Objective To investigate the effects of one-lung ventilation time on the concentration of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the bronchoalveolar lavage fluid (BALF), serum inflammatory markers and early pulmonary infection after radical resection of esophageal cancer. Methods Ninety patients with thoracoscope and laparoscopic radical resection of esophageal carcinoma were chosen. According to the thoracoscope operation time, the patients were divided into 3 groups including a T1 (0.5–1.5 hours) group, a T2 (1.5–2.5 hours) group and a T3 (>2.5 hours) group. Immediately after the operation, the ventilated and collapsed BALF were taken. Enzyme-linked immunosorbent assay (ELISA) method was used to determine the concentration of IL-6 and tumour necrosis TNF-α. The concentrations of procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) were measured on the first, third, fifth day after operation. The incidence of pulmonary infection was observed within 3 days after operation. Result The IL-6 values of the right collapsed lung in all groups were higher than those in the left ventilated lung. The TNF-α value of the right collapsed lung in the T2 group and T3 group was higher than that in the left ventilated lung (P<0.05). Compared with in the right collapsed lung, the TNF-α and IL-6 values gradually increased with the the duration of one-lung ventilation (P<0.05). Compared with the left ventilated lung groups, the IL-6 value increased gradually with the duration of one-lung ventilation time (P<0.05). The TNF-α value of the T3 group was higher than that of the T1 and T2 groups (P<0.05). The PCT value of the T3 group was higher than that of the T1 group and T2 group on the third, fifth day after operation (P<0.05). But there was no significant difference in CRP and WBC among the three groups at different time points. The incidence of pulmonary infection in the T3 group was significantly higher than that in the T1 group within 3 days after operation (P<0.05). Conclusion With the extension of one-lung ventilation time, the release of local and systemic inflammatory mediators is increased, and the probability of pulmonary infection is higher.
Objective To investigate the effect of heme oxygenase 1 (HO-1) on the apoptosis of human degenerated nucleus pulposus (NP) cells induced by tumor necrosis factor α (TNF-α), and explore its possible molecular mechanism. Methods The intervertebral disc tissues were derived from patients with lumbar intervertebral disc herniation. Then, the NP cells were cultured in vitro and the third generation of NP cells were used for subsequent experiments. Cell counting kit 8 (CCK-8) method was used to observe the proliferative effect of TNF-α on the NP cells in vitro at the concentration of 10, 20, 50, 100, and 200 ng/mL. The most apropriate concentration was selected according to the result of CCK-8. The NP cells were cultured with basal medium (control group), TNF-α (TNF-α group), TNF-α and CoPP 10 μmol/L (CoPP group), and TNF-α and ZnPP 15 μmol/L (ZnPP group), respectively. After cultured, the cell poptosis was detected by Hoechst staining and flow cytometry; the expression of cleaved Caspase-3, epithelial membrane protein 1 (EMP-1), HO-1, and p-P65 proteins were detected by Western blot. In order to further explore the potential molecular mechanisms of HO-1 for cell apoptosis, the NP cells were cultured with TNF-α (TNF-α stimulated group), TNF-α and pyrrolidine dithiocarbamate (PDTC) 5 μmol/L (TNF-α+PDTC stimulated group), respectively. Then the cell apoptosis rate was measured by flow cytometry at 24 hours after cultured. Results The optimal concentration of TNF-α was 100 ng/mL. Hoechst staining showed that a few apoptotic cells could be observed in control group and CoPP group; the apoptosis-like nucleis were observed in TNF-α group and ZnPP group, which was the most significant in ZnPP group. Flow cytometry showed that the cell apoptosis rates of TNF-α group, CoPP group, and ZnPP group were significantly increased when compared with the control group (P<0.05). Compared with TNF-α group, the cell apoptosis rate in CoPP group decreased (P<0.05), while in ZnPP group it increased (P<0.05). Western blot showed that the expression of HO-1 protein in TNF-α group was decreased, and the expressions of cleaved Caspase-3, EMP-1, and p-P65 proteins were increased when compared with the control group (P<0.05). Compared with TNF-α group, the expression of HO-1 protein in CoPP group increased, and the expressions of cleaved Caspase-3, EMP-1, and p-P65 proteins were reduced (P<0.05); the expression of HO-1 protein in ZnPP group decreased (P<0.05), the expressions of cleaved Caspase-3 and EMP-1 proteins increased (P<0.05), and the expression of p-P65 protein was not significantly changed (P>0.05). Compared with TNF-α stimulated group, the cell apoptosis rate in TNF-α+PDTC stimulated group was significantly reduced (t=3.076, P=0.031). Conclusion HO-1 can inhibit the apoptosis of degerated NP cells induced by TNF-α, and its mechanism effect is by inhibiting the nuclear factor кB signaling pathway.
The incidence of depression in patients with rheumatoid arthritis is higher. The concomitant depression will increase medical expense, reduce drug efficacy, lower its compliance, increase the incidence of complication, and affect the cure of rheumatoid arthritis. The influence of depression to rheumatoid arthritis is usually ignored in clinical work. In recent years, the pertinence between depression and immune disease in pathogenesis is found in research: depression will increase the risk of immune diseases in activate inflammation as well as extend and promote the release of inflammatory factors. This article reviews research progress of correlation between depression and rheumatoid arthritis.
ObjectiveTo investigate the efficacy and safety of recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein (rhTNFR:Fc) for treatment of active rheumatoid arthritis (RA). MethodsThis study included 86 patients with active rheumatoid arthritis treated between September 2011 and January 2013. They were divided into two groups randomly. Forty-three patients in the treatment group received rhTNFR:Fc (25 mg, twice a week) by subcutaneous injection and methotrexate (MTX) (10 mg, orally once a week), and the other 43 patients in the contrast group received MTX (10 mg, orally once a week), hydroxychloroquine (100 mg, orally twice daily), and leflunomide (10 mg, orally once daily). The clinical efficacy of the treatments 12 weeks later were compared between the two groups. American College of Rheumatology (ACR) 20, 50, and 70 evaluation criteria were used for efficacy evaluation. ResultsThe ACR 20, 50 and 70 effective rates in 4, 8 and 12 weeks after the treatment in the treatment group were significantly higher than those in the control group (P<0.05). The seven indicators including the duration of morning stiffness, joint tenderness index, joint swelling index, erythrocyte sedimentation rate, C-reactive protein, platelets and rheumatoid factors within 12 weeks after treatment were significantly improved in both the two groups, and the improvements in the treatment group were more significant (P<0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups (P>0.05). ConclusionRhTNFR:Fc is effecive and safe in treating active RA.
摘要:目的: 研究蛻皮甾酮對非酒精性脂肪性肝病大鼠模型腫瘤壞死因子α(TNFα)與核因子κB(NFκB)表達的影響，并探索其可能的作用機制。 方法 :健康成年SD大鼠36只,隨機分為正常對照組12只與實驗組24只;正常對照組喂以普通基礎飼料,實驗組應用高脂飼料喂養。實驗12周末時將造模成功的實驗組大鼠隨機分為模型組與蛻皮甾酮治療組2個亞組,每組12只;正常對照組喂以普通基礎飼料至16周,模型組繼續應用改良高脂飼料喂養至16周,蛻皮甾酮治療組大鼠在高脂飲食同時加用蛻皮甾酮灌胃。實驗16周末時處死3組所有大鼠;檢測肝臟指數,血清與肝組織生化指標及肝組織病理改變;ELISA法檢測肝臟TNFα水平;免疫組化檢測各組大鼠肝組織中核因子κB蛋白表達情況。 結果 :蛻皮甾酮治療組血清膽固醇(TC)、丙氨酸氨基轉移酶(ALT)和天門冬氨酸氨基轉移酶(AST)明顯低于模型組(212±058比263±024,Plt;005;5336±1848比8460±3627,P＜005;14020±3595比24359±3638,P＜001);蛻皮甾酮治療組與模型組相比肝組織丙二醛(MDA)水平降低明顯(18454±1645比23928±2376,P＜001),超氧化物歧化酶(SOD)活力增加顯著(942±052比518±043,P＜001),肝臟指數顯著降低(435±037比504±046,P＜001)，肝組織脂肪變性程度和炎癥活動度明顯減輕(546±037比630±049,P＜001)。蛻皮甾酮治療組與模型組相比TNFα與核因子κB水平明顯減輕(4304±748比6156±727,2465±539比4504±746,P值均＜001)。 結論 :蛻皮甾酮具有改善高脂飲食誘發的非酒精性脂肪性肝病大鼠肝臟酶學功能,通過增加肝組織SOD的含量和減少MDA的含量來減輕肝組織氧化應激水平,減輕肝組織TNFα和核因子κB來減輕肝臟炎癥,發揮防治非酒精性脂肪性肝病的作用。Abstract: Objective: To investigate the effect and possible mechanism of ecdysterone on the expression of tumor necrosis factoralpha (TNFα) and nuclear factor κ B (NFκB) in rats with nonalcoholic fatty liver disease of rats. Methods : A total of 36 male Sprague Dawley rats were randomly divided into two groups, who were fed with highfat diet (experimental group, n=24) and normal basic food (normal control, n=12) respectively. At the end of the 12th week, the experimental group was randomly divided into two subgroups: model group and ecdysterone group, each group contained 12 rats. From the 13th week, the rats in the normal control group and model group were lavaged with normal sodium, and the rats in the ecdysterone group were lavaged with ecdysterone at 10 mg·kg-1·d-1. At the end of the 16th week, all rats were weighed, narcotized, sacrificed, and the liver index, biochemical indicators in serum and liver tissues and the hepatic pathological changes were observed. The expression of TNFα was detected by ELISA and the expression of NFκB was measured by immunohistochemical staining. Results : At the end 16th week in ecdysterone group, the serum levels of cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were reduced markedly (212±058 vs 263±024 and 5336±1848 vs 8460±3627, both P＜005; 14020±3595 vs 24359±3638, P＜001); the tissue content of malondialdehyde (MDA) was decreased evidently (18454±1645 vs 23928±2376, P＜001), while the activity of superoxide dismutase (SOD) was enhanced notably (942±052 vs 518±043, P＜001); the liver index was decreased significantly in comparison with that inmodel group (435±037 vs 504±046, P＜001); the degree of fatty degeneration and inflammation were relieved dramatically (546±037 vs 630±049, P＜001). The expression of TNFα and the levels of NFκB were significantly lower (4304±748 vs 6156±727 and 2465±539 vs 4504±746, both P＜001) in ecdysterone group compared with model group. Conclusion : The effects of ecdysterone in preventing NAFLD in rats could be related to the increase of SOD content in hepatic tissue and the decrease of MDA content, tumor necrosis factorα and NFκB.
Objective To investigate effect of different resuscitation liquids and different resuscitation methods on contents of interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) in early resuscitation process of rats with traumatic hemorrhagic shock. Methods Sixty-four healthy SD rats (450–550 g) were chosen and divided into 4 groups randomly and averagely: crystal liquid limited resuscitation group, colloidal liquid limited resuscitation group, 7.5% NaCl limited resuscitation group, and colloidal liquid non-limited resuscitation group. There were 16 rats in each group. All the experimental rats were weighed before intraperitoneal injection of pentobarbital sodium anesthesia. Animal model was established via Chaudry’s method. The rats were killed and the abdominal aorta bloods were drew on hour 2, 6, 12, and 24 after recovering from anesthesia. The contents of IL-8 and TNF-α in plasmas were detected by enzyme linked immunosorbent assay. Results The contents of IL-8 and TNF-α among three kinds of limited resuscitation groups on hour 6 after resuscitation were significantly higher than those on hour 2 after resuscitation (P<0.05) and reached the peaks, then began to decrease. On hour 12 after resuscitation, the contents of IL-8 and TNF-α were decreased continuously among three kinds of limited resuscitation groups (P<0.05). The contents of IL-8 and TNF-α in the colloidal liquid non-limited resuscitation group at each point time were significantly higher than those among three kinds of limited resuscitation groups (P<0.05), which in the crystal liquid resuscitation group were significantly lower than those in the other limited liquid resuscitation groups (P<0.05). Conclusions In process of liquid resuscitation of rats with traumatic hemorrhagic shock, limited resuscitation method is better than that of non-limited resuscitation method. Among three kinds of limited resuscitation methods, crystal resuscitation liquid is more effective than the other two resuscitation liquids in prohibiting releases of IL-8 and TNF-α in rats with traumatic hemorrhagic shock.
As a new treatment option after conventional corticosteroids and immunomodulatory drugs, biologics have been widely used in the clinical management of non-infectious uveitis in many countries due to their approved efficacy and safety. Anti-tumor necrosis factor-alpha monoclonal antibody is the most commonly used one. However, the guidance on its standardized application is lacking. The Ocular Immunology Group of Immunology and Rheumatology Academy in Cross-Straits Medicine Exchange Association compiled the Chinese expert consensus on treatment of non-infectious uveitis with anti-tumor necrosis factor-alpha monoclonal antibody. This evidence-based consensus is made according to the principle of consensus building and combines the clinical experience of the experts. Twelve recommendations are formatted on the application of Adalimumab and Infliximab. The interpretation of this consensus point will help improve the normative and effective application of anti-tumor necrosis factor-alpha monoclonal antibody in ophthalmologists, rheumatologists and immunologists.
The gut mucus barrier and mechanical barrier are the most important natural barriers, the former is the first defense barrier, which separates pathogenic bacteria in intestinal lumen from the epithelial cells, and prevents them passing through the intestinal barrier into the human circulation system. Studies have shown that inflammation in the body affects the content of mucin 2, a key protein in the mucus layer, thereby changing the permeability of the mucus barrier and promoting the translocation of pathogenic microorganisms. Both tumor necrosis factor-α and c-jun N-terminal kinase signaling pathways have been reported to be closely related to the occurrence and development of inflammation. Therefore, this article reviews the relationship between tumor necrosis factor-α, c-jun N-terminal kinase signaling pathway and mucin 2 and intestinal barrier dysfunction, in order to provide new ideas and directions for exploring the related research of intestinal barrier function.
ObjectiveTo explore the effects of interleukin 10 (IL-10) gene modified bone marrow mesenchymal stem cells (BMSCs) on the expression of inflammatory cytokines and neuronal apoptosis in rats after cerebral ischemia reperfusion injury.MethodsBMSCs were cultured by whole bone marrow adherence screening method. The properties of BMSCs were identified by immunocytochemical methods. BMSCs at passage 3 were transfected with recombinant adenovirus IL-10 gene (AdIL-10-BMSCs). The model of middle cerebral artery occlusion was made in 40 adult male Sprague Dawley rats by thread embolism method. The rats were randomly divided into 4 groups (n=10). At 3 hours after modelling, the rats of groups A, B, C, and D received tail intravenous injection of 1 mL L-DMEM medium containing 10% FBS, 61.78 ng IL-10, 1 mL BMSCs suspension (2×106 cells/mL), and 1 mL AdIL-10-BMSCs cell suspension (2×106 cells/mL), respectively. The cells were labelled with BrdU before cell transplantation in groups C and D. At 7 days after reperfusion, the brain tissue was harvested to detect the expression of OX42 by immunohistochemical assay, to determine the concentration of tumor necrosis factor α (TNF-α) and IL-1β by ELISA, and to detect the apoptosis by TUNEL assay. BrdU labelled cells were observed by immunofluorescence staining in groups C and D.ResultsBrdU labelled positive cells with green fluorescence were observed in the brain tissue of groups C and D, which mainly distributed in the striatum, cerebral cortex, and subcortex around the infarction area. The number of OX42 positive cells was significantly less in groups B, C, and D than group A (P<0.05), and in group D than groups B and C (P<0.05). Compared with the other 3 groups, the contents of TNF-α and IL-1β significantly decreased in group D (P<0.05). TUNEL assay showed that the apoptotic cells (TUNEL positive cells) were mainly seen in the striatum and fronto parietal subcortical tissues (equivalent to ischemic penumbra). The number of TUNEL positive cells in group D was significantly less than that in groups A, B, and C (P<0.05).ConclusionAdIL-10-BMSCs can inhibit secretion of TNF-α and IL-1β from microglial cells and inhibit the nerve cell apoptosis around infarct brain tissue, which might contribute to its protective role upon cerebral ischemia reperfusion injury.
The aim of this article is to study the effect of tumor necrosis factor alpha (TNF-α) on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in keratoconus fibroblasts in vitro. Normal cornea and keratoconus fibroblasts were extracted using enzyme digestion method and were cultured in the medium containing TNF-α (0, 10 and 100 ng/mL). The expression of MMPs proteins in the supernatant of corneal fibroblasts and the expression of TIMPs in the normal cornea and keratoconus fibroblasts were detected by Western blot and real-time quantitative polymerase chain reaction respectively. The active form of MMP1 could be detected in the supernatant of keratoconus fibroblasts and upregulated by TNF-α. TNF-α could increase the protein expression of MMP2, MMP3, MMP9 in the supernatant of keratoconus fibroblasts and decrease the gene expression of TIMP1, TIMP2 in keratoconus fibroblasts. The increased MMPs and the decreased TIMPs can increase the degradation of the extracellular matrix. TNF-α may play an important role in the occurrence and development of keratoconus by regulating the expression of MMPs/TIMPs.