Effective Components of Periploca forrestii Against Rheumatoid Arthritis by Targeting TNF-α / 中国实验方剂学杂志

ObjectiveTo analyze the effective components of Periploca forrestii against rheumatoid arthritis（RA）by targeting tumor necrosis factor （TNF）-α based on network pharmacology and experimental verification. MethodThe preliminary research of the research group found that the alcohol extracts of P. forrestii （CDLF and CQAF） had significant anti-RA activities，and 10 monomers with such activities were identified. The anti-RA activities of active monomers，CDLF， and CQAF were compared by the enzyme-linked immunosorbent assay （ELISA）with interleukin（IL）-6，nitric oxide （NO），IL-1β， and prostaglandin E2（PGE2）as indicators. Network pharmacology was employed to analyze the possible molecular mechanism of P. forrestii against RA. The targeting ability of P. forrestii chemical monomers to TNF-α was verified by TNF-α molecular docking，surface plasmon resonance （SPR）， and TNF-α-induced L929 injury model. ResultELISA showed that the anti-RA activities of CDLF and CQAF were significantly stronger than those of identified 10 active monomers. Network pharmacology analysis showed that the core targets of P. forrestii against RA were signal transducer and activator of transcription protein 3 （STAT3），TNF， and IL-6. Gene Ontology（GO） analysis revealed collagen catabolism，inflammatory response，positive regulation of nuclear factor kappa-B（NF-κB） transcription factor activity，and positive regulation of B cell proliferation. Kyoto Encyclopedia of Genes and Genomes （EKGG） pathway enrichment analysis demonstrated TNF signaling pathway，phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway，NF-κB signaling pathway，Toll-like receptor signaling pathway，mitogen-activated protein kinase（MAPK） signaling pathway， etc. Verification experiments by TNF-α molecular docking，SPR， and TNF-α-induced L929 injury model found that CDLF and CQAF had good binding activities and could manifestly antagonize TNF-α. However， the active components separated and identified from CDLF and CQAF did not show the same anti-TNF-α activity. ConclusionThe CDLF and CQAF of P. forrestii may treat RA by targeting TNF-α. The experiments found that the isolated chemical components had weaker binding activity to TNF-α than CDLF and CQAF. Meanwhile，the research group isolated chemical components with a minimum mass fraction of 0.25 ng·g-1 from P. forrestii， which suggested that the active components generated by binding to TNF-α with anti-RA activities were presumedly trace components .

Therapeutic Effect of Gegentang Granules on Mouse Model with hCoV-229E Pneumonia and Hanshi Yidu Xifei Syndrome / 中国实验方剂学杂志

ObjectiveTo determine the therapeutic effect of Gegentang granules on a disease-syndrome mouse model combining human coronavirus 229E （hCoV-229E） pneumonia with Hanshi Yidu Xifei syndrome in vivo. MethodMice were randomly divided into normal group， infection group， cold-dampness group， model group， chloroquine phosphate group （0.18 g·kg-1）， interferon-α2b （IFN-α2b） group （1.83×106 U·kg-1）， Gegentang granules high-dose and low-dose groups （6.6， 3.3 g·kg-1） with 10 mice in each group. Cold-dampness environment and hCoV-229E infection were used for modeling， and the general status and lung index of mice in each group were observed. The viral load in lung tissue was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， the pathological changes in lung tissue were evaluated by hematoxylin-eosin （HE） staining， the levels of serum gastrointestinal hormones and inflammatory factors in lung tissue were detected by enzyme-linked immunosorbent assay （ELISA）， and the percentage of peripheral blood lymphocytes was detected by flow cytometry. ResultComparing with model group， Gegentang granules could significantly alleviate the physical signs of Hanshi Yidu Xifei syndrome， including listlessness， weakness of limbs， sticky stool， etc. Comparing with model group， Gegentang granules high-dose group significantly reduced lung index， histopathological score of interstitial lung and bronchus， and the level of serum motilin （P<0.05， P<0.01）， two doses of Gegentang granules could significantly increase the level of serum gastrin （P<0.05， P<0.01）， the percentage of CD4+， CD8+ T lymphocytes in peripheral blood （P<0.05， P<0.01）， and the level of tumor necrosis factor-α （TNF-α） in lung tissue was significantly decreased （P<0.01）， and the level of interleukin-6 （IL-6） showed decreasing tendency. ConclusionGegentang granules has therapeutic effect on model mice. It can improve the appearance and behavior characterization， regulate the level of gastrointestinal hormones， decrease lung index and histopathological score， and possibly play an immunomodulatory role by inhibiting the expression of inflammatory cytokines in lung tissue and restoring the percentage of peripheral blood lymphocytes.

Therapeutic Effect of Gegentang Granules on Mouse Model with hCoV-229E Pneumonia and Hanshi Yidu Xifei Syndrome / 中国实验方剂学杂志

ObjectiveTo determine the therapeutic effect of Gegentang granules on a disease-syndrome mouse model combining human coronavirus 229E （hCoV-229E） pneumonia with Hanshi Yidu Xifei syndrome in vivo. MethodMice were randomly divided into normal group， infection group， cold-dampness group， model group， chloroquine phosphate group （0.18 g·kg-1）， interferon-α2b （IFN-α2b） group （1.83×106 U·kg-1）， Gegentang granules high-dose and low-dose groups （6.6， 3.3 g·kg-1） with 10 mice in each group. Cold-dampness environment and hCoV-229E infection were used for modeling， and the general status and lung index of mice in each group were observed. The viral load in lung tissue was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， the pathological changes in lung tissue were evaluated by hematoxylin-eosin （HE） staining， the levels of serum gastrointestinal hormones and inflammatory factors in lung tissue were detected by enzyme-linked immunosorbent assay （ELISA）， and the percentage of peripheral blood lymphocytes was detected by flow cytometry. ResultComparing with model group， Gegentang granules could significantly alleviate the physical signs of Hanshi Yidu Xifei syndrome， including listlessness， weakness of limbs， sticky stool， etc. Comparing with model group， Gegentang granules high-dose group significantly reduced lung index， histopathological score of interstitial lung and bronchus， and the level of serum motilin （P<0.05， P<0.01）， two doses of Gegentang granules could significantly increase the level of serum gastrin （P<0.05， P<0.01）， the percentage of CD4+， CD8+ T lymphocytes in peripheral blood （P<0.05， P<0.01）， and the level of tumor necrosis factor-α （TNF-α） in lung tissue was significantly decreased （P<0.01）， and the level of interleukin-6 （IL-6） showed decreasing tendency. ConclusionGegentang granules has therapeutic effect on model mice. It can improve the appearance and behavior characterization， regulate the level of gastrointestinal hormones， decrease lung index and histopathological score， and possibly play an immunomodulatory role by inhibiting the expression of inflammatory cytokines in lung tissue and restoring the percentage of peripheral blood lymphocytes.

The research of brain glioma therapy for nude mouse using transgenic human umbilical cord mesenchymal stem cells overexpressing TRAIL / 中国输血杂志

【Objective】 To explore the establishment methods of transgenic human umbilical cord mesenchymal stem cells (hUC-MSCs) overexpressing tumor necrosis factor(TNF)-related apoptosis-inducing ligand (TRAIL) based on the transposons, and attempt to apply it on the nude mice mode with glioma. 【Methods】 PiggyBac transposon system specially designed by us was used to prepare non-targeting and Her2-targeting hUC-MSCs that can stably express TRAIL through puromycin screening. The glioma cells expressing firefly luciferase (U87MG-LUC) were injected into the skull of the immunodeficient mice (BALB/c-nu/nu) with 1×106 cells per mouse. After 7 days of injection, the mice transplanted with U87MG were detected with a small animal living imager to determine the size and location of the tumors in skull. Then we injected the glioma-transplantation nude mouse with two kinds of transgenic hUC-MSCs expressing TRAIL (named as untarget-TRAIL and target-TRAIL, respectively), or the non-transgenic hUC-MSCs (all 1×106 cells per mouse) or PBS (named as WT-MSCs and PBS for negative control) respectively, and then monitored the changes of tumor signals by a small animal living imager every week for 3~4 weeks. 【Results】 After six passages to expand the cells, the both transgenic cell lines can stably express TRAIL gene. Their ratio of green fluorescent protein (GFP) positive cells can reach 93%-97%, and the positive ratio of their MSC-specific surface markers still maintained normal (CD34+, CD45+, and HLA-DR+ all <0.1%, CD90>99%, CD73>88%, and CD105 >60%). The median survival time (d) of U87MG-transplanted nude mice in the groups of untarget-TRAIL, target-TRAIL, WT-MSCs, and PBS was 41 vs 39 vs 24 vs 23(P<0.05). 【Conclusion】 The transgenic hUC-MSCs overexpressing TRAIL gene can significantly prolong the survival time of nude mice with brain glioma.

Effect of phosphoglycerate mutase 5 mediated pyroptosis on liver ischemia-reperfusion injury / 器官移植

Objective To investigate the effect and its molecular mechanism of phosphoglycerate mutase 5 (PGAM5) mediated pyroptosis on liver ischemia-reperfusion injury (IRI). Methods C57 mouse models of liver IRI were established and randomly divided into the 6 h reperfusion (6 h group) and 12 h reperfusion (12 h group), and sham operation group (sham group) was established too, 10 rats in each group. The effect of IRI on the parameters in the liver tissues and serum samples was evaluated. The expression levels of PGAM5 and cysteinyl aspartate specific proteinase (Caspase)-1 in the liver tissues during IRI were quantitatively detected. The IRI models of liver cells were established (IRI group). The IRI models of liver cells were established after pretreatment with Caspase-1 inhibitor Z-YVAD-FMK (inhibitor group). The untreated AML12 cells were allocated into the control group. The effect of inhibiting Caspase-1 activity on pyroptosis was analyzed. AML12 cells were transfected with PGAM5 small interfering ribonucleic acid (siRNA) (siRNA group) and siRNA-negative control (siRNA-NC) (siRNA-NC group) by liposome 3000, and then IRI models of liver cells were established. The untreated AML12 cells were assigned into the control group. The effect of PGAM5 mediated pyroptosis on IRI of liver cells was assessed. Results In the 6 h and 12 h groups, partial liver cell edema, hepatic sinusoid narrowing, central vein congestion and occasional spot necrosis were observed in the mouse liver tissues, and these changes in the 12 h group were more aggravated than those in the 6 h group. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the 6 h and 12 h groups were higher than those in the sham group, and the values in the 12 h group were higher than those in the 6 h group. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were increased in the 6 h and 12 h groups, and the values in the 12 h group were lower than those in the 6 h group. The relative expression levels of IL-1β messenger ribonucleic acid (mRNA) in the mouse liver tissues in the 6 h and 12 h groups were up-regulated, and the value in the 12 h group was lower than that in the 6 h group. The cell apoptosis rates in the liver tissues were significantly increased in the 6 h and 12 h groups, and the value in the 12 h group was remarkably lower than that in the 6 h group (P < 0.01-0.05). Compared with the sham group, the relative expression levels of PGAM5 mRNA and protein in the mouse liver tissues in the 6 h and 12 h groups were significantly up-regulated, and the values in the 12 h group were significantly higher than those in the 6 h group (P < 0.01-0.05). The protein expression levels of PGAM5 and Caspase-1 in the liver tissues were up-regulated in the 6 h and 12 h groups. Compared with the control group, the relative expression levels of NOD-like receptor protein 3 (NLRP3), cleaved Caspase-1 and Gasdermin D (GSDMD) proteins were up-regulated and the fluorescence intensity of GSDMD was increased in the IRI group. Compared with the IRI group, the relative expression levels of NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly down-regulated and the fluorescence intensity of GSDMD was considerably decreased in the inhibitor group (P < 0.01-0.05). Compared with the control group, the cell survival rate was significantly decreased, and the relative expression levels of PGAM5, NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly up-regulated in the siRNA-NC group (P < 0.01-0.05). Compared with the siRNA-NC group, the cell survival rate was remarkably increased, whereas the relative expression levels of PGAM5, NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly down-regulated in the siRNA group (P < 0.01-0.05). Conclusions PGAM5 may aggravate the liver IRI in mouse models probably by mediating pyroptosis via PGAM5/Caspase-1/GSDMD signaling pathway and aggravating liver cell injury.

Effect of bone marrow mesenchymal stem cell on the expression of IL-10 and TNF-α in mice with ischemia-reperfusion acute kidney injury / 器官移植

Objective To evaluate the effect of bone marrow mesenchymal stem cell (BMSC) on the expression of interleukin (IL)-10 and tumor necrosis factor (TNF)-α in mice with ischemia-reperfusion acute kidney injury (IR-AKI). Methods All mice were randomly divided into the sham operation group (control group), ischemia-reperfusion injury group (IRI group) and BMSC treatment group (BMSC group), with 6 mice in each group, respectively. The renal function and pathological changes of mice were detected. The cell apoptosis of renal tissues of mice was determined. The expression levels of serum IL-10 and TNF-α of mice were quantitatively measured. The mouse BMSC was randomly divided into the control and hypoxia-reoxygenation groups (IRI group), and the expression levels of IL-10 and TNF-α in cell supernatant were determined. Results The renal structure of mice was normal in the control group, severe damage was observed in the IRI group, and mild damage occurred in the BMSC group. Compared with the control group, the renal tissue injury scores were significantly higher in the IRI and BMSC groups (both P < 0.05). Compared with the IRI group, the renal tissue injury score was significantly lower in the BMSC group (P < 0.05). Compared with the control group, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were remarkably up-regulated in the IRI group, and the level of BUN was significantly up-regulated in the BMSC group (all P < 0.05). Compared with the IRI group, the levels of Scr and BUN were significantly down-regulated in the BMSC group (both P < 0.05). In the IRI group, the quantity of apoptotic cells in the renal tissues was considerably higher than those in the BMSC and control groups, and the quantity of apoptotic cells in the BMSC group was significantly higher than that in the control group (all P < 0.05). Compared with the control group, the levels of serum IL-10 and TNF-α were significantly up-regulated in the IRI group, whereas the level of serum TNF-α was significantly down-regulated and the level of serum IL-10 was significantly up-regulated in the BMSC group (all P < 0.05). Compared with the IRI group, the levels of serum IL-10 and TNF-α were significantly down-regulated in the BMSC group (both P < 0.05). The levels of IL-10 and TNF-α in the cell supernatant did not significantly differ between the IRI and control groups (P=0.080、0.627). Conclusions BMSC infusion may reduce the incidence of renal IRI and inflammation, probably via the mechanism of down-regulating TNF-α expression rather than up-regulating IL-10 expression.

Laboratory Monitoring of Biological Therapies in Rheumatology: The Role of Immunogenicity

Biological drugs, such as proteins and immunogens, are increasingly used to treat various diseases, including tumors and autoimmune diseases, and biological molecules have almost completely replaced synthetic drugs in rheumatology. Although biological treatments such as anti-tumor necrosis factor (TNF) drugs seem to be quite safe, they cause some undesirable effects, such as the onset of infections due to weakening of the immune system. Given the biological nature of these drugs, they might be recognized as extraneous; this would induce an immune reaction that neutralizes their effectiveness or lead to more serious consequences. Laboratories play a pivotal role in appropriate therapeutic management. The aim of this review was to underline the production of anti-drug antibodies during treatment with biological drugs and highlight the role of laboratories in ensuring appropriate use of these drugs.

Effects of electroacupuncture preconditioning on cerebral infarct volume and contents of TNF-α, IL-10 in serum of rats after cerebral ischemia-reperfusion injury / 中国针灸

<p><b>OBJECTIVE</b>To explore the effect of electroacupuncture(EA) preconditioning on cerebral infarct volume and the contents of TNF-α, IL-10 in serum of rats with cerebral ischemia-reperfusion injury.</p><p><b>METHODS</b>Thirty-six rats were randomly divided into a sham operation group, a model group and an EA preconditioning group, 12 rats in each group, which were further divided into 12 h and 24 h after reperfusion subgroups, 6 rats in each one. EA was used before model establishment for 2 weeks in the EA preconditioning group. The model of cerebral ischemia-reperfusion injury in rats was established with modified Longa suture method. 12 h and 24 h after reperfusion, the degree of neurological deficit was assessed by the modified behavioral scoring scale; the cerebral infarct volume was measured by TTC method and the contents of TNF-α, IL-10 in serum were detected by ELISA method.</p><p><b>RESULTS</b>Compared with the model group, the neurological severity scores in the EA preconditioning group significantly reduced 12 h and 24 h after reperfusion (both<0.05), the cerebral infarct volume in the EA preconditioning group significantly reduced 12 h and 24 h after reperfusion (both<0.05). Compared with the sham operation group, the serum TNF-α, IL-10 contents in the model group increased 12 h and 24 h after reperfusion (both<0.05). Compared with the model group, the serum TNF-α content reduced, while the serum IL-10 content increased in the EA preconditioning group 12 h after reperfusion (both<0.05). Compared with the model group, the serum TNF-α, IL-10 contents reduced in the EA preconditioning group 24 h after reperfusion (both<0.05).</p><p><b>CONCLUSION</b>EA preconditioning can improve neurological deficit, reduce cerebral infarct volume after cerebral ischemia-reperfusion injury in rats. The mechanism may be related to the regulation of EA on the dynamic balance between pro-inflammatory cytokine TNF-α and anti-inflammatory cytokine IL-10 in peripheral blood of cerebral ischemia-reperfusion injury in acute phase, thus alleviate acute cerebral ischemia-reperfusion inflammatory response.</p>

The value of PCT, CRP, TNF-α and free DNA in predicting the development of MODS in patients with multiple trauma / 中华急诊医学杂志

Objective To explore the value of peripheral blood serum levels of PCT,CRP,TNF-α and free DNA of cells in predicting the development of MODS in patients with multiple trauma.Methods Complete detail clinical data of 54 casualties with multiple trauma admitted within 24 hours after accident from January 2011 through January 2012 were collected for retrospective study.The patients were divided into MODS group and non-MODS group according the criteria set forth by the Chinese Society of Critical Care and Emergency Medicine in 1995 national conference.The data of two groups are comparable,and data of another 20 healthy subjects undertaking routine annual physical examination were taken as control.The peripheral blood levels of PCT,CRP,TNF-α and free DNA of patients of two groups were determined 1 d,2 d,3 d,and 5 days after admission.Then the results were analyzed and compared between groups.Results Compared with non MODS group,the levels of PCT,CRP,free DNA of cells in MODS group were significantly higher (P ＜ 0.05),but there was no deference in TNF-α between MODS group and non-MODS group (P ＞ 0.05).When the relative risks of increased PCT (PCT≥6 mg/L),increased CRP (CRP≥ 130 mg/L)、and increased free DNA of cells (free DNA ≥ 10 0005/L) were analyzed,the presence of these 3 biomarkers with high levels occurred at the same time was the most accurate way to predicts MODS in 6.00 relative risk (RR),and the positive predictive value was 100％.Conclusions PCT,CRP,free DNA of cells could be the predictors of MODS in patients with severe multiple trauma,and the presence of high levels of these three biomarkers appearing together had high sensitivity and specificity for prediction.

Changes of IL-18, TNF-α and IFN-γ levels in rats with experimental cirrhosis and their significance / 西安交通大学学报(医学版)

Objective To investigate the changes of interleukin-18 (IL-18), tumor necrosis factor-α(TNF-α) and interferon-γ (IFN-γ) levels of liver cirrhosis induced by the composite factors of carbon tetrachloride (CCl_4) in SD rats and their significance. Methods Totally 80 male SD rats of clean class were randomly divided into normal control group (20 rats) and model groups, the latter of which were further divided into three groups according to the length of administration time, namely, 2-week group (2 wk group), 4-week group (4 wk group) and 6-week group (6 wk group), with 20 rats in each. Six rats were killed after 2 wk, 4 wk and 6 wk administration time, respectively. The rat serum levels of IL-18, TNF-α and IFN-γ and the hepatic homogenate supernatant of IL-18 were detected by ELISA; pathological changes of liver tissues were observed by HE staining. Results ① Pathological observation revealed that in the model groups hepatic cells degenerated and swelled at week 2 while large amounts of fibrosis and pseudolobules of some liver tissues occurred at week 6. ② The serum levels of IL-18, TNF-α and IFN-γ were gradually increased with the modeling time, and they were significantly higher in 6-week group than in normal control group (P<0.01). ③ The levels of hepatic homogenate supernatant of IL-18 in the model groups were elevated with liver damage, and they were significantly higher in 6-week group than in normal control group (P<0.01). Conclusion During the formation of liver cirrhosis induced by composite factors of CCl_4 in rats, IL-18, TNF-α and IFN-γ levels gradually increase, suggesting that the three cytokines play a certain role during the occurrence of liver cirrhosis in rats.

Acceleration of chrysin on apoptosis of hepatoma cell lines HepG2 induced by TNF-α / 中草药

Objective: To research whether chrysin can sensitize the cell death of hepatoma (HepG2) cell lines induced by TNF-α and explore the molecular mechanism of this sensitization. Methods: HepG2 Cells were pretreated with designed dose of chrysin (10, 20, and 40 μmol/L) for 2 h, then followed TNF-α (10 ng/mL) for 24 h, the morphologic changes were observed under inversed microscope and the percentage of sub-G1 was measured using flow cytometry, the proprotein and cleavage of caspase-3, caspase-8, and PARP, regarded as the protein mark of apoptosis induced by TNF-α, were determined by Western blotting; After treating with chrysin for different times, the time course of apoptosis inhibitory protein, such as Bcl-xL, and cIAPs, xIAP, and cFLIP, were also detected using Western blotting. Results: The cell death increasing was observed in the group with combination of chrysin and TNF-α, but no obvious cell death could be found in chrysin, TNF-α alone, and control groups. The data of sub-G1 supported this result that, with the enhancement of pretreatment dose of chrysin, the percentage of sub-G1 reached (27.84±0.54)%. There was significant difference between the combined group and the control one (1.52±0.13)% (P0.05). Chromatin condensation which was the indication of apoptosis could be observed when the cells were stained by Hochest 33342; The proprotein of caspase-3inverted commascaspase-8, and PARP degraded, their cleavage appeared, and there were dose-dependent effects; The pan-caspase inhibitor z-VAD-fmk could inhibit the apoptosis of HepG2 cells which were treated with the combination of chrysin and TNF-α, according to the percentage of sub-G1 and the activation of caspase-3, caspase-8, and PARP; The apoptosis inhibitory protein cFLIP-L could be observed the down-regulation compared to the control group in a time-dependent way. Other inhibitory protein, such as Bcl-xL, xIAP did not change too much. Conclusion: Chrysin could accelerate the apoptosis induced by TNF-α, the down-regulation of apoptosis inhibitory protein cFLIP-L, which is regulated by NF-κB and augmented by TNF-α, and plays an important role in the acceleration of apoptosis.

Effects of Peroxisome Proliferator-Activated Receptor-gamma on the Production of Tumor Necrosis Factor-alpha in Stimulated Human Monocoytes / 감염과화학요법

BACKGROUND: We evaluated the effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on the production of tumor necrosis factor-alpha (TNF-alpha) and expression of nuclear factor-kappaB (NF-kappaB) in stimulated THP-1 cells, a human monocyte cell line. MATERIALS AND METHODS: We evaluated the cytotoxic effect of 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), one of natural PPAR-gamma ligands, using commercial cell proliferation assay. Cells were pretreated with 15d-PGJ(2) and then stimulated with lipopolysaccharide (LPS) or lipoteichoic acid (LTA). The amount of TNF-alpha was measured by using commercial ELISA method. NF-kappaB activation was evaluated by Western blot analysis. RESULTS: 15d-PGJ(2) showed dose-dependent cytotoxic effect on the tested cells after 4 hr of treatment. Stimulation of cells by LPS or LTA induced TNF-alpha production. TNF-alpha production was markedly decreased in the cells pretreated with 15d-PGJ(2) compared to cells treated only with LPS or LTA in a dose-dependent manner. Pretreatment of 15d-PGJ(2) reduced LPS or LTA induced NF-kappaB expression in the nuclear extracts of THP-1 cells. CONCLUSION: 15d-PGJ(2) pretreatment decreased TNF-alpha production from the THP-1 cells stimulated by LPS or LTA, and this assumed to be associated with inhibition of NF-kappaB activation.

Effect of Joint Mobilization and Quadriceps Setting on NO and TNF of Experimental Knee Osteoarthritis in Rabbits / 中国康复理论与实践

@# Objective To explore the effect of joint mobilization and quadriceps setting on nitric oxide(NO) and tumor necrosis factor(TNF) of the experimental knee osteoarthritis in rabbits. Methods Rabbits model of knee osteoarthritis was induced by papain. 32 rabbits were divided into 4 groups randomly, 8 in each group. The changes of contents of NO and TNF in synovia were detected.Results Expression of NO and TNF in synovia of all treatment groups decreased compared to the control group(P<0.01).Conclusion Joint mobilization and quadriceps setting can decrease the level of NO and TNF in synovia.

Influence of Erythropoietin and Inflammatory Cytokines on Pathogenesis of Cerebral Palsy / 中国康复理论与实践

@#Objective To investigate the effect of erythropoietin(EPO)as a brain-protective factor and inflammatory cytokines in the pathogenesis of cerebral palsy(CP).Methods Serum samples from 31 CP patients,37 neonates with CP risk factors such as hypoxic-ischemic injury and/or perinatal infection,and 20 controls of neonates or children were obtained respectively.EPO,tumor necrosis factor(TNF)-α and interleukin(IL)-6 levels were measured with the enzyme-linked immunosorbent assay double sandwich method(ABC-ELISA).Results The serum EPO level of neonatal patients was higher than that of controls or CP group(P<0.01),but there was no significant difference between CP group and controls.The serum TNF-α and IL-6 levels of CP and neonatal patients were higher than that in controls(P<0.01).The serum TNF-α level of CP group was higher than that of neonatal patients(P<0.05).There was no significant difference between CP group and neonatal patients in serum IL-6 level.Conclusion The inflammatory responses mediated by proinflammatory cytokines may play a role in the pathogenesis of cerebral palsy.

Significance of the determination on sICAM-1 and its' combined indexes in the diagnosis and treatment of liver cirrhosis / 重庆医科大学学报

Objective:To investigate the change and significance of interleukin-8 (IL-8) and intercellular adhesion molecule-1(ICAM-1) in periheral blood of 41 healthy and 63 patients with liver cirrhosis. Methods: The serum level of TNF-?and IL-8 was analyzed using enzyme-linked immunosorbent assay (ELISA).The serum level of sICAM-1 was determined using flow cytometry. Results: Compare with normal control group,the serum level of ICAM-1,IL-8,and TNF-? showed significant difference(P

DETERMINATION OF URINE TUMOR NECROSIS FACTOR, IL-6, IL-8 AND SERUM IL-6 IN PATIENTS WITH HEMORRHAGIC FEVERS WITH RENAL SYNDROME / 药物分析学报

Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively (P＜0.001). The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β2-microglobulin (β2-MG), blood ureanitrogen (BUN) and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, P＜0.05; r=0.3760, P＜0.01). Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.

Regulation of Acupuncture on Interferon-γ and Tumor Necrosis Factor of Lung Cancer-Operative Cases / 针灸推拿医学（英文版）

Objective:To investigate the regulation of acupuncture on γ-interferon (INF-γ) and tumor necrosis factor (TNF) of lung cancer-operative cases. Methods: to determine the INF-γ and TNF contents in the blood serum of lung cancer patients by double antibody sandwich immuno-enzymatic method (ELISA); to measure the INF-γ and TNF contents of 30 lung cancer patients in the acupuncture anesthesia group and 30 lung cancer patients in general anesthesia group before the operation and at the 8th days, the 12th day after the operation respectively and make comparison between the two groups. Results:The pre-operation INF-γ contents of the two groups showed no significant difference (P＞0.05); the post-operation INF-γ contents of the two groups showed significant difference at 8th day and 12th day after the operation (P＜0.05); the acupuncture anesthesia group was superior to the general anesthesia group; the self-comparison of the anesthesia group showed significant difference at the 12th day and 8th day after the operation (P＜0.05); the pre-operation TNF contents of the two groups showed no significant difference (P＞0.05) and the post-operation TNF contents of the two groups showed significant difference at the 8th day and 12th day after the operation (P＜0.05). Conclusion:Acupuncture can increase the serum INF-γ and TNF contents of lung cancer patients and therefore regulate the immunity of the patients.

Change of TNF-?and VEGF on glucocorticoid-induced avascular necrosis of femoral head in rabbits / 中国矫形外科杂志

[Objective]To establish animal model of avascular necrosis of the femoral head in rabbits induced by glucocorti-coid, to further investigate the pathogenesis of glucocorticoid-induced osteonecrosis.[Method]Twenty NewZealand white rabbitswere used and randomly divided into two groups.Group A was injected with horse serum and prednisone. Group B was used asthe control.The concentration of TNF-?was measured by ELISA in rabbits serum of group A and group B.Femoral head speci-mens were studied by histopathologic examination and the expression of VEGF by immunohistochemical examination.[Result]The concentration of TNF-?in rabbits serum of group A was higher than that of group B(P

Effect of silbinin capsules on serum interleukin-8 and tumor necrosis factor-? in NAFLD patients / 中国实用内科杂志

Objective To observe the effect of Silbinin Capsuon serum interleukin-8 and tumor necrosis factor-?in NAFLD patients.Methods 58 patients with NAFLD were randomized into two groups.The treatment group including 29 cases received 70mg of Silbinin Capsules each time,three times a day.The control group including 29 cases received 100mg of goucurolactone tablets each time,three times a day.At the same time,both groups control food and drink and proper physical exercises.One course of treatment was 30 days in the study.Observe the changes of serum ALT,AST,IL-8 and TNF-?before and after treatment.Results The serum level of ALT,AST,IL-8 and TNF-?were improved significantly in both groups after treatment(P

Refractory Cases of Adult Onset Still's Disease Successfully Treated with TNF-alpha Blocker / 대한류마티스학회지

Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology characterized by spiking fever, evanescent salmon-colored rash, polyarthritis and leukocytosis. The diagnosis of AOSD remains a challenge to clinicians and requires a high index of suspicion because of its rarity and nonspecific symptoms. Although the etiology and pathogenesis of AOSD is not elucidated clearly, the pathogenetic role of inflammatory cytokines, such as interleukin (IL)-6, IL-8, IL-18 and tumor necrosis factor (TNF)-alpha were suggested and the correlations of their levels with disease activity were also reported. These results raise a possibility that the blocking of these cytokines may provide a therapeutic benefit in controlling disease activity and relieving the symptoms of AOSD. Recently, we experienced two cases of AOSD, who were refractory to the treatment with high dose glucocorticoid and immunosuppressive agents. Both were treated with TNF- blockers and experienced remissions thereafter. These experiences might support the use of biologic agents in refractory AOSD.