Up-regulation of Proinflammatory Cytokines in Rostral Ventromedial Medulla Contributes to Chronic Postsurgical Pain by Promoting 5-HT Release / 中山大学学报(医学科学版)

ObjectiveTo investigate the role of proinflammatory cytokines tumor necrosis factor alpha （TNFα） and interleukin-1β （IL-1β） in rostral ventromedial medulla （RVM） in chronic postsurgical pain （CPSP） induced by skin/muscle incision and retraction （SMIR）. MethodsSD rats were randomly divided into 5 groups： ① Sham group； ② SMIR group； ③ SMIR+TNFα/IL-1β neutralizing antibody group； ④ SMIR+TNFα/IL-1β group and ⑤ SMIR+vehicle group. 50% paw mechanical withdrawal threshold （MWT） was measured by the up-down method， immunofluroscence was used to detect the TNFα and IL-1β expression and ELISA for the 5-Hydroxytryptamine （5-HT） level. ResultsSMIR elicited persistent nociceptive sensitization， upregulated TNFα and IL-1β expression in RVM neurons and astrocytes. Microinjection of TNFα or IL-1β neutralizing antibody into RVM inhibited the development of nociceptive sensitization and decreased the level of 5-HT in both RVM and spinal dorsal horn. While microinjection of recombinant TNFα or IL-1β into RVM enhanced the development of nociceptive sensitization and increased the level of 5-HT in both RVM and spinal dorsal horn. ConclusionUp-regulation of proinflammatory cytokines in RVM may contribute to SMIR induced CPSP by promoting 5-HT release.

Liposome Encapsulated Astaxanthin Altered Biochemical Profile In Diethylnitrosamine (DEN) Induced Hepato Carcinoma On Swiss Albino Mice

Cancer is a disease in which a group of abnormal cells grow uncontrollably by disregarding the normal rules of cell division. Across several cancers, Hepatocellular carcinoma (HCC) is one of the most aggressive cancers in worldwide. It is held responsible for up to 1 million deaths globally per annum. HCC is an inflammation-related cancer, as a chronic inflammatory state is necessary for cancer appearance. In this study, the drug astaxanthin and encapsulated astaxanthin was tested against HCC. Mice were divided into 7 groups; Group I: control, Group II: DEN induced, Group III: DEN + 50 mg/kg astaxanthin, Group IV: DEN + 100 mg/kg astaxanthin, Group V: DEN + 50 mg/kg encapsulated astaxanthin, Group VI: DEN + 100 mg/kg encapsulated astaxanthin, Group VII: DEN + 10 mg/kg sorafenib. Regular diet was given. Body weight, Food intake, water intake was noted. Other biochemical parameters such as ALP, AST, Albumin, proteins and TNF-α was determined. Finally, the liver was removed from each mice of different group by sacrificing them and histopathology was done. In vivo evaluation in mice models showed significant antitumor activities by both encapsulated and non-encapsulated astaxanthin at 100 mg/kg as compared with the control, DEN induced group and positive drug sorafenib. This research suggested that encapsulated astaxanthin can also be used as chemotherapeutic agent for the treatment of Hepatocellular carcinoma (HCC).

High Levels of Inflammatory Adipokines and C-reactive protein, and Minimal Changes in Immune Cells in Overweight and Obese Saudi Female University Students

Increased body weight affects the whole body including the immune response, and leads to a state of non-specificinflammation, which leads to increased incidence of inflammatory diseases. The aim of this study was to determine therelationship between adiposity and the hematological profile, and serum concentrations of glucose, C-reactive protein(CRP), some pro-inflammatory [leptin, resistin, interlukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α)] and antiinflammatory (adiponectin) adipokines in 112 healthy Saudi female university students. Adiposity was determined using thebody mass index (BMI), waist-to-hip ratio (WHR), and waist circumference (WC). The results showed that the mean totalwhite blood cell counts were significantly higher for the high risk WHR group, and the mean platelet and red blood cellcounts were higher for the obese/morbidly obese BMI group compared to the respective controls. The white blood cell typesand hemoglobin did not show any significant differences. Mean serum CRP, leptin, resistin, and IL-6 concentrations weresignificantly higher for the obese/morbidly obese BMI and high risk WC subjects compared to the healthy weight subjects.The only significant difference for the WHR groups was a significantly higher mean resistin level for the moderate riskgroup compared to the control. Mean glucose, TNF-α and adiponectin concentrations were not significantly different amongthe groups. Thus, it may be concluded that the immune system cells and the hematological profile in subjects with highadiposity were minimally affected compared to the healthy weight subjects. They also had higher platelet counts, and CRP,leptin, resistin, and IL-6 concentrations, which are inflammatory effectors/markers, thus confirming that obese subjects hadheightened inflammation and a higher risk for inflammatory diseases.

Acupuncture combined with granule for nerve-root type cervical spondylosis and its effects on IL-6、TNF-α、IL-1β and hemorheological indexes / 中国针灸

OBJECTIVE@#To explore the clinical efficacy of acupuncture combined with granule for nerve-root type cervical spondylosis and its effects on serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and hemorheological indexes.@*METHODS@#A total of 114 patients with nerve-root type cervical spondylosis were randomly divided into an observation group and a control group, 57 cases in each group. The patients in both groups were treated with traction. The patients in the control group were treated with oral administration of granule, 4 g each time, 3 times a day, while based on the treatment of control group, the patients in the observation group were treated with acupuncture at Dazhui (GV 14), Tianzhu (BL 10), Houxi (SI 3), cervical Jiaji (EX-B 2), Quchi (LI 11), Hegu (LI 4) and Waiguan (TE 5), once a day. Both groups were treated for 4 weeks. The simplified McGill pain questionnaire (MPQ), neck disability index (NDI), numbness score, levels of IL-6, TNF-α, IL-1β in serum and hemorheological indexes were observed before and after treatment, and the clinical efficacy was compared between the two groups.@*RESULTS@#The total effective rate was 91.2% (52/57) in the observation group, which was higher than 71.9% (41/57) in the control group (<0.05). Compared before treatment, the scores of MPQ, NDI and numbness in the two groups were reduced after treatment (<0.05). After treatment, the scores of MPQ, NDI and numbness in the observation group were lower than those in the control group (<0.05). After treatment, the serum levels of IL-6, TNF-α and IL-1β in the two groups were reduced (<0.05), and those in the observation group were lower than the control group (<0.05). After treatment, the plasma viscosity, fibrinogen, low shear rate of whole blood viscosity and high shear rate of whole blood viscosity in the two groups were lower than before treatment (<0.05), and those in the observation group were lower than the control group (<0.05).@*CONCLUSION@#Acupuncture combined with granule have significant clinical efficacy for nerve-root type cervical spondylosis, which could reduce the serum levels of IL-6, TNF-α and IL-1β and improve hemorheology.

Immunoglobulin-like transcript-4 (ILT4) expression in mononuclear cells on the prognosis of sepsis / 中华急诊医学杂志

Objective To study the biological behaviors and effects of immunoglobulin-like transcript-4 (ILT4) expression in mononuclear cells on the prognosis of sepsis.Methods ILT4 +/+ (WT) and ILT4-knockout mice (ILT4-/-) male BALB/c mice were used for sepsis modeling using cecal ligation puncture (CLP).Flow cytometry was used to measure the levels of expression of ILT4 and major histocompatihility complex class Ⅱ molecules (MHC-Ⅱ) in mononuclear cells of peripheral blood 24 h after CLP.ELISA was used to measure the concentrations of interleukin-6 (IL-6) and serum tumor necrosis factor-alpha (TNF-α) in different groups of mice at 0 h,6 h,12 h,and 24 h after CLP to monitor the survival and prognosis over the course of 168 h.Results ILT4 was highly expressed in mononuclear cells of the peripheral blood of septic mice 24 h after CLP in comparison with that before CLP (1292.00 ± 143.70) vs.(193.50 ± 52.54),P ＜ 0.05.MHC-Ⅱ expression in mononuclear cells of the peripheral blood in ILT4-/-mice was significantly higher than that in WT mice (49.38 ± 5.66)％ vs.(24.25 ± 6.76) ％,P ＜ 0.05).Serum IL-6 was significantly elevated 24 h after CLP compared with that before CLP (470.75 ± 88.03) vs.(54.25 ± 20.04),P ＜ 0.05.The serum IL-6 concentration was much lower in ILT4-/-mice thanthatin MT mice (241.25 ± 45.10)vs.(470.75 ± 88.03),P ＜ 0.05;whereas,there was no significant difference in TNF-α expression between two groups of mice (50.88 ± 6.38) vs.(53.13 ± 5.49),P ＞ 0.05.The survival rate of ILT4-/-mice was significantly higher after CLP compared with WT mice (P ＜ 0.05).Conclusion The high level of ILT4 expression in mononuclear cells were observed in peripheral blood during sepsis and it was found to be associated with high serum IL-6 levels and low MHC-Ⅱ expression in mononuclear cells,leading to increased mortality.

A study of inhibitory effect of ulinastatin on hyper-permeability of endothelium induced by TNF-α / 中华急诊医学杂志

Objective To investigate the influence of Ulinastatin (UTI) on the hyper-permeability of vascular endothelial cells induced by tumor necrosis factor alpha (TNF-α).Methods Inflammation model was induced by TNF-α in human umbilical vein endothelial cell line (EA.hy926).The experiment was designed into 4 groups:normal group,TNF-α group,UTI group and TNF-α with UTI (U + T) group.Methyl thiazolyl tetrazolium (MTT) method and epithelial voltameter (EVOM) method were used to measure cell viability [absorbance (A) value] and transepithelial electrical resistance (TER) of EA.hy926 cells respectively.The expression of VE-cadherin was measured by reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry.Results Compared with normal group,the TER of EA.hy926 cells induced by TNF-α was significantly decreased (67.200 ± 8.937 vs.33.600 ± 8.771,P =0.010).The permeability in EA.hy926 cells increased obviously.The hyper-permeability of EA.hy926 cells induced by TNF-α could be alleviated by UTI at the concentrations of 1-100 U/mL in a dose-dependent manner (40.133 ±7.484 vs.33.600 ±8.771,P=0.382;49.232 ± 3.162 vs.33.600 ± 8.771,P =0.044;63.700 ± 8.515 vs.33.600 ± 8.771,P =0.013).The expression of VE-cadherin mRNA reduced significantly in the TNF-α group (1.089 ±0.018 vs.0.835±0.021,P =0.000) compared with normal group.This effect of TNF-α could be attenuated by UTI.When EA.hy926 cells exposed to UTI at 10 U/mL and 100 U/mL,a significant increase of the expression of VE-cadherin mRNA was observed (0.976 ±0.014 vs.0.835 ±0.021,P =0.001;1.115 ±0.015 vs.0.835 ± 0.021,P =0.000).And the inhibition of UTI manifested a dose-dependent manner (1-100 U/mL).The results of the immunocytochemistry showed that the expression of VE-cadherin in TNF-o group was decreased significantly (0.061 ± 0.013 vs.0.093 ± 0.014,P =0.049) compared with normal group.And the low-expression of VE-cadherin could be alleviated by UTI (0.032 ± 0.004 vs.0.061 ± 0.013,P =0.016).Conclusion The high permeability of EA.hy926 cells induced by TNF-α could be inhibited by UTI at the concentrations of 1-100 U/mL in a dose-dependent manner.

Evaluation of leptin, interleukin-1 beta and tumor necrosis factor alpha in serum of malaria patients as prognostic markers of treatment outcome

<p><b>OBJECTIVE</b>To analyze serum leptin levels in patients with malaria falciparum and compare them with healthy controls and correlate with development and outcome of malaria infection.</p><p><b>METHODS</b>Sixty cases of malaria falciparum were included in this study as patients. Thirty healthy individuals of comparable age, racial and body mass index were taken as controls. All patients were diagnosed by clinical picture and the presence of malaria parasites in blood film. Estimation of liver function test, kidney function test, complete blood count, fasting blood sugar, fasting serum insulin, pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) and interleukin 1 (IL1), estimation of morning serum leptin and calculation of body mass index (kg/m(2)) were done in both groups on the day of admission, on discharge and 7 d after discharge.</p><p><b>RESULTS</b>At admission, leptin levels were significantly higher in patients group than in control while fasting serum insulin levels were not significantly different between the two groups. There were significant increases as regard to TNFα and IL1 in malaria patients. Significant differences were observed between the control and the patient group for leptin, TNFα and IL1 at the time of admission and discharge. After discharge for 7 d, a significant decline in serum leptin levels, TNFα and IL1 in the patients group was observed as compared with time of admission and time of discharge, a positive correlation between serum leptin levels and TNFα and IL1.</p><p><b>CONCLUSIONS</b>Leptin hormone level might play an important role in development and outcome of malaria infection.</p>

Evaluation of leptin, interleukin-1 beta and tumor necrosis factor alpha in serum of malaria patients as prognostic markers of treatment outcome

Objective: To analyze serum leptin levels in patients with malaria falciparum and compare them with healthy controls and correlate with development and outcome of malaria infection. Methods: Sixty cases of malaria falciparum were included in this study as patients. Thirty healthy individuals of comparable age, racial and body mass index were taken as controls. All patients were diagnosed by clinical picture and the presence of malaria parasites in blood film. Estimation of liver function test, kidney function test, complete blood count, fasting blood sugar, fasting serum insulin, pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) and interleukin 1 (IL1), estimation of morning serum leptin and calculation of body mass index (kg/m

Effects of rhein lysinate on the expressions of TNF-α,IL-6 and NF-κB in the kidney tissue of SAMP 1 0 mice / 西安交通大学学报(医学版)

Objective To investigate the effects of rhein lysinate (RHL)on the expressions of TNF-α,IL-6 and NF-κB in the kidney tissue of senescence accelerated mouse prone 10 (SAMP 10)mice.Methods We selected 1 8 male mice (SAMP 1 0 )aged 7 months for the study and randomly divided them into blank control group and groups of different concentrations of RHL;six senescence accelerated mouse resistance 1 (SAMR 1 )served as the young control group.After 6 weeks’ treatment,HE staining was used to detect the pathological changes of the kidney.The expressions of TNF-α,IL-6 and NF-κB at the protein level were detected by immunohistochemistry and Western blotting.Results RHL treatment did not affect the body weight of SAMP 10 mice (P>0.05 ). Compared with SAMR 1 mice, contracted and destroyed renal glomeruli and infiltration of mononuclear macrophages were observed in control SAMP10 mice.However,this pathological process was blocked by RHL (25 mg/kg and 50 mg/kg ) treatments. In addition, the overexpressions of TNF-α, IL-6 and NF-κB and the phosphorylation of NF-κB in the kidney tissue of SAMP 10 mice could be inhibited by RHL treatments (P<0.05). Conclusion RHL inhibits the inflammatory reaction of the kidney tissue,which may be one of the mechanisms by which RHL exerts its kidney-protecting and anti-aging effects.

Evaluation of leptin, interleukin-1 beta and tumor necrosis factor alpha in serum of malaria patients as prognostic markers of treatment outcome

Objective: To analyze serum leptin levels in patients with malaria falciparum and compare them with healthy controls and correlate with development and outcome of malaria infection.Methods:healthy individuals of comparable age, racial and body mass index were taken as controls. All patients were diagnosed by clinical picture and the presence of malaria parasites in blood film. Estimation of liver function test, kidney function test, complete blood count, fasting blood sugar, fasting serum insulin, pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) and interleukin 1 (IL1), estimation of morning serum leptin and calculation of body mass index (kg/m2) were done in both groups on the day of admission, on discharge and 7 d after discharge.Results:Sixty cases of malaria falciparum were included in this study as patients. Thirty while fasting serum insulin levels were not significantly different between the two groups. There were significant increases as regard to TNFα and IL1 in malaria patients. Significant differences were observed between the control and the patient group for leptin, TNFα and IL1 at the time of admission and discharge. After discharge for 7 d, a significant decline in serum leptin levels, TNFα and IL1 in the patients group was observed as compared with time of admission and time of discharge, a positive correlation between serum leptin levels and TNFα and IL1. At admission, leptin levels were significantly higher in patients group than in control Conclusions: Leptin hormone level might play an important role in development and outcome of malaria infection.

Relationship between peritoneal macrophages and inflammatory reaction in a rat model of severe acute pancreatitis / 药物分析学报

Objective To investigate the relationship between peritoneal macrophages (PMAs) and inflammatory reaction in a rat model of severe acute pancreatitis (SAP). Methods Sprague-Dawley rats were randomly divided into control group and SAP group. To induce SAP in rats, 40 g/L sodium taurocholate (0.1 mL/100 g) was injected into the pancreatic duct through retrograde exposure of pancreatic bile duct in hepatic porta. One-third of rats were sacrificed at 3, 6 or 12 h after modeling. PMAs were extracted, and incubated for 24 h in a humidified 5% carbon dioxide incubator. The expressions of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) mRNA in PMAs were measured by semi-quantitative RT-PCR. The levels of TNF-α and IL-1β in culture medium and serum were evaluated.The histological changes of pancreas were examined. Rosults The expressions of TNF-α mRNA and IL-1β mRNA in PMAs were significantly higher in SAP group than in control group at each time point (P<0.01). The concentrations of TNF-α and IL-1β in culture medium and serum were significantly elevated in SAP group compared with control group (P<0.01). The histological analysis of pancreas indicated that the damage was more severe in SAP group than in cuntrol group (P<0.01). Conclusion PMAs secrete cytokines into pancreatitis-associated ascitic fluid, and this study demonstrates a correlation between SAP and the activation of PMAs.

Relationship between peritoneal macrophages and inflammatory reaction in a rat model of severe acute pancreatitis / 西安交通大学学报·英文版

Objective: To investigate the relationship between peritoneal macrophages (PMAs) and inflammatory reaction in a rat model of severe acute pancreatitis (SAP). Methods: Sprague-Dawley rats were randomly divided into control group and SAP group. To induce SAP in rats, 40 g/L sodium taurocholate (0.1 mL/100 g) was injected into the pancreatic duct through retrograde exposure of pancreatic bile duct in hepatic porta. One-third of rats were sacrificed at 3, 6 or 12 h after modeling. PMAs were extracted, and incubated for 24 h in a humidified 5% carbon dioxide incubator. The expressions of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) mRNA in PMAs were measured by semi-quantitative RT-PCR. The levels of TNF-α and IL-1β in culture medium and serum were evaluated. The histological changes of pancreas were examined. Results: The expressions of TNF-α mRNA and IL-1β mRNA in PMAs were significantly higher in SAP group than in control group at each time point (P<0.01). The concentrations of TNF-α and IL-1β in culture medium and serum were significantly elevated in SAP group compared with control group (P<0.01). The histological analysis of pancreas indicated that the damage was more severe in SAP group than in control group (P<0.01). Conclusion: PMAs secrete cytokines into pancreatitis-associated ascitic fluid, and this study demonstrates a correlation between SAP and the activation of PMAs.