Bacterial dissemination in Mycobacterium tuberculosis by CD+ T-cells & proinflammatory cytokines

Background & objectives: As CD4+ and CD8+ T lymphocyte numbers decline, the conventional, localized forms of tuberculosis shift to the atypical, disseminated forms. Variations in lymphocyte and immune cell expression levels affect how tuberculosis manifests in disseminated forms. Understanding the relationship between lymphocyte counts (CD4+ and CD8+) and pro-inflammatory cytokines such as tumour necrosis factor-alpha, interleukin-12 and interferon, we may therefore be able to shed light on how infections spread and suggest potential biomarkers for these immune factors. Methods: In this study, 15 guinea pigs were infected with Mycobacterium tuberculosis (M.tb) H37Rv strain and grouped into three groups of five each for further investigation. Serum samples and bronchoalveolar lavage (BAL) fluid were examined for the expression of pro-inflammatory cytokines and T-cell subsets in guinea pigs infected with pulmonary tuberculosis and disseminated tuberculosis. Results: We found that M.tb escapes macrophages due to pro-inflammatory cytokine dysregulation. Despite the protective immunity created by T-cells and cytokines, M.tb bacilli may spread to other organs due to inflammation induced by these immune components. A high number of T-cells and stimulated cytokine production are involved in triggering inflammation after necrotic tissue develops and tuberculosis spreads. Interpretation & conclusions: Our findings imply that increased bacilli in the spleen at the 8th wk of infection may be caused by the overexpression of CD4+ T-cell lymphocyte subsets and cytokines that generated inflammation during the 4th wk of infection. This is a pilot study with a small sample size and less assertive inference. Larger studies would be helpful to validate the results of the present investigation.

Estrogen deficiency influences TNF-α and IL-1ß gene expression in the odontogenic region of dental hypofunctional condition / A deficiência de estrógeno influencia a expressão gênica de TNF-α e IL-1ß na região odontogênica de dentes em hipofunção

Objetivo: Evidências científicas sugerem que a deficiência de estrógeno e fatores genéticos influenciam o desenvolvimento do sistema estomatognático. Este estudo teve como objetivo avaliar a influência da deficiência de estrógeno na expressão gênica de TNF-α, IL-1ß, IL-6 e IL-10 durante o desenvolvimento dentário em modelo murino. Material e Métodos: Ratas Wistar Hannover foram divididas em dois grupos de acordo com a intervenção recebida: Grupo Hipoestrogenismo - cirurgia de ovariectomia e Grupo Controle - cirurgia fictícia. Para avaliar o desenvolvimento dentário, o incisivo inferior foi escolhido. O modelo de hipofunção dos incisivos inferiores foi realizado por ajuste incisal. O incisivo homólogo exercia hiperfunção dentária. Os animais foram avaliados durante todo o período puberal. Após a eutanásia, as hemimandíbulas foram removidas para avaliar a expressão gênica do TNF-α, IL-1ß, IL-6 e IL-10 na região odontogênica dos incisivos por meio de PCR em tempo real. Foi realizado o teste de Kruskal-Wallis e o pós-teste de Dunn. O nível de significância foi de 5%. Resultados: Houve diferenças estatisticamente significativas na expressão gênica de TNF-α e IL-1ß entre os grupos hipoestrogenismo e controle sob condição de hipofunção dentária (p=0,0084, p=0,0072, respectivamente). Conclusão: A deficiência de estrógeno influencia a expressão gênica de TNF-α e IL-1ß na região odontogênica de dentes hipofuncionais (AU)

Objective: Scientific evidence suggests that estrogen deficiency and genetic factors have an influence on the development of the stomatognathic system. This study aimed to evaluate the influence of estrogen deficiency on the gene expression of TNF-α, IL-1ß, IL-6 and IL-10 during dental development in a murine model. Material and Methods: Wistar Hannover rats were divided into two groups according to the intervention received: Hypoestrogenism Group - ovariectomy surgery and Control Group - fictitious surgery. To evaluate the dental development, the lower incisor was chosen. The mandibular incisor hypofunction model was performed by incisal adjustment. The homologous incisor exerted a hyperfunction. The animals were evaluated throughout the pubertal period. After euthanasia, the hemimandibles were removed to evaluate the gene expression of the TNF-α, IL-1ß, IL-6 and IL-10 in the odontogenic region of the incisors through real time PCR. Kruskal-Wallis test and Dunn's posttest were performed. The level of significance was 5%. Results: There were statistically significant differences of TNF-α and IL-1ß gene expression between the hypoestrogenism and control groups under hypofunction condition (p=0.0084, p=0.0072, respectively). Conclusion: Estrogen deficiency influences TNF-α and IL-1ß gene expression in the odontogenic region of the hypofunctional teeth. (AU)

Hemolysin Sph2 from Leptospira interrogans amplified inflammatory response in murine macrophages J774A.1 through HMGB1 / 中华微生物学和免疫学杂志

Objective:To investigate the possible mechanism of high mobility group box-1 (HMGB1) in amplifing inflammatory responses in Leptospira interrogans hemolysin Sph2-treated J774A.1 macrophages. Methods:Recombinant Sph2 was incubated with J774A.1 macrophages. The damage of cell membrane was detected by lactate dehydrogenase(LDH) determination; the changes of cell structure were observed by cryo-electron microscope; ELISA was used to determine the expression of HMGB1. After the commercial recombinant HMGB1 was incubated with mouse J774A.1 macrophages, the phosphorylation of NF-κB, p38-MAPK and JNK signaling pathway wsa detected by Western blot, and the expression of IL-1β, IL-6, and KC (IL-8) was detected by ELISA.Results:Recombinant hemolysin rSph2 induced significant changes in the structures of J774A.1 cells, including nucleus disappearance, cell membrane structure damage, cell lysis and membrane swelling. The yields of LDH and HMGB1 also increased significantly. Phosphorylated-NF-κB, -p38-MAPK and -JNK were increased by HMGB1. The expression of IL-1β, IL-6 and KC in J774A.1 cells was up-regulated by HMGB1 and inhibited via inhibitors of NF-κB, p38-MAPK and JNK signal pathways.Conclusions:Hemolysin rSph2 damaged the membrane of J774A.1 cells, and induced the secretion of HMGB1. Secreted-HMGB1 might induce the expression of IL-1β, IL-6 and KC in J774A.1 cells via NF-κB, p38-MAPK and JNK signal pathways, thus amplifying the inflammatory responses caused by Sph2.

Influência do LED Violeta associado ou não ao gel clareador na inflamação, mineralização e maturação colágena do tecido dentinário e pulpar / Influence of violet LED associated or not with peroxide gel on inflammation, mineralization, and collagen fiber maturation in dentin and pulp tissue

Objetivo: Avaliar a influência do LED Violeta, associado ou não ao gel clareador a base de peróxido de hidrogênio (PH) a 17,5% no complexo dentino-pulpar de ratos. Materiais e métodos: Molares superiores de 80 ratos foram distribuídos nos grupos (n = 10): CONT ­ sem tratamento, PH ­ 1 aplicação de 30 minutos de PH a 17,5%, LED ­ 1 aplicação de 20 minutos do LED Violeta, e PH+LED - aplicação do PH e LED Violeta. Imediatamente (T0), e aos 7 (T1), 15 (T2) e 30 dias (T3) após o tratamento, os ratos foram eutanasiados e as maxilas processadas para avaliação histológica, imunoistoquímica (IL-17, IL-23 e osteocalcina), e de picrosírius red, sendo realizados os testes de Wilcoxon e Mann-Whitney e Teste-T pareado e Teste-T, respectivamente. (α = 0,05). Resultados: Necrose e infiltrado inflamatório severo foram observados nos grupos PH e PH+LED. Apenas o grupo PH+LED manteve a imunomarcação severa para IL-17 e IL-23, diferindo do grupo LED e PH que apresentaram moderada imunomarcação em T0. Os grupos PH e PH+LED apresentaram severa imunomarcação de OCN em T2 e moderada imunomarcação em T3. O grupo LED apresentou menor quantidade de fibras imaturas em T2 e T3 que o grupo CONT. Conclusão: A terapia com LED violeta não induziu inflamação e fibrose no tecido pulpar, apesar de acelerar a maturação das fibras de colágeno da dentina e, quando associada ao peróxido de hidrogênio, pode tornar os dentes mais sensíveis(AU)

Objective: Was to evaluated the influence of the Violet LED, associated or not with a 17.5% hydrogen peroxide (HP) bleaching gel in the dentin-pulp complex of rats. Materials and methods: Upper molars of eighty Wistar rats were distributed in the groups (n = 10): CONT - without treatment, HP - 1 application of 30 minutes of 17.5% HP, LED - 1 application of 20 minutes of the Violet LED, and HP+LED - application of HP and LED Violet. Immediately (T0), and at 7 (T1), 15 (T2) and 30 days (T3) after treatment, the rats were euthanized and the jaws were processed for histological, immunohistochemical evaluation (IL-17, IL-23 and osteocalcin), and picrosirius red, with Wilcoxon and Mann-Whitney tests and paired T-test and T-test, respectively (α = 0.05). Results: Necrosis and severe inflammatory infiltrate were observed in the PH and PH+LED groups. Only the PH+LED group maintained severe immunostaining for IL-17 and IL-23, differing from the LED and PH group which presented moderate T0 immunostaining. The PH and PH+LED groups presented severe immunostaining of OCN in T2 and moderate immunostaining in T3. The LED group had a lower amount of immature fibers in T2 and T3 than the CONT group. Conclusion: Violet LED therapy induced no inflammation and fibrosis in the pulp tissue, however accelerating the maturation of dentin collagen fibers and, when associated with hydrogen peroxide, can make the teeth more sensitive(AU)

Recent advances in the role of proinflammatory cytokines in the pathogenesis of idiopathic optic neuritis / 国际眼科杂志(Guoji Yanke Zazhi)

@#Optic neuritis(ON), which is the blinding optic nerve diseases that the young and middle-aged population are most susceptible to, is an optic neuropathy caused by various factors. Idiopathic optic neuritis(ION)occurs most frequently asmultiple sclerosis related optic neuritis(MS-ON)and neuromyelitis optica related optic neuritis(NMO-ON). ION has the characteristics of acute onset, easy recurrence, and serious dysfunction. Inflammation is an important mechanism of ION. By mediating inflammatory responses and participating in immune responses, proinflammatory cytokines, as one of cytokines which is a general term for a class of small molecule soluble peptides that regulate the immune system, have caused widespread concern in the pathogenesis of ION. This article reviews and discusses researches on the pathogenesis of proinflammatory cytokines-mediated ION at home and abroad in an effort to promote an in-depth study of the pathogenesis, diagnosis and treatment of ION.

Increased elastic modulus of the synovial membrane in a rat ACLT model of osteoarthritis revealed by atomic force microscopy

This study aimed to explore changes in nanoscale elastic modulus of the synovium using atomic force microscopy (AFM) in addition to investigate changes in synovial histomorphology and secretory function in osteoarthritis (OA) in a rat anterior cruciate ligament transection (ACLT) model. Sprague-Dawley rats were randomly assigned to sham control and ACLT OA groups. All right knee joints were harvested at 4, 8, or 12 weeks (W) after surgery for histological assessment of cartilage damage and synovitis in both the anterior and posterior capsules. AFM imaging and nanoscale biomechanical testing were conducted to measure the elastic modulus of the synovial collagen fibrils. Immunohistochemistry was used to visualize the expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-3 (MMP-3) in the synovium. The OA groups exhibited progressive development of disease in the cartilage and synovium. Histopathological scores of the synovium in the OA groups increased gradually. Significant differences were observed between all OA groups except for the posterior 4W group. The synovial fibril arrangement in all OA groups was significantly disordered. The synovial fibrils in all ACLT OA groups at each time point were stiffer than those in the sham controls. OA rats displayed a significantly higher expression of IL-1β and MMP3 in the anterior capsule. In summary, synovial stiffening was closely associated with joint degeneration and might be a factor contributing to synovitis and increased production of proinflammatory mediators. Our data provided insights into the role of synovitis, particularly stiffening of the synovium, in OA pathogenesis.

Anti-inflammatory Effect of a Goji Berry Extract (Lycium barbarum) in Rats Subjected to Inflammation by Lipopolysaccharides (LPS)

Abstract The present study aimed to evaluate the anti-inflammatory potential of a Lycium barbarum (L. barbarum) fruit extract in Wistar rats submitted to a palatable diet presenting systemic inflammation induced by lipopolysaccharides (LPS). Forty-two Wistar female rats (Rattus Novergicus) were used with 60 days old. The animals were feed for 60 days and divided in six groups (n=7): standard diet+water; standard diet+L. barbarum; palatable diet+water; palatable diet+L. barbarum; standard diet+water+LPS; standard diet+L. barbarum+LPS. A significant difference was shown between the analyzed groups concerning C-reactive protein, with the standard diet+water+LPS group presenting the highest inflammatory response in comparison to the other groups. Decreased inflammatory response was observed in the group administered a palatable diet along with the fruit extract when compared to the group that received only a palatable diet. Significant decrease in glutamic-oxaloacetic transaminase activity was observed in the standard diet+L. barbarum+LPS group compared to the standard diet+water group, as well as in the palatable diet+L. barbarum group compared to the palatable diet+water group. A significant increase in creatinine in the standard diet+water+LPS group was observed in according to the L. barbarum administration groups. The gene expression of the inflammatory markers genes in the liver showed a significant increase in TNF-α and IL-6 genes in the group treated with standard diet+L. barbarum+LPS when compared to the standard diet+LPS group. Thus, the administered L. barbarum extract displays the potential to reduce inflammatory responses induced by LPS and a palatable diet.

Incremento de la viabilidad, producción de especies reactivas de oxígeno, IL-1 y TNF-α en células mononucleares de sangre periférica humana tratadas con fucoidan de Lessonia trabeculata

Las algas pardas constituyen una fuente de alto contenido de polisacáridos como los fucoidanos que poseen importantes propiedades inmunomoduladoras. El objetivo fue determinar la viabilidad de células mononucleares de sangre periférica humana (CMSPh), producción de óxido nítrico (NO), especies reactivas de oxígeno (ROS) y de las citoquinas proinflamatorias IL-1α, IL-6, TNF-α e IFN-γ en cultivos tratados con fucoidan de Lessonia trabeculata. Se empleó fucoidan de Lessonia trabeculata proveniente de la bahía San Nicolás de Marcona-Ica. Las CMSPh se aislaron empleando Ficoll-Hypaque, se distribuyeron a una concentración de 1x105 células/pocillo en medio RPMI-1640 completo y se trataron con diferentes concentraciones de fucoidan durante 24 y 48 h. La actividad citotóxica se determinó por la reducción de MTT, la producción de NO por la reacción de Griess y las ROS por la reducción del NBT. La producción de citoquinas se cuantificó por ELISA. El fucoidan de L. trabeculata estimuló la proliferación de CMSPh y produjo el incremento de ROS a concentraciones de 100-2000 μg/mL respecto al control (p<0.001), la reacción para nitritos resultó negativa. El fucoidan incrementó la producción de IL-1α y TNF-α a concentraciones de 100 y 10 μg/mL respectivamente, mientras que la producción de IL-6 e IFN-γ no mostró diferencias significativas. Se concluye que el fucoidan de L. trabeculata estimula la proliferación de CMSPh, producción de especies reactivas de oxígeno y las citoquinas proinflamatorias IL-1α y TNF-α que poseen importantes propiedades inmunomoduladoras.

Brown algae are a source of high content of polysaccharides such as fucoidans that have important immunomodulatory properties. The aim was to determine the viability of human peripheral blood mononuclear cells (hPBMC), production of nitric oxide (NO), reactive oxygen species (ROS) and the proinflammatory cytokines IL-1α, IL-6, TNF-α and IFN -γ in cultures treated with fucoidan from Lessonia trabeculata. Fucoidan from Lessonia trabeculata from San Nicolás de Marcona-Ica Bay was used. The hPBMC were isolated using Ficoll-Hypaque, distributed at a concentration of 1x105 cells/well in complete RPMI-1640 medium and treated with different concentrations of fucoidan for 24 and 48 h. The cytotoxic activity was determined by the reduction of MTT, NO production by the Griess reaction and ROS by the reduction of NBT. The production of cytokines was quantified by ELISA. The fucoidan of L. trabeculata stimulated the proliferation of hPBMC and produced the increase of ROS at concentrations of 100-2000 μg/mL with respect to the control (p <0.001), the reaction for nitrites was negative. Fucoidan increased the production of IL-1α and TNF-α at concentrations of 100 and 10 μg/mL respectively, while the production of IL-6 and IFN-γ did not show significant differences. It is concluded that the fucoidan of L. trabeculata stimulates the proliferation of hPBMC, production of reactive oxygen species and the proinflammatory cytokines IL-1α and TNF-α that possess important immunomodulatory properties.

Phonopheresis Associated with Nanoparticle Gel from Phyllanthus amarus Relieves Pain by Reducing Oxidative Stress and Proinflammatory Markers in Adults with Knee Osteoarthritis / 中国结合医学杂志

OBJECTIVE@#To determine the changes in serum levels of inflammatory biomarkers and antioxidant levels among the knee osteoarthritis (OA) patients after treatment with Phyllanthus amarus (PP) by nanoparticle gel phonophoresis.@*METHODS@#This study was a randomized, double-blind, placebo-control, parallel-group, clinical trial involving 30 subjects with mild-to-moderate degree of knee OA. The patients were allocated to two groups using a computer-generated random numbers, and received conventional ultrasound therapy (control group, 15 cases) and PP (treatment group, 15 cases) once daily for 10 sessions. The pain was evaluated by visual analogue scale (VAS). Serum levels of tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbnent assay (ELISA). Nitric oxide (NO) was determined by modified Griess reagent. The antioxidant effects, including superoxide dismutase (SOD) and total antioxidant capacity (TAC), were also measured by ELISA assay.@*RESULTS@#The VAS score was significantly decreased in the treatment group compared with the control group after treatment (P<0.01). The serum concentrations of TNF-α and NO were significantly reduced in the treatment group compared with the control group (P<0.01) after treatment. However, the serum concentrations of SOD and TAC in the treatment group were significantly higher after treatment compared with the control group (P<0.01).@*CONCLUSION@#PP could alleviate knee pain and significantly reduce systemic anti-inflammatory effects in knee OA patients.

Aloe barbadensis Miller peptide/polypeptide fraction alleviates inflammation through inhibition of proinflammatory cytokines and mediators in vitro and in rats with Freund's adjuvant-induced hind paw edema

Objective: To evaluate the anti-inflammatory potential of peptide/polypeptide fraction of Aloe vera through in vitro and in vivo studies. Methods: The peptide/polypeptide fraction from Aloe vera was obtained through trichloroacetic acid precipitation. The anti-inflammatory property of the peptide/polypeptide fraction was tested by protein denaturation, membrane stabilization assays. The effect of the fraction on RAW 264.7 cell viability was examined by MTT assays. The nitric oxide level was determined through Griess reagent. TNF-α and IL-6 levels were estimated using ELISA kits. In vivo studies were carried out in male Wistar rats through injection of Freund's adjuvant in the hind paw. Paw edema was measured through the Vernier scale and levels of alanine aminotransferase, aspartate transaminase, TNF-α, IL-6, and secretory phospholipase A2 were estimated through their respective kits after fourteen days of treatment. GraphPad Prism6 was used for analyzing the results. Results: The peptide/polypeptide extract inhibited protein denaturation with an IC50 value of (218.9±15.6) μg/mL and stabilized the membrane of red blood cells with an IC50 value of (275.9±19.1) μg/mL. The extract showed no changes in cell morphology or cytotoxicity up to the concentration of 20 μg/mL in MTT assays. The peptide/polypeptide fraction markedly reduced the levels of proinflammatory markers and mediators in both in vitro and in vivo studies. Conclusions: The results indicate that the peptide/polypeptide fraction of Aloe vera has antiinflammatory property through inhibition of inflammatory markers and mediators responsible for NF-κB and mitogen-activated protein kinase pathways.

Aloe barbadensis Miller peptide/polypeptide fraction alleviates inflammation through inhibition of proinflammatory cytokines and mediators in vitro and in rats with Freund's adjuvant-induced hind paw edema

Objective: To evaluate the anti-inflammatory potential of peptide/polypeptide fraction of Aloe vera through in vitro and in vivo studies. Methods: The peptide/polypeptide fraction from Aloe vera was obtained through trichloroacetic acid precipitation. The anti-inflammatory property of the peptide/polypeptide fraction was tested by protein denaturation, membrane stabilization assays. The effect of the fraction on RAW 264.7 cell viability was examined by MTT assays. The nitric oxide level was determined through Griess reagent. TNF-α and IL-6 levels were estimated using ELISA kits. In vivo studies were carried out in male Wistar rats through injection of Freund's adjuvant in the hind paw. Paw edema was measured through the Vernier scale and levels of alanine aminotransferase, aspartate transaminase, TNF-α, IL-6, and secretory phospholipase A2 were estimated through their respective kits after fourteen days of treatment. GraphPad Prism6 was used for analyzing the results. Results: The peptide/polypeptide extract inhibited protein denaturation with an IC

RIP140 and TNF-α regulate energy metabolism in cardiomyocytes / 中国药理学通报

Aim: To explore whether RIP140 and TNF-a regulate energy metabolism in cardiomyocytes. Methods: H9c2 cardiomyocytes were infected with Ad-RIP140, simultaneously with or without TNF-α treatment. The mRNA levels of PPAR-α, PPAR-β/δ, and PDK4 were measured. H9c2 was exposed to adenovirus expressing RIP140-specific or nonspecific control. Expression of p65 in the nucleus and IκB-α: in cytoplasm were measured by Western blotting, and mRNA levels of IL-1β, IL-2 and TNF-α were measured by real-time PCR. H9c2 was treated with or without TNF-α. The mRNA and protein levels of RIP140 were measured. Results: Overexpression of RIP140 led to a decrease in mRNA levels of PPAR-α, PPAR-β/δ, PDK4, while TNF-α aggravated down-regulation of key metabolic genes by superabundant RIP140. A marked increase of p65-NF-κB in nuclear, a significant decrease of IκB-α in cytoplasm and a notable increase in mRNA levels of TNF-α, IL-β and IL-2 in H9c2 cell line were observed following overexpression of RIP140. The mRNA and protein levels of RIP140 were up-regulated by TNF-α treatment. Conclusions: RIP140 and TNF-a may collaborate in mediating proinflammatory processes and metabolic dysregulation in cardiomyocytes.

Effects of Jiaotai Pill on inflammatory cytokines in depression model mice with chronic unpredictable mild stress / 中草药

Objective: To study the mechanism of Jiaotai Pill on inflammation and anti-inflammatory cytokines in mice with chronic unpredictable mild stress (CUMS) depression. Methods: Mice were treated with CUMS depression model, then the weight comparison, sugar test, opening experiment was conducted; The levels of IL-1β, IL-6 and TNF-α, IL-4, and IL-10 in the serum and hippocampus of rats were measured by enzyme-linked immunosorbent assay (ELISA), and rat hippocampal neuron morphology was observed by Nissl's staining. Results: Compared with the blank group, the consumption of sugar, the number of crosses and the number of vertical bars in the model group were significantly decreased; The levels of IL-1β, IL-6, TNF-α, and IL-4 in serum and hippocampus were significantly higher than those in the blank group, and IL-10 significantly reduced; Hippocampal neurons stratified unclear, arranged disorder, Nissie shallow staining or disappear. Compared with the model group, the consumption of sugar, the number of crosses and the number of vertical bars in Jiaotai Pill administration group were significantly increased; The levels of IL-1β, IL-6, and TNF-α in serum and hippocampus were significantly decreased, and the levels of IL-4 and IL-10 was significantly increased; Hippocampal neuronal stratification was more obvious, Nissl shallow staining. Conclusion: Jiaotai Pill can significantly improve the behavior of rat depression and hippocampal neuronal injury whose mechanism may be related to down-regulation of serum and hippocampus proinflammatory cytokines IL-1β, IL-6, TNF-α, up-regulation of anti-inflammatory cytokines IL-4 and IL-10.

The regulation mechanism of silencing the DUSP1 gene on the release of proinflammatory cytokines in mice with acute pancreatitis / 中华实用儿科临床杂志

Objective To investigate the regulation mechanism of silencing the DUSP1 gene on the release of proinflammatory cytokines in mice with acute pancreatitis(AP). Methods Two DUSP1 - siRNA and one scramble siRNA sequences were designed,and the sequence with higher silence efficiency was selected. Mice models with AP were established,and KM mice were divided into 6 groups:control group,AP group,AP + PD98059 group,AP + scram-ble group,AP + siRNA group and AP + PD98059 + siRNA group. Expressions of proinflammatory cytokines tumor necro-sis factor - α(TNF - α),interleukin(IL)- 1β and IL - 6 in serum were detected by using enzyme linked immunosor-bent assay(ELISA)after 12 h,24 h,48 h of modeling. Serum amylase levels were detected. The mRNA expression levels of DUSP1,TNF - α,IL - 1β and IL - 6 in pancreatic tissues were detected by using quantitative real time poly-merase chain reaction (qPCR). The protein expression levels of DUSP1,extracellular regulated protein kinases(ERK), c - Jun N - terminal kinase(JNK),p38,p - ERK,p - JNK and p - p38 in pancreatic tissues were detected by using Western blot. Results Compared with the control group,the other 5 groups displayed the increased expressions of TNF - α,IL - 1β,IL - 6 and amylase in serum,and expressions of DUSP1,TNF - α,IL - 1β,IL - 6,p - ERK,p -JNK,p - p38 in tissues,and there was a statistical significance (all P < 0. 05). Compared with the AP group,the AP +PD98059 + siRNA group showed the decreased DUSP1 expression in tissues,and there was a statistical significance (all P < 0. 05);the AP + PD98059 group had decreased expressions of TNF - α,IL - 1β,IL - 6 and amylase in serum,and expressions of TNF - α,IL - 1β,IL - 6,p - ERK,p - JNK,p - p38 in tissues,and there were statistical significances (all P < 0. 05);while the opposite results were observed in the AP + siRNA group with DUSP1 expression decreased. Conclusions The results support that silencing the DUSP1 gene promotes the release of proinflammatory cytokines through activating the mitogen - activated protein kinase signaling pathway in mice with AP.

Expression of Astrocyte,Neuron,and Proinflammatory Cytokines Derived from Frontal Cortex of Methamphetamine Dependent rats after Gastrodin Administration / 昆明医科大学学报

Objective To observe the curative mechanism and effect of neurotoxicity injury induced by methamphetamine (MA) and the neuroprotective effects of gastrodin interfered. Whether the expression of astrocyte and proinflammatory cytokines has contributed to the effects of gastrodin.Methods 48 healthy male SD rats were randomly divided into three groups: control group (Daily intraperitoneal injection of saline for 8 weeks),MA group (A dose of 10 mg/kg MA was administered every day for four weeks,then given daily intraperitoneal injection with 10 mg/kg saline for 4 weeks) and gastrodin group (A dose of 10 mg/kg MA was administered every day for four weeks,then given daily intraperitoneal injection with 10 mg/kg gastrodin for 4weeks) . The behavioral changes of rats were measured by conditioned place preference ( CPP) and sterotyped behavior ( SB) induced by methamphetamine. Immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein (GFAP) and NEUN in rat frontal cortex.The expression of IL－6 and TNF－α were detected by quantity RT－PCR and westrn bloting.Results Compa MA depndent 4 weeks group with control group, the scores of sterotyped behavior of MA depndent groups had signficantly increased (P＜0.01) . Comparing MA depndent 4 weeks group with MA depndent 4 weeks+gastrodin group, the scores of sterotyped behavior of MA dependent 4 weeks group had obviously decreaseed (P＜0.01) . Compared with the control group, the expression of GFAP of MA dependent 4 weeks group decreased and the expression of NEUN increased. Compared MA dependent 4 weeks group with control group, the expression of IL－ 6 and TNF－α increased (P＜0.01) . Compared MA dependent 4 weeks+gastrodian group with MA dependent 4 weeks group, the expression of TNF－α and IL－6 significantly reduced (P＜0.01) . Conclusion The neurological damage induced by methamphetamine might be related to the activation of astrocytes and the high expression of inflammatory cytokines including IL－6 and TNF－α. Gastrodin could abate the neurological injury of methamphetamine dependence via reducing the activation of astrocytes and decreasing the expression of IL－6 and TNF－α.

Increased ROS production and DNA damage in monocytes are biomarkers of aging and atherosclerosis

BACKGROUND: New evidence demonstrates that aging and dyslipidemia are closely associated with oxidative stress, DNA damage and apoptosis in some cells and extravascular tissues. However, in monocytes, which are naturally involved in progression and/or resolution of plaque in atherosclerosis, this concurrence has not yet been fully investigated. In this study, we evaluated the influence of aging and hypercholesterolemia on serum pro-inflammatory cytokines, oxidative stress, DNA damage and apoptosis in monocytes from apolipoprotein E-deficient (apoE-/-) mice compared with age-matched wild-type C57BL/6 (WT) mice. Experiments were performed in young (2-months) and in old (18-months) male wild-type (WT) and apoE-/- mice. RESULTS: Besides the expected differences in serum lipid profile and plaque formation, we observed that atherosclerotic mice exhibited a significant increase in monocytosis and in serum levels of pro-inflammatory cytokines compared to WT mice. Moreover, it was observed that the overproduction of ROS, led to an increased DNA fragmentation and, consequently, apoptosis in monocytes from normocholesterolemic old mice, which was aggravated in age-matched atherosclerotic mice. CONCLUSIONS: In this study, we demonstrate that a pro-inflammatory systemic status is associated with an impairment of functionality of monocytes during aging and that these parameters are fundamental extra-arterial contributors to the aggravation of atherosclerosis. The present data open new avenues for the development of future strategies with the purpose of treating atherosclerosis.

Effects of Ganlu Xiaodu Pills and Its Residues on PSGL-1 and Proinflammatory Cytokines in CoxA16 Mouse Model / 中国中医药信息杂志

Objective To investigate the effects of Ganlu Xiaodu Pills and its residues on PSGL-1 and proinflammatory cytokines in Coxsackie virus A16 (CoxA16) mouse model; To discuss its antiviral mechanism of action. Methods Totally 150 ICR mice at age of 7 days were randomly divided into normal group, model group, all-side group, aromatic residual group, clearing residual group and removing residual group, with 25 mice in each group. Except for normal group, other groups were injected intraperitoneally with 20 μL of 107TCID50 CoxA16 standard stock solution to establish models. Except for normal group and model group, other groups were given relevant medicine for intervention. The expressions of PSGL-1, TNF-α, IL-1β and IL-4 and histopathological observation were detected after 10 days of medication. Results Except for the normal group, the existence of a large number of CoxA16 in other groups of mouse muscle tissues proved successful modeling. HE staining showed that Ganlu Xiaodu Pills and residual could reduce damage to the muscle by CoxA16 virus. Compared with the normal group, the expression of PSGL-1 protein in the model group increased (P<0.01); compared with the model group, all-side group, aromatic residue group, clearing residual group, removing residual group inhibited the expression of PSGL-1 protein, reduced the inflammatory factors of TNF-α, IL-1β, and IL-4 (P<0.01). Conclusion Ganlu Xiaodu Pills and its residues have anti-inflammatory effects, and the all-side group shows the best efficacy.

Study on applications of rheum sterile solution in rats following sepsis and effect on inflammatory factors / 中华急诊医学杂志

Objective To study the therapeutic effect of rheum(Chinese herbal medicine) preparation made by using ultrasonic technique on pro-inflammatory cytokines and sepsis in rats.In order to offer novel measure for the treatment of critically ill patients.Methods Firstly, rheum sterile solution was prepared through ultrasonic technique.Secondly, fifty healthy male SD rats were randomly(random number) divided to CLP group and rheum group.Moderate degree of sepsis model was established by using cecal ligation and puncture(CLP).Rats in group rheum received the liquid rheumpreparation via intragastric administration, while rats in group CLP received saline instead.The 7-day survival rate was recorded and was compared between two groups.In addition, another fifty-four rats were randomly(random number) divided to sham group, CLP group and rheum group(n=18 in each group).CLP was performed to induce sepsis in CLP group and rheum group.Then rats in rheum group received rheum sterile solution via intragastric administration, while rats in CLP group received saline instead.At 12 hours, 24 hours and 48 hours after modeling, six rats in each group were randomly sacrificed.Serum TNF-α and HMGB1 levels were detected by ELISA method.Levels of RAGE, HMGB1 and NF-κB P65 in small intestine were detected by Western Blot.Results Level of anthraquinones extracted from rheum by ultrasonic technique was higher than that by conwentional decoction method.The 7-day survival rate of rats in rheum group(76%) was higher than that in CLP group(48%)(P0.05).At 24 hours and 48 hours after modeling, serum HMGB1 levels were significantly lower in rheum group than those in CLP group(P<0.05).Compared with sham group, protein levels of HMGB1, RAGE and NF-κB in small intestine were elevated in CLP group and rheum group at 48 hours after modeling(P<0.01), while protein levels of above biomarker were higher in CLP group than those in rheum group(P<0.05).Conclusions Rheum sterile solution could down-regulate the level of pro-inflammatory cytokines, modulate the inflammatory response, and improve the survival rate in rats with sepsis.

Effects of dexmedetomidine on renal function in patients with hemorrhagic shock / 临床麻醉学杂志

Objective To investigate the effects of dexmedetomidine on renal function in patients with hemorrhagic shock undergoing emergency surgery.Methods Sixty patients (27 males, 33 females) with hemorrhagic shock, aged 18-69 years, ASA physical status Ⅲ or Ⅳ, required emergency surgery under general anesthesia, were randomized into two groups (n=30 each): dexmedetomidine group (group D) and control group (group C).The patients in group D receiving a loading dose of dexmedetomidine (0.5 μg/kg within 10 min) after the induction of anesthesia followed by a continuous infusion rate of 0.4 μg·kg-1·h-1 till 30 min before the end of surgery, while those in group C received equal volume of normal saline.Venous blood were obtained immediately before beginning of surgery (T1), immediately after surgery (T2), 24 h after surgery (T3) and 72 h after surgery (T4) for detecting the concentrations of the serum creatinine (Scr) and blood urea nitrogen (BUN), the contents of neutrophil gelatinase-associated lipocalin (NGAL) and high mobility group box-1 (HMGB1).The range ability of the concentration of the serum Scr from T4 to T1 (ΔScr) and the content of the serum HMGB1 from T4 to T1 (ΔHMGB1) were also calculated and recorded.Hemodynamic index (including MAP, HR) and arterial blood gas results were recorded during surgery.Results Compared with T1, MAP, CVP and BE were increased, meanwhile, HR and Lac were decreased at T2, but there was no statistically significant difference between the two groups.No statistical difference was found in BUN at any time point between group D and group C.Compared with T1, Scr decreased in both groups at T2-T4.The ΔScr in group D was higher than that in group C at T4 (P＜0.05).The content of serum NGAL at T4 in group D was significantly dropped when compared with T1 (P＜0.01) and was lower than that in group C (P＜0.05).Compared with T1, the content of serum HMGB1 was significantly decreased in both groups at T2 (P＜0.05);the content of serum HMGB1 at T3 in group C was significantly increased and was higher than that in group D;the ΔHMGB1 in group C was higher than that in group D.Conclusion Hemorrhagic shock could induce acute kidney injury.Perioperative continuous infusion of dexmedetomidine facilitated renal function recovery after ischemia-reperfusion injury in patients with hemorrhagic shock through inhibiting the elevation of serum HMGB1.

Clinical efficacy of rosuvastatincombined with oxycodone sustained release tablets in patients with advanced non-small cell lung cancer and its effects on serum IL-6 and TNF-αlevels / 中国生化药物杂志

Objective To explore the clinical efficacy of rosuvastatin combined with oxycodone sustained release tablets in patients with advanced non-small cell lung cancer and its effects on serum IL-6 and TNF-αlevels.Methods 62 cases with advanced non-small cell lung cancer from May 2014 to May 2016were divided into observation group and control group according to random number table, each group with 31 cases.Control group were treated with oxycodone sustained-release tablets, and observation group were treated with rosuvastatin and oxycodone sustained-release tablets.The levels of serum IL-6 and TNF-αwere compared pre-and post-treatment betweene two groups.The effective dose, the number of painful pain, the NRS score, the improvement of quality of life of oxycodone hydrochloride sustained-release tablets after treatment and adverse reaction rate were observed. Results After treatment, serum IL-6, TNF-αlevels in two groups were significantly lower than pre-treatment (P <0.05), and which in observation group were significantly lower than control group (P<0.05).Compared with control group, the effective dose of Oxycodone Hydrochloride Prolonged-release Tablets, broke out pain, NRS score in observation group were significantly higher ( P <0.05 ) .The effective rate of cancer pain treatment in observation group was 96.77% (30/31), significantly higher than 74.19% (23/31) of control group (χ2 =12.269, P<0.0001).The improvement of quality of life incontrol group was 32.25%, significantly lower than 80.64% in observation group (P<0.05).There was no significant difference in adverse reactions between two groups.Conclusion Rosuvastatin combined with oxycodone sustained release tablets in treatment with advanced non-small cell lung cancer were effective, and can reduce the patient's serum IL-6, TNF-αlevels effectively.