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
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 Refractory pouchitis is a common cause of pouch failure,which may require surgical excision of the pouch or permanent diversion.We aimed to show the effect of vedolizumab on treatment of the patient with re...BACKGROUND Refractory pouchitis is a common cause of pouch failure,which may require surgical excision of the pouch or permanent diversion.We aimed to show the effect of vedolizumab on treatment of the patient with refractory pouchitis.CASE SUMMARY A 32-year-old male with pancolonic ulcerative colitis since the age of 25 with primary failure of infliximab and mesalamine and intolerance of azathioprine,underwent a total proctocolectomy with ileal pouch-anal anastomosis in 2012.He developed chronic diarrhea in 2014,which was watery,30 per day and accompanied with blood and mucus affecting his quality of life.CONCLUSION Vedolizumab is safe and effective in the management of anti-tumor necrosis factor alpha refractory pouchitis.展开更多
AIM:To investigate the role of claudin 1 in the regulation of genes involved in cell migration and tumor necrosis factor alpha(TNF-α)-induced gene expression in human gastric adenocarcinoma cells.METHODS:Knockdown ex...AIM:To investigate the role of claudin 1 in the regulation of genes involved in cell migration and tumor necrosis factor alpha(TNF-α)-induced gene expression in human gastric adenocarcinoma cells.METHODS:Knockdown experiments were conducted with claudin 1 small interfering RNA(si RNA),and theeffects on the cell cycle,apoptosis,migration and invasion were analyzed in human gastric adenocarcinoma MKN28 cells.The gene expression profiles of cells were analyzed by microarray and bioinformatics.RESULTS:The knockdown of claudin 1 significantly inhibited cell proliferation,migration and invasion,and increased apoptosis.Microarray analysis identified 245genes whose expression levels were altered by the knockdown of claudin 1.Pathway analysis showed that the top-ranked molecular and cellular function was the cellular movement related pathway,which involved MMP7,TNF-SF10,TGFBR1,and CCL2.Furthermore,TNFand nuclear frctor-κB were the top-ranked upstream regulators related to claudin 1.TNF-αtreatment increased claudin 1 expression and cell migration in MKN28 cells.Microarray analysis indicated that the depletion of claudin1 inhibited 80%of the TNF-α-induced m RNA expression changes.Further,TNF-αdid not enhance cell migration in the claudin 1 si RNA transfected cells.CONCLUSION:These results suggest that claudin 1 is an important messenger that regulates TNF-α-induced gene expression and migration in gastric cancer cells.A deeper understanding of these cellular processes may be helpful in establishing new therapeutic strategies for gastric cancer.展开更多
BACKGROUND Ulcerative colitis(UC)is an uncommon inflammatory bowel disease(IBD).However,its incidence has recently increased in South Korea.Moreover,UC diagnoses are frequently delayed,and the relationship between dia...BACKGROUND Ulcerative colitis(UC)is an uncommon inflammatory bowel disease(IBD).However,its incidence has recently increased in South Korea.Moreover,UC diagnoses are frequently delayed,and the relationship between diagnostic delay and UC prognosis has not been extensively studied in South Korean patients.AIM To identify meaningful diagnostic delay affecting UC prognosis and to evaluate risk factors associated with diagnostic delay in South Korean patients.METHODS Medical records of 718 patients with UC who visited the outpatient clinic of six university hospitals in South Korea were reviewed;167 cases were excluded because the first symptom date was unknown.We evaluated the relationship between the prognosis and a diagnostic delay of 3,6,12,18,and 24 mo by comparing the prognostic factors[anti-tumor necrosis factor(TNF)-αuse,admission history due to acute flare-ups,frequent admission due to flare-ups,surgery associated with UC,and the clinical remission state at the latest followup]at each diagnostic interval.RESULTS The mean diagnostic interval was 223.3±483.2 d(median,69 d;75th percentile,195 d).Among the prognostic factors,anti-TNFαuse was significantly increased after a diagnostic delay of 24 mo.Clinical risk factors predictive of a 24-mo diagnostic delay were age<60 years at diagnosis[odd ratio(OR)=14.778,95%confidence interval(CI):1.731-126.121],smoking history(OR=2.688,95%CI:1.239-5.747,P=0.012),and misdiagnosis of hemorrhoids(OR=11.066,95%CI:3.596-34.053).Anti-TNFαuse was associated with extensive UC at diagnosis(OR=3.768,95%CI:1.860-7.632)and 24-mo diagnostic delay(OR=2.599,95%CI:1.006-4.916).CONCLUSION A diagnostic delay>24 mo was associated with increased anti-TNFαuse.Age<60 years at diagnosis,smoking history,and misdiagnosis of hemorrhoids were risk factors for delayed diagnosis.展开更多
Objective:Avidly phagocytosed hemozoin(malarial pigment) alters several functions of human monocytes and stimulates generation of several cytokines.Recently,we showed that phagocytosis of hemozoin by human monocytes i...Objective:Avidly phagocytosed hemozoin(malarial pigment) alters several functions of human monocytes and stimulates generation of several cytokines.Recently,we showed that phagocytosis of hemozoin by human monocytes increases expression and activity of matrix metalloproteinase-9,a proteolytic enzyme available in specific gelatinase granules,which contain several enzymes including lysozyme.Present work investigated active lysozyme release after phagocytosis of hemozoin and its dependence on production of tumor necrosis factor alpha. Methods:After phagocytosis of hemozoin,hemozoin-containing trophozoites or control meals(opsonized nonparasitized red blood cells and latex particles),monocyte supematants were monitored for 2 hours,in presence of blocking anti-human tumor necrosis factor alpha antibodies or recombinant human tumor necrosis factor alpha cytokine in selected experiments.Lysozyme release was evaluated by a specific spectrometric assay measuring lysozyme activity after coincubation of cell supematants with suspensions of Mycrococcus Lysodeikticus,while levels of soluble tumor necrosis factor alpha were analyzed by specific enzyme-linked immunodsorbent assay. Results:Levels of lysozyme activity and soluble tumor necrosis factor alpha protein were increased in hemozoin in-or trophozoites-laden monocytes supematants.Phagocytosis per se(control meals) also increased lysozyme release,but levels were significantly lower than those obtained after phagocytosis of hemozoin or trophozoites. Interestingly,all effects on lysozyme release observed after phagocytosis were abrogated by blocking anti-human tumor necrosis factor alpha antibodies,while they were mimicked by recombinant human tumor necrosis factor alpha cytokine.Conclusions:Present work shows that phagocytosis of hemozoin promotes monocyte degranulation and enhances active lysozyme release.The effect requires tumor necrosis factor alpha mediation.展开更多
Objective:To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment.Methods:Adherent human monocytes were fed for 3 hours with different meals(native hemo...Objective:To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment.Methods:Adherent human monocytes were fed for 3 hours with different meals(native hemozoin;lipid free hemozoin;and control latex particles),then tumor necrosis factor alpha was monitored in cell supernatants up to 48 hours through western blotting or specific enzyme-linked immunoadsorbent assay.In selected experiments,unfed monocytes were treated with different doses of 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid or 4-hydroxynonenal instead of phagocytosis.Results:Hemozoin-fed monocytes produced higher levels of tumor necrosis factor alpha than unstimulated and latex-fed cells, while lipid-free hemozoin did not reproduce these results.Additionally,hemozoin effects were mimicked dose-dependently by 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid,but not by 4-hydroxynonenal.Conclusions:Present data suggest an essential role for lipids in hemozoindependent enhanced release of tumor necrosis factor alpha from monocytes,and 15(S,R)hydroxy -6,8,11,13-eicosatetraenoic acid could be one possible specific mediator.展开更多
AIM: To investigate associations between the tumor necrosis factor alpha(TNF-α)-1031 T>C,-863 C>A,-857 C>T,-308 G>A,and-238 G>A polymorphisms and HCC in Korea.METHODS: Hepatocellular carcinoma(HCC) cas...AIM: To investigate associations between the tumor necrosis factor alpha(TNF-α)-1031 T>C,-863 C>A,-857 C>T,-308 G>A,and-238 G>A polymorphisms and HCC in Korea.METHODS: Hepatocellular carcinoma(HCC) cases were diagnosed at CHA Bundang Medical Center from June 1996 to August 2008. The association between TNF-α polymorphisms and HCC was analyzed in 157HCC patients and 201 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. We investigated five TNF-α polymorphisms,which are TNF-α-1031 T>C,-863 C>A,-857 C>T,-308 G>A,and-238 G>A. The TNF-α genotype frequencies,genotype combinations and haplotypes were analyzed to disclose the association with HCC.RESULTS: None of the TNF-α polymorphisms was significantly associated with HCC. However,nine genotype combinations had associations with increased likelihood of HCC. Among them,TNF-α-1031/-857/-238 TT/CC/GA(AOR = 18.849,95%CI: 2.203-161.246,P = 0.007),TNF-α-1031/-308/-238 TT/GG/GA(AOR = 26.956,95%CI: 3.071-236.584,P = 0.003),and TNF-α-1031/-238 TT/GA(AOR = 21.576,95%CI: 2.581-180.394,P = 0.005) showed marked association with HCC. There were five haplotypes of TNF-α polymorphisms which were significantly associated with HCC. They are TNF-α-1031/-863/-857/-308/-238 T-C-C-G-A(OR = 25.824,95%CI: 1.491-447.223,P = 0.0005),TNF-α-1031/-857/-308/-238 T-C-G-A(OR = 12.059,95%CI: 2.747-52.950,P < 0.0001),TNF-α-1031/-857/-238 T-C-A(OR = 10.696,95%CI: 2.428-47.110,P = 0.0001),TNF-α-1031/-308/-238 T-G-A(OR = 7.556,95%CI: 2.173-26.280,P = 0.0002) and TNF-α-1031/-238 T-A(OR = 10.865,95%CI: 2.473-47.740,P = 0.0001). Moreover,HCC Okuda stage Ⅲ cases with the TNF-α-1031 CC genotype had better survival than those with the TT genotype(AOR = 5.795,95%CI: 1.145-29.323). CONCLUSION: Although no single TNF-α polymorphism is associated with HCC in this study,some TNF-α genotype combinations and haplotypes are associated with HCC. In addition,HCC Okuda stage Ⅲ cases with the TNF-α-1031 TT genotype may have a better prognosis than those with the CC genotype.展开更多
Objective:To analyze scrum leptin levels in patients with malaria falciparum and compare them with healthy controls and correlate with development and outcome of malaria infection.Methods:Sixty cases of malaria falcip...Objective:To analyze scrum leptin levels in patients with malaria falciparum and compare them with healthy controls and correlate with development and outcome of malaria infection.Methods:Sixty cases of malaria falciparum were included in this study as patients.Thirty healthy individuals of comparable age,racial and body mass index were taken as controls.All patients were diagnosed by clinical picture and the presence of malaria parasites in blood film.Estimation of liver function test,kidney function test,complete blood count,fasting blood sugar,fasting serum insulin,pro-inflammatory cytokine tumor necrosis factor alpha(TNFα)and interleukin 1(IL1),estimation of morning serum leptin and calculation of body mass index(kg/m^2)were done in both groups on the day of admission,on discharge and 7 d after discharge.Results:At admission,leptin levels were significantly higher in patients group than in control while lasting serum insulin levels were not significantly different between the two groups.There were significant increases as regard to TNFαand IL1 in malaria patients.Significant differences were observed between the control and the patient group for leptin,TNFαand IL1 at the time of admission and discharge.After discharge for 7 d.a significant decline in scrum leptin levels,TNFαand IL1 in the patients group was observed as compared with time of admission and time of discharge,a positive correlation between serum leptin levels and TNFαand IL1.Conclusions:Leptin hormone level might play an important role in development and outcome of malaria infection.展开更多
Anti-tumor necrosis factor alpha (TNF-α) inhibitors are effective in the treatment of various inflammatory rheumatic conditions. Increased risks of serious infections are the major issues concerning the long-term saf...Anti-tumor necrosis factor alpha (TNF-α) inhibitors are effective in the treatment of various inflammatory rheumatic conditions. Increased risks of serious infections are the major issues concerning the long-term safety of these agents. We present a case of a young male Behcet’s patient whose disease was complicated by cytomegalovirus (CMV) colitis. Colitis started 10 d after the third Infliximab dose and responded to the cessation of TNF blocking treatment and administration of ganciclovir. Tumor necrosis factor alpha and interferon gamma act at several levels in combating viral infections.CMV infections should be kept in mind and included in the differential diagnosis of severe gastrointestinal symptoms in patients receiving anti-TNF agents.展开更多
AIM:To determine the effect of tumor necrosis factor alpha(TNF-α) on intestinal permeability(IP) in mice with fulminant hepatic failure(FHF),and the expression of tight junction proteins.METHODS:We selected D-lactate...AIM:To determine the effect of tumor necrosis factor alpha(TNF-α) on intestinal permeability(IP) in mice with fulminant hepatic failure(FHF),and the expression of tight junction proteins.METHODS:We selected D-lactate as an index of IP,induced FHF using D-galactosamine/lipopolysaccharide and D-galactosamine/TNF-α,assessed the results using an enzymatic-spectrophotometric method,transmission electron microscopy,immunohistochemistry,Western blotting and real-time quantitative polymerase chain reaction.The effect of the administration of antiTNF-α immunoglobulin G(IgG) antibody,before the administration of D-galactosamine/lipopolysaccharide,on TNF-α was also assessed.RESULTS:IP was significantly increased in the mouse model of FHF 6 h after injection(13.57 ± 1.70 mg/L,13.02 ± 1.97 mg/L vs 3.76 ± 0.67 mg/L,P = 0.001).Electron microscopic analysis revealed tight junction(TJ) disruptions,epithelial cell swelling,and atrophy of intestinal villi.Expression of occludin and claudin-1 mRNA was significantly decreased in both FHF models(occludin:0.57 ± 0.159 fold vs baseline,P = 0.000;claudin-1:0.3067 ± 0.1291 fold vs baseline,P = 0.003),as were the distribution density of proteins in the intestinal mucosa and the levels of occludin and claudin-1 protein(occludin:0.61 ± 0.0473 fold vs baseline,P = 0.000;claudin-1:0.6633 ± 0.0328 fold vs baseline,P = 0.000).Prophylactic treatment with antiTNF-α IgG antibody prevented changes in IP(4.50 ± 0.97 mg/L vs 3.76 ± 0.67 mg/L,P = 0.791),intestinal tissue ultrastructure,and the mRNA levels of occludin and claudin-1 expression(occludin:0.8865 ± 0.0274 fold vs baseline,P = 0.505;claudin-1:0.85 ± 0.1437 fold vs baseline,P = 0.1),and in the protein levels(occludin:0.9467 ± 0.0285 fold vs baseline,P > 0.05;claudin-1:0.9533 ± 0.0186 fold vs baseline,P = 0.148).CONCLUSION:Increased in IP stemmed from the downregulation of the TJ proteins occludin and claudin-1,and destruction of the TJ in the colon,which were induced by TNF-α in FHF mice.展开更多
This article describes cases of anti-tumor necrosis factor(TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of ...This article describes cases of anti-tumor necrosis factor(TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis(AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-α antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune-mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics.展开更多
Mastitis or other infectious diseases have been related to reduced fertility in cattle. Inflammatory cytokines such as tumor necrosis factor a (TNFa) are released in response to infection and may have negative effects...Mastitis or other infectious diseases have been related to reduced fertility in cattle. Inflammatory cytokines such as tumor necrosis factor a (TNFa) are released in response to infection and may have negative effects on embryo development. In the current study the effect of exposure to TNFa on the development of in vitro fertilized bovine embryos was examined. Indomethacin, a prostaglandin synthesis inhibitor, was used to determine if blockade of prostaglandin synthesis would alter the effects of TNFa. Ovaries were obtained from a local abattoir and immature COC were isolated from 2-10 mm follicles, in vitro matured and fertilized. After fertilization, groups of presumptive zygotes were randomly placed into either control development medium, medium containing 25 ng/mL TNFa or medium containing 25 ng/mL TNFa plus 1 μg/mL indomethacin. The proportion of blastocysts formed was assessed at day 7 of culture. Fewer embryos exposed to TNFa alone reached the blastocyst stage (17.5 ± 2.4%, P < 0.01) compared with controls (30.5 ± 2.4%) or embryos developed in TNFa plus indomethacin (25.8 ± 2.8%). There was no difference between control embryos and embryos developed in TNFa plus indomethacin. These results indicate that TNFa is inhibitory to the in vitro development of bovine embryos and that this inhibition may be mediated by prostaglandins because it can be blocked by indomethacin.展开更多
Background and Importance: Chronic subdural hematomas (cSDH) are a common problem for which solutions remain imperfect. Surgery is effective, but not without risk. Recent data have suggested a role for inflammation in...Background and Importance: Chronic subdural hematomas (cSDH) are a common problem for which solutions remain imperfect. Surgery is effective, but not without risk. Recent data have suggested a role for inflammation in the genesis of cSDH and several reports have documented some benefit to steroid treatment. In this report, a possible role for tumor necrosis factor alpha blockade in the resolution of a multiply recurrent cSDH is described. Clinical Presentation: An 86-year-old man with rheumatoid arthritis treated with infliximab presented with a large, symptomatic, multiloculated cSDH. Infliximab was withheld and craniotomy for evacuation was uncomplicated, but recurrent symptoms were noted and a recurrence was operated upon again several weeks later. Follow up CT showed a second recurrence. The patient requested to go back on his infliximab due to painful arthralgias. After a single dose of 10 mg/kg, follow up CT showed that the cSDH resolved and did not recur. Conclusion: Anti-TNF-alpha treatment with infliximab may have played a role in the resolution of this patient’s cSDH. Further investigation of this possible effect seems warranted.展开更多
Aim: To study the roles of tumor necrosis factor alpha (TNF-a)on the sperm acrosin activity and acrosome reaction. Methods:The sperm acrosin activity was tested by the method of BAEE/ADH Unity and the acrosome reactio...Aim: To study the roles of tumor necrosis factor alpha (TNF-a)on the sperm acrosin activity and acrosome reaction. Methods:The sperm acrosin activity was tested by the method of BAEE/ADH Unity and the acrosome reaction by the Triple-stain technique. Results: TNF-a decreased the sperm acrosin activityand acrosome reaction (P＜0.01, P＜0.01, respectively);展开更多
BACKGROUND: Lots of evidences have demonstrated that acute inflammatory reaction plays an important role in cerebral ischemia and cerebral ischemia/reperfusion injury. Tumor necrosis factor (TNF), as one of important ...BACKGROUND: Lots of evidences have demonstrated that acute inflammatory reaction plays an important role in cerebral ischemia and cerebral ischemia/reperfusion injury. Tumor necrosis factor (TNF), as one of important inflammatory cytokines, also participates in the injury. OBJECTIVE: To observe the changes in TNF-α expression and myeloperoxidase (MPO) activity of mouse models of local cerebral infarction induced by photochemical method, and analyze the correlation of TNF-α expression and MPO activity. DESIGN: Randomized controlled experiment. SETTING: Laboratory of Cerebral Microcirculation, Taishan Medical College. MATERIALS: Sixty involved male adult Kunming mice were provided by the Experimental Animal Center of Shandong University. TNF-α primary antibody, kits for enzyme-linked immunosorbent assay(ELISA) and streptavidin-biotin complex immunohistochemical dyeing kit were purchased from Boster Company(Wuhan). MPO kit was purchased from Jiancheng Bioengineering Institute (Nanjing). Cold light source was developed by Hengfa Co.,Ltd.( LG-150, Xuzhou). METHODS: This experiment was carried out in the Laboratory of Cerebral Microcirculation of Taishan Medical College between July 2004 and July 2005. The involved 60 Kunming mice were randomized into 3 groups: normal control group (n =6), sham-operation group (n =6) and model group (n =48). Mice in the model group were observed at 30 minutes, 1, 3, 6, 12, 24, 48 and 72 hours after illumination, separately, 6 mice at each time point. In the model group, mice models of local cerebral infarction were developed as follows: The mice were anesthetized to expose left skulls. Taking 2 mm left to sagittal suture and 2 mm posterior to coronal suture as center, a field with diameter of 3 mm for illumination was set. The optical fiber detecting head of cold light source was vertically close to exposed skull. The mice were injected with rose Bengal for 5 minutes, and then cold light source was open for 10 minutes. Illumination was omitted in the sham-operation group. Mice in the control group were not modeled. At postoperative 6 hours, TNF-α expression in infracted-side cortex was detected with immunohistochemical method and ELISA, and MPO activity in infracted-side cortex with chromatometry. MPO activity could reflect the infiltration degree of neutrophils in tissue. Stronger activity indicated severer infiltration. Single-factor analysis of variance was used for comparison among groups, q test for pairwise comparison and correlative analysis for detecting the inter-parameter correlation. MAIN OUTCOME MEASURES: Changes in TNF-α expression and MPO activity of left cortex of mice in each group. RESULTS: Sixty mice were involved in the final analysis. After cerebral infarction, TNF-α positive cells were neurons and glial cells mainly, distributing in and around the infarct region. TNF-α expression in cortex of mice of sham-operation group was (615.7±16.1) ng/L, and that of model group increased to (792.2±17.8) ng/L at 3 hours after illumination, and reached peak [(921.9±23.9) ng/L] at 6 hours after illumination, and decreased to (848.0±30.6) ng/L at 12 hours after illumination and recovered to the normal level [(625.3±14.3) ng/L] at 72 hours after illumination. MPO activity of sham-operation group was (7.151±0.433) nkat/g, and that of model group increased to (10.469±0.600) nkat/g at 3 hours after illumination, reached the peak ([15.486±0.650) nkat/g] at 12 hours after illumination, decreased to (11.052±0.617) nkat/g at 24 hours after illumination and recovered to the normal level [(7.418± 0.617) nkat/g] at 72 hours after illumination. Change of MPO activity lagged behind that of TNF-α, andcorrelative analysis showed that the both were positively correlated(r =0.953, P < 0.01). CONCLUSION: In the acute stage of cerebral infarction of mice induced by photochemical method, TNF-α expression in infarcted-side cortex is closely related with infiltration of neutrophils. TNF-α induces inflammatory cells to intrude into ischemic brain tissue, and participates in the inflammatory reaction process at the early stage of cerebral ischemia.展开更多
Background: Tuberculosis (TB) is one of the world’s deadliest infectious diseases. Tumor necrosis factor-Alpha (TNF-α) and Interleukin 8 (IL-8) are involved in the pathogenesis of pulmonary TB (PTB). However, the co...Background: Tuberculosis (TB) is one of the world’s deadliest infectious diseases. Tumor necrosis factor-Alpha (TNF-α) and Interleukin 8 (IL-8) are involved in the pathogenesis of pulmonary TB (PTB). However, the contribution of polymorphisms of these cytokines to PTB susceptibility needed more investigation across geographic regions and ethnic groups. Purpose: The aim of this study was to investigate the association of the TNF-α-308 G/A and IL-8-251T/A polymorphisms with PTB risk in the Congolese population. Methods: This case-control study included 150 PTB patients and 160 control subjects. Blood samples were collected from all participants and were used for the TNF-α-308 G/A and IL-8-251T/A genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Odds ratios (OR) were calculated to estimate the potential polymorphism associations. A P level of Results: A significant difference was found between PTB patients and controls regarding the TNF-α-308AA genotype (P = 0.035) distribution. Moreover, this genotype was associated with risk to TB (OR = 7.19, 95% CI = 0.85 - 60.65, P = 0.035). The A allele was significantly more frequent in PTB patients than in controls, and was associated with risk to PTB (OR = 1.68, 95% CI = 1.05 - 2.68, P = 0.014). Regarding the IL-8-251T/A gene, TA and AA genotypes were significantly more frequent in PTB patients compared to controls, and were associated with increased risk to PTB (OR = 2.64, 95% CI = 0.97 - 7.18, P = 0.031 and OR = 3.0, 95% CI = 1.13 - 7.98, P = 0.014, respectively). However, the IL-8-251 A allele was not associated to PTB susceptibility (OR = 0.27, 95% CI = 0.15 - 0.44). Conclusion: TNF-α-308G/A and IL-8-251T/A polymorphisms may be associated to PTB susceptibility in the Congolese population, and the AA genotype of both cytokines could be a risk factor.展开更多
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 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
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.
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 Refractory pouchitis is a common cause of pouch failure,which may require surgical excision of the pouch or permanent diversion.We aimed to show the effect of vedolizumab on treatment of the patient with refractory pouchitis.CASE SUMMARY A 32-year-old male with pancolonic ulcerative colitis since the age of 25 with primary failure of infliximab and mesalamine and intolerance of azathioprine,underwent a total proctocolectomy with ileal pouch-anal anastomosis in 2012.He developed chronic diarrhea in 2014,which was watery,30 per day and accompanied with blood and mucus affecting his quality of life.CONCLUSION Vedolizumab is safe and effective in the management of anti-tumor necrosis factor alpha refractory pouchitis.
基金Supported by Grants-in-Aid for Young Scientists(B)No.22791295,No.23791557 and No.24791440Grant-in-Aid for Scientific Research(C)from the Japan Society for the Promotion of Science,No.22591464 and No.24591957
文摘AIM:To investigate the role of claudin 1 in the regulation of genes involved in cell migration and tumor necrosis factor alpha(TNF-α)-induced gene expression in human gastric adenocarcinoma cells.METHODS:Knockdown experiments were conducted with claudin 1 small interfering RNA(si RNA),and theeffects on the cell cycle,apoptosis,migration and invasion were analyzed in human gastric adenocarcinoma MKN28 cells.The gene expression profiles of cells were analyzed by microarray and bioinformatics.RESULTS:The knockdown of claudin 1 significantly inhibited cell proliferation,migration and invasion,and increased apoptosis.Microarray analysis identified 245genes whose expression levels were altered by the knockdown of claudin 1.Pathway analysis showed that the top-ranked molecular and cellular function was the cellular movement related pathway,which involved MMP7,TNF-SF10,TGFBR1,and CCL2.Furthermore,TNFand nuclear frctor-κB were the top-ranked upstream regulators related to claudin 1.TNF-αtreatment increased claudin 1 expression and cell migration in MKN28 cells.Microarray analysis indicated that the depletion of claudin1 inhibited 80%of the TNF-α-induced m RNA expression changes.Further,TNF-αdid not enhance cell migration in the claudin 1 si RNA transfected cells.CONCLUSION:These results suggest that claudin 1 is an important messenger that regulates TNF-α-induced gene expression and migration in gastric cancer cells.A deeper understanding of these cellular processes may be helpful in establishing new therapeutic strategies for gastric cancer.
文摘BACKGROUND Ulcerative colitis(UC)is an uncommon inflammatory bowel disease(IBD).However,its incidence has recently increased in South Korea.Moreover,UC diagnoses are frequently delayed,and the relationship between diagnostic delay and UC prognosis has not been extensively studied in South Korean patients.AIM To identify meaningful diagnostic delay affecting UC prognosis and to evaluate risk factors associated with diagnostic delay in South Korean patients.METHODS Medical records of 718 patients with UC who visited the outpatient clinic of six university hospitals in South Korea were reviewed;167 cases were excluded because the first symptom date was unknown.We evaluated the relationship between the prognosis and a diagnostic delay of 3,6,12,18,and 24 mo by comparing the prognostic factors[anti-tumor necrosis factor(TNF)-αuse,admission history due to acute flare-ups,frequent admission due to flare-ups,surgery associated with UC,and the clinical remission state at the latest followup]at each diagnostic interval.RESULTS The mean diagnostic interval was 223.3±483.2 d(median,69 d;75th percentile,195 d).Among the prognostic factors,anti-TNFαuse was significantly increased after a diagnostic delay of 24 mo.Clinical risk factors predictive of a 24-mo diagnostic delay were age<60 years at diagnosis[odd ratio(OR)=14.778,95%confidence interval(CI):1.731-126.121],smoking history(OR=2.688,95%CI:1.239-5.747,P=0.012),and misdiagnosis of hemorrhoids(OR=11.066,95%CI:3.596-34.053).Anti-TNFαuse was associated with extensive UC at diagnosis(OR=3.768,95%CI:1.860-7.632)and 24-mo diagnostic delay(OR=2.599,95%CI:1.006-4.916).CONCLUSION A diagnostic delay>24 mo was associated with increased anti-TNFαuse.Age<60 years at diagnosis,smoking history,and misdiagnosis of hemorrhoids were risk factors for delayed diagnosis.
基金supported in the context of the Italian Malaria Network by grants from Compagnia di San Paolo-IMIthe University of Torino Intramural FundsRegione Piemonte,Ricerca Sanitaria Finalizzata 2007 to PA
文摘Objective:Avidly phagocytosed hemozoin(malarial pigment) alters several functions of human monocytes and stimulates generation of several cytokines.Recently,we showed that phagocytosis of hemozoin by human monocytes increases expression and activity of matrix metalloproteinase-9,a proteolytic enzyme available in specific gelatinase granules,which contain several enzymes including lysozyme.Present work investigated active lysozyme release after phagocytosis of hemozoin and its dependence on production of tumor necrosis factor alpha. Methods:After phagocytosis of hemozoin,hemozoin-containing trophozoites or control meals(opsonized nonparasitized red blood cells and latex particles),monocyte supematants were monitored for 2 hours,in presence of blocking anti-human tumor necrosis factor alpha antibodies or recombinant human tumor necrosis factor alpha cytokine in selected experiments.Lysozyme release was evaluated by a specific spectrometric assay measuring lysozyme activity after coincubation of cell supematants with suspensions of Mycrococcus Lysodeikticus,while levels of soluble tumor necrosis factor alpha were analyzed by specific enzyme-linked immunodsorbent assay. Results:Levels of lysozyme activity and soluble tumor necrosis factor alpha protein were increased in hemozoin in-or trophozoites-laden monocytes supematants.Phagocytosis per se(control meals) also increased lysozyme release,but levels were significantly lower than those obtained after phagocytosis of hemozoin or trophozoites. Interestingly,all effects on lysozyme release observed after phagocytosis were abrogated by blocking anti-human tumor necrosis factor alpha antibodies,while they were mimicked by recombinant human tumor necrosis factor alpha cytokine.Conclusions:Present work shows that phagocytosis of hemozoin promotes monocyte degranulation and enhances active lysozyme release.The effect requires tumor necrosis factor alpha mediation.
基金supported in the context of the Italian Malaria Network by grants from Compagnia di San Paolo-IMI and from Regione Piemonte,Ricerca Sanitaria Finalizzata 2008bis to PA
文摘Objective:To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment.Methods:Adherent human monocytes were fed for 3 hours with different meals(native hemozoin;lipid free hemozoin;and control latex particles),then tumor necrosis factor alpha was monitored in cell supernatants up to 48 hours through western blotting or specific enzyme-linked immunoadsorbent assay.In selected experiments,unfed monocytes were treated with different doses of 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid or 4-hydroxynonenal instead of phagocytosis.Results:Hemozoin-fed monocytes produced higher levels of tumor necrosis factor alpha than unstimulated and latex-fed cells, while lipid-free hemozoin did not reproduce these results.Additionally,hemozoin effects were mimicked dose-dependently by 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid,but not by 4-hydroxynonenal.Conclusions:Present data suggest an essential role for lipids in hemozoindependent enhanced release of tumor necrosis factor alpha from monocytes,and 15(S,R)hydroxy -6,8,11,13-eicosatetraenoic acid could be one possible specific mediator.
基金Supported by Basic Science Research Program through National Research Foundation of Korea Grants funded by the Korean GovernmentNo.NRF-2012R1A1A2007033 and No.2009-0093821South Korea
文摘AIM: To investigate associations between the tumor necrosis factor alpha(TNF-α)-1031 T>C,-863 C>A,-857 C>T,-308 G>A,and-238 G>A polymorphisms and HCC in Korea.METHODS: Hepatocellular carcinoma(HCC) cases were diagnosed at CHA Bundang Medical Center from June 1996 to August 2008. The association between TNF-α polymorphisms and HCC was analyzed in 157HCC patients and 201 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. We investigated five TNF-α polymorphisms,which are TNF-α-1031 T>C,-863 C>A,-857 C>T,-308 G>A,and-238 G>A. The TNF-α genotype frequencies,genotype combinations and haplotypes were analyzed to disclose the association with HCC.RESULTS: None of the TNF-α polymorphisms was significantly associated with HCC. However,nine genotype combinations had associations with increased likelihood of HCC. Among them,TNF-α-1031/-857/-238 TT/CC/GA(AOR = 18.849,95%CI: 2.203-161.246,P = 0.007),TNF-α-1031/-308/-238 TT/GG/GA(AOR = 26.956,95%CI: 3.071-236.584,P = 0.003),and TNF-α-1031/-238 TT/GA(AOR = 21.576,95%CI: 2.581-180.394,P = 0.005) showed marked association with HCC. There were five haplotypes of TNF-α polymorphisms which were significantly associated with HCC. They are TNF-α-1031/-863/-857/-308/-238 T-C-C-G-A(OR = 25.824,95%CI: 1.491-447.223,P = 0.0005),TNF-α-1031/-857/-308/-238 T-C-G-A(OR = 12.059,95%CI: 2.747-52.950,P < 0.0001),TNF-α-1031/-857/-238 T-C-A(OR = 10.696,95%CI: 2.428-47.110,P = 0.0001),TNF-α-1031/-308/-238 T-G-A(OR = 7.556,95%CI: 2.173-26.280,P = 0.0002) and TNF-α-1031/-238 T-A(OR = 10.865,95%CI: 2.473-47.740,P = 0.0001). Moreover,HCC Okuda stage Ⅲ cases with the TNF-α-1031 CC genotype had better survival than those with the TT genotype(AOR = 5.795,95%CI: 1.145-29.323). CONCLUSION: Although no single TNF-α polymorphism is associated with HCC in this study,some TNF-α genotype combinations and haplotypes are associated with HCC. In addition,HCC Okuda stage Ⅲ cases with the TNF-α-1031 TT genotype may have a better prognosis than those with the CC genotype.
基金supported by College of Health Sciences(Grant No,HS-10-01)
文摘Objective:To analyze scrum leptin levels in patients with malaria falciparum and compare them with healthy controls and correlate with development and outcome of malaria infection.Methods:Sixty cases of malaria falciparum were included in this study as patients.Thirty healthy individuals of comparable age,racial and body mass index were taken as controls.All patients were diagnosed by clinical picture and the presence of malaria parasites in blood film.Estimation of liver function test,kidney function test,complete blood count,fasting blood sugar,fasting serum insulin,pro-inflammatory cytokine tumor necrosis factor alpha(TNFα)and interleukin 1(IL1),estimation of morning serum leptin and calculation of body mass index(kg/m^2)were done in both groups on the day of admission,on discharge and 7 d after discharge.Results:At admission,leptin levels were significantly higher in patients group than in control while lasting serum insulin levels were not significantly different between the two groups.There were significant increases as regard to TNFαand IL1 in malaria patients.Significant differences were observed between the control and the patient group for leptin,TNFαand IL1 at the time of admission and discharge.After discharge for 7 d.a significant decline in scrum leptin levels,TNFαand IL1 in the patients group was observed as compared with time of admission and time of discharge,a positive correlation between serum leptin levels and TNFαand IL1.Conclusions:Leptin hormone level might play an important role in development and outcome of malaria infection.
文摘Anti-tumor necrosis factor alpha (TNF-α) inhibitors are effective in the treatment of various inflammatory rheumatic conditions. Increased risks of serious infections are the major issues concerning the long-term safety of these agents. We present a case of a young male Behcet’s patient whose disease was complicated by cytomegalovirus (CMV) colitis. Colitis started 10 d after the third Infliximab dose and responded to the cessation of TNF blocking treatment and administration of ganciclovir. Tumor necrosis factor alpha and interferon gamma act at several levels in combating viral infections.CMV infections should be kept in mind and included in the differential diagnosis of severe gastrointestinal symptoms in patients receiving anti-TNF agents.
基金Supported by National Ministry of Health of China,No.97100252
文摘AIM:To determine the effect of tumor necrosis factor alpha(TNF-α) on intestinal permeability(IP) in mice with fulminant hepatic failure(FHF),and the expression of tight junction proteins.METHODS:We selected D-lactate as an index of IP,induced FHF using D-galactosamine/lipopolysaccharide and D-galactosamine/TNF-α,assessed the results using an enzymatic-spectrophotometric method,transmission electron microscopy,immunohistochemistry,Western blotting and real-time quantitative polymerase chain reaction.The effect of the administration of antiTNF-α immunoglobulin G(IgG) antibody,before the administration of D-galactosamine/lipopolysaccharide,on TNF-α was also assessed.RESULTS:IP was significantly increased in the mouse model of FHF 6 h after injection(13.57 ± 1.70 mg/L,13.02 ± 1.97 mg/L vs 3.76 ± 0.67 mg/L,P = 0.001).Electron microscopic analysis revealed tight junction(TJ) disruptions,epithelial cell swelling,and atrophy of intestinal villi.Expression of occludin and claudin-1 mRNA was significantly decreased in both FHF models(occludin:0.57 ± 0.159 fold vs baseline,P = 0.000;claudin-1:0.3067 ± 0.1291 fold vs baseline,P = 0.003),as were the distribution density of proteins in the intestinal mucosa and the levels of occludin and claudin-1 protein(occludin:0.61 ± 0.0473 fold vs baseline,P = 0.000;claudin-1:0.6633 ± 0.0328 fold vs baseline,P = 0.000).Prophylactic treatment with antiTNF-α IgG antibody prevented changes in IP(4.50 ± 0.97 mg/L vs 3.76 ± 0.67 mg/L,P = 0.791),intestinal tissue ultrastructure,and the mRNA levels of occludin and claudin-1 expression(occludin:0.8865 ± 0.0274 fold vs baseline,P = 0.505;claudin-1:0.85 ± 0.1437 fold vs baseline,P = 0.1),and in the protein levels(occludin:0.9467 ± 0.0285 fold vs baseline,P > 0.05;claudin-1:0.9533 ± 0.0186 fold vs baseline,P = 0.148).CONCLUSION:Increased in IP stemmed from the downregulation of the TJ proteins occludin and claudin-1,and destruction of the TJ in the colon,which were induced by TNF-α in FHF mice.
文摘This article describes cases of anti-tumor necrosis factor(TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis(AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-α antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune-mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics.
基金supported by an assistantship from the Department of Animal Science,North Carolina State University
文摘Mastitis or other infectious diseases have been related to reduced fertility in cattle. Inflammatory cytokines such as tumor necrosis factor a (TNFa) are released in response to infection and may have negative effects on embryo development. In the current study the effect of exposure to TNFa on the development of in vitro fertilized bovine embryos was examined. Indomethacin, a prostaglandin synthesis inhibitor, was used to determine if blockade of prostaglandin synthesis would alter the effects of TNFa. Ovaries were obtained from a local abattoir and immature COC were isolated from 2-10 mm follicles, in vitro matured and fertilized. After fertilization, groups of presumptive zygotes were randomly placed into either control development medium, medium containing 25 ng/mL TNFa or medium containing 25 ng/mL TNFa plus 1 μg/mL indomethacin. The proportion of blastocysts formed was assessed at day 7 of culture. Fewer embryos exposed to TNFa alone reached the blastocyst stage (17.5 ± 2.4%, P < 0.01) compared with controls (30.5 ± 2.4%) or embryos developed in TNFa plus indomethacin (25.8 ± 2.8%). There was no difference between control embryos and embryos developed in TNFa plus indomethacin. These results indicate that TNFa is inhibitory to the in vitro development of bovine embryos and that this inhibition may be mediated by prostaglandins because it can be blocked by indomethacin.
文摘Background and Importance: Chronic subdural hematomas (cSDH) are a common problem for which solutions remain imperfect. Surgery is effective, but not without risk. Recent data have suggested a role for inflammation in the genesis of cSDH and several reports have documented some benefit to steroid treatment. In this report, a possible role for tumor necrosis factor alpha blockade in the resolution of a multiply recurrent cSDH is described. Clinical Presentation: An 86-year-old man with rheumatoid arthritis treated with infliximab presented with a large, symptomatic, multiloculated cSDH. Infliximab was withheld and craniotomy for evacuation was uncomplicated, but recurrent symptoms were noted and a recurrence was operated upon again several weeks later. Follow up CT showed a second recurrence. The patient requested to go back on his infliximab due to painful arthralgias. After a single dose of 10 mg/kg, follow up CT showed that the cSDH resolved and did not recur. Conclusion: Anti-TNF-alpha treatment with infliximab may have played a role in the resolution of this patient’s cSDH. Further investigation of this possible effect seems warranted.
文摘Aim: To study the roles of tumor necrosis factor alpha (TNF-a)on the sperm acrosin activity and acrosome reaction. Methods:The sperm acrosin activity was tested by the method of BAEE/ADH Unity and the acrosome reaction by the Triple-stain technique. Results: TNF-a decreased the sperm acrosin activityand acrosome reaction (P＜0.01, P＜0.01, respectively);
基金the Natural Science Foundation of Shandong Province, No. Z2002C04
文摘BACKGROUND: Lots of evidences have demonstrated that acute inflammatory reaction plays an important role in cerebral ischemia and cerebral ischemia/reperfusion injury. Tumor necrosis factor (TNF), as one of important inflammatory cytokines, also participates in the injury. OBJECTIVE: To observe the changes in TNF-α expression and myeloperoxidase (MPO) activity of mouse models of local cerebral infarction induced by photochemical method, and analyze the correlation of TNF-α expression and MPO activity. DESIGN: Randomized controlled experiment. SETTING: Laboratory of Cerebral Microcirculation, Taishan Medical College. MATERIALS: Sixty involved male adult Kunming mice were provided by the Experimental Animal Center of Shandong University. TNF-α primary antibody, kits for enzyme-linked immunosorbent assay(ELISA) and streptavidin-biotin complex immunohistochemical dyeing kit were purchased from Boster Company(Wuhan). MPO kit was purchased from Jiancheng Bioengineering Institute (Nanjing). Cold light source was developed by Hengfa Co.,Ltd.( LG-150, Xuzhou). METHODS: This experiment was carried out in the Laboratory of Cerebral Microcirculation of Taishan Medical College between July 2004 and July 2005. The involved 60 Kunming mice were randomized into 3 groups: normal control group (n =6), sham-operation group (n =6) and model group (n =48). Mice in the model group were observed at 30 minutes, 1, 3, 6, 12, 24, 48 and 72 hours after illumination, separately, 6 mice at each time point. In the model group, mice models of local cerebral infarction were developed as follows: The mice were anesthetized to expose left skulls. Taking 2 mm left to sagittal suture and 2 mm posterior to coronal suture as center, a field with diameter of 3 mm for illumination was set. The optical fiber detecting head of cold light source was vertically close to exposed skull. The mice were injected with rose Bengal for 5 minutes, and then cold light source was open for 10 minutes. Illumination was omitted in the sham-operation group. Mice in the control group were not modeled. At postoperative 6 hours, TNF-α expression in infracted-side cortex was detected with immunohistochemical method and ELISA, and MPO activity in infracted-side cortex with chromatometry. MPO activity could reflect the infiltration degree of neutrophils in tissue. Stronger activity indicated severer infiltration. Single-factor analysis of variance was used for comparison among groups, q test for pairwise comparison and correlative analysis for detecting the inter-parameter correlation. MAIN OUTCOME MEASURES: Changes in TNF-α expression and MPO activity of left cortex of mice in each group. RESULTS: Sixty mice were involved in the final analysis. After cerebral infarction, TNF-α positive cells were neurons and glial cells mainly, distributing in and around the infarct region. TNF-α expression in cortex of mice of sham-operation group was (615.7±16.1) ng/L, and that of model group increased to (792.2±17.8) ng/L at 3 hours after illumination, and reached peak [(921.9±23.9) ng/L] at 6 hours after illumination, and decreased to (848.0±30.6) ng/L at 12 hours after illumination and recovered to the normal level [(625.3±14.3) ng/L] at 72 hours after illumination. MPO activity of sham-operation group was (7.151±0.433) nkat/g, and that of model group increased to (10.469±0.600) nkat/g at 3 hours after illumination, reached the peak ([15.486±0.650) nkat/g] at 12 hours after illumination, decreased to (11.052±0.617) nkat/g at 24 hours after illumination and recovered to the normal level [(7.418± 0.617) nkat/g] at 72 hours after illumination. Change of MPO activity lagged behind that of TNF-α, andcorrelative analysis showed that the both were positively correlated(r =0.953, P < 0.01). CONCLUSION: In the acute stage of cerebral infarction of mice induced by photochemical method, TNF-α expression in infarcted-side cortex is closely related with infiltration of neutrophils. TNF-α induces inflammatory cells to intrude into ischemic brain tissue, and participates in the inflammatory reaction process at the early stage of cerebral ischemia.
文摘Background: Tuberculosis (TB) is one of the world’s deadliest infectious diseases. Tumor necrosis factor-Alpha (TNF-α) and Interleukin 8 (IL-8) are involved in the pathogenesis of pulmonary TB (PTB). However, the contribution of polymorphisms of these cytokines to PTB susceptibility needed more investigation across geographic regions and ethnic groups. Purpose: The aim of this study was to investigate the association of the TNF-α-308 G/A and IL-8-251T/A polymorphisms with PTB risk in the Congolese population. Methods: This case-control study included 150 PTB patients and 160 control subjects. Blood samples were collected from all participants and were used for the TNF-α-308 G/A and IL-8-251T/A genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Odds ratios (OR) were calculated to estimate the potential polymorphism associations. A P level of Results: A significant difference was found between PTB patients and controls regarding the TNF-α-308AA genotype (P = 0.035) distribution. Moreover, this genotype was associated with risk to TB (OR = 7.19, 95% CI = 0.85 - 60.65, P = 0.035). The A allele was significantly more frequent in PTB patients than in controls, and was associated with risk to PTB (OR = 1.68, 95% CI = 1.05 - 2.68, P = 0.014). Regarding the IL-8-251T/A gene, TA and AA genotypes were significantly more frequent in PTB patients compared to controls, and were associated with increased risk to PTB (OR = 2.64, 95% CI = 0.97 - 7.18, P = 0.031 and OR = 3.0, 95% CI = 1.13 - 7.98, P = 0.014, respectively). However, the IL-8-251 A allele was not associated to PTB susceptibility (OR = 0.27, 95% CI = 0.15 - 0.44). Conclusion: TNF-α-308G/A and IL-8-251T/A polymorphisms may be associated to PTB susceptibility in the Congolese population, and the AA genotype of both cytokines could be a risk factor.
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.
