Effects of estradiol and progesterone on the proinflammatory cytokine production by mononuclear cells from patients with chronic hepatitis C

AIM:To investigate the effects of estradiol (E2) and progesterone on the unstimulated and oxidative stressstimulated production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, and macrophage chemotactic protein (MCP)-1 by peripheral blood mononuclear cells (PBMCs) from patients with chronic hepatitis C and healthy controls. METHODS:The PBMCs were separated from agematched 72 males and 71 females with and without chronic hepatitis C, who were divided into two groups based on a mean menopausal age of 50 years. Oxidative stress was induced by hydrogen peroxide in the cells incubated in serum-free media. Cytokines in the culture supernatant were measured by an enzyme-linked immunosorbent assay. RESULTS:The highest levels of the spontaneous production of TNF-α, IL-1β, IL-8, and MCP-1 by the unstimulated PBMCs were in the older male patients with chronic hepatitis C and the lowest levels were in the premenopausal female healthy controls. E2 inhibited the cytokine production by the unstimulated PBMCs from the older male and post-menopausal female patients, which was further stimulated by progesterone. The exposure to hydrogen peroxide in the PBMCs from the younger male and pre-menopausal female healthy subjects induced the production of cytokines. The change rates of the hydrogen peroxide-stimulated cytokine production were suppressed by E2 and enhanced by progesterone. CONCLUSION:These findings suggest that E2 may play a favorable role in the course of persistent liver injury by preventing the accumulation of monocytes-macrophages and by inhibiting proinflammatory cytokine production, whereas progesterone may counteract the favorable E2 effects.

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-αand 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.Graph Pad 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/m L and stabilized the membrane of red blood cells with an IC50 value of(275.9±19.1)μg/m L.The extract showed no changes in cell morphology or cytotoxicity up to the concentration of 20μg/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.

Lipid-associated membrane proteins of Mycoplasma penetrans induce production of proinflammatory cytokines in human monocytic cells

The aim of this study is to explore potential pathogenicity of Mycoplasma penetrans, and to investigate whether M. penetrans lipid-associated membrane proteins （LAMPs） could induce human monocytic cell line （THP- 1 ） to produce some proinflammatory cytokines in vitro, including interleukin- 1β （ IL- 1β）, tumor necrosis factor alpha （TNF-α）, and IL-8. THP-1 was stimulated with different concentrations of M.penetrans LAMPs and at different time to analyze the production of human IL-1β, TNF-α and IL-8. The protein levels of human IL-1β, TNF-α and IL-8 were measured by enzyme-linked immunoadsorbent assay （ELISA） and the mRNA levels of these proinflammatory cytokines were detected by reverse transcriptase-PCR （RT-PCR）. It was demonstrated in the present study that the production of IL-1β, TNF-α and IL-8 increased in dose- and time-dependent manner after stimulation with M. penetrans LAMPs in THP-1 cells. M. penetrans LAMPs also induced the expression of IL-1β, TNF-α and IL-8 mRNA. The production of IL-1β, TNF-α and IL-8 and the expression of mRNA were down-regulated by pyrrolidine dithiocarbamate （PDTC）. This study demonstrated that M. penetrans LAMPs can induce the production of proinflammatory cytokines in human monocytic cells in vitro, thus suggesting that it may be an important etiological factor.

Regulation of the expression of proinflammatory cytokines induced by SARS-CoV-2

An outbreak of a novel coronavirus was reported in Wuhan,China,in late 2019.It has spread rapidly through China and many other countries,causing a global pandemic.Since February 2020,over 28 countries/regions have reported confirmed cases.Individuals with the infection known as coronavirus disease-19(COVID-19)have similar clinical features as severe acute respiratory syndrome first encountered 17 years ago,with fever,cough,and upper airway congestion,along with high production of proinflammatory cytokines(PICs),which form a cytokine storm.PICs induced by COVID-19 include interleukin(IL)-6,IL-17,and monocyte chemoattractant protein-1.The production of cytokines is regulated by activated nuclear factor-kB and involves downstream pathways such as Janus kinase/signal transducers and activators transcription.Protein expression is also regulated by post-translational modification of chromosomal markers.Lysine residues in the peptide tails stretching out from the core of histones bind the sequence upstream of the coding portion of genomic DNA.Covalent modification,particularly methylation,activates or represses gene transcription.PICs have been reported to be induced by histone modification and stimulate exudation of hyaluronic acid,which is implicated in the occurrence of COVID-19.These findings indicate the impact of the expression of PICs on the pathogenesis and therapeutic targeting of COVID-19.

Effects of p38 MAPK inhibitor on the rat pain behavior and proinflammatory cytokines in a metastatic bone cancer pain model

Objective： To observe the effects of p38 mitogen activated protein kinase （MAPK） inhibitor SB203580 by intrathecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone cancer pain induced by breast cancer cells. Methods： Eleven rats were used to establish the models of bone cancer pain, six rats were treated by intrathecal SB203580 injection, and the other 5 were as the controls. The paw withdrawal latency （PWL）, histology and the spinal levels of IL-1β and TNF-α were detected. Results： All the 11 rats presented evident bone destruction and thermal hyperalgesia after intra-tibial injection of breast cancer cells. No effect of SB203580 on the bone destruction was observed. However, following intrathecal injection of SB203580, the left PWLs （12.12± 1.26 s at 16 days and 12.99 ± 1.65 s at 19 days） were significant higher than that of controls （9.05 ± 1.08 s at 16 days and 8.55 ± 1.60 s at 19 days）, P 〈 0.05. Meanwhile, inkathecal injection of SB203580 evidently reduced the levels of spinal IL-1β and TNF-α. Conclusion： Intrathecal injection of SB203580 in a rat model of bone cancer pain cannot prevent the tibial destruction but significantly depress the thermalgia sensitivity, which might result from inhibiting inkacellular p38 MAPK signaling transduction, and thereby reducing the release of the proinflammatory cytokines.

The Diagnostic Value of the Investigation of the Proinflammatory and Anti-inflammatory Cytokines Levels in the Immune System of Patients with Breast Cancer

Diagnostic value of serumal levels of proinflammatory(TNF-α,IL-1β,IL-6 and IFN-γ) and anti-inflammatory(IL-4 and IL-10) cytokines of immune system is investigated at 54 mammary glands sick by a cancer.The analysis carried out has allowed to tap the raised concentration of such proinflammatory cytokines,as IL-1β,TNF-α and IL-6 in serum of peripheric blood of MGC patients.The analysis of antiinflammatory cytokines in Serum of peripheric blood of MGC patients also has taped authentically raised value of IL-4 and IL-10.The obtained data testify to presence imbalance cellular and humoral factors of the immune system which studying will serve as the important diagnostic criterion of breast cancer.

Adipokines,cytokines and body fat stores in hepatitis Cvirus liver steatosis

AIM: To identify patients with or without liver steatosis and its severity in treatment-na?ve patients affected by hepatitis C virus(HCV) infection.METHODS: We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body(by densitometry), hormones [insulin, homeostatic model assessment(HOMA)], adipokines(resistin, adiponectin, leptin), and cytokines(tumor necrosis factor α, interleukin-6).RESULTS: Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunkfat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin.CONCLUSION: Steatosis in HCV infection is common(67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines.

Production of proinflammatory cytokines in the human THP-1 monocyte cell line following induction by Tp0751,a recombinant protein of Treponema pallidum

The tissue destruction characteristic of syphilis infection may be caused by inflammation due to Treponema pallidum and the ensuing immune responses to the pathogen.T.pallidum membrane proteins are thought to be potent inducers of inflammation during the early stages of infection.However,the actual membrane proteins that induce inflammatory cytokine production are not known,nor are the molecular mechanisms responsible for triggering and sustaining the inflammatory cascades.In the present study,Tp0751 recombinant protein from T.pallidum was found to induce the production of proinflammatory cytokines,including TNF-α,IL-1βand IL-6,in a THP-1 human monocyte cell line.The signal transduction pathways involved in the production of these cytokines were then further investigated.No inhibition of TNF-a,IL-1β,or IL-6 production was observed following treatment with the SAPK/JNK specific inhibitor SP600125 or with an ERK inhibitor PD98059.By contrast,anti-TLR2 mAb,anti-CD14 mAb,and the p38 inhibitor SB203580 significantly inhibited the production of all three cytokines.In addition,pyrrolidine dithiocarbamate (PDTC),a specific inhibitor of NF-κB,profoundly inhibited the production of these cytokines.Tp0751 treatment strongly activated NF-κB,as revealed by Western blotting.However,NF-κB translocation was significantly inhibited by treatment with PDTC.These results indicated that TLR2,CD14,MAPKs/p38,and NF-κB might be implicated in the inflammatory reaction caused by T.pallidum infection.

Characteristics of Proinflammatory Cytokines and Chemokines in Airways of Asthmatics： Relationships with Disease Severity and Infiltration of Inflammatory Cells

Background：Increased proinflammatory cytokines and chemokines might contribute to infiltration of inflammatory cells and remodeling in airways of asthma.Although these molecules may be associated with asthma,there is lack of systemic evidence showing which and how important these events are in the disease.We aimed to analyze the concentrations of these molecules in the airways and relationships with disease severity and with airway infiltration of inflammatory cells in a large cohort of asthmatics （n =70,including 37 mild and 33 moderate/severe asthmatics） compared with controls （n =30）.Methods：Meso scale discovery system and commercial ELISA kits were used to measure the concentrations ofproinflammatory cytokines interleukin （IL）-1 β;tumor necrosis factor-alpha （TNF-α）;IL-6;and IL-17 and CC and CXC chemokines CCL2,CCL4,CCL 11,CCL 13,CCL17,CCL22,and CCL26 and CXCL8,CXCL9,CXCL10,and CXCL1 1 in bronchoalveolar lavage fluid of asthmatics and controls.Results：The concentrations ofIL-1,TNF-α,IL-6,CXCL8 and CXCL 10,and CCL4,CCL 11,CCL 17,and CCL22 were significantly elevated in asthmatics compared with controls （P 〈 0.05）.The concentrations of TNF-α and CXCL8,but not others,were negatively correlated with severity of disease （lung function forced expiratory volume in 1 s） （TNF-α vs.total：r =-0.359,P =0.002 vs.moderate/severe：r =-0.541,P =0.001;CXCL8 vs.total：r =-0.327,P =0.006 vs.moderate/severe：r =-0.625,P =0.0001,respectively）.In addition,concentrations of these two molecules were also correlated with the absolute numbers of infiltrating eosinophils and neutrophils in asthmatic airways.Conclusions：Increased concentrations of TNF-α and CXCL8 are associated with pathogenesis of asthma.Targeting these molecules might provide an alternative therapeutic for this disease.

Drug-containing serum of Xinfeng capsules protect against H9C2 from death by enhancing miRNA-21 and inhibiting toll-like receptor 4/phosphorylated p-38(p-p38)/p-p65 signaling pathway and proinflammatory cytokines expression

OBJECTIVE: To investigate effect of drug-containing serum of Xinfeng capsules on myocardial cell growth.METHODS: Drug-containing serum of Xinfeng capsules rat models were established by intragastricly administrated Xinfeng capsules. MTT assay wasused to evaluated H9C2 cells viability. H9C2 cells were divided into normal control group, triptolide group, lipopolysaccharide(LPS) group, drug-containing serum group and mi RNA-21 inhibitor group. micro RNA-21(mi RNA-21) inhibitor was structured and transfected into H9C2 cells. Western blot and immunofluorescence assay were applied to examine toll-like receptor 4(TLR4), phosphorylated p-38(p-p38) and p-p65 expression. Quantitative real-time PCR(q RT-PCR) was used to evaluated m RNA levels of mi RNA-21. Enzyme linked immunosorbent(ELISA) was used to measure tumor necrosis factor α(TNF-α), IL-6 and IL-17 levels.RESULTS: Drug-containing serum treatment significantly increased cell viability compared to LPS treated group. q RT-PCR results indicated that mi RNA-21 levels were significantly decreased in drugcontaining serum group compared to LPS group.Early and late apoptosis in drug-containing serum group were significantly decreased compared to LPS group. Western blot and immunofluorescence assay results showed that TLR4, p-p38 and p-p65 levels in drug-containing serum group were significantly decreased compared to LPS group. ELISA findings indicated that drug-containing serum significantly decreased inflammatory cytokine levels of TNF-α, IL-6 and IL-17.CONCLUSION: Drug-containing serum of Xinfeng capsules protect against lipopolysaccharide instructed H9C2 cells from death by enhancing mi RNA-21 and inhibiting TLR4/p-p38/p-p65 signaling pathway and proinflammatory cytokines expression.

Reproductive stage associated changes in plasma fatty acid profile and proinflammatory cytokine expression in rat mammary glands

Mastitis is a common disease for mammals all around the world. Figuring out why mastitis mainly occurs around parturition may be helpful for dealing with the disease. Lipolytic activity and oxidative stress take place around parturition, which may leads to alteration in fatty acids profile and proinflammatory cytokine expression. Thus, the aim of the present study was to further our understanding about the high incidence of mastitis around parturition by comparison of plasma fatty acid profile and mammary inflammation indicators at different reproductive stages. A total of 47 female rats were included in the present study. After mating, all the pregnant and non-pregnant rats began to receive the same experimental diet. Blood samples were collected at day 1 and 14 of gestation as well as day 3 postpartum.Mammary samples were collected at day 14 of gestation and day 3 postpartum from pregnant and nonpregnant rats. The results showed that rats at d 3 postpartum had greater(P < 0.05) plasma concentrations of non-esterified fatty acids(NEFA), arachidonic acid(ARA) and docosahexaenoic acid(DHA) as well as ARA: eicosapentaenoic acid(EPA) ratio than those at d 14 of gestation. The mRNA abundances of interleukin-1 β(IL-1β), tumor necrosis factor-α(TNF-α),IL-8 and xanthine oxidoreductase(XOR) in mammary of the pregnant rats were greater(P < 0.05) than those in age-matched non-pregnant rats.Rats at d 3 postpartum had higher(P < 0.05) protein expression levels of IL-1β and TNF-α as well as meloperoxidase(MPO) activity and polymorphonuclear neutrophils(PMN) prevalence than those at d 1 of gestation. The rats at d 3 postpartum also had greater(P < 0.05) IL-1β and MPO activity than those at d 14 of gestation. The results indicated that elevated mammary expression of proinflammatory cytokines and XOR as well as altered fatty acid profile around parturition might facilitate the recruitment of neutrophils into mammary glands.

霍山黄芽提取物对棕榈酸诱导下细胞脂质积累和炎症反应的影响

本研究比较分析了4个不同等级(特一级、特二级、一级、二级)霍山黄芽的主要生化成分和抗氧化活性差异,并选取特一级霍山黄芽,基于棕榈酸诱导的小鼠正常肝细胞AML-12(alpha mouse liver 12)、小鼠神经小胶质细胞BV-2、人肾皮质近曲小管上皮细胞HK-2(human kidney-2)、人胃腺癌细胞(human gastric adenocarcinoma,AGS)细胞模型,研究霍山黄芽提取物(Huoshanhuangya tea extract, HTE)对脂质积累和促炎细胞因子的影响。结果表明:特一级霍山黄芽的可溶性糖质量分数最低,咖啡碱质量分数、儿茶素类质量分数与游离氨基酸总量最高,且抗氧化活性最强;一定质量浓度的HTE处理后,棕榈酸诱导的AML-12、BV-2、HK-2、AGS细胞的细胞活力显著增加,棕榈酸诱导的脂质积累得到改善,棕榈酸诱导的AML-12、BV-2、HK-2细胞中肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)的释放水平明显降低。进一步探究其作用机制发现,HTE使BV-2细胞中炎症信号通路Toll样受体4(Toll-like receptor 4, TLR4)和核因子-κB RelA(nuclear factor-κB RelA, NF-κB p65)基因的表达下调,表明其可能通过抑制TLR4/NF-κB信号通路的活化来缓解棕榈酸诱导的BV-2细胞炎症损伤。

Antidepressant effects of Yuanzhi (Polygalae Radix) extract on chronic unpredictable mild stress-induced depression in rats: modulation of the NLRP3 inflammasome and NF-κB pathway

Objective To investigate the antidepressant effects of Yuanzhi(Polygalae Radix;PR)aqueous extract on chronic unpredictable mild stress(CUMS)-induced depression rat models and the underlying mechanisms.Methods A total of 40 male Sprague Dawley(SD)rats were randomly divided into control;model;low dose of PR(PR-L;0.5 g/kg);high dose of PR(PR-H;1 g/kg);and fluoxetine(10 mg/kg)groups;with 8 rats in each group.Except for the rats in control group;those in the other four groups underwent CUMS-induced depression modeling.PR and fluoxetine were administered intragastrically once daily;30 min prior to the CUMS procedure;for 14 consecu-tive days until the behavioral tests were performed.After CUMS modeling;the sucrose prefer-ence test(SPT);open field test(OFT);novelty-suppressed feeding test(NSFT);forced swim test(FST);and tail suspension test(TST)were employed to assess the pharmacological ef-fects of PR on the mitigation of depressive-like behaviors in rat models.Additionally;the en-zyme-linked immunosorbent assay(ELISA)was utilized to quantify the serum levels of tumor necrosis factor(TNF)-α;interleukin(IL)-6;and IL-1βin the rats.Western blot analysis was al-so conducted to evaluate the protein expression levels of nuclear factor kappa-B(NF-κB);in-ducible nitric oxide synthase(iNOS);cyclooxygenase-2(COX-2);nucleotide-binding oligomerization domain(NOD)-like receptor family pyrin domain containing 3(NLRP3);apoptosis-associated speck-like protein containing caspase recruitment domain(ASC);and caspase-1 in the hippocampal tissues of the rats.Immunofluorescence staining was per-formed to observe the morphological changes in ionized calcium-binding adapter molecule 1 positive(Iba-1+)cells in the dentate gyrus(DG)of rats with CUMS-induced depression.Results(i)Treatment with PR-H and fluoxetine resulted in significant enhancements in both the total distance and time the rats moved during tests(P<0.01 and P<0.05;respectively).Post-administration of PR-H and fluoxetine also led to statistically significant increase in su-crose preference among rats(P<0.05).Besides;PR-L;PR-H;and fluoxetine treatment markedly decreased the latency of ingestion(P<0.05;P<0.05;and P<0.01;respectively).As observed from the FST;PR-L;PR-H;and fluoxetine presented antidepressant effects on rats with CUMS-induced depression;leading to the reduction in time of their immobility(P<0.05;P<0.01;and P<0.01;respectively).The results of TST indicated reduced immobility time in rats receiving PR-H and fluoxetine treatment as well(P<0.01).(ii)Rats in model group showed an increase in the levels of Iba-1+microglia in their left and right brains in compari-son with control group(P<0.01).However;such increase was negated post PR treatment(P<0.01).Treatment with PR-L;PR-H;and fluoxetine considerably reduced the levels of inflam-matory factors(TNF-α;IL-1β;and IL-6;P<0.01).In addition;treatment of PR-L and PR-H ef-fectively counteracted the elevated levels of NLRP3;ASC;and caspase-1;and markedly down-regulated the expression levels of phosphorylated p65(p-p65);COX-2;and iNOS in rats’hip-pocampus(P<0.01).Conclusion Collectively;these findings indicate that PR exerts an antidepressant effect on rats with CUMS-induced depression partially through the modulation of the NLRP3 and NF-κB signaling pathways.

构树花粗多糖对紫外线诱导小鼠皮肤光损伤的保护作用及机制研究

研究构树花粗多糖对紫外线诱导小鼠皮肤光损伤的保护作用,并探讨其作用机制。采用雌性昆明鼠建立长波紫外线(UVA)诱导小鼠皮肤光损伤模型,并对小鼠背部皮肤进行评分。采用苏木素-伊红(HE)、Masson染色考察小鼠皮肤组织病理学变化、皮肤厚度和胶原纤维的变化;考察皮肤组织Hyp、抗氧化酶SOD、GSH-Px、CAT和MDA,TNF-α、IL-1β、IL-6的含量,MMPs、Nrf2、HO-1和NF-κB通路相关蛋白的表达。结果显示,构树花粗多糖凝胶可不同程度改善皮肤粗糙溃烂现象,抑制皮肤增厚,提高真皮层胶原含量,使胶原纤维排列趋于紧密;提高皮肤组织中SOD、GSH-Px和CAT活力,降低MDA含量(P<0.05);降低皮肤促炎因子TNF-α、IL-1β和IL-6含量(P<0.05);MMP-1和MMP-3含量明显降低(P<0.05),Nrf2蛋白和HO-1蛋白表达显著升高(P<0.01),p-p65/p65蛋白表达比例显著降低(P<0.05)。可见,构树花粗多糖对紫外线致小鼠皮肤光损伤具有显著的保护作用,其机制可能与构树花粗多糖激活Nrf2通路、增强SOD等抗氧化酶活性,抑制NF-κB通路有关。

开颅术后颅内感染患者脑脊液促炎性细胞因子及血脑屏障破坏程度与预后的关系分析

目的:分析开颅术后颅内感染患者脑脊液促炎性细胞因子及血脑屏障破坏程度与预后的关系。方法:回顾性分析2019年6月—2023年6月于宜春市人民医院实施开颅术后发生颅内感染的60例患者的临床资料。所有患者均检测脑脊液促炎性细胞因子[高迁移率族蛋白B-1(HMGB-1)、巨噬细胞炎症蛋白-1α(MIP-1α)、γ干扰素(IFN-γ)、白细胞介素-6(IL-6)]和血脑屏障破坏程度[脑脊液白蛋白/血清白蛋白比值]。根据预后情况[格拉斯哥昏迷量表(GCS)评分]将患者分为预后良好组(GCS评分>8分,n=24)和预后不良组(GCS评分≤8分,n=36),比较两组脑脊液HMGB-1、MIP-1α、IFN-γ、IL-6水平和脑脊液白蛋白/血清白蛋白比值,使用Pearson相关系数分析脑脊液促炎性细胞因子、血脑屏障破坏程度与预后的相关性。以受试者操作特征(ROC)曲线分析脑脊液促炎性细胞因子联合血脑屏障破坏程度预测开颅术后颅内感染患者预后情况的价值。结果:预后不良组脑脊液HMGB-1、MIP-1α、IFN-γ、IL-6水平和脑脊液白蛋白/血清白蛋白比值均显著高于预后良好组,差异均有统计学意义(P<0.05)。Pearson相关系数分析结果显示,脑脊液HMGB-1、MIP-1α、IFN-γ、IL-6水平和脑脊液白蛋白/血清白蛋白比值与开颅术后颅内感染患者GCS评分均呈负相关(P<0.05)。ROC曲线中,脑脊液HMGB-1、MIP-1α、IFN-γ、IL-6水平联合脑脊液白蛋白/血清白蛋白比值预测开颅术后颅内感染患者预后情况的曲线下面积(AUC)为0.977,敏感度为94.44%,特异度为92.50%。结论:开颅术后颅内感染患者脑脊液促炎性细胞因子及血脑屏障破坏程度与预后密切相关,临床可通过检测其水平,预测患者预后。

pORF5 plasmid protein of Chlamydia trachomatis induces MAPK-mediated pro-inflammatory cytokines via TLR2 activation in THP-1 cells

Infection with Chlamydia trachomatis induces inflammatory pathologies in the urogenital tract that can lead to infertility and ectopic pregnancy. Pathogenesis of infection has been mostly attributed to excessive cytokine production. However, precise mechanisms on how C. trachomatis triggers this production, and which protein（s） stimulate inflammatory cytokines remains unknown. In the present study, the C. trachomatis pORF5 protein induced tumor necrosis factor alpha （TNF-a）, interleukin-1 beta （IL-1β） and interleukin-8 （IL-8） in dose and time-dependent manners in the THP-1 human monocyte cell line. We found that intracellular p38/mitogen-activated protein kinase （MAPK） and extracellular signal-regulated kinase （ERK）/MAPK signaling pathways were required for the induction of TNF- a, IL-1β and IL-8. Blockade of toll-like receptor 2 （TLR2） signaling reduced induction levels of TNF-a, IL-8 and IL-1β. We concluded that the C. trachomatis pORF5 protein might contribute to the inflammatory processes associated with chlamydial infections.

A new compound W026B alleviates ischemic brain injury through inhibiting the production of inflammatory cytokines in pMCAO and tMCAO, and enhances the beneficial effect of tPA

Neruoprotection is considered as one of important therapeutic approaches for ischemic stroke.Inflammation plays an important role in the pathogenesis of ischemic stroke,and the inhibition of inflammation in the ischemic brain tissue may provide neuroprotective effect.In this study,we observed the influence of permanent middle cerebral artery occlussion（pMCAO） and transient MCAO（tMCAO） on NF-κB level and production of several inflammatory cytokines in injured hemisphere in mice,investigated the regulative effect of a new compound W026 B on these influences in the two MCAO models.In pMCAO model,10 μg/kg and 100 μg/kg of W026 B（i.v.） significantly reduced infarct volumes,100 μg/kg of W026 B significantly decreased neurologic deficit scores and brain water contents,and 10 μg/kg and 100 μg/kg of W026 B reduced Evans blue exudation from ischemic brain tissue.The level of NF-κB was elevated by 17.6 times in injured hemisphere,and the levels of TNF-α,IL-1β and IL-17 were elevated by 2.3 times,2.2 times and 3.8 times compared with the sham operation group,respectively,100 μg/kg of W026 B significantly reduced these inflammatory cytokines.In tMCAO model,the elevation of NF-κB,TNF-α,IL-1β and IL-17 was 2.3 times,1.4 times,1.5 times and 1.4 times compared with the sham operation group,respectively.Moreover,100 μg/kg of W026 B significantly decreased the levels of these inflammatory cytokines.In embolic MCAO mice model,W026 B alone significantly reduced infarct volumes,and combined application with tPA further reduced infarct volume.In conclusion,W026 B displayed significant protecive effect on three brain ischemia models.It could protect brain against injury induced by ischmia and ischemia-reperfusion through inhibiting the production of NF-κB,TNF-α,IL-1β and IL-17.These results suggest that W026 B has a value for further study.

Inhibition of lovastatin on proliferation and expression of promflammatory cytokines in cultured human glomerular mesangial cells

Objective To study the effects and mechanism of lovastatin on cell proliferation and expression of proinflammatory cytokines in cultured human glomerular mesangial cells.Methods The influence of lovastatin on HMC proliferation was evaluated with 3H-thymidine incorporation. mRNA expression of proinflammatory cytokines (IL-1β, IL-6, TNF-α, and MCP-1) and activation of NF-KB of HMC were measured using Reverse transcription-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA) respectively.Results Lovastatin was found to have inhibitory effects on human mesangial cell (HMC) proliferation and lipopolysaccharide ( LPS )-mediated human mesangine cell HMC mRNA expression of proinflammatory cytokines via activation of NF-KB. The effect of lovstatin on HMC could be prevented when the mevalonate and farnesol were added to the culture.Conclusion Lovastatin may decrease HMC proliferation and production of proinflammatory cytokines through the inhibition of NF-KB activation. This provided experimental evidence for further evaluation of the renal protective effect of HRI, suggesting that it may be a potent agent for prevention of progressive reanl diseases aside from its lipid-lowering effect.

高压氧同步舱内经颅直流电刺激治疗卒中后疲劳的临床研究

目的:评估高压氧同步舱内经颅直流电刺激治疗卒中后疲劳的临床疗效及对血清炎性因子的影响。方法:收集2021年6月~2022年11月在我院住院的90例出现卒中后疲劳的缺血性脑卒中患者,将其随机分为3组,每组30例。A组给予常规治疗,B组在A组治疗基础上加用高压氧同步舱内经颅直流电刺激治疗,C组在A组治疗基础上加用高压氧同步舱内经颅直流电假刺激治疗。评估3组治疗前及治疗4周后疲劳严重程度量表(FSS)、多维疲劳量表(MFI-20)评分变化,并检测血清C反应蛋白(CRP)、血清白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)浓度变化。结果:治疗后,A组FSS及MFI-20评分与治疗前相比有下降趋势,但差异无统计学意义,B组和C组的FSS及MFI-20评分均较治疗前及A组下降(均P<0.05),且B组低于C组(P<0.05)。治疗后,3组血清CRP、IL-1β、IL-6、TNF-α浓度均较治疗前降低(P<0.05)。治疗后,3组血清CRP浓度比较差异无统计学意义;B组和C组的IL-1β、IL-6、TNF-α浓度均低于A组(均P<0.05),且B组低于C组(P<0.05)。B组治疗4周后血清IL-1β、TNF-α、IL-6浓度与FSS评分、MFI-20评分均成正相关(P<0.05)。结论:高压氧同步舱内经颅直流电刺激能有效改善卒中后疲劳患者的疲劳程度,其机制可能与血清炎性因子浓度降低有关。