Study of tumor necrosis factor receptor in the inflammatory bowel disease

Ulcerative colitis(UC)and Crohn’s disease(CD)are part of Inflammatory Bowel Diseases(IBD)and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells.In addition,the main inflammatory mediator is related to the tumor necrosis factor-alpha(TNF-α).TNF-αis a mediator of the intestinal inflammatory processes,thus being one of the main cytokines involved in the pathogenesis of IBD,however,its levels,when measured,are present in the serum of patients with IBD.In addition,TNF-αplays an important role in promoting inflammation,such as the production of interleukins(IL),for instance IL-1βand IL-6.There are two receptors for TNF as following:The tumor necrosis factor 1 receptor(TNFR1);and the tumor necrosis factor 2 receptor(TNFR2).They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity.The soluble TNF form binds to the TNFR1 receptor with,and its activation results in a signaling cascade effects such as apoptosis,cell proliferation and cytokine secretion.In contrast,the transmembrane TNF form can bind both to TNFR1 and TNFR2.Recent studies have suggested that TNF-αis one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD,since TNF levels are present in the serum of both patients with UC and CD.Intravenous and subcutaneous biologics targeting TNF-αhave revolutionized the treatment of IBD,thus becoming the best available agents to induce and maintain IBD remission.The application of antibodies aimed at neutralizing TNF-αin patients with IBD that induce a satisfactory clinical response in up to 60%of patients,and also induced long-term maintenance of disease remission in most patients.It has been suggested that anti-TNF-αagents inactivate the pro-inflammatory cytokine TNF-αby direct neutralization,i.e.,resulting in suppression of inflammation.However,anti-TNF-αantibodies perform more complex functions than a simple blockade.

Tumor necrosis factor-α and interleukin-6 in cirrhotic patients with spontaneous bacterial peritonitis

AIM: To evaluate the role of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis (SBP).

Interleukin-1β,Tumor Necrosis Factor-α and Lipopolysaccharide Induce Expression of Monocyte Chemoattractant Protein-1 in Calf Aortic Smooth Muscle Cells

Summary: To investigate whether interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) induce expression of monocyte chemoattractant protein-1 (MCP-1 ) mRNA and protein in calf aortic smooth muscle cells(SMCs), calf aortic SMCs were cultured by a substrate-attached explant method. The cultured SMCs were used between the third to the fifth passage. After the cells became confluent, the SMCs were exposed to 2 ng/ml IL-1β, 20ng/ml TNF-1α and 100 ng/ml LPS respectively, and the total RNA of SMCs which were incubated for 4 h at 37℃ were extracted from the cells by using guanidinium isothiocyanate method. The expres- ion of MCP-1 mRNA in SMCs was detected by using dot blotting analysis using a probe of γ-32 P- end-labelled 35-mer oligonucleotide. After a 24-h incubation, the media conditioned by the cul- tured SMCs were collected. The MCP-1 protein content in the conditioned media was determined by using sandwich ELISA. The results were as follows: Dot blotting analysis showed that the cul- tured SMCs could express MCP-1 mRNA. After a 4-h exposure to IL-1β, TNF-α and LPS, the MCP-1 mRNA expression in SMCs was increased (3.6-fold, 2. 3-fold and 1. 6-fold, respectively). ELISA showed that the levels of MCP-1 protein in the conditioned media were also increased (2.9- fold, 1.7-fold and 1.1-fold, respectively). The results suggest that calf aortic SMCs could ex- press MCP-1 mRNA and protein. IL-1β and TNF-α can induce strong expression of MCP-1 mRNA and protein, and the former is more effective than the latter.

Protective effect of curcumin on tumor necrosis factor-alpha-induced neuronal damage in the rat hippocampus A relationship to the inhibition of neuronal Ca^(2+) influx

BACKGROUND： Previous studies of curcumin have focused mainly on its cytotoxic properties for antitumor therapy. There are few studies addressing the application of curcumin in the prevention and treatment of nervous system diseases. OBJECTIVE： To observe the protective effect of curcumin against tumor necrosis factor-alpha （TNF-α）-induced neuronal damage in the rat hippocampus and to explore the intervention effect of curcumin on Ca^2＋ influx following neuronal damage. DESIGN, TIME AND SETTING： A cell morphological and physiological study was performed at the Institute of Brain Research, Medical College of Jinan University, China, from December 2006 to June 2007. MATERIALS： Curcumin （Sigma, USA） and TNF-α （Sigma, USA） were used in this study. METHODS： Hippocampal neurons were isolated from one-day neonatal rats and primarily cultured for 5 days. Following this they received 1 pmol/L curcumin and 100 ng/mL TNF-a pre-treatment. Dynamic morphological changes were observed for 1 hour by inverted microscopy. At 48 hours post-treatment, static morphological characteristics of the neurons were observed using inverted microscopy. Subsequently, hippocampal neurons were primarily cultured for 7 days, after receiving 1 pmol/L curcumJn and 4.5 ng/mL TNF-a pre-treatment. Intracellular free Ca^2＋ was measured using Fluo 3/acetoxymethyl ester. MAIN OUTCOME MEASURES： Effects of curcumin on TNF-a-induced neuronal damage and Ca^2＋ influx in the rat hippocampus were measured. RESULTS： Following curcumin treatment, TNF-a-induced neurons grew as normal. TNF-a induced a rapid Ca^2＋ influx into the neuronal cytoplasm; however, Ca2＋ fluorescence intensity only slightly increased when neurons were co-perfused with curcumin and TNF-α. CONCLUSION： Curcumin has a protective effect on rat hippocampal neurons possibly by reducing the TNF-α-induced rapid Ca^2＋ influx into neuronal cytoplasm and by maintaining the Ca^2＋ homeostasis.

Upregulation of stromal cell-derived factor-1 alpha/CXCR4 axis-induced migration of human neural progenitors by tumor necrosis factor-alpha and interleukin-8

BACKGROUND： Studies of several animal models of central nervous system diseases have shown that neural progenitor cells （NPCs） can migrate to injured tissues. Stromal cell-derived factor 1 alpha （SDF-la）, and its primary physiological receptor CXCR4, have been shown to contribute to this process. OBJECTIVE： To investigate migration efficacy of human NPCs toward a SDF-1α gradient, and the regulatory roles of tumor necrosis factor-α （TNF-α） and interleukin-8 （IL-8） in SDF-1α/CXCR4 axis-induced migration of NPCs. DESIGN, TIME AND SETTING： An in vitro, randomized, controlled, cellular and molecular biology study was performed at the Laboratory of Department of Cell Biology, Medical College of Soochow University between October 2005 and November 2007. MATERIALS： SDF-1α and mouse anti-human CXCR4 fusion antibody were purchased from R＆D Systems, USA. TNF-αwas purchased from Biomyx Technology, USA and IL-8 was kindly provided by the Biotechnology Research Institute of Soochow University. METHODS： NPCs isolated from forebrain tissue of 9 to 10-week-old human fetuses were cultured in vitro. The cells were incubated with 0, 20, and 40 ng/mL TNF-α, or 0, 20, and 40 ng/mL IL-8, for 48 hours prior to migration assay. For antibody-blocking experiments, cells were further pretreated with 0, 20, and 40 μg/mL mouse anti-human CXCR4 fusion antibody for 2 hours. Subsequently, the transwell assay and CXCR4 blockade experiments were performed to evaluate migration of human NPCs toward a SDF-1α gradient. Serum-free culture medium without SDF-1α served as the negative control. MAIN OUTCOME MEASURES： The transwell assay was performed to evaluate migration of human NPCs toward a SDF-1α gradient, which was blocked by fusion antibody against CXCR4. In addition, CXCR4 expression in human NPCs stimulated by TNF-α and IL-8 was measured by flow cytometry. RESULTS： Results from the transwell assay demonstrated that SDF-1α was a strong chemoattractant for human NPCs （P 〈 0.01）, and 20 ng/mL produced the highest levels of migration. Anti-human CXCR4 fusion antibody significantly blocked the chemotactic effect （P 〈 0.05）. Flow cytometry results showed that treatment with TNF-α and IL-8 resulted in increased CXCR4 expression and greater chemotaxis efficiency of NPCs towards SDF-1α（P 〈 0.01）. CONCLUSION： These results demonstrated that SDF-la significantly attracted NPCs in vitro, and neutralizing anti-CXCR4 antibody could block part of this chemotactic function. TNF-α and IL-8 increased chemotaxis efficiency of NPCs towards the SDF-1αgradient by upregulating CXCR4 expression in NPCs.

Elevated levels of interleukin-1β, interleukin-6, tumor necrosis factor-α and vascular endothelial growth factor in patients with knee articular cartilage injury

BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor (VEGF) are involved in the pathogenesis of keen articular cartilage injury remains poorly understood. AIM To measure the levels of inflammatory factors [IL-1β, IL-6, TNF-α and VEGF] in patients with knee articular cartilage injury. METHODS Fifty-five patients with knee articular cartilage injury were selected as patient groups, who were divided into three grades [mild (n = 20), moderate (n = 19) and severe (n = 16)] according to disease severity and X-ray examinations. Meanwhile, 30 healthy individuals who underwent physical examination were selected as the control group. The levels of IL-1β, IL-6, TNF-α and VEGF were measured by ELISA and immunohistochemical staining. RESULTS Compared with the control group, patient groups displayed significantly higher levels of IL-1β, IL-6, TNF-α and VEGF, and the extent of increase was directly proportional to the severity of injury (P < 0.05). In addition, the number of cells with positive staining of IL-1β, IL-6, TNF-α and VEGF in the synovial membrane were significantly increased, along with increased disease severity (P < 0.05). After treatment, the scores of visual analogue scale and the Western Ontario and McMaster University of Orthopaedic Index in patient groups were 2.26 ± 1.13 and 15.56 ± 7.12 points, respectively, which were significantly lower than those before treatment (6.98 ± 1.32 and 49.48 ± 8.96). Correlation analysis suggested that IL-1β and TNF-α were positively correlated with VEGF. CONCLUSION IL-1β, IL-6, TNF-α and VEGF levels are increased in patients with knee articular cartilage injury, and are associated with the disease severity, indicating they might play an important role in the occurrence and development of knee articular cartilage injury. Furthermore, therapeutically targeting them might be a novel approach for the treatment of keen articular cartilage injury.

Construction of murine interleukin-3 and murine tumor necrosis factor-α hepatoma-specific retroviral vectors and specific expression in the hepatoma cell lines

PSV23SMTNF and pSPMoIL-3 plasmids were cleaved to release murine interleukin-3 (mIL-3)and murine tumor necrosis factor (mTNF) complementary DNA (cDNA) resectively.The 3'terminal instable sequence of mIL-3 cDNA was deleted with Nco I digestion. Both cDNAs

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

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

Effects of erythropoietin on the expression of tumor necrosis factor-alpha and Bax after facial nerve axotomy in rats

This study sought to evaluate the effect of high-dose erythropoietin （EPO; 5 000 IU/kg） on the expression of tumor necrosis factor-alpha （TNF-α） and Bax in the facial nucleus after facial nerve transection in rats. A total of 42 Wistar rats of both genders were used in this study, and 40 rats were randomly divided into 2 groups： EPO group and model group. The EPO group was treated with EPO once a day for 5 days at a dose of 5 000 IU/kg body weight. The model group was treated with saline of the same amount. At day 3 after EPO （or saline） treatment, the right facial nerves of the 40 rats were transected at the level of the stylomastoid foramen, with the left sides untreated. The remaining 2 rats that did not undergo axotomy served as the control group. The surviving motor neurons in operated rats were counted in coronal paraffin sections of the facial nucleus. The expression of TNF-a and Bax in the facial nucleus was detected by immunohistochemical staining at days 3, 7, 14, 21, and 28 after axotomy. At days 14, 21, and 28 after facial nerve axotomy, a significantly greater proportion of facial motor neurons survived in the EPO group than in the model group. After axotomy, the expression of TNF-a and Bax increased in motor neurons in both the EPO and the model groups. TNF-o expression reached its peak level at day 14 after axotomy, while Bax expression reached its peak level at day 21. TNF-α expression was much lower in the EPO group than in the model group at all time points. No significant difference in Bax expression was found between the EPO and the model groups. These results indicate that high-dose EPO treatment attenuates the increase in TNF-α expression in the facial nucleus and reduces the loss of motor neurons after facial nerve transection in rats. However, high-dose EPO treatment has little effect on Bax expression.

Tumor necrosis factor alpha receptor 1 deficiency in hepatocytes does not protect from non-alcoholic steatohepatitis, but attenuates insulin resistance in mice

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.

Moxibustion Treatment Restoring the Intestinal Epithelium Barrier in Rats with Crohn's Disease by Down-Regulating Tumor Necrosis Factor Alpha,Tumor Necrosis Factor Receptor 1,and Tumor Necrosis Factor Receptor 2

Objective： To investigate whether moxibustion regulates tumor necrosis factor alpha （TNF-α）, tumor necrosis factor receptor 1 （TNFR1）, and TNFR2 in the intestinal mucosa and to explore whether moxibustion could be used by means of this mechanism, to repair the intestinal epithelium barrier disruption in Crohn＇s disease （CD）. Methods： The CD rat models were established by tdnitrobenzene sulfonic acid （TNBs）, randomly divided into a model control （MC） group, an herb-partition moxibustion （HPM） group, a mild-warm moxibustion （MWM） group, and a salicylazosulfapyridine （SASP） group, and all were compared with a normal control （NC） group. The HPM and MWM groups were treated by moxibustion at Tianshu （ST25） and Qihai （RN6） for 14 days, and the SASP group obtained the SASP solution orally for the same pedod of time. The intestinal epithelium morphology and TNF-α, TNFR1, and TNFR2 contents were observed by the transmission electron microscopy and enzyme linked immunosorbent assay. Results： The sevedty of morphological changes in CD intestinal epithelium was obviously improved, and the levels of TNF-α, TNFR1, and TNFR2 in the intestinal mucosa all significantly decreased in the HPM and MWM groups. However, there were no significant differences between the HPM and MWM groups. Conclusion： The moxibustion therapies （HPM and MWM） could reduce intestinal inflammation and restore intestinal epithelium barrier disruption in CD, which might be due to down- regulating TNF- α, TNFR1, and TNFR2 in intestinal mucosa and improving intestinal epithelium morphology.

Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor-induced interleukin-6 expression via human antigen R

Background Human antigen R （HuR） is a ubiquitously expressed member of the ELAV family, and has relatively high cytoplasmic abundance in lung tissue regenerating after injury. In this study, we investigated whether mitogen-activated protein kinase （MAPK）-activated protein kinase 2 （MK2） and HuR participate in the tumor necrosis factor （TNF）-induced expression of interleukin-6 （IL-6）. Methods Human pulmonary microvascular endothelial cells were treated with TNF following short interfering RNAmediated knockdown of MK2 or HuR. Cell supernatants were collected to detect the mRNA and protein expression of IL-6 at different time points, The expression and half-life of IL-6 mRNA were then determined in cells that had been treated with actinomycin D. Finally, after knockdown of MK2, the cytoplasmic expression of HuR protein was analyzed using Western blotting. Results MK2 or HuR knockdown decreased both the mRNA and protein expression of IL-6 in TNF-stimulated cells. In MK2 knockdown cells, the half-life of IL-6 mRNA was reduced to 36 minutes, compared with 67 minutes in the control group. In HuR knockdown cells, the half-life of IL-6 mRNA decreased from 62 minutes to 24 minutes. Further analysis revealed that knockdown of MK2 resulted in reduced HuR protein expression in the cytoplasm. Conclusions MK2 regulates the TNF-induced expression of IL-6 by influencing the cytoplasmic levels of HuR.

ENDOTOXIN-INDUCED LIVER INJURY AND CHANGES IN THE LEVELS OF PLASMA TUMOR NECROSIS FACTOR-α AND INTERLEUKIN-6 IN RABBITS

ELISA was employed to detect changes in plasma TNF-α and IL-6 level in rabbits having endotoxin-induced generalized Shwartzman reaction. Liver injury was assessed by the increase of serum ALT and hepatic histopathologic changes. The results showed that plasma TNF-α and IL-6 levels increased remarkably 12h after intravenous injection of endotoxin twice at a 24h interval, and these changes corresponded with the degree of liver injury. Coinjection of dexamethasone and endotoxin partly prevented the elevation of TNF-α and IL-6 levels and reduced liver injury. These results indicated that TNF-α and IL-6 were involved in endotoxin-induced liver injury.

Tumor necrosis factor a accelerates Hep-2 cells proliferation by suppressing TRPP2 expression

TRPP2, a Ca2＋-permeable non-selective cation channel, has been shown to negatively regulate cell cycle, but the mechanism underlying this regulation is unknown. Tumor necrosis factor a （TNF-a） is a proinflammatory cytokine extensively involved in immune system regulation, cell proliferation and cell survival. However, the effects and mechanisms for the role of TNF-a in laryngeal cancer remain unclear. Here, we demonstrated using western blot analyses and intracellular Ca〉 concentration measurements that TNF-a treatment suppressed both TRPP2 expression and ATP-induced Ca2＋ release in a laryngeal cancer cell line （Hep-2）. Knockdown of TRPP2 by a specific siRNA significantly decreased ATP-induced Ca2＋ release and abolished the effect of TNF-a on the ATP-induced Ca2＋ release. TNF-a treatment also enhanced Hep-2 cell proliferation and growth, as determined using cell counting and flow cytometry cell cycle assays. Moreover, TNF-a treatment down-regulated phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK） and phosphorylated eukaryotic translation initiation factor （p-elF2c0 expression levels, without affecting PERK and elF2ct expression levels in Hep-2 cells. We concluded that suppressing TRPP2 expression and TRPP2-mediated Ca2＋ signaling may be one mechanism underlying TNF〈t-enhanced Hep-2 cell proliferation. These results offer new insights into the mechanisms of TNF-a-mediated laryngeal cancer cell proliferation, and provide evidences showing a potential role of TNF-a in the development of laryngeal cancer.

Human immunodeficiency virus p24 antigen and antibody,herpes simplex virus-2 IgM and tumor necrosis factor alpha plasma levels in adult female children living in sing le-parent households:a case-control observational study

Objective: Human immunodeficiency virus (HIV) p24 antigen and antibody and herpes simplex virus 2 IgM are seromarkers indicating infection with HIV and herpes simplex virus-2 (HSV-2), respectively, whereas tumor necrosis factor α is an inflammatory biomarker that can be triggered by infections. Female children of single parents are faced with many socio-economic challenges that make them vulnerable to sexual influences and prone to sexually transmitted infections. The goal of this work was to determine HIV p24 antigen/antibody, HSV-2 IgM and tumor necrosis factor-α plasma levels in adult female children living in single-parent households.Methods: In this case-control observational study, 100 adult female children living with a single parent (50 living with a single mother and 50 living with a single father;age: 18-22 years) and 100 age-matched women living with both parents were recruited to serve as the test and control groups, respectively. All subjects were negative for acid-fast bacilli, plasmodium, hepatitis C virus, and hepatitis B virus. Human tumor necrosis factor α, HSV-2 IgM, antibody to hepatitis C virus, hepatitis B surface antigen and human immunodeficiency virus p24 antigen and antibody (HIV p24 Ag/Ab) levels were determined by ELISA, while the detection of acid-fast bacilli in sputum andPlasmodium in blood was carried out by optical microscopy. This work was carried out in the Owo/Ose Federal Constituency in Ondo State that shares boundaries with Edo State. The study protocol was approved by the Research and Ethical Committee of the Department of Medical Laboratory Science, Achievers University, Owo, Nigeria (AUO/MLS/2020/127) on August 27, 2020.Results: HIV p24 Ag/Ab was detected in 0 adult female children living with a single mother, 1 (2%) adult female child living with a single father and 1 (1 %) adult female child living with both parents. HSV-2 IgM was detected in 9 (18%) adult female children living with a single mother, 13 (26%) adult female children living with a single father, and 5 (10%) adult female children living with both parents.Conclusion: This work shows that adult female children of single parents are vulnerable to sexual influences, and thereby more prone to HSV-2 and possibly HIV, especially adult female children of single fathers.

Effects of Puerarin on Plasma Endothelin and Serum Tumor Necrosis Factor-α in Type 2 Diabetes Mellitus Patients with Vascular Complications

Objective: To study the changes of endothelin (ET), tumor necrosis factor-α (TNF-α) before and after puerarin treatment in patients with diabetes mellitus vascular complications (DMVC). Methods: Ninety-eight DMVC patients were divided into 2 groups, they were given puerarin (n=68) and normal saline (n=30) respectively, 20 diabetic patients without vascular complications (NDMVC) were taken as control, who were also given puerarin. All the patients were treated on the basis of controlling blood glucose. Plasma ET and serum TNF-α were determined by radioimmunoassay (RIA) before and after treatment. Results: Plasma ET and serum TNF-α in DMVC got higher than that of NDMVC patients (P<0.05), and ET level was correlated with TNF-α (r=0.69, r=0.73, P<0.01). After treatment, the levels of ET and TNF-α were significantly lower than those before treatment of DMVC patients with puerarin (P<0.05). Conclusion: Puerarin could regulate the levels of plasma ET and serum TNF-α of DMVC patients, suggesting that it has the function of regulating endothelial cells.

Effect of Zhuyeshigao granule on tumor necrosis factor-α and inter leukins serum protein levels in rats with radiation esophagitis

OBJECTIVE： To investigate the effects of Zhuyesh- igao granule （ZSG） on tumor necrosis factor-a （TNF-a）, interleukin-1 （IL-1）, IL-2, IL-6, and IL-8 in rats with radiation esophagitis. METHODS： Fifty Wistar rats were randomly divid- ed into five groups （10 rats in each group）： con- trol （without radiation）, saline-treated, and low, medium, and high-dose ISG-treated groups. Rats were given normal saline （10 mL/kg） or 1.15, 2.3, or 4.6 g/kg ZSG by intragastric administration once a day for 7 days. A rat model of radiation esophagi- tis was established by local irradiation of Co60 （490.25 cGy/min, totaling 30 Gy）. The administra- tion of ZSG was continued for another 7 days and on the 7th day post-irradiation, inferior vena cavablood was collected. The serum was separated, and TNF-a, IL-1, IL-2, 11_-6, and IL-8 protein levels were determined. RESULTS： Inflammatory response factors were found in the serum of each group. However, levels in ZSG-treated groups were significantly lower than in the saline-treated group （P〈0.05）. CONCLUSION： ZSG may prevent the development of radiation esophagitis, perhaps by inhibiting the generation and release of the inflammatory re- sponse factors TNF-a, IL-1, IL-2, IL-6, and IL-8.

Prevention of Tumor Necrosis Factor-α Induced Insulin Resistance by Radix Astragali

Objective: To investigate the preventive effect of Radix Astragali on tumor necrosis factor-α(TNF-α). induced insulin resistance. Methods: Rats were treated orally with Radix Astragali before TNF-α intravenous injection. The changes of K value in glucose-insulin tolerance test, the concentrations of glucagon(GC), ACTH and lipids in serum and the contents of glycogen, triglyceride (TG) in liver and red quadricepswere tested 4 hours after the injection and compared with the control. Results: Exogenous TNF-α can inducehyperinsulinemia in normal rats, and the K value decreased, the concentration of serum ACTH, GC and lipidsall increased, the glycogen contents in liver and red quadriceps muscle decreased, and the liver TG depots increased. Radix Astragali can improve all the parameters significantly except the serum lipids level and livertriglyceride dePOts. Conclusions: Radix Astragali has preventive effect on insulin resistance induced by TNF-αand is useful in the treatment of type 2 diabetes. The mechanism may be due to the decrease of insulin-antagonistic hormones and the increase of tissue glycogen contents.

清燥救肺汤联合痰热清注射液防治放射性肺损伤的临床疗效及对免疫指标、IL-2和TNF-α表达的影响

目的探讨清燥救肺汤联合痰热清注射液防治放射性肺损伤的临床疗效及对免疫指标、白细胞介素-2(interleukin-2,IL-2)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)表达的影响。方法选择2020年9月~2022年12月在唐山市人民医院放化科接受胸部三维适形放射治疗的肺癌患者100例,随机分为对照组和治疗组各50例。对照组采用单纯放疗,治疗组在对照组基础上给予清燥救肺汤联合痰热清注射液。放疗结束后3个月比较两组近期疗效、放射性肺炎和不良反应发生情况,及放疗前与放疗结束后3个月生存质量、免疫指标、IL-2和TNF-α水平变化。结果治疗组近期有效率高于对照组(P<0.05)。2组放疗结束后3个月卡氏功能状态(karnofsky performance status,KPS)评分高于放疗前(P<0.05);治疗组放疗结束后3个月KPS评分改善情况优于对照组(P<0.05)。2组放疗结束后3个月中医证候积分均低于放疗前(P<0.05);治疗组放疗结束后3个月中医证候积分改善优于对照组(P<0.05)。治疗组患者放疗结束后3个月CD3+、CD4+和CD4+/CD8+高于放疗前(P<0.05),改善情况优于对照组(P<0.05),对照组患者放疗结束后3个月CD3+、CD4+/CD8+较放疗前无明显变化(P>0.05)。2组患者放疗结束后3个月血清IL-2水平高于放疗前,而TNF-α水平低于放疗前(P<0.05);治疗组患者放疗结束后3个月血清IL-2水平和TNF-α水平改善情况均优于对照组(P<0.05)。2组不良反应发生情况比较差异无统计学意义(P>0.05)。结论清燥救肺汤联合痰热清注射液可明显降低放射性肺炎发生率,改善部分免疫指标水平,减轻细胞炎性反应。

外周血sIL-2R、CD4^(+)/CD8^(+)、TNF-α对初治活动性肺结核老年患者化疗疗效的评估价值

目的探讨外周血可溶性白细胞介素2受体(sIL-2R)、CD4^(+)淋巴细胞百分比/CD8^(+)淋巴细胞百分比比值(下称CD4^(+)/CD8^(+))、肿瘤坏死因子-α(TNF-α)对初治活动性肺结核老年患者化疗疗效的评估价值。方法将2019年12月至2022年12月该院收治的102例初治活动性肺结核老年患者纳入研究作为观察组,另选取102例年龄≥60岁且同期于该院体检的健康者作为对照组。比较两组外周血sIL-2R、TNF-α、CD4^(+)/CD8^(+)水平并分析sIL-2R、TNF-α、CD4^(+)/CD8^(+)间的相关性。观察组均采用2HRZE/4HR抗结核治疗方案,比较观察组治疗前、治疗1个月、治疗6个月时不同疗效患者外周血sIL-2R、TNF-α、CD4^(+)/CD8^(+);分析sIL-2R、CD4^(+)/CD8^(+)、TNF-α水平与疗效的相关性;采用受试者工作特征(ROC)曲线分析各指标用于老年患者化疗疗效评估的效能。结果观察组sIL-2R、TNF-α水平高于对照组,而CD4^(+)/CD8^(+)低于对照组,差异均有统计学意义(P<0.05)。观察组sIL-2R、TNF-α与CD4^(+)/CD8^(+)呈负相关(P<0.05),sIL-2R与TNF-α呈正相关(P<0.05)。治疗1个月、治疗6个月时显效患者sIL-2R、TNF-α水平低于有效患者,而后者又低于无效患者,显效患者CD4^(+)/CD8^(+)高于有效患者,而后者又高于无效患者,差异均有统计学意义(P<0.05)。sIL-2R、TNF-α水平与疗效呈负相关(P<0.05),CD4^(+)/CD8^(+)与疗效呈正相关(P<0.05)。ROC曲线分析显示,治疗1个月、6个月时sIL-2R、CD4^(+)/CD8^(+)、TNF-α联合用于评估疗效的曲线下面积(AUC)明显大于各时间点单项指标用于评估的AUC(P<0.05),而且治疗6个月时各指标联合评估的AUC大于治疗1个月(P<0.05)。结论初治活动性肺结核老年患者sIL-2R、CD4^(+)/CD8^(+)、TNF-α水平与患者疗效密切相关,将以上指标联合用于评估患者化疗疗效具有一定参考价值。