Ulcerative colitis(UC)and Crohn’s disease(CD)are part of Inflammatory Bowel Diseases(IBD)and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells.In addition,the main i...Ulcerative colitis(UC)and Crohn’s disease(CD)are part of Inflammatory Bowel Diseases(IBD)and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells.In addition,the main inflammatory mediator is related to the tumor necrosis factor-alpha(TNF-α).TNF-αis a mediator of the intestinal inflammatory processes,thus being one of the main cytokines involved in the pathogenesis of IBD,however,its levels,when measured,are present in the serum of patients with IBD.In addition,TNF-αplays an important role in promoting inflammation,such as the production of interleukins(IL),for instance IL-1βand IL-6.There are two receptors for TNF as following:The tumor necrosis factor 1 receptor(TNFR1);and the tumor necrosis factor 2 receptor(TNFR2).They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity.The soluble TNF form binds to the TNFR1 receptor with,and its activation results in a signaling cascade effects such as apoptosis,cell proliferation and cytokine secretion.In contrast,the transmembrane TNF form can bind both to TNFR1 and TNFR2.Recent studies have suggested that TNF-αis one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD,since TNF levels are present in the serum of both patients with UC and CD.Intravenous and subcutaneous biologics targeting TNF-αhave revolutionized the treatment of IBD,thus becoming the best available agents to induce and maintain IBD remission.The application of antibodies aimed at neutralizing TNF-αin patients with IBD that induce a satisfactory clinical response in up to 60%of patients,and also induced long-term maintenance of disease remission in most patients.It has been suggested that anti-TNF-αagents inactivate the pro-inflammatory cytokine TNF-αby direct neutralization,i.e.,resulting in suppression of inflammation.However,anti-TNF-αantibodies perform more complex functions than a simple blockade.展开更多
Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improv...Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improving prognosis.However,up to one-third of treated patients show primary nonresponse(PNR)to anti-TNF-αtherapies,and 23%-50%of IBD patients experience loss of response(LOR)to these biologics during subsequent treatment.There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs.This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients.Most predictors remain controversial,and only previous surgical history,disease manifestations,drug concentrations,antidrug antibodies,serum albumin,some biologic markers,and some genetic markers may be potentially predictive.In addition,we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists.Therapeutic drug monitoring plays an important role in treatment selection.Dose escalation,combination therapy,switching to a different anti-TNF drug,or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.展开更多
Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumo...Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(P<0.05 for all).The areas under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.展开更多
Tumor necrosis factor inhibitors(anti-TNFs)are widely used therapies for the treatment of inflammatory bowel diseases(IBD);however,their administration is not risk-free.Heart failure(HF),although rare,is a potential a...Tumor necrosis factor inhibitors(anti-TNFs)are widely used therapies for the treatment of inflammatory bowel diseases(IBD);however,their administration is not risk-free.Heart failure(HF),although rare,is a potential adverse event related to administration of these medications.However,the exact mechanism of development of HF remains obscure.TNFαis found in both healthy and damaged hearts.Its effects are concentration-and receptor-dependent,promoting either cardio-protection or cardiomyocyte apoptosis.Experimental rat models with TNFαreceptor knockout showed increased survival rates,less reactive oxygen species formation,and improved diastolic left ventricle pressure.However,clinical trials employing anti-TNF therapy to treat HF had disappointing results,suggesting abolishment of the cardioprotective properties of TNFα,making cardiomyocytes susceptible to apoptosis and oxidation.Thus,patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy.This review aims to discuss adverse events associated with the administration of anti-TNF therapy,with a focus on HF,and propose some approaches to avoid cardiac adverse events in patients with IBD.展开更多
AIM:To examine the association of genetic polymorphisms(-308)G/A TNFα,(+250)A/G Ltα,(+36)A/G TNFR1,(+1663)A/G TNFR2 with the development of primary open angle glaucoma(POAG) among people in Central Russia.METHODS:Th...AIM:To examine the association of genetic polymorphisms(-308)G/A TNFα,(+250)A/G Ltα,(+36)A/G TNFR1,(+1663)A/G TNFR2 with the development of primary open angle glaucoma(POAG) among people in Central Russia.METHODS:The study sample included 443 individuals,of which 252 patients with POAG and 191 individuals in the control group.Genotyping of(-308)G/A TNFα,(+250)A/G Ltα,(+36)A/G TNFR1,(+1663)A/G TNFR2 was performed using polymerase chain reaction.The distribution of alleles and genotypes of the studied DNA markers in the groups was examined by 2×2 contingency tables and χ2 with the Yates' s correction for continuity and odds ratios(OR) with 95% confidence intervals(CI).RESULTS:Allele(-308)G TNFα(Р=0.01,OR=1.78,95%CI 1.12-2.85) was identified as a risk factor for POAG.Homozygotes(-308) AA TNFα are at a lowest risk for development of the disease(Р=0.01,OR=0.0005).The following combination of genetic variants of cytokines were associated with a reduced risk of POAG:(+1663)A TNFR2 and(+250)G Ltα(OR=0.34)CONCLUSION:Genetic polymorphisms(-308)G/A TNFα,(+250)A/G Ltα,(+1663)A/G TNFR2 associated with the development of POAG in the population of Central Russia.展开更多
Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome（HFRS）. Methods Double-antibody sandwich ELISA was used to determine serum interleukin （IL）-6, urine tumor ne...Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome（HFRS）. Methods Double-antibody sandwich ELISA was used to determine serum interleukin （IL）-6, urine tumor necrosis factor （TNF）, IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively （P<0.001）. The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β2-microglobulin （β2-MG）, blood ureanitrogen （BUN） and creatinine （Cr）. Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 （r=0.5768, P<0.05; r=0.3760, P<0.01）. Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.展开更多
BACKGROUND End-stage liver disease caused by non-alcoholic steatohepatitis(NASH)is the second leading indication for liver transplantation.To date,only moderately effective pharmacotherapies exist to treat NASH.Unders...BACKGROUND End-stage liver disease caused by non-alcoholic steatohepatitis(NASH)is the second leading indication for liver transplantation.To date,only moderately effective pharmacotherapies exist to treat NASH.Understanding the pathogenesis of NASH is therefore crucial for the development of new therapies.The inflammatory cytokine tumor necrosis factor alpha(TNF-α)is important for the progression of liver disease.TNF signaling via TNF receptor 1(TNFR1)has been hypothesized to be important for the development of NASH and hepatocellular carcinoma in whole-body knockout animal models.AIM To investigate the role of TNFR1 signaling in hepatocytes for steatohepatitis development in a mouse model of diet-induced NASH.METHODS NASH was induced by a western-style fast-food diet in mice deficient for TNFR1 in hepatocytes(TNFR1ΔHEP)and their wild-type littermates(TNFR1fl/fl).Glucose tolerance was assessed after 18 wk and insulin resistance after 19 wk of feeding.After 20 wk mice were assessed for features of NASH and the metabolic syndrome such as liver weight,liver steatosis,liver fibrosis and markers of liver inflammation.RESULTS Obesity,liver injury,inflammation,steatosis and fibrosis was not different between TNFR1ΔHEP and TNFR1fl/fl mice.However,Tnfr1 deficiency in hepatocytes protected against glucose intolerance and insulin resistance.CONCLUSION Our results indicate that deficiency of TNFR1 signaling in hepatocytes does not protect from diet-induced NASH.However,improved insulin resistance in this model strengthens the role of the liver in glucose homeostasis.展开更多
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....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-IA 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.展开更多
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 cytotoxi...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.展开更多
BACKGROUND: Recent researches have indicated that estrogen has extensive neuroprotective effects. So some studies designed ovariectomized animal models and administrated with estrogen, so as to verify its neuroprotect...BACKGROUND: Recent researches have indicated that estrogen has extensive neuroprotective effects. So some studies designed ovariectomized animal models and administrated with estrogen, so as to verify its neuroprotective effects. OBJECTIVE: To observe the effect of 17 beta-estradiol on the content of norepinephrine (NE) and level of tumor necrosis factor (TNF) in submandibular glands of rats with sympathetic nerve injury, and analyze the dose-dependence and pathway of action. DESIGN: A randomized control animal study.SETTINGS: Department of Hand Surgery, the 252 Hospital of Chinese PLA; Department of Hand Surgery, Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: Fifty healthy female Wistar rats were randomly divided into 5 groups with 10 rats in each group: sham-operated group, ovariectomy+6-OHDA+saline group, ovariectomy+6-OHDA+17β-estradiol 50, 200 and 500 μg/kg groups. METHODS: The experiments were carried out in Tongji Medical College, Huazhong University of Science and Technology between October 2005 and March 2006. Bilateral ovaries were only exposed but not resected for the rats in the sham-operated group, but bilateral ovaries were resected in all the other groups. In the ovariectomy+6-OHDA+17β-estradiol 50, 200 and 500 μg/kg groups, the rats were administrated with intraperitoneal injection of 6-OHDA (8 mg/kg), and then immediately given 17β-estradiol of corresponding dosages respectively, once a day for 10 days continuously. Rats in the sham-operated group and ovariectomy+6-OHDA+saline group were administrated with saline of the same volume. After administration, 5 rats in each group were killed to determine the NE contents in bilateral submandibular glands with high performance liquid chromatography-electrochemical detector (HPLC-ECD), and the other 5 rats were used to determine the TNF levels in submandibular glands with enzyme-linked immunosorbant assay.MAIN OUTCOME MEASURES: The NE contents and TNF levels in submandibular glands of rats in each group were observed. RESULTS: All the 50 rats were involved in the analysis of results. ① The NE content was obviously lower in the ovariectomy+6-OHDA+saline group than in the sham-operated group [(1 035±196), (1 823±314) ng/g, P < 0.05], there were no significant differences between the ovariectomy+6-OHDA+17β-estradiol 50 μg/kg group and ovariectomy+6-OHDA+saline group [(1 004±253), (1 035±196) ng/g, P > 0.05], but obviously higher in the ovariectomy+6-OHDA+17β-estradiol 200 and 500 μg/kg groups than in the ovariectomy+6-OHDA+saline group [(1 487±268), (1 939±274), (1 035±196) ng/g, P < 0.05]. ② The TNF level was obviously higher in the ovariectomy+6-OHDA+saline group than in the sham-operated group [(3.498±0.792), (1.893±0.533) ng/g, P < 0.05], there were no significant differences between the ovariectomy+ 6-OHDA+17β-estradiol 50 μg/kg group and ovariectomy+6-OHDA+saline group [(3.328±0.712), (3.498±0.792) ng/g, P > 0.05], but obviously lower in the ovariectomy+6-OHDA+17β-estradiol 200 and 500 μg/kg groups than in the ovariectomy+6-OHDA+saline group [(2.639±0.438), (2.016±0.619), (3.498±0.792) ng/g, P < 0.05]. CONCLUSION: Estrogen has obvious protective effect dose-dependently on 6-OHDA induced chemical sympathetic nerve terminal injury in rats, and it may play its protective role by reducing TNF level and ameliorating inflammatory reaction.展开更多
TRPP2, a Ca^(2+)-permeable non-selective cation channel, has been shown to negatively regulate cell cycle, but the mechanism underlying this regulation is unknown. Tumor necrosis factor a(TNF-α) is a proinflammatory ...TRPP2, a Ca^(2+)-permeable non-selective cation channel, has been shown to negatively regulate cell cycle, but the mechanism underlying this regulation is unknown. Tumor necrosis factor a(TNF-α) is a proinflammatory cytokine extensively involved in immune system regulation, cell proliferation and cell survival. However, the effects and mechanisms for the role of TNF-αin laryngeal cancer remain unclear. Here, we demonstrated using western blot analyses and intracellular Ca^(2+) concentration measurements that TNF-α treatment suppressed both TRPP2 expression and ATP-induced Ca^(2+) release in a laryngeal cancer cell line(Hep-2). Knockdown of TRPP2 by a specific siRNA significantly decreased ATP-induced Ca^(2+) release and abolished the effect of TNF-α on the ATP-induced Ca^(2+) release. TNF-α treatment also enhanced Hep-2 cell proliferation and growth, as determined using cell counting and flow cytometry cell cycle assays. Moreover, TNF-α treatment down-regulated phosphorylated protein kinase R-like endoplasmic reticulum kinase(p-PERK) and phosphorylated eukaryotic translation initiation factor(p-eIF2α)expression levels, without affecting PERK and eIF2 a expression levels in Hep-2 cells. We concluded that suppressing TRPP2 expression and TRPP2-mediated Ca^(2+) signaling may be one mechanism underlying TNF-α-enhanced Hep-2 cell proliferation.These results offer new insights into the mechanisms of TNF-α-mediated laryngeal cancer cell proliferation, and provide evidences showing a potential role of TNF-α in the development of laryngeal cancer.展开更多
Background:Tumor necrosis factor receptor-associated protein 1(TRAP1)plays a protective effect in hypoxic cardiomyocytes,but the precise mechanisms are not well clarified.The study is aimed to identify the mechanism o...Background:Tumor necrosis factor receptor-associated protein 1(TRAP1)plays a protective effect in hypoxic cardiomyocytes,but the precise mechanisms are not well clarified.The study is aimed to identify the mechanism of TRAP1 on hypoxic damage in cardiomyocytes.Methods:In this study,the effects of TRAP1 and cytochrome c oxidase subunit Ⅱ(COXⅡ)on apoptosis in hypoxia-induced cardiomyocytes were explored using overexpression and knockdown methods separately.Results:Hypoxia induced cardiomyocyte apoptosis,and TRAP1 overexpression notably inhibited apoptosis induced by hypoxia.Conversely,TRAP1 silencing promoted apoptosis in hypoxic cardiomyocytes.Further investigation revealed that the proapoptotic effects caused by the silencing of TRAP1 were prevented by COXⅡ overexpression,whereas COXⅡ knockdown reduced the antiapoptotic function induced by TRAP1 overexpression.Additionally,changes in the release of cytochrome c from mitochondria into the cytosol and the caspase-3 activity in the cytoplasm,as well as reactive oxygen species production,were found to be correlated with the changes in apoptosis.Conclusions:The current study uncovered that TRAP1 regulates hypoxia-induced cardiomyocyte apoptosis through a mitochondria-dependent apoptotic pathway mediated by COXⅡ,in which reactive oxygen species presents as an important component.展开更多
Tumor Necrosis Factor α(TNFα) is best known as a mediator of inflammation and immunity, and also plays important roles in tumor biology. However, the role of TNFα in tumor biology is complex and not completely unde...Tumor Necrosis Factor α(TNFα) is best known as a mediator of inflammation and immunity, and also plays important roles in tumor biology. However, the role of TNFα in tumor biology is complex and not completely understood. In a human melanoma cell line, M2, and a lung carcinoma cell line, A549, TNFα up-regulates prion protein(PrP) level, and promotes tumor cell migration in a PrP dependent manner. Silencing PRNP abrogates TNFα induced tumor cell migration;this phenotype is reversed when PRNP is re-introduced. Treatment with TNFα activates nuclear factor kappa B(NF-κB)signaling, which then mitigates autophagy by reducing the expression of Forkhead Box P3(FOXP3). Down regulation of FOXP3 reduces the transcription of synaptosome associated protein 29(SNAP29), which is essential in the fusion of autophagosome and lysosome creating autolysosome. FOXP3 being a bona fide transcription factor for SNAP29 is confirmed in a promoter binding assay. Accordingly, silencing SNAP29 in these cell lines also up-regulates PrP, and promotes tumor cell migration without TNFα treatment. But, when SNAP29 or FOXP3 is silenced in these cells, they are no longer respond to TNFα. Thus, a reduction in autophagy is the underlying mechanism by which expression of PrP is up-regulated,and tumor cell migration is enhanced upon TNFα treatment. Disrupting the TNFα-NF-κB-FOXP3-SNAP29 signaling axis may provide a therapeutic approach to mitigate tumor cell migration.展开更多
Aim:The cytokine receptor tumor necrosis factor receptor superfamily member 9(TNFRSF9)is mainly considered to be a co-stimulatory activation marker in hematopoietic cells.Several preclinical models have shown a dramat...Aim:The cytokine receptor tumor necrosis factor receptor superfamily member 9(TNFRSF9)is mainly considered to be a co-stimulatory activation marker in hematopoietic cells.Several preclinical models have shown a dramatic beneficial effect of treatment approaches targeting TNFRSF9 with agonistic antibodies.However,preliminary clinical phase I/II studies were stopped after the occurrence of several severe deleterious side effects.In a previous study,it was demonstrated that TNFRSF9 was strongly expressed by reactive astrocytes in primary central nervous system(CNS)tumors,but was largely absent from tumor or inflammatory cells.The aim of the present study was to address the cellular source of TNFRSF9 expression in the setting of human melanoma brain metastasis,a highly immunogenic tumor with a prominent tropism to the CNS.Methods:Melanoma brain metastasis was analyzed in a cohort of 78 patients by immunohistochemistry for TNFRSF9 and its expression was correlated with clinicopathological parameters including sex,age,survival,tumor size,number of tumor spots,and BRAF V600E expression status.Results:Tumor necrosis factor receptor superfamily member 9 was frequently expressed independently on both melanoma and endothelial cells.In addition,TNFRSF9 was also present on smooth muscle cells of larger vessels and on a subset of lymphomonocytic tumor infiltrates.No association between TNFRSF9 expression and patient survival or other clinicopathological parameters was seen.Of note,several cases showed a gradual increase in TNFRSF9 expression on tumor cells with increasing distance from blood vessels,an observation that might be linked to hypoxia-driven TNFRSF9 expression in tumor cells.Conclusion:The findings indicate that the cellular source of TNFRSF9 in melanoma brain metastasis largely exceeds the lymphomonocytic pool,and therefore further careful(re-)assessment of potential TNFRSF9 functions in cell types other than hematopoietic cells is needed.Furthermore,the hypothesis of hypoxia-driven TNFRSF9 expression in brain metastasis melanoma cells requires further functional testing.展开更多
Objective: Human immunodeficiency virus (HIV) p24 antigen and antibody and herpes simplex virus 2 IgM are seromarkers indicating infection with HIV and herpes simplex virus-2 (HSV-2), respectively, whereas tumor necro...Objective: Human immunodeficiency virus (HIV) p24 antigen and antibody and herpes simplex virus 2 IgM are seromarkers indicating infection with HIV and herpes simplex virus-2 (HSV-2), respectively, whereas tumor necrosis factor α is an inflammatory biomarker that can be triggered by infections. Female children of single parents are faced with many socio-economic challenges that make them vulnerable to sexual influences and prone to sexually transmitted infections. The goal of this work was to determine HIV p24 antigen/antibody, HSV-2 IgM and tumor necrosis factor-α plasma levels in adult female children living in single-parent households.Methods: In this case-control observational study, 100 adult female children living with a single parent (50 living with a single mother and 50 living with a single father;age: 18-22 years) and 100 age-matched women living with both parents were recruited to serve as the test and control groups, respectively. All subjects were negative for acid-fast bacilli, plasmodium, hepatitis C virus, and hepatitis B virus. Human tumor necrosis factor α, HSV-2 IgM, antibody to hepatitis C virus, hepatitis B surface antigen and human immunodeficiency virus p24 antigen and antibody (HIV p24 Ag/Ab) levels were determined by ELISA, while the detection of acid-fast bacilli in sputum andPlasmodium in blood was carried out by optical microscopy. This work was carried out in the Owo/Ose Federal Constituency in Ondo State that shares boundaries with Edo State. The study protocol was approved by the Research and Ethical Committee of the Department of Medical Laboratory Science, Achievers University, Owo, Nigeria (AUO/MLS/2020/127) on August 27, 2020.Results: HIV p24 Ag/Ab was detected in 0 adult female children living with a single mother, 1 (2%) adult female child living with a single father and 1 (1 %) adult female child living with both parents. HSV-2 IgM was detected in 9 (18%) adult female children living with a single mother, 13 (26%) adult female children living with a single father, and 5 (10%) adult female children living with both parents.Conclusion: This work shows that adult female children of single parents are vulnerable to sexual influences, and thereby more prone to HSV-2 and possibly HIV, especially adult female children of single fathers.展开更多
Objective To investigate association between tumor necrosis factor alpha (TNF-α) and obsessive compulsive disorder (OCD) in Chinese Han population.Methods Plasma concentrations of TNF-α were measured in 61 drug-free...Objective To investigate association between tumor necrosis factor alpha (TNF-α) and obsessive compulsive disorder (OCD) in Chinese Han population.Methods Plasma concentrations of TNF-α were measured in 61 drug-free patients who fulfilled DSM-Ⅳ criteria for OCD and 93 healthy controls.TNF-α concentrations in blood were determined by enzyme-linked immunosorbent assay (ELISA).Two polymorphisms of TNF-α gene were investigated in the same patients and healthy controls:-308 G/A and-238 G/A.The allelic and genotypic frequencies of these polymorphisms were examined by using DNA sequencing method.Results Plasma levels of TNF-α did not differ between patients and controls (P=0.292).No significant results were observed for any of the alleles at the-308 G/A or-238 G/A polymorphism of the TNF-α gene.Finally a haplotype consisting of genotypes of these two markers was also examined.No association was observed for any haplotype (P=0.108).Conclusion No significant differences were observed between patients and controls in plasma levels of TNF-α.There is no association between the-308 G/A and-238 G/A TNF-α gene polymorphisms and OCD in our Chinese samples.However,the results need to be replicated in larger samples.展开更多
Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular funct...Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.展开更多
Objective:To explore the effect of the Xian Fang Huo Ming Yin(XFHM)for treating cutaneous infections and promoting wound healing in patients with perianal abscesses.Methods:Sixty-one patients with perianal abscesses w...Objective:To explore the effect of the Xian Fang Huo Ming Yin(XFHM)for treating cutaneous infections and promoting wound healing in patients with perianal abscesses.Methods:Sixty-one patients with perianal abscesses who were admitted to our hospital(Xinghua City People’s Hospital)from May 2022 to May 2023 were selected and randomly divided into two groups,a control group(30 cases)and a study group(31 cases).Both groups received surgical treatment.The control group received conventional treatment and warm water fumigation,sitz bath,and surgical dressing change after surgery,while the research group received XFHM based on the control group.XFHM was taken orally and replaced with warm water for fumigation and sitz bathing.Both groups received treatment for 4 weeks but discontinued sitz bathing after 2 weeks.Various clinical indicators between the two groups were compared.Results:The total clinical effective rate and wound recovery rate of the study group were higher than that of the control group.There were differences in the wound pain scores,surrounding tissue edema,and wound secretions at different time points.Both groups experienced wound pain.The scores of wound pain,surrounding tissue edema,and wound secretions of the study group were lower than those of the control group,7 and 14 days after surgery.The serum interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α)levels,and pH values of the study group were lower than those of the control group 10 days after surgery(P<0.05).Conclusion:The application of XFHM for treating cutaneous infections and promoting wound healing in patients with perianal abscesses improved the treatment outcome,alleviated clinical symptoms,and promoted healing.展开更多
The inhibitory effect of hydroxyapatite ultrofine powder on tumor and the effect on the immunity function of body were investigated. The levels of IL 2 in the spleen cells and serum TNF levels in the tumor bearing mic...The inhibitory effect of hydroxyapatite ultrofine powder on tumor and the effect on the immunity function of body were investigated. The levels of IL 2 in the spleen cells and serum TNF levels in the tumor bearing mice at the 7th day and 14th after peritoneal injection of HAUFP were detected by using the methods of colorimetric analysis of MTT and crystal purple decoration, respectively. The disappearance of the ascites of the mice was observed. The results showed that the levels of IL 2 and TNF in the tumor bearing mice were higher obviously in the drug treated group than in the control group , the ascites growth was inhibited. It was suggested that HAUFP could increase the levels of IL 2 and TNF of the tumor bearing mice and improve the immune function of body.展开更多
BACKGROUND Cytokine release syndrome(CRS)is defined as systemic inflammation that usually occurs following chimeric antigen receptor T-cell therapy administration;however,it has not been reported in patients with untr...BACKGROUND Cytokine release syndrome(CRS)is defined as systemic inflammation that usually occurs following chimeric antigen receptor T-cell therapy administration;however,it has not been reported in patients with untreated non-small cell lung cancer to date.CASE SUMMARY A 44-year-old nonsmoking woman presented to the hospital due to fever,palpitation,nausea,and cough for 1 mo and was diagnosed with stage cT3N3M0(IIIc)adenocarcinoma of the lung.Auxiliary examinations revealed elevated cytokine[tumor necrosis factor-α,interleukin(IL)-1β,and IL-6]and inflammatory factor levels,which decreased after treatment with corticosteroids and immunoglobulin and when tumor growth was controlled following chemotherapy,radiotherapy,and antiangiogenesis therapy.However,tumor recurrence was observed.After administration of nivolumab as third-line treatment,the patient’s condition was transiently controlled;however,CRS-like symptoms suddenly emerged,which led to a resurgence of cytokines and inflammatory factors and rapid death.CONCLUSION CRS can develop in treatment-naïve lung cancer patients.Patients with tumorrelated CRS may be at risk of CRS recurrence,aggravation,and onset of immune checkpoint inhibitor-related adverse events.展开更多
基金Research Support Foundation of the State of São Paulo(FAPESP,Brazil),No.2014/25927-2,No.2018/07862-1National Council for Scientific and Technological Development(CNPq,Brazil)Higher Education Personnel Improvement Coordination(CAPES,Brazil).
文摘Ulcerative colitis(UC)and Crohn’s disease(CD)are part of Inflammatory Bowel Diseases(IBD)and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells.In addition,the main inflammatory mediator is related to the tumor necrosis factor-alpha(TNF-α).TNF-αis a mediator of the intestinal inflammatory processes,thus being one of the main cytokines involved in the pathogenesis of IBD,however,its levels,when measured,are present in the serum of patients with IBD.In addition,TNF-αplays an important role in promoting inflammation,such as the production of interleukins(IL),for instance IL-1βand IL-6.There are two receptors for TNF as following:The tumor necrosis factor 1 receptor(TNFR1);and the tumor necrosis factor 2 receptor(TNFR2).They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity.The soluble TNF form binds to the TNFR1 receptor with,and its activation results in a signaling cascade effects such as apoptosis,cell proliferation and cytokine secretion.In contrast,the transmembrane TNF form can bind both to TNFR1 and TNFR2.Recent studies have suggested that TNF-αis one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD,since TNF levels are present in the serum of both patients with UC and CD.Intravenous and subcutaneous biologics targeting TNF-αhave revolutionized the treatment of IBD,thus becoming the best available agents to induce and maintain IBD remission.The application of antibodies aimed at neutralizing TNF-αin patients with IBD that induce a satisfactory clinical response in up to 60%of patients,and also induced long-term maintenance of disease remission in most patients.It has been suggested that anti-TNF-αagents inactivate the pro-inflammatory cytokine TNF-αby direct neutralization,i.e.,resulting in suppression of inflammation.However,anti-TNF-αantibodies perform more complex functions than a simple blockade.
文摘Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improving prognosis.However,up to one-third of treated patients show primary nonresponse(PNR)to anti-TNF-αtherapies,and 23%-50%of IBD patients experience loss of response(LOR)to these biologics during subsequent treatment.There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs.This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients.Most predictors remain controversial,and only previous surgical history,disease manifestations,drug concentrations,antidrug antibodies,serum albumin,some biologic markers,and some genetic markers may be potentially predictive.In addition,we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists.Therapeutic drug monitoring plays an important role in treatment selection.Dose escalation,combination therapy,switching to a different anti-TNF drug,or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.
基金This research was funded by Guangzhou Science and Technology Plan Projects(No.202002020066)the Young Scientists to the NSFC Application of Guangdong Provincial People’s Hospital(No.8210120306)the Open Foundation of the State Key Laboratory of Bioactive Seaweed Substance(No.SKL-BMSG2022-03)。
文摘Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(P<0.05 for all).The areas under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.
文摘Tumor necrosis factor inhibitors(anti-TNFs)are widely used therapies for the treatment of inflammatory bowel diseases(IBD);however,their administration is not risk-free.Heart failure(HF),although rare,is a potential adverse event related to administration of these medications.However,the exact mechanism of development of HF remains obscure.TNFαis found in both healthy and damaged hearts.Its effects are concentration-and receptor-dependent,promoting either cardio-protection or cardiomyocyte apoptosis.Experimental rat models with TNFαreceptor knockout showed increased survival rates,less reactive oxygen species formation,and improved diastolic left ventricle pressure.However,clinical trials employing anti-TNF therapy to treat HF had disappointing results,suggesting abolishment of the cardioprotective properties of TNFα,making cardiomyocytes susceptible to apoptosis and oxidation.Thus,patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy.This review aims to discuss adverse events associated with the administration of anti-TNF therapy,with a focus on HF,and propose some approaches to avoid cardiac adverse events in patients with IBD.
文摘AIM:To examine the association of genetic polymorphisms(-308)G/A TNFα,(+250)A/G Ltα,(+36)A/G TNFR1,(+1663)A/G TNFR2 with the development of primary open angle glaucoma(POAG) among people in Central Russia.METHODS:The study sample included 443 individuals,of which 252 patients with POAG and 191 individuals in the control group.Genotyping of(-308)G/A TNFα,(+250)A/G Ltα,(+36)A/G TNFR1,(+1663)A/G TNFR2 was performed using polymerase chain reaction.The distribution of alleles and genotypes of the studied DNA markers in the groups was examined by 2×2 contingency tables and χ2 with the Yates' s correction for continuity and odds ratios(OR) with 95% confidence intervals(CI).RESULTS:Allele(-308)G TNFα(Р=0.01,OR=1.78,95%CI 1.12-2.85) was identified as a risk factor for POAG.Homozygotes(-308) AA TNFα are at a lowest risk for development of the disease(Р=0.01,OR=0.0005).The following combination of genetic variants of cytokines were associated with a reduced risk of POAG:(+1663)A TNFR2 and(+250)G Ltα(OR=0.34)CONCLUSION:Genetic polymorphisms(-308)G/A TNFα,(+250)A/G Ltα,(+1663)A/G TNFR2 associated with the development of POAG in the population of Central Russia.
文摘Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome（HFRS）. Methods Double-antibody sandwich ELISA was used to determine serum interleukin （IL）-6, urine tumor necrosis factor （TNF）, IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively （P<0.001）. The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β2-microglobulin （β2-MG）, blood ureanitrogen （BUN） and creatinine （Cr）. Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 （r=0.5768, P<0.05; r=0.3760, P<0.01）. Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.
基金Supported by the Swiss National Science Foundation,No.P2SKP3_158649,No.P3400PB_171581,and No.P3P3PB_171582(to Bluemel S)NIH grants(in part),No.R01 AA24726,No.U01 AA026939,and services provided by P30 DK120515(to Schnabl B).
文摘BACKGROUND End-stage liver disease caused by non-alcoholic steatohepatitis(NASH)is the second leading indication for liver transplantation.To date,only moderately effective pharmacotherapies exist to treat NASH.Understanding the pathogenesis of NASH is therefore crucial for the development of new therapies.The inflammatory cytokine tumor necrosis factor alpha(TNF-α)is important for the progression of liver disease.TNF signaling via TNF receptor 1(TNFR1)has been hypothesized to be important for the development of NASH and hepatocellular carcinoma in whole-body knockout animal models.AIM To investigate the role of TNFR1 signaling in hepatocytes for steatohepatitis development in a mouse model of diet-induced NASH.METHODS NASH was induced by a western-style fast-food diet in mice deficient for TNFR1 in hepatocytes(TNFR1ΔHEP)and their wild-type littermates(TNFR1fl/fl).Glucose tolerance was assessed after 18 wk and insulin resistance after 19 wk of feeding.After 20 wk mice were assessed for features of NASH and the metabolic syndrome such as liver weight,liver steatosis,liver fibrosis and markers of liver inflammation.RESULTS Obesity,liver injury,inflammation,steatosis and fibrosis was not different between TNFR1ΔHEP and TNFR1fl/fl mice.However,Tnfr1 deficiency in hepatocytes protected against glucose intolerance and insulin resistance.CONCLUSION Our results indicate that deficiency of TNFR1 signaling in hepatocytes does not protect from diet-induced NASH.However,improved insulin resistance in this model strengthens the role of the liver in glucose homeostasis.
文摘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-IA 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.
基金Supported by Instituto de Salud Carlos III and European Structural Funds in SpainEuropean Regional Development Fund,No.PI19/00206.
文摘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.
文摘BACKGROUND: Recent researches have indicated that estrogen has extensive neuroprotective effects. So some studies designed ovariectomized animal models and administrated with estrogen, so as to verify its neuroprotective effects. OBJECTIVE: To observe the effect of 17 beta-estradiol on the content of norepinephrine (NE) and level of tumor necrosis factor (TNF) in submandibular glands of rats with sympathetic nerve injury, and analyze the dose-dependence and pathway of action. DESIGN: A randomized control animal study.SETTINGS: Department of Hand Surgery, the 252 Hospital of Chinese PLA; Department of Hand Surgery, Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: Fifty healthy female Wistar rats were randomly divided into 5 groups with 10 rats in each group: sham-operated group, ovariectomy+6-OHDA+saline group, ovariectomy+6-OHDA+17β-estradiol 50, 200 and 500 μg/kg groups. METHODS: The experiments were carried out in Tongji Medical College, Huazhong University of Science and Technology between October 2005 and March 2006. Bilateral ovaries were only exposed but not resected for the rats in the sham-operated group, but bilateral ovaries were resected in all the other groups. In the ovariectomy+6-OHDA+17β-estradiol 50, 200 and 500 μg/kg groups, the rats were administrated with intraperitoneal injection of 6-OHDA (8 mg/kg), and then immediately given 17β-estradiol of corresponding dosages respectively, once a day for 10 days continuously. Rats in the sham-operated group and ovariectomy+6-OHDA+saline group were administrated with saline of the same volume. After administration, 5 rats in each group were killed to determine the NE contents in bilateral submandibular glands with high performance liquid chromatography-electrochemical detector (HPLC-ECD), and the other 5 rats were used to determine the TNF levels in submandibular glands with enzyme-linked immunosorbant assay.MAIN OUTCOME MEASURES: The NE contents and TNF levels in submandibular glands of rats in each group were observed. RESULTS: All the 50 rats were involved in the analysis of results. ① The NE content was obviously lower in the ovariectomy+6-OHDA+saline group than in the sham-operated group [(1 035±196), (1 823±314) ng/g, P < 0.05], there were no significant differences between the ovariectomy+6-OHDA+17β-estradiol 50 μg/kg group and ovariectomy+6-OHDA+saline group [(1 004±253), (1 035±196) ng/g, P > 0.05], but obviously higher in the ovariectomy+6-OHDA+17β-estradiol 200 and 500 μg/kg groups than in the ovariectomy+6-OHDA+saline group [(1 487±268), (1 939±274), (1 035±196) ng/g, P < 0.05]. ② The TNF level was obviously higher in the ovariectomy+6-OHDA+saline group than in the sham-operated group [(3.498±0.792), (1.893±0.533) ng/g, P < 0.05], there were no significant differences between the ovariectomy+ 6-OHDA+17β-estradiol 50 μg/kg group and ovariectomy+6-OHDA+saline group [(3.328±0.712), (3.498±0.792) ng/g, P > 0.05], but obviously lower in the ovariectomy+6-OHDA+17β-estradiol 200 and 500 μg/kg groups than in the ovariectomy+6-OHDA+saline group [(2.639±0.438), (2.016±0.619), (3.498±0.792) ng/g, P < 0.05]. CONCLUSION: Estrogen has obvious protective effect dose-dependently on 6-OHDA induced chemical sympathetic nerve terminal injury in rats, and it may play its protective role by reducing TNF level and ameliorating inflammatory reaction.
基金supported by the Anhui Provincial Natural Science Foundation (1408085MH157)Supporting Program for Excellent Young Talents in Universities of Anhui Province, Outstanding Young Investigator of Anhui Medical University, National Natural Science Foundation of China (81570403, 81371284)Scientific Research Grant ofAnhui Medical University (2015xk1080)
文摘TRPP2, a Ca^(2+)-permeable non-selective cation channel, has been shown to negatively regulate cell cycle, but the mechanism underlying this regulation is unknown. Tumor necrosis factor a(TNF-α) is a proinflammatory cytokine extensively involved in immune system regulation, cell proliferation and cell survival. However, the effects and mechanisms for the role of TNF-αin laryngeal cancer remain unclear. Here, we demonstrated using western blot analyses and intracellular Ca^(2+) concentration measurements that TNF-α treatment suppressed both TRPP2 expression and ATP-induced Ca^(2+) release in a laryngeal cancer cell line(Hep-2). Knockdown of TRPP2 by a specific siRNA significantly decreased ATP-induced Ca^(2+) release and abolished the effect of TNF-α on the ATP-induced Ca^(2+) release. TNF-α treatment also enhanced Hep-2 cell proliferation and growth, as determined using cell counting and flow cytometry cell cycle assays. Moreover, TNF-α treatment down-regulated phosphorylated protein kinase R-like endoplasmic reticulum kinase(p-PERK) and phosphorylated eukaryotic translation initiation factor(p-eIF2α)expression levels, without affecting PERK and eIF2 a expression levels in Hep-2 cells. We concluded that suppressing TRPP2 expression and TRPP2-mediated Ca^(2+) signaling may be one mechanism underlying TNF-α-enhanced Hep-2 cell proliferation.These results offer new insights into the mechanisms of TNF-α-mediated laryngeal cancer cell proliferation, and provide evidences showing a potential role of TNF-α in the development of laryngeal cancer.
基金supported by the National Natural Science Foundation of China(NSFC)(Grant No:81101426,81571898).
文摘Background:Tumor necrosis factor receptor-associated protein 1(TRAP1)plays a protective effect in hypoxic cardiomyocytes,but the precise mechanisms are not well clarified.The study is aimed to identify the mechanism of TRAP1 on hypoxic damage in cardiomyocytes.Methods:In this study,the effects of TRAP1 and cytochrome c oxidase subunit Ⅱ(COXⅡ)on apoptosis in hypoxia-induced cardiomyocytes were explored using overexpression and knockdown methods separately.Results:Hypoxia induced cardiomyocyte apoptosis,and TRAP1 overexpression notably inhibited apoptosis induced by hypoxia.Conversely,TRAP1 silencing promoted apoptosis in hypoxic cardiomyocytes.Further investigation revealed that the proapoptotic effects caused by the silencing of TRAP1 were prevented by COXⅡ overexpression,whereas COXⅡ knockdown reduced the antiapoptotic function induced by TRAP1 overexpression.Additionally,changes in the release of cytochrome c from mitochondria into the cytosol and the caspase-3 activity in the cytoplasm,as well as reactive oxygen species production,were found to be correlated with the changes in apoptosis.Conclusions:The current study uncovered that TRAP1 regulates hypoxia-induced cardiomyocyte apoptosis through a mitochondria-dependent apoptotic pathway mediated by COXⅡ,in which reactive oxygen species presents as an important component.
基金supported by grants from the National Science Foundation of China (31670170 & 81560442)from MOST (2018YFA0507201)from the Natural Science Foundation of Guangdong Province (2017ZC0236)。
文摘Tumor Necrosis Factor α(TNFα) is best known as a mediator of inflammation and immunity, and also plays important roles in tumor biology. However, the role of TNFα in tumor biology is complex and not completely understood. In a human melanoma cell line, M2, and a lung carcinoma cell line, A549, TNFα up-regulates prion protein(PrP) level, and promotes tumor cell migration in a PrP dependent manner. Silencing PRNP abrogates TNFα induced tumor cell migration;this phenotype is reversed when PRNP is re-introduced. Treatment with TNFα activates nuclear factor kappa B(NF-κB)signaling, which then mitigates autophagy by reducing the expression of Forkhead Box P3(FOXP3). Down regulation of FOXP3 reduces the transcription of synaptosome associated protein 29(SNAP29), which is essential in the fusion of autophagosome and lysosome creating autolysosome. FOXP3 being a bona fide transcription factor for SNAP29 is confirmed in a promoter binding assay. Accordingly, silencing SNAP29 in these cell lines also up-regulates PrP, and promotes tumor cell migration without TNFα treatment. But, when SNAP29 or FOXP3 is silenced in these cells, they are no longer respond to TNFα. Thus, a reduction in autophagy is the underlying mechanism by which expression of PrP is up-regulated,and tumor cell migration is enhanced upon TNFα treatment. Disrupting the TNFα-NF-κB-FOXP3-SNAP29 signaling axis may provide a therapeutic approach to mitigate tumor cell migration.
文摘Aim:The cytokine receptor tumor necrosis factor receptor superfamily member 9(TNFRSF9)is mainly considered to be a co-stimulatory activation marker in hematopoietic cells.Several preclinical models have shown a dramatic beneficial effect of treatment approaches targeting TNFRSF9 with agonistic antibodies.However,preliminary clinical phase I/II studies were stopped after the occurrence of several severe deleterious side effects.In a previous study,it was demonstrated that TNFRSF9 was strongly expressed by reactive astrocytes in primary central nervous system(CNS)tumors,but was largely absent from tumor or inflammatory cells.The aim of the present study was to address the cellular source of TNFRSF9 expression in the setting of human melanoma brain metastasis,a highly immunogenic tumor with a prominent tropism to the CNS.Methods:Melanoma brain metastasis was analyzed in a cohort of 78 patients by immunohistochemistry for TNFRSF9 and its expression was correlated with clinicopathological parameters including sex,age,survival,tumor size,number of tumor spots,and BRAF V600E expression status.Results:Tumor necrosis factor receptor superfamily member 9 was frequently expressed independently on both melanoma and endothelial cells.In addition,TNFRSF9 was also present on smooth muscle cells of larger vessels and on a subset of lymphomonocytic tumor infiltrates.No association between TNFRSF9 expression and patient survival or other clinicopathological parameters was seen.Of note,several cases showed a gradual increase in TNFRSF9 expression on tumor cells with increasing distance from blood vessels,an observation that might be linked to hypoxia-driven TNFRSF9 expression in tumor cells.Conclusion:The findings indicate that the cellular source of TNFRSF9 in melanoma brain metastasis largely exceeds the lymphomonocytic pool,and therefore further careful(re-)assessment of potential TNFRSF9 functions in cell types other than hematopoietic cells is needed.Furthermore,the hypothesis of hypoxia-driven TNFRSF9 expression in brain metastasis melanoma cells requires further functional testing.
文摘Objective: Human immunodeficiency virus (HIV) p24 antigen and antibody and herpes simplex virus 2 IgM are seromarkers indicating infection with HIV and herpes simplex virus-2 (HSV-2), respectively, whereas tumor necrosis factor α is an inflammatory biomarker that can be triggered by infections. Female children of single parents are faced with many socio-economic challenges that make them vulnerable to sexual influences and prone to sexually transmitted infections. The goal of this work was to determine HIV p24 antigen/antibody, HSV-2 IgM and tumor necrosis factor-α plasma levels in adult female children living in single-parent households.Methods: In this case-control observational study, 100 adult female children living with a single parent (50 living with a single mother and 50 living with a single father;age: 18-22 years) and 100 age-matched women living with both parents were recruited to serve as the test and control groups, respectively. All subjects were negative for acid-fast bacilli, plasmodium, hepatitis C virus, and hepatitis B virus. Human tumor necrosis factor α, HSV-2 IgM, antibody to hepatitis C virus, hepatitis B surface antigen and human immunodeficiency virus p24 antigen and antibody (HIV p24 Ag/Ab) levels were determined by ELISA, while the detection of acid-fast bacilli in sputum andPlasmodium in blood was carried out by optical microscopy. This work was carried out in the Owo/Ose Federal Constituency in Ondo State that shares boundaries with Edo State. The study protocol was approved by the Research and Ethical Committee of the Department of Medical Laboratory Science, Achievers University, Owo, Nigeria (AUO/MLS/2020/127) on August 27, 2020.Results: HIV p24 Ag/Ab was detected in 0 adult female children living with a single mother, 1 (2%) adult female child living with a single father and 1 (1 %) adult female child living with both parents. HSV-2 IgM was detected in 9 (18%) adult female children living with a single mother, 13 (26%) adult female children living with a single father, and 5 (10%) adult female children living with both parents.Conclusion: This work shows that adult female children of single parents are vulnerable to sexual influences, and thereby more prone to HSV-2 and possibly HIV, especially adult female children of single fathers.
基金Supported by National High Technology Research and Development Program of China (863 Program,2007AAO2Z420 and 2008AA02Z412)Joint Key Project of New Frontier Technology in Shanghai Municipal Hospitals(SHDC12006105)+2 种基金the National Natural Science Foundation of China(30770772)Municipal Committee of Shanghai Science and Technology(09411968200)Doctorate Foundation of Shanghai Jiaotong University School of Medicine (BXJ201047)
文摘Objective To investigate association between tumor necrosis factor alpha (TNF-α) and obsessive compulsive disorder (OCD) in Chinese Han population.Methods Plasma concentrations of TNF-α were measured in 61 drug-free patients who fulfilled DSM-Ⅳ criteria for OCD and 93 healthy controls.TNF-α concentrations in blood were determined by enzyme-linked immunosorbent assay (ELISA).Two polymorphisms of TNF-α gene were investigated in the same patients and healthy controls:-308 G/A and-238 G/A.The allelic and genotypic frequencies of these polymorphisms were examined by using DNA sequencing method.Results Plasma levels of TNF-α did not differ between patients and controls (P=0.292).No significant results were observed for any of the alleles at the-308 G/A or-238 G/A polymorphism of the TNF-α gene.Finally a haplotype consisting of genotypes of these two markers was also examined.No association was observed for any haplotype (P=0.108).Conclusion No significant differences were observed between patients and controls in plasma levels of TNF-α.There is no association between the-308 G/A and-238 G/A TNF-α gene polymorphisms and OCD in our Chinese samples.However,the results need to be replicated in larger samples.
基金supported by the Natural Science Foundation of Zhejiang Province,No.LQ23C090003 (to CZ)the Major Project on Brain Science and Analog Brain Research of Ministry of Science and Technology of China,No.2022ZD0204701 (to MQ)the National Natural Science Foundation of China,No.32170969 (to MQ)。
文摘Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.
文摘Objective:To explore the effect of the Xian Fang Huo Ming Yin(XFHM)for treating cutaneous infections and promoting wound healing in patients with perianal abscesses.Methods:Sixty-one patients with perianal abscesses who were admitted to our hospital(Xinghua City People’s Hospital)from May 2022 to May 2023 were selected and randomly divided into two groups,a control group(30 cases)and a study group(31 cases).Both groups received surgical treatment.The control group received conventional treatment and warm water fumigation,sitz bath,and surgical dressing change after surgery,while the research group received XFHM based on the control group.XFHM was taken orally and replaced with warm water for fumigation and sitz bathing.Both groups received treatment for 4 weeks but discontinued sitz bathing after 2 weeks.Various clinical indicators between the two groups were compared.Results:The total clinical effective rate and wound recovery rate of the study group were higher than that of the control group.There were differences in the wound pain scores,surrounding tissue edema,and wound secretions at different time points.Both groups experienced wound pain.The scores of wound pain,surrounding tissue edema,and wound secretions of the study group were lower than those of the control group,7 and 14 days after surgery.The serum interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α)levels,and pH values of the study group were lower than those of the control group 10 days after surgery(P<0.05).Conclusion:The application of XFHM for treating cutaneous infections and promoting wound healing in patients with perianal abscesses improved the treatment outcome,alleviated clinical symptoms,and promoted healing.
基金The project was supported by a grant from national naturalscience foundation of China(No.39770 2 2 5 )
文摘The inhibitory effect of hydroxyapatite ultrofine powder on tumor and the effect on the immunity function of body were investigated. The levels of IL 2 in the spleen cells and serum TNF levels in the tumor bearing mice at the 7th day and 14th after peritoneal injection of HAUFP were detected by using the methods of colorimetric analysis of MTT and crystal purple decoration, respectively. The disappearance of the ascites of the mice was observed. The results showed that the levels of IL 2 and TNF in the tumor bearing mice were higher obviously in the drug treated group than in the control group , the ascites growth was inhibited. It was suggested that HAUFP could increase the levels of IL 2 and TNF of the tumor bearing mice and improve the immune function of body.
基金Supported by National Multidisciplinary Cooperative Diagnosis and Treatment Capacity Building Project for Major Diseases(Lung Cancer)National Key R&D Program of China,No.2016YFC1303300Xiangya Clinical Big Data Project of Central South University(Clinical big data project of lung cancer).
文摘BACKGROUND Cytokine release syndrome(CRS)is defined as systemic inflammation that usually occurs following chimeric antigen receptor T-cell therapy administration;however,it has not been reported in patients with untreated non-small cell lung cancer to date.CASE SUMMARY A 44-year-old nonsmoking woman presented to the hospital due to fever,palpitation,nausea,and cough for 1 mo and was diagnosed with stage cT3N3M0(IIIc)adenocarcinoma of the lung.Auxiliary examinations revealed elevated cytokine[tumor necrosis factor-α,interleukin(IL)-1β,and IL-6]and inflammatory factor levels,which decreased after treatment with corticosteroids and immunoglobulin and when tumor growth was controlled following chemotherapy,radiotherapy,and antiangiogenesis therapy.However,tumor recurrence was observed.After administration of nivolumab as third-line treatment,the patient’s condition was transiently controlled;however,CRS-like symptoms suddenly emerged,which led to a resurgence of cytokines and inflammatory factors and rapid death.CONCLUSION CRS can develop in treatment-naïve lung cancer patients.Patients with tumorrelated CRS may be at risk of CRS recurrence,aggravation,and onset of immune checkpoint inhibitor-related adverse events.
