Study of tumor necrosis factor receptor in the inflammatory bowel disease

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.

Increase of tumor necrosis factor receptor 1 expression in women with unexplained early spontaneous abortion

Objective: To investigate membrane tumor necrosis factor receptor 1 protein expression level in decidua and concentration of soluble tumor necrosis factor receptor 1 in serum in women with unexplained early spontaneous abortion, threatened abortion, and compare the levels with healthy pregnant women. Methods: Thirty-seven women with unexplained early spontaneous abortion, 27 women with threatened abortion, and 34 healthy pregnant women undergoing artificial abortion of pregnancy at 6 - 10 weeks of gestation were selected. Decidual samples were collected when women were undergoing artificial abortion, and blood samples were collected at the same time. The level of membrane tumor necrosis factor receptor 1 in decidua was detected by flow cytometer, and the concentration of soluble tumor necrosis factor receptor 1 in sera was measured with an enzyme-linked immunosorbent assay. Results: The percentages of membrane tumor necrosis factor receptor 1 positive decidual cells were 16.42 ± 7.10 Mean ± SD for women with unexplained early spontaneous abortion and 13. 14 ± 6.30 for healthy pregnant women ( P < 0.05). Serum concentration of soluble tumor necrosis factor receptor 1 was significantly higher in women with unexplained early spontaneous abortion than in healthy pregnant women and in women with threatened abortion, and no difference was found between healthy pregnant women and women with threatened abortion. Conclusion: Women with unexplained early spontaneous abortion present significantly higher expression of tumor necrosis factor receptor 1 than healthy pregnant women, suggesting that over-expression of tumor necrosis factor receptor 1 may contribute to the development of early spontaneous abortion.

Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas

AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-α and its receptors in 62 colorectal adenoma patients and 34 healthy controls. The protein expression of TNF-α, TNF-R1, TNF-R2 and downstream signals of the TNF receptors, such as c-Jun N-terminal kinase (JNK), nuclear factor-κ B and caspase-3, were also investigated in human colorectal adenomas and in normal colorectal mucosal tissues by immunohistochemistry. Immunofluorescence confocal microscopy was used to investigate the consistency of expression of TNF-R1 and phospho-JNK (p-JNK). RESULTS: The serum levels of soluble TNF-R1 (sTNF-R1) in adenoma patients were significantly higher than in the control group (3.67 ± 0.86 ng/mL vs 1.57 ± 0.72 ng/mL, P < 0.001). Receiver operating characteristic analysis revealed the high diagnostic sensitivity of TNF-R1 measurements (AUC was 0.928) for the diagnosis of adenoma, and the best cut-off level of TNF-R1 was 2.08 ng/mL, with a sensitivity of 93.4% and a specificity of 82.4%. There were no significant differences in the serum levels of TNF-α or sTNF-R2 between the two groups. Immunohistochemistry showed high levels of TNF-R1 and p-JNK expression in the epithelial cells of adenomas. Furthermore, a high incidence of co-localization of TNF-R1 and p-JNK was identified in adenoma tissue. CONCLUSION: TNF-R1 may be a promising biomarker of colorectal adenoma, and it may also play an important role in the very early stages of colorectal carcinogenesis.

EFFECT OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ACTIVATORS ON TUMOR NECROSIS FACTOR-αEXPRESSION IN NEONATAL RAT CARDIAC MYOCYTES

Objective To investigate the effect of peroxisome proliferator-activated receptor-α(PPARα) and PPARγactivators on tumor necrosis factor-α(TNFα) expression in neonatal rat cardiac myocytes. Methods Primary cultures of cardiac myocytes from 1- to 3-day-old Wistar rats were prepared, and myocytes were ex-posed to lipopolysaccharide (LPS) and varying concentrations of PPARαor PPARγactivator (fenofibrate or pioglitazone).RT-PCR and ELISA were used to measure TNFα, PPARα, and PPARγexpression in cultured cardiac myocytes. Transient tr-ansfection of TNFαpromoter with or without nuclear factor-kappaB (NF-κB) binding site to cardiac myocytes was performed. Results Pretreatment of cardiac myocytes with fenofibrate or pioglitazone inhibited LPS-induced TNFαmRNA and protein expression in a dose-dependent manner. However, no significant changes were observed on PPARαor PPARγmRNA expression when cardiac myocytes were pretreated with fenofibrate or pioglitazone. Proportional suppression of TNFαpromoter activity was observed when myocytes was transiently transfected with whole length of TNFαpromoter (-721/+17) after being stimulated with LPS and fenofibrate or pioglitazone, whereas no change of promoter activity was observed with transfection of TNFαreporter construct in deletion of NF-κB binding site (-182/+17). Conclusions PPARαand PPARγactivators may inhibit cardiac TNFαexpression but not accompanied by change of PPARαor PPARγmRNA expression. Therefore PPARαand PPARγactivators appear to play a role in anti-inflammation. The mechanism may partly be involved in suppression of the NF-κB pathway.

Genes of tumor necrosis factors and their receptors and the primary open angle glaucoma in the population of Central Russia

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 andχ2with the Yates’s correction for continuity and odds ratios（OR）with95%confidence intervals（CI）.RESULTS：Allele（-308）G TNFα（Р=0.01,OR=1.78,95%CI1.12-2.85）was identified as a risk factor for POAG.Homozygotes（-308）AA TNFαare 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.

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.

The interleukin-1 receptor antagonist (IL-1-Ra) and soluble tumor necrosis factor receptor I (sTNF RI) in periodontal disease

The course and severity of periodontitis can be significantly affected by bacterial virulence as well as host immunity dysfunction. Periodontal tissue destruction has been proved to result from cascade of cytokines synthesized by reactive cells upon stimulation by pathogenic bacteria and lipopolysaccharides within their cell membranes. The clinical use of genetically programmed cells, producing substances blocking IL-1, based on recombinant IL-1 antagonist, as well as cytokines activating fibroblasts and osteoblasts to regenerate the destroyed periodontal tissue could prove alternative to the conventional treatment. Another cytokine of interest in respect to periodontitis ethiopathogenesis is soluble tumor necrosis factor receptor I (sTNF RI). Observation of soluble TNF receptors as physiologic inhibitors of TNF led to its administration in therapeutic process as well as in therapy selected cases of aggressive periodontitis.

Effects of liraglutide on soluble tumor necrosis factor receptor in patients with diabetic nephropathy

Objective:To observe the effects of Liraglutide combined with sequential dialysis on soluble tumor necrosis factor receptor in patients with diabetic nephropathy.Methods: A total of 110 patients with early diabetic nephropathy who had been seeking treatment in the hospital between December 2016 and December 2017 were selected and according to the random number table method, these patients were randomly divided into two groups, with 55 cases in each group. Patients in the control group were given conventional symptomatic treatment such as hypoglycemic therapy, whereas the observation group was treated with Liraglutide based on the conventional symptomatic treatment given to the control group. The renal function, blood glucose metabolism level, serum indexes, vascular endothelial function and adverse drug reactions were compared between the two groups.Results: After treatment, the levels of 24 hUpor, UAER and Scr in the two groups were both shown to be lower than those before treatment, and the levels in the observation group were shown to be lower than those in the control group, with the differences being statistically significant. After treatment, the levels of PBG, FPG, HOMA-IR , HbA1c and FIns in the two groups were both significantly lower than before treatment, and the levels of PBG, FPG, HOMA-IR , HbA1c and FIns in the observation group were shown to be lower than those in the control group, where the differences were statistically significant. After treatment, the levels of TNF-α, sTNFR1 and hs-CRP in the two groups were significantly reduced than before treatment, and the levels in the observation group were shown to be significantly lower than the control group, with statistically significant differences. After treatment, the NO levels in both groups were significantly increased and ET-1 level significantly reduced than before treatment, and the NO level in the observation group was shown to be higher and the ET-1 level lower than the control group, where the difference was statistically significant.Conclusion: Liraglutide is with higher safety for patients with diabetic nephropathy, which can effectively improve their renal function and blood glucose, enhance insulin sensitivity, reduce the levels of inflammatory factors, and improve the endothelial function.

Effects of hemoperfusion combined with sequential dialysis on soluble tumor necrosis factor receptor in patients with diabetic kidney disease

Objective: To observe the effects of hemoperfusion combined with sequential dialysis on soluble tumor necrosis factor receptor in patients with diabetic kidney disease. Methods:A total of 100 patients with diabetic kidney disease who had been seeking treatment in the hospital between May 2015 and July 2017 were selected, and then according to the random number table method, these patients were divided into a control group and an observation group, with 50 cases in each group. The control group was treated with hemodialysis only, whereas the observation group was given hemoperfusion combined with sequential dialysis for treatment. The changes of soluble tumor necrosis factor receptor, oxidant factor and metabolic indexes after 12 weeks of treatment were compared between the two groups. Results: After treatment, the metabolic indexes in the observation group were shown to be lower than the control group, the levels of soluble tumor necrosis factor receptor related indexes in the former group were lower than the control group, and the level of oxidative stress indicators in the former group was shown to be better than the control group, where the differences were statistically significant. Conclusion: For patients with diabetic kidney disease, hemoperfusion combined with sequential dialysis is with significant clinical curative effects, which can effectively relieve their oxidative stress, better control the blood glucose level, significantly improve their renal function and significantly reduce the level of soluble tumor necrosis factor receptor.

Effects of Irbesartan and Metformin on tumor necrosis factor receptor and monocyte chemotactic protein 1 in patients with early diabetic nephropathy

Objective: To explore the effect of Irbesartan and Metformin on tumor necrosis factor receptor 1 and monocyte chemoattractant protein-1 in patients with early diabetic nephropathy. Methods: A total of 162 patients with early diabetic nephropathy who had been admitted to the Hospital between February 2017 and February 2018 were randomly assigned into a Metformin group, an Irbesartan group, and a combination therapy group. The Metformin group were treated with oral Metformin, those in the Irbesartan group were given oral Irbesartan for treatment, and the combination therapy group was treated with Metformin combined with Irbesartan. After 3 months of continuous treatment, the levels of sTNFR1, high-sensitivity C-reactive protein, monocyte chemoattractant protein-1, glucose metabolism index, proteinuria, and serum creatinine levels in the two groups were compared. Results:After treatment, the levels of sTNFR1, sICAM-1, hs-CRP, and MCP-1 in the three groups decreased compared with those before treatment, and the levels in the combination therapy group were all shown to be lower than those of the Metformin group and the Irbesartan group, with statistically significant differences (P<0.05). The levels of glycosylated hemoglobin and fasting blood glucose in the three groups were significantly lower than before treatment, and those in the combination therapy group were lower than the Metformin group and Irbesartan group, where the difference was statistically significant (P<0.05). The 24-hour urinary protein quantification, urinary albumin excretion rate, and serum creatinine in the combination therapy group were lower than those in the Metformin group and in the Irbesartan group, where the differences were statistically significant (P<0.05). Conclusion: The effects of metformin combined with irbesartan on early diabetic nephropathy patients were significant, which can effectively reduce the levels of serum sTNFR1 and MCP-1, relieve inflammation and improve glucose metabolism and proteinuria level.

Effect of Llinagliptin on tumor necrosis factor receptor and monocyte chemoattractant protein-1 in patients with diabetic nephropathy

Objective:To explore the effect of Linagliptin on tumor necrosis factor receptor and monocyte chemoattractant protein-1 in patients with diabetic nephropathy.Methods: A total of 98 patients with diabetic nephropathy admitted to the Hospital from January 2017 to September 2018 were enrolled. The patients were divided into two groups according to the random double-blind method, with 49 cases in each group. The control group was treated with Metformin, whereas the experimental group was treated with Linagliptin plus Metformin. After 3 months of continuous treatment, the renal function [urinary albumin excretion rate, 24 h urine protein quantitation and serum creatinine], glycolipids metabolic levels [glycated hemoglobin, fasting blood glucose, total cholesterol and triglycerides], monocyte chemoattractant protein-1, tumor necrosis factor receptor, high-sensitivity C-reactive protein, and adverse reactions were compared between the two groups.Results:After 3 months of treatment, the levels of UAER, 24 h Upor and Scr in the experimental group were shown to be lower than those in the control group, and the difference was statistically significant. After 3 months of treatment, the levels of HbA1c, FPG, TC and TG in the experimental group were shown to be lower than the control group, and the difference was statistically significant. After 3 months of treatment, the levels of MCP-1, sTNFR1 and hs-CRP in the experimental group were lower than those in the control group, and the difference was statistically significant. There was no significant difference in incidence of adverse reactions between the two groups.Conclusion: For patients with diabetic nephropathy, Linagliptin is with higher safety, which can help improve their glycolipids metabolic levels and renal function, reduce the inflammatory response and the levels of MCP-1 and sTNFR1, and yet incur fewer adverse reactions.

Association between genetic variations in tumor necrosis factor receptor genes and survival of patients with T-cell lymphoma

The prognosis of T-cell lymphoma (TCL) has been shown to be associated with the clinical characteristics of patients. However, there is little knowledge of whether genetic variations also affect the prognosis of TCL. This study investigated the associations between single nucleotide polymorphisms(SNPs) in tumor necrosis factor receptor superfamily(TNFRSF) genes and the survival of patients with TCL. A total of 38 tag SNPs in 18 TNFRSF genes were genotyped using Sequenom platform in 150 patients with TCL. Kaplan-Meier survival estimates were plotted and significance was assessed using log-rank tests. Cox proportional hazard models were used to analyze each of these 38 SNPs with adjustment for covariates that might influence patient survival, including sex and international prognostic Index score. Hazard ratios (HRs) and their 95% confidence intervals(CIs) were calculated. Among the 38 SNPs tested, 3 were significantly associated with the survival of patients with TCL. These SNPs were located at LTβR (rs3759333C>T) and TNFRSF17(rs2017662C>T and rs2071336C>T). The 5-year survival rates were significantly different among patients carrying different genotypes and the HRs for death between the different genotypes ranged from 0.45 to 2.46. These findings suggest that the SNPs in TNFRSF genes might be important determinants for the survival of TCL patients.

Choroid plexus tumor necrosis factor receptor 1:a new neuroinflammatory piece of the complex Alzheimer's disease puzzle

Due to the aging of the population and despite the enormous scientific effort,Alzheimer's disease remains one of the biggest medical and pharmaceutical challenges in current medicine.Novel insights highlight the importance of neuroinflammation as an undeniable player in the onset and progression of Alzheimer's disease.Tumor necrosis factor is a master inflammatory cytokine that signals via tumor necrosis factor receptor 1 and tumor necrosis factor receptor 2,but that also regulates several brain functions in health and disease.However,clinical trials investigating drugs that interfere with the tumor necrosis factor pathway in Alzheimer's disease led to inconclusive results,partially because not only the pro-inflammatory tumor necrosis factor/tumor necrosis factor receptor 1,but also the beneficial tumor necrosis factor/tumor necrosis factor receptor 2 signaling was antagonized in these trials.We recently found that tumor necrosis factor is the main upregulated cytokine in the choroid plexus of Alzheimer's disease patients,signaling via tumor necrosis factor receptor 1.In agreement with this,choroidal tumor necrosis factor/tumor necrosis factor receptor 1 signaling was also upregulated in different Alzheimer's disease mouse models.Interestingly,both genetic and nanobody-based pharmacological blockage of tumor necrosis factor receptor 1 signaling was accompanied by favorable effects on Alzheimer's disease-associated inflammation,choroidal morphology and cognitive functioning.Here,we briefly summarize the detrimental effects that can be mediated by tumor necrosis factor/tumor necrosis factor receptor 1 signaling in(early) Alzheimer's disease,and the consequences this might have on the disease progression.As the main hypothesis in Alzheimer's disease clinical trials is still based on the amyloid beta-cascade,the importance of Alzheimer's disease-associated neuroinflammation urge the development of novel therapeutic strategies that might be effective in the early stages of Alzheimer's disease and prevent the irreversible neurodegeneration and resulting memory decline.

Expression of tumor necrosis factor related apoptosis inducing ligand receptor in glioblastoma

BACKGROUND： Receptors for tumor necrosis factor related apoptosis inducing ligand （TRAIL） include death receptor 4, death receptor 5, decoy receptor 1, and decoy receptor 2. Activation of death receptor 4 and 5 selectively kills tumor cells. OBJECTIVE： To detect TRAIL receptor expression in glioblastoma by immunohistochemistry and RT-PCR, and to compare this expression to that in normal brain tissue. DESIGN： Observational analysis. SETTING： Department of Pathology, the First Affiliated Hospital of Zhengzhou University; Henan Tumor Pathology Key Laboratory. PARTICIPANTS： Twenty-five patients （17 males and 8 females） who received glioblastoma resection were selected from the Fifth Affiliated Hospital of Zhengzhou University, between September 2003 to June 2004. All glioblastoma samples were diagnosed pathologically. Twenty patients （12 males and 8 females） with craniocerebral injury who received normal brain tissue resection were selected in the same time period. There were no significant differences in sex and age between glioblastoma patients or between craniocerebral injury patients （P 〉 0.05）. All patients and appropriate relatives provided informed consent, and this study was approved by the local research ethics committee. METHODS： Polyclonal antibody against TRAIL receptors and an immunohistochemical kit （batch number： 200502） were purchased from Boster Company, Wuhan. Immunohistochemistry： Expression of death receptor 4, death receptor 5, decoy receptor l, and decoy receptor 2 were observed in both glioblastoma and normal brain tissue. The experiment was performed according to the kit instructions, and positive staining was brown-yellow. Assessment： There were no positive signals （-）; weakly positive signals, positive cells 〈 25% （＋）; weakly positive signals, positive cells 25%-50% （＋＋）; strongly positive signals, positive cells 50%-75% （＋＋＋）; strongly positive signals, positive cells 〉 75% （＋＋＋＋）. Evaluation： Expression levels of TRAIL receptors were estimated in both normal brain tissue and glioblastoma. Expression of decoy receptor 1 and decoy receptor 2 mRNA in glioblastoma were detected by reverse transcription polymerase chain reaction, and expression of decoy receptor in glioblastoma was estimated. MAIN OUTCOME MEASURES： Comparison of death receptor and decoy receptor protein expression between glioblastoma and normal brain tissue; decoy receptor mRNA expression in glioblastoma. RESULTS： Death receptor protein expression was strongly positive （＋＋＋） in glioblastoma, while it was weakly positive （＋, ＋＋） in normal brain tissue. Therefore, expression rate of death receptor protein in the glioblastoma was significantly higher than that in the normal brain tissue （.~ 2 = 18.48, 23.03, P 〈 0.01）. Decoy receptor protein expression in the glioblastoma was significantly lower than that in the normal brain tissue （ x2 = 6.65, 18.76, P 〈 0.01）. The level of decoy receptor mRNA expression in glioblastoma was significantly higher than those of protein expression （ x 2 = 9.82, 10.09, P〈 0.01）. CONCLUSION： High expression of death receptor and low expression of decoy receptor are frequently observed in glioblastoma, suggesting that TRAIL receptor genes show an anti-tumor and expressive response during the initiation and development of the tumor. There are significant differences in decoy receptor expression between normal brain tissue and glioblastoma, suggesting that the restricted expression of decoy receptor in glioblastoma is regulated at the post-transcriptional level.

Effect of Mifepristone on Transforming Growth Factor -βand its Receptor Transcription in Decidua, Villi and Serum Tumor Necrosis Factor -α Level in Early Human Gestation

Objective To investigate the role of mifepristone in regulating cytokines of materno-fetal interface and serum of human early gestationMethods Thirty-five women with early pregnancy received mifepristone 50 mg orallyon study d 1 and d 2, respectively, followed by undergoing artificial abortion to getdecidua and villi on study d 3. Twenty-five women with early pregnancy withoutmifepristone administration as control also underwent artificial abortion to get de-cidua and villi. The expressions of TGF-β1 and TGF-β1 receptor mRNA in the earlydecidua and villi were assessed by using RT-PCR . The concentrations of serum TNF-α were measured by radioimmunoassay.Results The decidual expressions of TGF- β1 mRNA and TGF-β1 receptor mRNA in thetreated group were significantly lower than those of the control (P<0.05), while thevillus expressions of TGF-β1 and TGF-β1 receptor mRNA in the treated group were notsignificantly different from those of the control (P>0.05). The serum TNF-β1 levelselevated significantly after mifepristone treatment.Conclusion The antigestational effect of mifepristone might act through suppressingthe transcription of TGF-β1 and TGF-β1 receptor in the decidua and increasing theserum TNF-α level, which interfered in the materno-fetal interface Th2 bias.

Early screening to identify and diagnose primary nasal tuberculosis in patients with tumor necrosis factor inhibitors

In this editorial,we comment on the article by Liu et al.Based on our analysis of a case report,we consider that early screening and recognition of primary nasal tuberculosis are crucial for patients undergoing treatment with tumor necrosis factor inhibitor(TNFi).While TNFi therapy increases the risk of reactivating latent tuberculosis,primary nasal tuberculosis remains rare due to the protective mechanisms of the nasal mucosa.Risk factors for primary nasal tuberculosis include minimally invasive nasal surgery,diabetes,and human immunodefi ciency virus.Patients with early symptoms such as nasal congestion,rhinorrhea,altered olfaction,epistaxis,or ulceration,and unresponsive to conventional antibiotics and antihistamines should undergo early rhinoscopy,possibly followed by repeated tissue biopsies and acid-fast bacilli culture when necessary.When diagnosis is challenging,it is essential to consider local tuberculosis epidemiology and the efficacy of diagnostic antituberculosis treatment.The preferred method for tuberculosis screening is the Interferon Gamma Release Assay,with a general recommendation for screening at 3 and 6 months after initial treatment and then every six months.However,the optimal frequency is not yet consensus-driven and may be increased in economically viable settings.

Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy(CAR–T)cell immunotherapy

Chimeric antigen receptor T-cesll therapy(CAR–T)has achieved groundbreaking advancements in clinical application,ushering in a new era for innovative cancer treatment.However,the challenges associated with implementing this novel targeted cell therapy are increasingly significant.Particularly in the clinical management of solid tumors,obstacles such as the immunosuppressive effects of the tumor microenvironment,limited local tumor infiltration capability of CAR–T cells,heterogeneity of tumor targeting antigens,uncertainties surrounding CAR–T quality,control,and clinical adverse reactions have contributed to increased drug resistance and decreased compliance in tumor therapy.These factors have significantly impeded the widespread adoption and utilization of this therapeutic approach.In this paper,we comprehensively analyze recent preclinical and clinical reports on CAR–T therapy while summarizing crucial factors influencing its efficacy.Furthermore,we aim to identify existing solution strategies and explore their current research status.Through this review article,our objective is to broaden perspectives for further exploration into CAR–T therapy strategies and their clinical applications.

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.

Acute heart failure as an adverse event of tumor necrosis factor inhibitor therapy in inflammatory bowel disease:A review of the literature

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.