Increased expression of tumor necrosis factor-a is associated with advanced colorectal cancer stages

AIM:To detect the expression of tumor necrosis factor-a(TNF-a)in colorectal cancer(CRC)cells among Saudi patients,and correlate its expression with clinical stages of cancer.METHODS:Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital.Patient demographic information,including age and gender,tumor sites,and histological type of CRC,was recorded.To measure TNF-a m RNA expression in CRC,total RNA was extracted from tumor formalin-fixed,paraffinembedded,and adjacent normal tissues.Reverse transcription and reverse transcription polymerase chain reaction were performed.Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-a by immunohistochemistry.RESULTS:The relative expression of TNF-a m RNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue.High TNF-a gene expression was associated with StageⅢandⅣneoplasms when compared with earlier tumor stages(P=0.004).Eighty-three percent of patients(25/30)showed strong TNF-a positive staining,while only 10%(n=3/30)of patients showed weak staining,and 7%(n=2/30)were negative.We showed the presence of elevated TNF-a gene expression in cancer cells,which strongly correlated with advanced stages of tumor.CONCLUSION:High levels of TNF-a expression could be an independent diagnostic indicator of colorectal cancer,and targeting TNF-a might be a promising prognostic tool by assessment of the clinical stages of CRC.

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

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

Up-regulation of tumor necrosis factor-a pathway survival genes and of the receptor TNFR2 in gastric cancer

BACKGROUND Gastric carcinogenesis can be induced by chronic inflammation triggered by Helicobacter pylori(H. pylori) infection. Tumor necrosis factor(TNF)-α and its receptors(TNFR1 and TNFR2) regulate important cellular processes, such as apoptosis and cell survival, and the disruption of which can lead to cancer. This signaling pathway is also modulated by microRNAs(miRNAs), altering gene expression.AIM To evaluate the mRNA and miRNAs expression involved in the TNF-α signaling pathway in gastric cancer(GC) tissues and its relationship.METHODS Quantitative polymerase chain reaction(qPCR) by TaqMan? assay was used to quantify the RNA transcript levels of TNF-α signaling pathway(TNF, TNFR1,TNFR2, TRADD, TRAF2, CFLIP, NFKB1, NFKB2, CASP8, CASP3) and miRNAs that targets genes from this pathway(miR-19 a, miR-34 a, miR-103 a, miR-130 a,miR-181 c) in 30 GC fresh tissue samples. Molecular diagnosis of H. pylori was performed by nested PCR for gene HSP60. A miRNA:mRNA interaction network was construct using Cytoscape v3.1.1 from the in silico analysis performed using public databases.RESULTS Up-regulation of cellular survival genes as TNF, TNFR2, TRADD, TRAF2, CFLIP,and NFKB2, besides CASP8 and miR-34 a was observed in GC tissues, whereas mediators of apoptosis such as TNFR1 and CASP3 were down-regulated. When the samples were stratified by histological type, the expression of miR-103 a and miR-130 a was significantly increased in the diffuse-type of GC compared to the intestinal-type. However, no influence of H. pylori infection was observed on the expression levels of mRNA and miRNAs analyzed. Moreover, the miRNA:mRNA interaction network showed several interrelations between the miRNAs and their target genes, highlighting miR-19 a and miR-103 a, which has as predicted or validated target a large number of genes in the TNF-α pathway,including TNF, TNFR1, TNFR2, CFLIP, TRADD, CASP3 and CASP8.CONCLUSION Our findings show that cell survival genes mediated by TNF/TNFR2 binding is up-regulated in GC favoring its pro-tumoral effect, while pro-apoptotic genes as CASP3 and TNFR1 are down-regulated, indicating disbalance between apoptosis and cell proliferation processes in this neoplasm. This process can also be influenced by an intricate regulatory network of miRNA:mRNA.

Relationship of Tumor Necrosis Factor-α and Nitrogen Oxide with Treatment of Frequent Relapse Nephrotic Syndrome by Shenkangling(肾康灵)Granule in Children

Objective: To observe the relationship of tumor necrosis factor-o (TNF-a) and nitrogen oxide (NO) with the treatment of frequent relapse nephrotic syndrome (FRNS) and to explore the patho-genesis of FRNS and the therapeutic mechanism of Shenkangling (肾康灵,SKL) Granule in children. Methods: Sixty children suffering from FRNS were randomly divided into the treated group and control group, 30 in each, and the other 30 healthy children were taken as healthy group. The patients were treated with prednisone for a long-term course, and those with no effect or partial effect shown were treated with additional Tripterygium or Cytoxan in the control group, while in the treated group patients were treated with prednisone and additional SKL. The two groups were compared as to their changes of TNF-a, NO before and after treatment, and the relapses after treatment. Results: The levels of TNF-a and NO in the sick children before treatment were markedly higher than those after treatment and normal group (P< 0. 01). The positive correlation between TNF-o of FRNS cases and relapse risk displayed more significance than that between the relapse of FRNS and NO. The difference between treated group and control group was significant (P<0. 01). Conclusion: TNF-a can be regarded as the monitoring parameter of the active phase in FRNS, and the higher the level, the more possible the relapse would occur. SKL could markedly reduce the relapse rate of FRNS in children.

Tumor necrosis factor-a and its role as a mediator in myocardial infarction:A brief review

Tumor necrosis factor-a (TNF-a) contributes to myocardial infarction (MI) injury. Polymorphism of TNF-a gene promoter region and secretion and release of TNF-a and its transformation by a series of signaling pathways are all changed at different points of pathophysiological process in MI. Researches also investigated TNF-a antagonists and their potential therapeutic role in the setting of MI and heart failure at both molecular and clinical level. This article briefly reviews TNF-a and its mechanism as a mediator in MI. Copyright ? 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Effects of morphine and fentanyl on tumor necrosis factor-α and interleukin-6 concentrations in human whole blood in vitro

Cytokines are essential for hematopoiesis and immune responses, and play a key role in the defense against infections. Lipopolysaccharide ( LPS) is a potent inducer of the agents involved in the pathogenesis of inflammation responses. Tumor necrosis factor-α ( TNF-α ) and interleukin-6 (IL-6) are two important proinflammatory

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

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

Sustained Contraction of Isolated Rabbit Thoracic Aortic Rings in Endothelial-dependent Manner Induced by βγ-CAT

In vertebrates, non-lens βγ-crystallins are widely expressed in various tissues and their functions are not well known. The molecular mechanisms of trefoil factors （TFFs）, which involved in mucosal healing and tumorigenesis, have remained elusive. βγ-CAT is a novel multifunctional protein complex of non-lens βγ-crystallin and trefoil factor from frog skin secretions. Here we report that βγ-CAT could induce sustained contraction of isolated rabbit aortic rings in dosage （2-35nmol/L） and endothelium dependent manners （P〈0.01 ）. In addition, in situ immunofluorescence indicated that positive TNF-α signals were mainly detected at the endothelial cell layer of βγ-CAT （25nmol/L） treated rings. Furthermore, βγ-CAT induced primary cultured rabbit thoracic aortic endothelial cells （RAECs） rapidly to release TNF-α. After βγ-CAT （25nmol/L） treated for 10 and 30min, the levels of the endothelial cells released TNF-ct were 34.17±5.10 pg/mL and 98.01±4.67 pg/mL （P〈0.01）, respectively. In conclusion, βγ-CAT could induce sustained contraction of isolated aortic rings, and the contractile effect might be partially explained by the release of TNF-α. These findings will give new insight into understanding the functions and physiological roles of non-lens βγ-crystallins and trefoil factors.

Ischemic preconditioning ameliorates intestinal injury induced by ischemia-reperfusion in rats

AIM: To evaluate preventative effects of ischemic preconditioning(IP) in a rat model of intestinal injury induced by ischemia-reperfusion(IR).METHODS: Male Sprague-Dawley rats(250-300 g) were fasted for 24 h with free access to water prior to the operation.Eighteen rats were randomly divided into three experimental groups: S group(n = 6),rats were subjected to isolation of the superior mesenteric artery(SMA) for 40 min,then the abdomen was closed; IRgroup(n = 6),rats were subjected to clamping the SMA 40 min,and the abdomen was closed followed by a 4-h reperfusion; IP group(n = 6) rats underwent three cycles of 5 min ischemia and 5 min reperfusion,then clamping of the SMA for 40 min,then the abdomen was closed and a 4-h reperfusion followed.All animals were euthanized by barbiturate overdose(150 mg/kg pentobarbital sodium,i.v.) for tissue collection,and the SMA was isolated via median abdominal incision.Intestinal histologic injury was observed.Malondialdehyde(MDA),myeloperoxidase(MPO) and tumor necrosis factor(TNF)-a concentrations in intestinal tissue were measured.Intercellular adhesion molecule(ICAM)-1 and vascular cell adhesion molecule(VCAM)-1 expression,as well as nuclear factor(NF)-κB activity and expression in intestinal tissue were also determined.RESULTS: Compared with the IR group,IP reduced IR-induced histologic injury of the intestine in rats(2.00 ± 0.71 vs 3.60 ± 0.84,P < 0.05).IP significantly inhibited the increase in MDA content(5.6 ± 0.15 μmol/L vs 6.84 ± 0.18 μmol/L,P < 0.01),MPO activity(0.13 ± 0.01 U/L vs 0.24 ± 0.01 U/L,P < 0.01),and TNF-a levels(7.79 ± 2.35 pg/m L vs 10.87 ± 2.48 pg/m L,P < 0.05) in the intestinal tissue of rats.IP also markedly ameliorated the increase in ICAM-1(204.67 ± 53.27 vs 353.33 ± 45.19,P < 0.05) and VCAM-1(256.67 ± 58.59 vs 377.33 ± 41.42,P < 0.05) protein expression in the intestinal tissues.Additionally,IP remarkably decreased NF-κB activity(0.48 ± 0.16 vs 0.76 ± 0.22,P < 0.05) and protein expression(320.23 ± 38.16 vs 520.76 ± 40.53,P < 0.01) in rat intestinal tissue.CONCLUSION: IP may protect against IR-induced intestinal injury by attenuation of the neutrophilendothelial adhesion cascade via reducing ICAM-1 and VCAM-1 expression and TNF-a-induced NF-κB signaling pathway activity.

Expression and distribution of TNF-α and PGE_2 of periodontal tissues in rat periodontitis model

Objective:To simulate the expression of TNF-α and PGE2 of periodontal tissues in rat periodontitis model.Methods:40 Wistar rats were randomly divided into the periodontitis group and the control group（n=20）.After the successful establishment of periodontitis rat model,raising for six weeks before the animals were sacrificed.The periodontal tissues were obtained and made into slices.Observed the histopathological changes of the periodontal tissues and measured TNF-α,PGE2 levels change by immunohistochemistry.Western blot analysis and EI.ISA.Results:TNF-α,PGE2 expression of the periodontitis group was significantly higher than that in the control group,the difference was significant（P【0.0S）.Conclusions:The TNF-α.PGE2expression of the rat periodontal tissue in the periodontitis group was significantly higher than the control group.

Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus

Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both an-tioxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum （by intragastric administration） in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-a and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and an-tiinflammatory actions.

Atorvastatin Attenuates TNF-alpha Production via Heme Oxygenase-1 Pathway in LPS-stimulated RAW264.7 Macrophages

Objective To assess the effect of atorvastatin on lipopolysaccharide （LPS）-induced TNF-a production in RAW264.7 macrophages. Methods RAW264.7 macrophages were treated in different LPS concentrations or at different time points with or without atorvastatin. TNF-a level in supernatant was measured. Expressions of TNF-a mRNA and protein and heme oxygenase-1 （HO-1） were detected by ELISA, PCR, and Western blot, respectively. HO activity was assayed. Results LPS significantly increased the TNF-a expression and secretion in a dose- and time-dependent manner. The HO-1 activity and HO-1 expression level were significantly higher after atorvastatin treatment than before atorvastatin treatment and attenuated by SB203580 and PD98059 but not by SP600125, suggesting that the ERK and p38 mitogen-activated protein kinase （MAPK） pathways participate in regulating the above-mentioned effects of atorvastatin. Moreover, the HO-1 activity suppressed by SnPP or the HO-1 expression inhibited by siRNA significantly attenuated the effect of atorvastatin on TNF-c~ expression and production in LPS-stimulated macrophages. Conclusion Atorvastatin can attenuate LPS-induced TNF-e expression and production by activating HO-1 via the ERK and p38 MAPK pathways, suggesting that atorvastatin can be used in treatment of inflammatory diseases such as sepsis, especially in those with atherosclerotic diseases.

Impact of Probiotics on Toll-like Receptor 4 Expression in an Experimental Model of Ulcerative Colitis

Toll-like receptors （TLRs） are key components of the innate immune system which trigger antimicrobial host defense responses. This study aimed to investigate the impact of probiotics （Lactoba- cillus, Bifiidobacterium） on the expression of TLR4 and tumor necrosis factor-alpha （TNF-α in the co- lon mucosa of rat experimental ulcerative colitis model induced by trinitrobenzene sulfonic acid （TNBS）/ethanol and immune complexes. The gross and histological changes of the colonic mucosa were observed and assessed by the means-standard deviation and independent samples t-test. The pro- tein expression levels of TLR4 and TNF-α were detected by using immunohistochemistry and Westem blotting, respectively. It was revealed that there was visible infiltration of inflammatory cells, formation of crypt abscess, and the reduction of goblet cells in the colon tissue of experimental models. As com- pared with the control group, the levels of TLR4 and TNF-α protein were significantly increased in the model group （P〈0.01 for both）. No significant difference was found in the expression of TLR4 and TNF-α between the two-week probiotics treatment group and the model group （P〉0.05）, whereas sig- nificant reductions were shown in rats which were treated with probiotics for four weeks as compared with the model group （P〈0.01）. There was no significant difference between two probiotics-treated groups. Our results implied that probiotics were likely to play a key role in protecting ulcerative colitis by reducing the inflammatory factor TNF-α expression through inhibiting the TLR4 expression in the colon tissue of experimental models.

Curcumin prevents indomethacin-induced gastropathy in rats

AIM： To investigate the effects of curcumin on gastric microcirculation and inflammation in rats with indo- methacin-induced gastric damage. METHODS： Male Sprague-Dawley rats were randomly divided into three groups. Group 1 （control group, n = 5） was fed with olive oil and 5% NaHCOf （vehicle）. Group 2 [indomethacin （IMN） group, n = 5] was fed with olive oil 30 min prior to indomethacin 150 mg/kg body weight （BW） dissolved in 5% NaHCO3- at time 0th and 4th h. Group 3 （INN ± Cur group, n = 4） was fed with curcumin 200 mg/kg BW dissolved in olive oil 0.5 mL, 30 min prior to indomethacin at 0th and 4th h. Leukocyte-endothelium interactions at postcapillary venules were recorded after acridine orange injection. Blood samples were determined for intercellular ad- hesion molecule （ICAM）-1 and tumor necrosis factor （TNF）-a levels using enzyme linked immunosorbent assay method. Finally, the stomach was removed for histopathological examination for gastric lesions and grading for neutrophil infiltration. RESULTS： In group 2, the leukocyte adherence in postcapillary venules was significantly increased com- pared to the control group （6.40±2.30 cells/frame vs 1.20 ± 0.83 cells/frame, P = 0.001）. Pretreatment with curcumin caused leukocyte adherence to postcapil- lary venule to decline （3.00±0.81 cells/frame vs 6.40 ± 2.30 cells/frame, P = 0.027）. The levels of ICAM-1 and TNF-aincreased significantly in the indomethacin- treated group compared with the control group （1106.50 ± 504.22 pg/mL vs 336.93 a= 224.82 pg/mL, P = 0.011 and 230.92±114.47 pg/mL vs 47.13±65.59 pg/mL, P = 0.009 respectively）. Pretreatment with curcumin sig- nificantly decreased the elevation of ICAM-1 and TNF-a levels compared to treatment with indomethacin alone （413.66 ± 147.74 pg/mL vs 1106.50 ± 504.22 pg/mL, P = 0.019 and 58.27 ± 67.74 pg/mL vs 230.92 ± 114.47 pg/mL, P = 0.013 respectively）. The histological appear- ance of the stomach in the control group was normal. In the indomethacin-treated group, the stomachs showed a mild to moderate neutrophil infiltration score. Gastric lesions were erosive and ulcerative. In rats treated with indomethacin and curcumin, stomach histopathology improved and showed only a mild neutrophil infiltration score and fewer erosive lesions in the gastric mucosa. CONCLUSION： The results indicate that curcumin pre- vents indomethacin-induced gastropathy through the improvement of gastric microcirculation by attenuating the level of ICAM-1 and TNF-a,

Berberine inhibits inflammatory activation of rat brain microglia

Chronic activation of microglial cells endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. Berberine, the effective ingredient of Coptidis Rhizoma and Cortex Phellodendti, has a wide range of pharmacological functions, including anti-inflammatory, anti-atherosclerotic and anti-cancer effects. The neuroprotective potential of berberine has previously been demonstrated. The present study aimed to examine whether berberine could repress microglial activation and can be considered a potential therapeutic candidate to target neurodegenerative diseases. Primary microglial cells and BV2 microglial cells were cultured and stimulated with bacterial lipopolysaccharide （LPS）. Berberine chloride was treated prior to LPS or simultaneously with LPS stimulation. Results revealed that berberine was effective at inhibiting nitric oxide release from primary microglial cells when cells were exposed to the compound prior to LPS or simultaneously with LPS. It also reduced the LPS-stimulated production of tumor necrosis factor-α, interleukin-1β, prostaglandin E2, and intracellular reactive oxygen species and nuclear factor-kappa activation. Additionally, berberine reduced nitric oxide release from microglia stimulated with interferon-γ and amyloid β. These results suggest that berberine provides neuroprotection by reducing the production of various neurotoxic molecules from activated microglia.

Neuroprotective effects of vagus nerve stimulation on traumatic brain injury

Previous studies have shown that vagus nerve stimulation can improve the prognosis of trau- matic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain ex- plosive injury received continuous stimulation （10 V, 5 Hz, 5 ms, 20 minutes） of the right cervical vagus nerve. Tumor necrosis factor-a, interleukin-l~ and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-a and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-a, interleukin-1 β and interleukin-10 in the serum and brain tissue.

TNF-α gene polymorphisms: association with age-related macular degeneration in Russian population

AIM: To study polymorphisms in promotor regions of tumor necrosis factor(TNF)-α TNF-863 A/C(rs1800630), TNF-308 A/G(rs1800629), and TNF-238 A/G(rs361525) in patients with age-related macular degeneration(AMD) and associations of complex TNF-α genotypes with AMD. METHODS: One hundred and two patients(82 women, 20 men; mean age 64.2±1.2 y) with AMD and 100 healthy age-and sex-matched controls(82 women, 18 men; 60±1.4 y) were included in the study. All subjects were Caucasian, all subjects and their parents were inhabitants of Russia. Genomic DNA was obtained from EDTA-preserved blood using the standard phenol-chloroform method. Polymorphisms were detected by polymerase chain reaction followed by the restriction fragment length polymorphism method. The following TNF-α genotypes were studied: TNF-α-238 AA, GA, GG, TNF-α-308 AA, GA, GG, TNF-α-863 AA, CA, CC. RESULTS: Differences in TNF-α-863 and TNF-α-238 genotypes frequencies in patients with AMD and healthy controls were not found. The distribution of TNF-α-308 AA and TNF-α-308 GA genotypes was significantly different between the studied group and the controls [odds ratios(OR) =0.22, P=0.0287 and OR=2.91, P=0.0063, respectively]. TNF-863 CC/TNF-308 GA and TNF-308 GA/TNF-238 GG genotypes were associated with the increased risk of AMD(OR=2.48, P=0.0332 and OR=2.51, P=0.0187, respectively). Five genotypes combinations appeared to be protective. CONCLUSION: In the present study, single nucleotide polymorphisms and complex polymorphisms of one of the key inflammatory cytokines TNF-α, and a number of significant associations of these polymorphisms with AMD in Russian population have been shown. Complexanalysis of genotypes could be important in AMD risk factors detection and studying pathogenesis.

Curcumin reduces inflammatory reactions following transient cerebral ischemia/reperfusion injury

Inflammatory reactions are important pathophysiological mechanisms of ischemic brain injury. The present study analyzed the anti-inflammatory characteristics of curcumin via myeloperoxidase activity and nitric oxide content after 2-hour ischemia/24-hour reperfusion in Sprague Dawley rats. In addition, expressions of nuclear factor kappa B, tumor necrosis factor-α and interleukin-lβ protein were measured. Curcumin significantly reduced myeloperoxidase and nitric oxide synthase activities and suppressed expressions of nuclear factor kappa B, tumor necrosis factor-α, and interleukin-lβ in ischemia/reperfusion brain tissue. Results suggested that the neuroprotective effect of curcumin following cerebral ischemia/reperfusion injury could be associated with inhibition of inflammatory reactions.

Visfatin levels in patients with severe pneumonia

BACKGROUND： As a cytokine highly expressed in internal organs, visfatin could be used as a biomarker of systemic inflammation response for chronic obstructive pulmonary diseases, but few studies have reported the use of visfatin in severe pneumonia. The present study was undertaken to determine the plasma levels of visfatin in patients with severe pneumonia. METHODS：A total of 70 patients, including 40 patients with severe pneumonia （group A） and 30 patients with non severe pneumonia （group B） who had been admitted to the ICU from June 2009 to June 2010, were enrolled in this prospective study. And another 30 healthy physical examinees served as healthy controls （group C）. Patients were excluded if they suffered from severe diseases of the heart, brain and kidney, cancers, autoimmune diseases, or received special treatment in the latest month. The plasma levels of visfatin, IL-6, IL-8 and TNF-α were measured by ELISA, while the level of CRP was determined by immuneturbidimetry, and the routine blood test was performed. Blood gas analysis and Acute Physiology and Chronic Health Evaluation II （APACHE II） were performed in patients with pneumonia. Comparisons between the groups were conducted by Student＇s t test, ANOVA or nonparametric test. Correlation analysis was carried out by Pearson＇s correlation test or Spearman＇s rank-order correlation test. RESULTS：The plasma level of visfatin in group A was significantly higher than that in groups B and C （P〈0.001）, and the level of visfatin in group B was significantly higher than that in group C （P〈0.001）. The plasma level of visfatin was positively correlated with CRP, TNF-α, APACHE II and PMN% in patients with severe pneumonia （rho=0.653, r=0.554, r=0.558, r=0.484, respectively, P〈0.05 for all）, while it was negatively correlated with PaO2 and PaO2/FiO2 （rho=-0.422, r=-0.543, respectively, P〈0.05 for all）. CONCLUSION：Visfatin may be involved in the systematic inflammation response in patients with severe pneumonia as a pro-inflammatory cytokine, and it is valuable in assessing the severity of pneumonia..

Temporal dynamic changes of connexin 43 expression in C6 cells following lipopolysaccharide stimulation

Connexin 43, a gap junction protein, is expressed mainly in glia in the central nervous system. Neuroinflammation plays an important role in central nervous system injury. Changes to glial connexin 43 levels and neuroinflammation may trigger brain injury and neurodegenerative diseases To illustrate the relationship between connexin 43 and neuroinflammation, this study investigated how connexin 43 expression levels change in lipopolysaccharide-stimulated rat C6 glioma cells. C6 cells were treated with 0.05, 0.25, 0.5, 1,2.5 and 5 IJg/mL lipopolysaccharide for 24 hours. The nitrite estimation-detected nitric oxide release level was elevated substantially after lipopolysaccharide stimulation. To test the transcriptional level changes of inducible nitric oxide synthase, tumor necrosis factor-a and connexin 43 mRNA, C6 cells were treated with 5 pg/mL lipopolysaccharide for 3 48 hours. Reverse transcription-PCR showed that the expression of inducible nitric oxide synthase and tumor necrosis factor-a mRNA increased over time, but connexin 43 mRNA levels increased in lipopolysaccharide-stimulated C6 cells at 3 and 6 hours, and then decreased from 12 to 48 hours. Connexin 43 protein expression was detected by immunofluorescence staining, and the protein levels matched the mRNA expression levels. These results suggest that connexin 43 expression is biphasic in lipopo^ysacchadde-induced neuroinflammation in C6 cells, which may be correlated with the connexin 43 compensatory mechanism.