Abnormalities in liver function tests,including transient and self-limiting hypertransaminasemia,cholestatic disease and hepatitis,can develop during treatment with anti-tumour-necrosis-factor(TNF)therapy.The optimal ...Abnormalities in liver function tests,including transient and self-limiting hypertransaminasemia,cholestatic disease and hepatitis,can develop during treatment with anti-tumour-necrosis-factor(TNF)therapy.The optimal management of liver injury related to antiTNF therapy is still a matter of debate.Although some authors recommend discontinuing treatment in case of both a rise of alanine aminotransferase more than5 times the upper limit of normal,or the occurrence of jaundice,there are no standard guidelines for the management of anti-TNF-related liver injury.Bibliographical searches were performed in Pub Med,using the following key words:inflammatory bowel disease(IBD);TNF inhibitors;hypertransaminasemia;drugrelated liver injury;infliximab.According to published data,elevation of transaminases in patients with IBD treated with anti-TNF is a common finding,but resolution appears to be the usual outcome.Anti-TNF agents seem to be safe with a low risk of causing severe drugrelated liver injury.According to our centre experience,we found that hypertransaminasemia was a common,mainly self-limiting finding in our IBD cohort and was not correlated to infliximab treatment on both univariate and multivariate analyses.An algorithm for the management of liver impairment occurring during antiTNF treatment is also proposed and this highlights the need of a multidisciplinary approach and suggests liver biopsy as a key-point in the management decision in case of severe rise of transaminases.However,hepatic injury is generally self-limiting and drug withdrawal seems to be an exception.展开更多
BACKGROUND Zinc-α2-glycoprotein 1 (AZGP1) plays important roles in metabolism-related diseases. The underlying molecular mechanisms and therapeutic effects of AZGP1 remain unknown in non-alcoholic fatty liver disease...BACKGROUND Zinc-α2-glycoprotein 1 (AZGP1) plays important roles in metabolism-related diseases. The underlying molecular mechanisms and therapeutic effects of AZGP1 remain unknown in non-alcoholic fatty liver disease (NAFLD). AIM To explore the effects and potential mechanism of AZGP1 on NAFLD in vivo and in vitro. METHODS The expression of AZGP1 and its effects on hepatocytes were examined in NAFLD patients, CCl4-treated mice fed a high fat diet (HFD), and human LO2 cells. RESULTS AZGP1 levels were significantly decreased in liver tissues of NAFLD patients and mice. AZGP1 knockdown was found to activate inflammation;enhance steatogenesis, including promoting lipogenesis [sterol regulatory elementbinding protein (SREBP)-1c, liver X receptor (LXR), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and stearoyl CoA desaturase 1 (SCD)-1], increasing lipid transport and accumulation [fatty acid transport protein (FATP), carnitine palmitoyl transferase (CPT)-1A, and adiponectin], and reducing fatty acid β-oxidation [farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR)-α];accelerate proliferation;and reverse apoptosis in LO2 cells. AZGP1 overexpression (OV-AZGP1) had the opposite effects. Furthermore, AZGP1 alleviated NAFLD by blocking TNF-α-mediated inflammation and intracellular lipid deposition, promoting proliferation, and inhibiting apoptosis in LO2 cells. Finally, treatment with OV-AZGP1 plasmid dramatically improved liver injury and eliminated liver fat in NAFLD mice. CONCLUSION AZGP1 attenuates NAFLD with regard to ameliorating inflammation, accelerating lipolysis, promoting proliferation, and reducing apoptosis by negatively regulating TNF-α. AZGP1 is suggested to be a novel promising therapeutic target for NAFLD.展开更多
Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events represent...Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events representing a true challenge for patients, clinicians and health care systems.Consequently, a crucial question is raised namely if therapy can be stopped once remission is achieved and if so, how and in whom.Additionally, in a real-life clinical setting, discontinuation may also be considered for other reasons such as the patient's preference, pregnancy, social reasons as moving to countries or continents with less access, or different local policy or reimbursement.In contrast to initiation of anti-TNFα therapy guidelines regarding stopping of this treatment are missing.As a result, the decision of discontinuation is still a challenging aspect in the use of anti-TNFα therapy.Currently this is typically based on an estimated, case-by-case, benefit-risk ratio.This editorial is intended to provide an overview of recent data on this topic and shed light on the proposed drug withdrawal strategies.展开更多
This study used in vivo microdialysis to examine the effects of intragingival application of lipopolysaccharide（LPS） derived from Porphyromonas gingivalis（Pg-LPS） on gingival tumour necrosis factor（TNF）-a and in...This study used in vivo microdialysis to examine the effects of intragingival application of lipopolysaccharide（LPS） derived from Porphyromonas gingivalis（Pg-LPS） on gingival tumour necrosis factor（TNF）-a and interleukin（IL）-6 levels in rats. A microdialysis probe with an injection needle attached to the surface of the dialysis membrane was implanted into the gingiva of the upper incisor. For comparison, the effects of LPS derived from Escherichia coli（Ec-LPS） on IL-6 and TNF-a levels were also analysed. Pg-LPS（1 mg/1 m L） or Ec-LPS（1 or 6 mg/1 m L） was applied by microsyringe, with gingival dialysates collected every hour. Enzyme-linked immunosorbent assay（ELISA） revealed that gingival dialysates contained approximately 389 pg？m L21 of IL-6 basally; basal TNF-a levels were lower than the detection limit of the ELISA. Pg-LPS failed to alter IL-6 levels but markedly increased TNF-a levels, which remained elevated for 2 h after treatment. Neither IL-6 nor TNF-a were affected by Ec-LPS. Reverse transcriptase-polymerase chain reaction（RT-PCR） analysis revealed that the gingiva expresses Toll-like receptor（TLR） 2 and TLR4 m RNA. Immunohistochemical examination showed that TLR2 and TLR4 are expressed by gingival epithelial cells. The present study provides in vivo evidence that locally applied Pg-LPS, but not Ec-LPS, into the gingiva transiently increases gingival TNF-a without affecting IL-6. The present results suggest that TLR2 but not TLR4 expressed on gingival epithelial cells may mediate the Pg-LPS-induced increase in gingival TNF-a in rats.展开更多
Objective:To study the effects of propofol on Bax and Bcl-2 expression induced by tumour necrosis factor-α(TNF-α) in mouse spinal cord neurons in vitro. Methods:Spinal cord neurons were isolated from fetal mice and ...Objective:To study the effects of propofol on Bax and Bcl-2 expression induced by tumour necrosis factor-α(TNF-α) in mouse spinal cord neurons in vitro. Methods:Spinal cord neurons were isolated from fetal mice and cultured in Neurobasal medium with B27 supplement. On the 7^th day, cultured neurons were randomly divided into 6 groups: control group, propofol (50 umol/L)group, TNF-α group, propofol (25 umol/L) with TNF-α group, propofol (50 umol/ L) with TNF-α group, and propofol ( 100 umol/L)with TNF-α group. Propofol was added to the cultured cells respectively and the cells were incubated for 30 min. Then TNF-α was added to the cultured cells(the final concentration of TNF-α was 2 000 U/ml) and incubated for 24 h. The Bax and Bcl-2 expression were measured by immunocytochemical technique. Results:In TNF-α group, the expression of Eax increased and the expression of Bcl-2 decreased (P<0.01, vs control). However, treatment with various concentrations of propofol (25, 50, 100 umol/L) decreased the expression of Bax and increased the expression of Bcl-2 (P<0.05, P<0.05, P<0.05, vs TNF-α). Conclusion: Propofol can inhibit the apoptosis induced by TNF-α by modulating the expression of Bax and Bcl-2.展开更多
Background and Aims: Lung cancer is a leading cause of cancer mortality worldwide and is associated with the release of tumour necrosis factor-α (TNF-α), subsequent cellular apoptosis and the generation of oxidative...Background and Aims: Lung cancer is a leading cause of cancer mortality worldwide and is associated with the release of tumour necrosis factor-α (TNF-α), subsequent cellular apoptosis and the generation of oxidative stress. Exhaled breath condensate (EBC) analysis is a non-invasive method for sampling biofluids from the lower respiratory tract. This study aimed to evaluate possible biomarkers of lung cancer by measuring the levels of TNF-α and the oxidation of ascorbic acid in EBC. Patients with lung cancer were enrolled into the study prior to treatment, during treatment and post-treatment, and results compared with an age-matched control population. Material and Methods: Patients with Stage II-IV non small cell lung cancer (NSCLC) were recruited prior to and at stages of their treatment. EBC levels of TNF-α, and rate of ascorbic acid oxidation were measured. Results: A total of 19 patients with NSCLC (mean age 71.37 ± 7.77 yrs) and 25 age-matched control subjects were enrolled. Levels of EBC TNF-α were elevated in the EBC of patients with lung cancer compared with control subjects (1.02 ± 0.07 pg/ml vs. 0.51 ± 0.06 pg/ml, p < 0.0001). Moreover, the rate of ascorbic acid oxidation was significantly greater in the EBC of patients with lung cancer compared with control subjects (2.20% [0.4 – 11.0] vs. 1.00% [0.1 – 8.5], p = 0.0244). Conclusion: TNF-α and the rate of ascorbic acid oxidation was elevated in the EBC of patients with lung cancer regardless of treatment. Longitudinal studies in a larger population are required to evaluate these markers for the effect of treatment and prognosis.展开更多
Purpose : Effects of Tryptergium Wilfordii Polyglycosidium (TWP) on the Tumour Necrosis Factor (TNF) levels in aqueous humor after intraocular lens (IOL) implantation were studied in rabbits.Methods: Twenty-seven pigm...Purpose : Effects of Tryptergium Wilfordii Polyglycosidium (TWP) on the Tumour Necrosis Factor (TNF) levels in aqueous humor after intraocular lens (IOL) implantation were studied in rabbits.Methods: Twenty-seven pigmented rabbits were divided into three groups. In the first group, the IOL were placed in the capsular bag after lens extraction. In the second group, rabbits received TWP therapy after IOL implantation. And in the third group, rabbit received prednisone therapy after IOL implantation. Aqueous humor samples were aspirated on the 1st, 3rd, 7th, and 14th postoperative day. A modified double antibodies indirect sandwich EL ISA was used to detect for the presence of TNF. The data were closely studied by means of analysis of variance with SAS software.Results; It was found that TNF level in aqueous humor reached its maximum on the 7th postoperative day in the group with IOL implantation. It was also found that the TNF levels in aqueous humor on the 7th and 14th postoperative day were展开更多
AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand popula...AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies. METHODS: DNA samples from 388 patients with Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-α receptor: -238 G→A, -308 G→A and -857C→T, using a TaqmanR assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies. RESULTS: Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, χ2 = 17.36, P < 0.0001) increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, χ2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (OR = 0.56, χ2 =4.32, P = 0.037), and the need for a bowel resection (OR = 0.59, χ2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (OR = 0.48, χ2 = 4.86, P = 0.028). CONCLUSION: TNF-α is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-α promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco- or nutrigenomic approaches may be desir- able for individuals with such affected genotypes.展开更多
AIMTo establish the role of nitric oxide (NO), ascorbic acid and tumour necrosis factor-α (TNF-α) in the pathogenesis of pseudoexfoliation glaucoma (XFG).METHODSOur study included 120 patients ...AIMTo establish the role of nitric oxide (NO), ascorbic acid and tumour necrosis factor-α (TNF-α) in the pathogenesis of pseudoexfoliation glaucoma (XFG).METHODSOur study included 120 patients who were referred for cataract surgery. All patients were divided into four groups according to clinical findings: XFG, early and late pseudoexfoliation syndrome (XFS), and cataract (without pseudoexfoliation). Serum and aqueous humour levels of the ascorbic acid, NO and TNF-α were measured. The concentrations of the ascorbic acid and NO were measured by an appropriate spectrophotometric method. Enzyme-linked immunosorbent assay (ELISA) was used to determine TNF-α level.RESULTSAqueous humour concentration of ascorbic acid was significantly lower in patients with late XFS (0.61±0.11 mmol/L) and XFG (0.48±0.15 mmol/L) compared to patients with early XFS (0.9±0.15 mmol/L) and cataract (1.16±0.22 mmol/L), while there was no difference in serum concentration in all examined groups. Aqueous humour concentration of NO was significantly higher in patients with XFG (77.7±11.4 µmol/L) compared to patients with early XFS (50.27±9.34 µmol/L) and cataract (49.77±7.1 µmol/L), while serum concentration was increased in the early stage of XFS (73.26±8.29 µmol/L). Aqueous humour level of proinflammatory cytokine TNF-α was increased in patients with XFS (early 460.04±18.32 pg/mL; late 502.42±53.23 pg/mL) and XFG (510.34±43.07 pg/mL), while there was no difference in serum level in all examined groups of patients.CONCLUSIONReduced ascorbic acid and elevated NO and inflammation related cytokine TNF-α level in aqueous humour of the patients with developed XFG suggest that oxidative stress induces local inflammation.展开更多
Purpose. This paper studies the tumour necrosis factor (TNF) levels in aqueous humor after traumatic cataract extraction and posterior chamber (PC) intraocular lens (IOL) implantation in rabb...Purpose. This paper studies the tumour necrosis factor (TNF) levels in aqueous humor after traumatic cataract extraction and posterior chamber (PC) intraocular lens (IOL) implantation in rabbits,and discusses the effect of TNF on postoperative anterior ocular inflammation. Methods. Twenty seven pigmented rabbits were divided into three groups: for the first group, the IOL were placed in the capsular bag after traumatic cataract extraction; for the second, the Extracapsular cataract extraction without IOL implantation; and for the third, the control group without surgical intervention. On the 1st, 3rd, 7th and 14th day postoperatively, aqueous humor samples were obtained. A modified double antibodies indirect sandwich ELISA was used to detected for the presence of TNF. The data were studied by means of analysis of variance in SAS software. Result. The TNF level was increased in aqueous humor and reached its maximum on the 1st postoperative days after traumatic cataract extraction and PC IOLs implantation, and the TNF levels are significantly higher (P<0 05) on the 1st, 3rd, 7th and 14th day postoperatively in traumatic cataract extraction and PC IOL implanted group than that in the non surgical intervention group and extracapsular cataract extraction group. Conclusions. The increase of TNF levels had a close relationship with presence of the IOL itself which induces the secretion of TNF. This suggested that TNF as the principal mediators of immunological and inflammatory responses, so that may play critical role in anterior ocular inflammative response after traumatic cataract extraction and IOL implantation.展开更多
Purpose: The tumour necrosis factor (TNF) level in aqueous humor after transscleral fixation of intraocular lens (IOL) implantation in rabbits and discuss the effect of TNF on postoperative anterior ocular inflammatio...Purpose: The tumour necrosis factor (TNF) level in aqueous humor after transscleral fixation of intraocular lens (IOL) implantation in rabbits and discuss the effect of TNF on postoperative anterior ocular inflammation.Methods: Twenty - seven pigmented rabbits were divided into three groups. Group 1: transscleral fixation of posterior chamber (PC) IOL implantation;Group 2; Lens of rabbits was removed without IOL implantation; Group 3; the comtrol group, without surgical intervention. On the 1st, 3rd, 7th and 14th postoperative days,aqueous humor samples were obtained. An modified double antibodies indirect sandwich ELISA was used to detected for the presence of TNF. The data were analyzed by using analysis of variance of SAS software. Results: It was found that TNF level in aqueous humor was increased after transscleral fixation of IOL implantation. TNF level reached its maximum on the 14th postoperative day in the IOL implanted group. TNF level on 1st, 3rd, 7th and 14th days postoperatively was展开更多
AIM： To determine the temporal expression and pattern of Rel/nuclear factor （NF）-κB proteins in renal tissue in polycystic kidney disease （PKD）. METHODS： The renal expression of Rel/NF-κB proteins was determin...AIM： To determine the temporal expression and pattern of Rel/nuclear factor （NF）-κB proteins in renal tissue in polycystic kidney disease （PKD）. METHODS： The renal expression of Rel/NF-κB proteins was determined by immunohistochemistry, immunofuorescence and immunoblot analysis in Lewis polycystic kidney rats （LPK, a genetic ortholog of human nephronopthsis-9） from postnatal weeks 3 to 20. At each timepoint, renal disease progression and the mRNA expression of NF-κB-dependent genes （TNFa and CCL2） were determined. NF-κB was also histologically assessed in human PKD tissue.RESULTS： Progressive kidney enlargement in LPK rats was accompanied by increased renal cell proliferation and interstitial monocyte accumulation （peaking at weeks 3 and 10 respectively）, and progressive interstitial fibrosis （with a smooth muscle actin and Sirius Red deposition significantly increased compared to Lewis kidneys from weeks 3 to 6 onwards）. Rel/NF-κB proteins （phosphorylated-p105, p65, p50, c-Rel and RelB） were expressed in cystic epithelial cells （CECs） of LPK kidneys as early as postnatal week 3 and sustained until late-stage disease at week 20. From weeks 10 to 20, nuclear p65, p50, RelB and cytoplasmic IκBa protein levels, and TNFa and CCL2 expression, were upregulated in LPK compared to Lewis kidneys. NF-κB proteins were consistently expressed in CECs of human PKD. The DNA damage marker γ-H2AX was also identifed in the CECs of LPK and human polycystic kidneys. CONCLUSION： Several NF-κB proteins are consistently expressed in CECs in human and experimental PKD. These data suggest that the upregulation of both the canonical and non-canonical pathways of NF-κB signaling may be a constitutive and early pathological feature of cystic renal diseases.展开更多
Background Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). A single nucleotide polymorphism (SNP) of tumour necrosis factor-α (TNF-α) has...Background Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). A single nucleotide polymorphism (SNP) of tumour necrosis factor-α (TNF-α) has been reported but inconsistent results may arise from different populations and phenotypes of COPD. There are only a few published studies of interleukin-13 (IL-13) SNPs on COPD. The SNPs of TNF-α and IL-13 have not been studied in the Chinese population. This research was conducted to study the frequencies of IL-13 gene promoter 1055 (IL-13-1055) and TNF-α gene-308 polymorphisms in the patients with COPD and to investigate the effect of those genetic polymorphisms on COPD in the Chinese population.Methods A cohort of COPD patients and age matched controls were recruited from an inpatient hospital service in Beijing. Venous blood was obtained and genomic DNA was extracted from peripheral blood monocytes using standard method. Genomic DNA was used as a template for amplification by polymerase chain reaction (PCR) to determine the polymorphism at -1055 in the IL-13 gene promoter region. PCR restriction fragment length polymorphism (RFLP) was used to determine polymorphisms in the TNF-α gene-308 position. The products were investigated by sequence analysis also. Results One hundred and eleven COPD patients and 97 controls were studied. Seventy-five cases were current smokers in COPD patients and 36 were current smokers in controls. The frequencies of TT genotype in the IL-13 gene promoter region were 11.7% (13/111) in the COPD group and 13.4% (13/97) in the controls (P=0.713). However, the OR value of TT genotype was significantly increased to 6.4 (95% CI 1.62-25.39) in the smokers with COPD. TT genotype was also positively related to family history of COPD, OR=7.7 (95% CI 1.37-43.80). The frequencies of A allele in the TNF-α gene were 5.9% in COPD and 3.1% in controls (P=0.131). The OR value of A allele was 5.0 (95% CI 1.011 to 25.059) in smokers with COPD. Conclusions There is no significant difference in the frequencies of the TT genotype of IL-13-1055 or the A allele of the TNF-α between Han Chinese patients with COPD versus control. Thus, it does not appear that theseSNPs are independent factors in COPD for Han nationality in (Beijing. However,)these SNPs may increase the risk of COPD among smokers.展开更多
文摘Abnormalities in liver function tests,including transient and self-limiting hypertransaminasemia,cholestatic disease and hepatitis,can develop during treatment with anti-tumour-necrosis-factor(TNF)therapy.The optimal management of liver injury related to antiTNF therapy is still a matter of debate.Although some authors recommend discontinuing treatment in case of both a rise of alanine aminotransferase more than5 times the upper limit of normal,or the occurrence of jaundice,there are no standard guidelines for the management of anti-TNF-related liver injury.Bibliographical searches were performed in Pub Med,using the following key words:inflammatory bowel disease(IBD);TNF inhibitors;hypertransaminasemia;drugrelated liver injury;infliximab.According to published data,elevation of transaminases in patients with IBD treated with anti-TNF is a common finding,but resolution appears to be the usual outcome.Anti-TNF agents seem to be safe with a low risk of causing severe drugrelated liver injury.According to our centre experience,we found that hypertransaminasemia was a common,mainly self-limiting finding in our IBD cohort and was not correlated to infliximab treatment on both univariate and multivariate analyses.An algorithm for the management of liver impairment occurring during antiTNF treatment is also proposed and this highlights the need of a multidisciplinary approach and suggests liver biopsy as a key-point in the management decision in case of severe rise of transaminases.However,hepatic injury is generally self-limiting and drug withdrawal seems to be an exception.
基金Supported by the National Natural Science Foundation of China,No.81570547 and No.81770597the Development Program of China during the 13~(th) Five-year Plan Period,No.2017ZX10203202003005
文摘BACKGROUND Zinc-α2-glycoprotein 1 (AZGP1) plays important roles in metabolism-related diseases. The underlying molecular mechanisms and therapeutic effects of AZGP1 remain unknown in non-alcoholic fatty liver disease (NAFLD). AIM To explore the effects and potential mechanism of AZGP1 on NAFLD in vivo and in vitro. METHODS The expression of AZGP1 and its effects on hepatocytes were examined in NAFLD patients, CCl4-treated mice fed a high fat diet (HFD), and human LO2 cells. RESULTS AZGP1 levels were significantly decreased in liver tissues of NAFLD patients and mice. AZGP1 knockdown was found to activate inflammation;enhance steatogenesis, including promoting lipogenesis [sterol regulatory elementbinding protein (SREBP)-1c, liver X receptor (LXR), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and stearoyl CoA desaturase 1 (SCD)-1], increasing lipid transport and accumulation [fatty acid transport protein (FATP), carnitine palmitoyl transferase (CPT)-1A, and adiponectin], and reducing fatty acid β-oxidation [farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR)-α];accelerate proliferation;and reverse apoptosis in LO2 cells. AZGP1 overexpression (OV-AZGP1) had the opposite effects. Furthermore, AZGP1 alleviated NAFLD by blocking TNF-α-mediated inflammation and intracellular lipid deposition, promoting proliferation, and inhibiting apoptosis in LO2 cells. Finally, treatment with OV-AZGP1 plasmid dramatically improved liver injury and eliminated liver fat in NAFLD mice. CONCLUSION AZGP1 attenuates NAFLD with regard to ameliorating inflammation, accelerating lipolysis, promoting proliferation, and reducing apoptosis by negatively regulating TNF-α. AZGP1 is suggested to be a novel promising therapeutic target for NAFLD.
文摘Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events representing a true challenge for patients, clinicians and health care systems.Consequently, a crucial question is raised namely if therapy can be stopped once remission is achieved and if so, how and in whom.Additionally, in a real-life clinical setting, discontinuation may also be considered for other reasons such as the patient's preference, pregnancy, social reasons as moving to countries or continents with less access, or different local policy or reimbursement.In contrast to initiation of anti-TNFα therapy guidelines regarding stopping of this treatment are missing.As a result, the decision of discontinuation is still a challenging aspect in the use of anti-TNFα therapy.Currently this is typically based on an estimated, case-by-case, benefit-risk ratio.This editorial is intended to provide an overview of recent data on this topic and shed light on the proposed drug withdrawal strategies.
基金supported by a Grant-in-Aid for Scientific Research (C) (#25463100 to Tadashi Saigusa)a Grant-in-Aid for Young Scientists (B) (#25861763 to Yuri Aono) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan+4 种基金a grant for the Promotion and Mutual Aid Corporation for Private Schools of Japan (Hiroko Taguchi, Takayuki Kawato, Masatake Asano, Noriyoshi Shimizu, Tadashi Saigusa)a Nihon University Multidisciplinary Research Grant for 2014–2015 (Yuri Aono, Tadashi Saigusa)research grants from the Sato Fund (Takayuki Kawato, Masatake Asano, Noriyoshi Shimizu, Tadashi Saigusa)the Uemura Fund (Noriyoshi Shimizu, Tadashi Saigusa)the Dental Research Centre (Takayuki Kawato, Masatake Asano, Noriyoshi Shimizu, Tadashi Saigusa) of the Nihon University School of Dentistry
文摘This study used in vivo microdialysis to examine the effects of intragingival application of lipopolysaccharide（LPS） derived from Porphyromonas gingivalis（Pg-LPS） on gingival tumour necrosis factor（TNF）-a and interleukin（IL）-6 levels in rats. A microdialysis probe with an injection needle attached to the surface of the dialysis membrane was implanted into the gingiva of the upper incisor. For comparison, the effects of LPS derived from Escherichia coli（Ec-LPS） on IL-6 and TNF-a levels were also analysed. Pg-LPS（1 mg/1 m L） or Ec-LPS（1 or 6 mg/1 m L） was applied by microsyringe, with gingival dialysates collected every hour. Enzyme-linked immunosorbent assay（ELISA） revealed that gingival dialysates contained approximately 389 pg？m L21 of IL-6 basally; basal TNF-a levels were lower than the detection limit of the ELISA. Pg-LPS failed to alter IL-6 levels but markedly increased TNF-a levels, which remained elevated for 2 h after treatment. Neither IL-6 nor TNF-a were affected by Ec-LPS. Reverse transcriptase-polymerase chain reaction（RT-PCR） analysis revealed that the gingiva expresses Toll-like receptor（TLR） 2 and TLR4 m RNA. Immunohistochemical examination showed that TLR2 and TLR4 are expressed by gingival epithelial cells. The present study provides in vivo evidence that locally applied Pg-LPS, but not Ec-LPS, into the gingiva transiently increases gingival TNF-a without affecting IL-6. The present results suggest that TLR2 but not TLR4 expressed on gingival epithelial cells may mediate the Pg-LPS-induced increase in gingival TNF-a in rats.
基金Supported by the Science and Technology DevelopmentFoundation of Shanghai Health Bureau(No.024 097)
文摘Objective:To study the effects of propofol on Bax and Bcl-2 expression induced by tumour necrosis factor-α(TNF-α) in mouse spinal cord neurons in vitro. Methods:Spinal cord neurons were isolated from fetal mice and cultured in Neurobasal medium with B27 supplement. On the 7^th day, cultured neurons were randomly divided into 6 groups: control group, propofol (50 umol/L)group, TNF-α group, propofol (25 umol/L) with TNF-α group, propofol (50 umol/ L) with TNF-α group, and propofol ( 100 umol/L)with TNF-α group. Propofol was added to the cultured cells respectively and the cells were incubated for 30 min. Then TNF-α was added to the cultured cells(the final concentration of TNF-α was 2 000 U/ml) and incubated for 24 h. The Bax and Bcl-2 expression were measured by immunocytochemical technique. Results:In TNF-α group, the expression of Eax increased and the expression of Bcl-2 decreased (P<0.01, vs control). However, treatment with various concentrations of propofol (25, 50, 100 umol/L) decreased the expression of Bax and increased the expression of Bcl-2 (P<0.05, P<0.05, P<0.05, vs TNF-α). Conclusion: Propofol can inhibit the apoptosis induced by TNF-α by modulating the expression of Bax and Bcl-2.
文摘Background and Aims: Lung cancer is a leading cause of cancer mortality worldwide and is associated with the release of tumour necrosis factor-α (TNF-α), subsequent cellular apoptosis and the generation of oxidative stress. Exhaled breath condensate (EBC) analysis is a non-invasive method for sampling biofluids from the lower respiratory tract. This study aimed to evaluate possible biomarkers of lung cancer by measuring the levels of TNF-α and the oxidation of ascorbic acid in EBC. Patients with lung cancer were enrolled into the study prior to treatment, during treatment and post-treatment, and results compared with an age-matched control population. Material and Methods: Patients with Stage II-IV non small cell lung cancer (NSCLC) were recruited prior to and at stages of their treatment. EBC levels of TNF-α, and rate of ascorbic acid oxidation were measured. Results: A total of 19 patients with NSCLC (mean age 71.37 ± 7.77 yrs) and 25 age-matched control subjects were enrolled. Levels of EBC TNF-α were elevated in the EBC of patients with lung cancer compared with control subjects (1.02 ± 0.07 pg/ml vs. 0.51 ± 0.06 pg/ml, p < 0.0001). Moreover, the rate of ascorbic acid oxidation was significantly greater in the EBC of patients with lung cancer compared with control subjects (2.20% [0.4 – 11.0] vs. 1.00% [0.1 – 8.5], p = 0.0244). Conclusion: TNF-α and the rate of ascorbic acid oxidation was elevated in the EBC of patients with lung cancer regardless of treatment. Longitudinal studies in a larger population are required to evaluate these markers for the effect of treatment and prognosis.
文摘Purpose : Effects of Tryptergium Wilfordii Polyglycosidium (TWP) on the Tumour Necrosis Factor (TNF) levels in aqueous humor after intraocular lens (IOL) implantation were studied in rabbits.Methods: Twenty-seven pigmented rabbits were divided into three groups. In the first group, the IOL were placed in the capsular bag after lens extraction. In the second group, rabbits received TWP therapy after IOL implantation. And in the third group, rabbit received prednisone therapy after IOL implantation. Aqueous humor samples were aspirated on the 1st, 3rd, 7th, and 14th postoperative day. A modified double antibodies indirect sandwich EL ISA was used to detect for the presence of TNF. The data were closely studied by means of analysis of variance with SAS software.Results; It was found that TNF level in aqueous humor reached its maximum on the 7th postoperative day in the group with IOL implantation. It was also found that the TNF levels in aqueous humor on the 7th and 14th postoperative day were
基金Foundation for Research, Science and Technology, C02X0403: Gene-specific Foods
文摘AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies. METHODS: DNA samples from 388 patients with Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-α receptor: -238 G→A, -308 G→A and -857C→T, using a TaqmanR assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies. RESULTS: Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, χ2 = 17.36, P < 0.0001) increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, χ2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (OR = 0.56, χ2 =4.32, P = 0.037), and the need for a bowel resection (OR = 0.59, χ2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (OR = 0.48, χ2 = 4.86, P = 0.028). CONCLUSION: TNF-α is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-α promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco- or nutrigenomic approaches may be desir- able for individuals with such affected genotypes.
文摘AIMTo establish the role of nitric oxide (NO), ascorbic acid and tumour necrosis factor-α (TNF-α) in the pathogenesis of pseudoexfoliation glaucoma (XFG).METHODSOur study included 120 patients who were referred for cataract surgery. All patients were divided into four groups according to clinical findings: XFG, early and late pseudoexfoliation syndrome (XFS), and cataract (without pseudoexfoliation). Serum and aqueous humour levels of the ascorbic acid, NO and TNF-α were measured. The concentrations of the ascorbic acid and NO were measured by an appropriate spectrophotometric method. Enzyme-linked immunosorbent assay (ELISA) was used to determine TNF-α level.RESULTSAqueous humour concentration of ascorbic acid was significantly lower in patients with late XFS (0.61±0.11 mmol/L) and XFG (0.48±0.15 mmol/L) compared to patients with early XFS (0.9±0.15 mmol/L) and cataract (1.16±0.22 mmol/L), while there was no difference in serum concentration in all examined groups. Aqueous humour concentration of NO was significantly higher in patients with XFG (77.7±11.4 µmol/L) compared to patients with early XFS (50.27±9.34 µmol/L) and cataract (49.77±7.1 µmol/L), while serum concentration was increased in the early stage of XFS (73.26±8.29 µmol/L). Aqueous humour level of proinflammatory cytokine TNF-α was increased in patients with XFS (early 460.04±18.32 pg/mL; late 502.42±53.23 pg/mL) and XFG (510.34±43.07 pg/mL), while there was no difference in serum level in all examined groups of patients.CONCLUSIONReduced ascorbic acid and elevated NO and inflammation related cytokine TNF-α level in aqueous humour of the patients with developed XFG suggest that oxidative stress induces local inflammation.
文摘Purpose. This paper studies the tumour necrosis factor (TNF) levels in aqueous humor after traumatic cataract extraction and posterior chamber (PC) intraocular lens (IOL) implantation in rabbits,and discusses the effect of TNF on postoperative anterior ocular inflammation. Methods. Twenty seven pigmented rabbits were divided into three groups: for the first group, the IOL were placed in the capsular bag after traumatic cataract extraction; for the second, the Extracapsular cataract extraction without IOL implantation; and for the third, the control group without surgical intervention. On the 1st, 3rd, 7th and 14th day postoperatively, aqueous humor samples were obtained. A modified double antibodies indirect sandwich ELISA was used to detected for the presence of TNF. The data were studied by means of analysis of variance in SAS software. Result. The TNF level was increased in aqueous humor and reached its maximum on the 1st postoperative days after traumatic cataract extraction and PC IOLs implantation, and the TNF levels are significantly higher (P<0 05) on the 1st, 3rd, 7th and 14th day postoperatively in traumatic cataract extraction and PC IOL implanted group than that in the non surgical intervention group and extracapsular cataract extraction group. Conclusions. The increase of TNF levels had a close relationship with presence of the IOL itself which induces the secretion of TNF. This suggested that TNF as the principal mediators of immunological and inflammatory responses, so that may play critical role in anterior ocular inflammative response after traumatic cataract extraction and IOL implantation.
文摘Purpose: The tumour necrosis factor (TNF) level in aqueous humor after transscleral fixation of intraocular lens (IOL) implantation in rabbits and discuss the effect of TNF on postoperative anterior ocular inflammation.Methods: Twenty - seven pigmented rabbits were divided into three groups. Group 1: transscleral fixation of posterior chamber (PC) IOL implantation;Group 2; Lens of rabbits was removed without IOL implantation; Group 3; the comtrol group, without surgical intervention. On the 1st, 3rd, 7th and 14th postoperative days,aqueous humor samples were obtained. An modified double antibodies indirect sandwich ELISA was used to detected for the presence of TNF. The data were analyzed by using analysis of variance of SAS software. Results: It was found that TNF level in aqueous humor was increased after transscleral fixation of IOL implantation. TNF level reached its maximum on the 14th postoperative day in the IOL implanted group. TNF level on 1st, 3rd, 7th and 14th days postoperatively was
文摘目的探讨行体外受精-胚胎移植(in vitro fertilization and embryo transfer,IVF-ET)助孕的多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者血清中补体C1q/肿瘤坏死因子相关蛋白9(complement C1q/tumour necrosis factor-related protein 9,CTRP9)、抗苗勒管激素(anti-mullerian hormone,AMH)对治疗结果的预测价值。方法选取2022年3月—2023年7月于重庆医科大学附属第一医院生殖中心行IVF-ET的85例PCOS患者。根据妊娠结局分为临床妊娠组43例与临床未妊娠组42例。记录2组患者的一般资料,测定血清CTRP9和AMH水平,分析其与妊娠结局的关系。结果临床未妊娠组血清CTRP9为(290.19±58.97)ng/mL,AMH为3.39(2.09,5.42)ng/mL,均低于临床妊娠组的(413.63±89.56)ng/mL、7.42(5.45,9.90)ng/mL(P<0.05)。血清CTRP9、AMH水平、优胚数是PCOS患者IVF-ET妊娠成功的保护因素(P<0.05)。血清CTRP9预测行IVF-ET的PCOS患者妊娠成功的敏感度与特异度为74.40%和90.50%,曲线下面积(area under the curve,AUC)值为0.836;血清AMH预测敏感度与特异度为83.70%和73.80%,AUC值为0.859;血清CTRP9和AMH联合预测的敏感度和特异度分别为88.40%和92.90%,AUC值为0.924,高于单独使用CTRP9或AMH预测的价值。结论血清CTRP9、AMH与PCOS患者IVF-ET治疗结局密切相关,且与单一指标检测比较,两者联合检测可提高预测价值。
基金Supported by Funding from the National Health and Medical Research Council of Australia,Nos.457575 and 632647 to Rangan GKthe Baltimore Polycystic Kidney Disease Research and Clinical Core Center,No.P30DK090868+2 种基金DK095036 to Watnick Tsupported by an Australian Postgraduate Award(University of Sydney)the Michael Stern Polycystic Kidney Disease Research Fellowship
文摘AIM： To determine the temporal expression and pattern of Rel/nuclear factor （NF）-κB proteins in renal tissue in polycystic kidney disease （PKD）. METHODS： The renal expression of Rel/NF-κB proteins was determined by immunohistochemistry, immunofuorescence and immunoblot analysis in Lewis polycystic kidney rats （LPK, a genetic ortholog of human nephronopthsis-9） from postnatal weeks 3 to 20. At each timepoint, renal disease progression and the mRNA expression of NF-κB-dependent genes （TNFa and CCL2） were determined. NF-κB was also histologically assessed in human PKD tissue.RESULTS： Progressive kidney enlargement in LPK rats was accompanied by increased renal cell proliferation and interstitial monocyte accumulation （peaking at weeks 3 and 10 respectively）, and progressive interstitial fibrosis （with a smooth muscle actin and Sirius Red deposition significantly increased compared to Lewis kidneys from weeks 3 to 6 onwards）. Rel/NF-κB proteins （phosphorylated-p105, p65, p50, c-Rel and RelB） were expressed in cystic epithelial cells （CECs） of LPK kidneys as early as postnatal week 3 and sustained until late-stage disease at week 20. From weeks 10 to 20, nuclear p65, p50, RelB and cytoplasmic IκBa protein levels, and TNFa and CCL2 expression, were upregulated in LPK compared to Lewis kidneys. NF-κB proteins were consistently expressed in CECs of human PKD. The DNA damage marker γ-H2AX was also identifed in the CECs of LPK and human polycystic kidneys. CONCLUSION： Several NF-κB proteins are consistently expressed in CECs in human and experimental PKD. These data suggest that the upregulation of both the canonical and non-canonical pathways of NF-κB signaling may be a constitutive and early pathological feature of cystic renal diseases.
文摘Background Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). A single nucleotide polymorphism (SNP) of tumour necrosis factor-α (TNF-α) has been reported but inconsistent results may arise from different populations and phenotypes of COPD. There are only a few published studies of interleukin-13 (IL-13) SNPs on COPD. The SNPs of TNF-α and IL-13 have not been studied in the Chinese population. This research was conducted to study the frequencies of IL-13 gene promoter 1055 (IL-13-1055) and TNF-α gene-308 polymorphisms in the patients with COPD and to investigate the effect of those genetic polymorphisms on COPD in the Chinese population.Methods A cohort of COPD patients and age matched controls were recruited from an inpatient hospital service in Beijing. Venous blood was obtained and genomic DNA was extracted from peripheral blood monocytes using standard method. Genomic DNA was used as a template for amplification by polymerase chain reaction (PCR) to determine the polymorphism at -1055 in the IL-13 gene promoter region. PCR restriction fragment length polymorphism (RFLP) was used to determine polymorphisms in the TNF-α gene-308 position. The products were investigated by sequence analysis also. Results One hundred and eleven COPD patients and 97 controls were studied. Seventy-five cases were current smokers in COPD patients and 36 were current smokers in controls. The frequencies of TT genotype in the IL-13 gene promoter region were 11.7% (13/111) in the COPD group and 13.4% (13/97) in the controls (P=0.713). However, the OR value of TT genotype was significantly increased to 6.4 (95% CI 1.62-25.39) in the smokers with COPD. TT genotype was also positively related to family history of COPD, OR=7.7 (95% CI 1.37-43.80). The frequencies of A allele in the TNF-α gene were 5.9% in COPD and 3.1% in controls (P=0.131). The OR value of A allele was 5.0 (95% CI 1.011 to 25.059) in smokers with COPD. Conclusions There is no significant difference in the frequencies of the TT genotype of IL-13-1055 or the A allele of the TNF-α between Han Chinese patients with COPD versus control. Thus, it does not appear that theseSNPs are independent factors in COPD for Han nationality in (Beijing. However,)these SNPs may increase the risk of COPD among smokers.
