-like factor 2,KLF2)和肿瘤坏死因子超家族成员15(tumor necrosis factor superfamily member 15,TNFSF15)的影响。方法选取2017年1月—2019年1月收治的190例乙型肝炎后肝硬化,按照治疗方法的不同,分为观察组与对照组,每组各95例。观察组予恩替卡韦+乳果糖+常规治疗,对照组予恩替卡韦+常规治疗。两组均治疗6个月。记录治疗后6个月的临床疗效,检测治疗前、治疗后6个月的肝功能相关指标[丙氨酸转氨酶(ALT)、总胆红素(TB)]、肝纤维化相关指标[透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原(PC-Ⅲ)]及细胞因子相关指标(KLF2、TNFSF15)的水平变化,比较治疗前及治疗后3、6个月血清HBV-DNA水平,观察不良反应发生情况。结果与对照组比较,观察组治疗总有效率升高,差异有统计学意义(P<0.05)。与对照组比较,观察组治疗后6个月ALT、TB、HA、LN、PC-Ⅲ、KLF2水平下降,TNFSF15水平升高,差异有统计学意义(P<0.01);与本组治疗前比较,两组治疗后6个月ALT、TB、HA、LN、PC-Ⅲ、KLF2水平下降,TNFSF15水平升高,差异有统计学意义(P<0.01)。与对照组比较,观察组治疗后3、6个月血清HBV-DNA水平下降,差异有统计学意义(P<0.01);与本组治疗前比较,两组治疗后3、6个月血清HBV-DNA水平下降,差异有统计学意义(P<0.01);与本组治疗后3个月比较,两组治疗后6个月血清HBV-DNA水平下降,差异有统计学意义(P<0.01)。两组不良反应总发生率比较差异无统计学意义(P>0.05),均予对症处理后症状消失。结论恩替卡韦联合乳果糖治疗乙型肝炎后肝硬化的临床效果较好,可改善肝功能,抑制肝纤维化,降低血清HBV-DNA水平,调控细胞因子的表达,且不良反应未明显增加。

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合甲氨蝶呤短期治疗银屑病关节炎15例临床观察

目的探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(recombinant human tumor necrosis factor-α receptorⅡ:IgG Fc fusion protein for injection,rhTNFR:Fc)联合甲氨蝶呤(methotrexate,MTX)短期治疗银屑病关节炎(psoriaticarthritis,PsA)的疗效与安全性。方法对入院前传统治疗方案(非甾体类消炎药联合甲氨蝶呤或其他免疫抑制剂)治疗3个月以上疗效欠佳的15例患者,入院后给予重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(益赛普,etanercept)25mg,2次/周,皮下注射,同时给予甲氨蝶呤7.5～15mg,1次/周,12周后停用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白,观察患者治疗前后的临床症状、炎性实验室指标的改善情况及药物安全性。结果15例患者关节压痛数、关节肿胀数、银屑病面积和严重度指数(psoriasis area and severity index,PASI)均明显降低,同时血沉及C反应蛋白亦明显下降,且与治疗前相比差异具有统计学意义。1例患者出现注射部位皮肤片状红肿及瘙痒,未予特殊处理后消失,其余患者均未出现明显不良反应。结论重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合甲氨蝶呤短期治疗银屑病关节炎有效、安全、可行。

浙江地区汉族人TNFSF15基因多态性与克罗恩病相关性研究

目的检测TNF超家族成员15(TNFSF15)基因多态性与浙江地区汉族人克罗恩病患者遗传易感性的相关性。方法抽取42例克罗恩病患者(克罗恩病组)、49名健康者(对照组)外周静脉血并提取DNA,设计TNFSF15三个单核苷酸多态性(SNP)(rs3810936,rs6478109,rs7848647)目的基因特异性引物,扩增样本中的目的基因进行测序,分析等位基因的多态性与遗传易感性及与临床亚型的关系。结果两组rs3810936,rs6478109,rs7848647三个位点的等位基因携带频率及基因型频率比较差异无统计学意义。三个基因多态性位点组成的亚型B1(cc-gg-cc)即包含三个危险等位基因的亚型,与对照组相比,其亚型频率分别为38%和26%(χ2=1.393,P=0.238),而亚型A1(tt-aa-tt)即包含三个保护等位基因的亚型,与对照组相比,其亚型频率分别为14%和12%(χ2=0.082,P=0.774),无明显保护作用。多因素Logistic回归分析显示TNFSF15的SNP可能与克罗恩病的临床亚型无显著相关性,但rs3810936与rs6478109有相关性(r=0.802,P<0.01),rs3810936与rs7848647有相关性(r=0.793,P<0.01),rs6478109与rs7848647有相关性(r=0.948,P<0.01)。结论 TNFSF15的三个SNP(rs3810936,rs6478109,rs7848647)与浙江地区汉族人克罗恩病遗传易感性、临床亚型无显著相关性。TNFSF15基因rs3810936,rs6478109,rs7848647的SNP可能存在种族及地域差异。