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.

Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.

Pretreated Oenan the Javanica extract increases anti-inflammatory cytokines, attenuates gliosis, and protects hippocampal neurons following transient global cerebral ischemia in gerbils

Recently,we have reported that Oenanthe javanica extract(OJE)displays strong neuroprotective effect against ischemic damage after transient global cerebral ischemia.However,neuroprotective mechanisms of OJE have not been fully identified.Thus,this study investigated the neuroprotection of OJE in the hippocampal CA1 area and its anti-inflammatory activity in gerbils subjected to 5 minutes of transient global cerebral ischemia.We treated the animals by intragastrical injection of OJE(100 and 200 mg/kg)once daily for 1 week prior to transient global cerebral ischemia.Neuroprotection of OJE was observed by immunohistochemistry for neuronal nuclear antigen and histofluorescence staining for Fluoro-Jade B.Immunohistochemistry of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 was done for astrocytosis and microgliosis,respectively.To investigate the neuroprotective mechanisms of OJE,we performed immunohistochemistry of tumor necrosis factor-alpha and interleukin-2 for pro-inflammatory function and interleukin-4 and interleukin-13 for anti-inflammatory function.When we treated the animals by intragastrical administration of 200 mg/kg of OJE,hippocampal CA1 pyramidal neurons were protected from transient global cerebral ischemia and cerebral ischemia-induced gliosis was inhibited in the ischemic hippocampal CA1 area.We also found that interleukin-4 and-13 immunoreactivities were significantly increased in pyramidal neurons of the ischemic CA1 area after OJE pretreatment,and the increased immunoreactivities were sustained in the CA1 pyramidal neurons after transient global cerebral ischemia.However,OJE pretreatment did not increase interleukin-2 and tumor necrosis factor-alpha immunoreactivities in the CA1 pyramidal neurons.Our findings suggest that pretreatment with OJE can protect neurons and attenuate gliosis from transient global cerebral ischemia via increasing expressions of interleukin-4 and-13.The experimental plan of this study was reviewed and approved by the Institutional Animal Care and Use Committee(IACUC)in Kangwon National University(approval No.KW-160802-1)on August 10,2016.

Pro-and anti-inflammatory cytokines profiles among Nigerian children infected with Plasmodium falciparum malaria

Objective:To examine array of some pro- and anti-inflammatory cytokines,namely, interleukin-4(IL-4),interleukin-10(IL-10),interferon-γ(IFN-γ),interleukin-5(IL-5), interleukin-6(IL-6),interleukin-12(IL-12) and tumor necrosis factor-α(TNF-α) concentrations in some Nigerians with falciparum malaria.Methods:Sera were obtained from the blood samples of 96 Nigerian children with Plasmodium falciparum infection.The sera were subjected to cytokine evaluation using commercial standard enzyme linked immunosorbent assay kits(Abcam,UK).Results:Mean pro-inflammatory cytokines in serum of children with uncomplicated and complicated malaria were IL-5 482.2 pg/mL versus 526.7 pg/mL,IL-6 98.8 pg/mL versus 82.6 pg/mL,IL-12 24.1 pg/mL versus 15.9 pg/mL,TNF-α107 pg/mL versus 511.7 pg/mL and IFN- 7 2.1 pg/mL versus 2.5 pg/mL.The anti-inflammatory cytokines status of IL-4 were 4.7 pg/mL versus 20.3 pg/mL,and IL-10 were 216 pg/mL versus 143.8 pg/mL in uncomplicated versus complicated/severe malaria cases.Participants with uncomplicated malaria had mean parasitaemia level of 3 158.9 parasites/μL while mean parasitaemia level for participants with complicated malaria was 12 550.5 parasite/μL and this difference was statistically significant(χ~2 =5 614.6,P【0.05).The difference between mean haemoglobin level for uncomplicated malaria(9.6 g/dL) and severe malaria(3.9 g/dL) was statistically significant (χ~2 = 2.3,P【0.05).The relationship between serum level of IL-6,IL-12,IFN-γ,IL-10 and IL-4 and ages showed positive correlation at r=0.92,0.99,0.86,0.95 and 0.85,respectively;while IL-5 and TNF-αhad negative correlation at r=-0.99 and -0.99,respectively.Conclusion: IL-4,IL-5,IL-6,IL-10,IL-12,TNF-αand IFN-γare involved in the immunopathology and immunoregulation of uncomplicated and complicated malaria infections.IL-6,IL-12,IFN-γand IL-10 depressed in complicated/severe malaria may not provide any protective immunity and may be indicators of poor prognosis in Plasmodium falciparum infected Nigerian children.

Effects of structural modification of anti-inflammatory steroidal antedrug on pro-inflammatory mediators and inhibitory cytokines in human alveolar epithelial cells

The anti-inflammatory effects of the new ster-oidal antedrug, 21-acetyloxy-9α-fluoro-11β-hy-droxyl-3, 20-dioxo-1, 4-pregnadieno-[16α, 17α-d] isoxazoline (FP-ISO-21AC), on nitric oxide (NO) and interleukin 8 (IL-8) production, were inves-tigated together with its parent steroid predni-solone (PRED). PRED is one of the anti-in-flammatory steroids but has systemic side ef-fects which limit the use of it. PRED was modi-fied with ‘antedrug concept’ to create safer drugs that attack problems such as inflamma-tion, then quickly become inactive before they can cause systemic side effect. We had a test about the effect of the modified anti-inflamma-tory steroidal antedrug on anti-inflammatory activity. The present study evaluated their ability to inhibit cytokine-induced NO and IL-8 produc-tion in human alveolar epithelial cells. We also investigated their ability to enhance the expres-sion of inhibitory cytokine receptor, interleukin 22 receptor (IL-22R) in human alveolar epithelial cells. Our results showed that FP-ISO-21AC sh- owed higher ability to inhibit the cytokine - in-duced production of NO than PRED. Exogenous IL-22 was added to the media of both human alveolar epithelial cells (A549) and human lung fibroblast (HLF-1). In the presence of the ex-ogenous inhibitory cytokine IL-22, further re-duction of NO production was observed in A549 cells, which express IL-22R, but not in HLF1, which does not express IL-22R. These data suggested that the steroidal antedrugs en-hanced the expression of IL-22R. FP-ISO- 21AC showed higher potency than PRED to restore the expression of IL-22R. FP-ISO-21AC further reduced NO production to 27% and PRED further reduced NO production to 39%. In con-clusion, a synthesized steroidal antedrug FP- ISO-21AC showed higher anti-inflammatory ef-fects than PRED by inhibiting the expression of pro-inflammatory mediator NO and stimulating the expression of IL-22R.

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.

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.

Role of inflammatory cytokines in peripheral nerve injury

Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery. The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration. Cytokines can be divided into pro- and anti-inflammatory cytokines that upregulate and downregulate, respectively, the production of inflammatory mediators. While pro-inflammatory cytokines are expressed in the first phase of Wallerian degeneration and promote the recruitment of macrophages, anti-inflammatory cytokines are expressed after this recruitment and downregulate the production of all cytokines, thus determining the end of the process. In this review, we describe the major inflammatory cytokines involved in Wallerian degeneration and the early phases of nerve regeneration. In particular, we focus on interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor-β, interleukin-10 and transforming growth factor-β.

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.

Pharmacological evaluation of a novel enhydrazone ester (CEE-1) as a dual inhibitor of the release of pro-inflammatory cytokines and prostanoids from human monocytes

CEE-1 (ethyl 4-phenylhydrazinocyclohex-3-en-2-oxo-6-phenyl-1-oate)—a novel enhydrazone ester, was tested in vitro for anti-inflammatory activity against the release of pro-inflammatory cytokine and prostanoid from lipopolysaccharide-activated human monocytes or human monocytic cell line (U937). The effects were compared with those of standard anti-inflammatory drugs dexamethasone and indomethacin. CEE-1 potently and strongly inhibited the release of both tumor necrosis factor-alpha (TNF-α) and prostaglandin E2 (PGE2). The concentrations producing 50% inhibition (IC50 values) were 2.0 μM and 2.4 μM for TNF-α and PGE2, respectively. At 30 μM, the drug achieved almost complete inhibition of both mediators. Dexamethasone had similar effects but indomethacin inhibited only the PGE2 release, and although CEE-1 was less potent than these two drugs, it had comparable efficacy. The compound appeared to act, at least, in part by inhibiting the up-regulation of the mRNA for TNF-α as well as that of the prostanoid-synthetic enzyme, cyclo-oxygenase-2 (COX-2). However, like dexamethasone, but unlike indomethacin, CEE-1 did not affect COX-2 enzyme function. Thus, the profile of activity of CEE-1 is similar to that of steroids rather than the non-steroidal anti-inflammatory drugs. Structure-activity study showed that the presence of a simple aromatic ring attached via an NH-NH group was critical for activity. At the concentrations that completely inhibited mediator release, the compound displayed no significant in vitro toxicity on the cells. These results show that CEE-1 is a dual inhibitor of the release of cytokines and prostanoids, and therefore could be a potential alternative to steroids in the treatment of inflammatory diseases.

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。

In vitro modulation of TH1 and TH2 cytokine expression by edible tuber of Dioscorea alata and study of correlation patterns of the cytokine expression

The underground tuber of Dioscorea alata is a palatable food and is also claimed to have therapeutic effects.Various groups of researchers demonstrated different activities of this tuber such as antioxidant,hepatoprotective,anti-ulcer and anti-diabetic activities.Therefore,the aim of the present study was to evaluate the immunomodulatory potentialities of 70%hydro-methanolic extract of D.alata underground tubers by investigating different parameters like the expression of interferon gamma(IFN-),interleukin(IL)-2,IL-4 and IL-10,in addition to its effect on the proliferation of murine splenic T-lymphocytes in vitro.Results demonstrated that D.alata can actively polarize the TH0 lymphocyte population towards the expression of TH1 immune response by up-regulating the IFN-and IL-2 expression and down-regulating the IL-4 and IL-10 expression.The tuber extract also proved to possess mitogenic activity as evidenced by the proliferation of lymphocytes in vitro.©2014 Beijing Academy of Food Sciences.Production and hosting by Elsevier B.V.All rights reserved.

Differences in the Histopathology and Cytokine Expression Pattern between Chronological Aging and Photoaging of Hairless Mice Skin

Skin photoaging is a complex, multifactorial process resulting in functional and structural changes of the skin, and different phenotypes from chronological skin aging are well-recognized. Ultraviolet (UV)-irradiated hairless mice have been used as a skin photoaging animal model. However, differences in morphology and gene expression patterns between UV-induced and chronological skin changes in this mouse model have not been fully elucidated. Here we investigated differences in histopathology and cytokine expression between UV-irradiated and non-irradiated aged hairless mice to clarify the factor(s) that differentiate photoaging from chronological skin aging phenotypes. Eight-week-old HR-1 hairless mice were divided into UV-irradiated (UV-irradiated mice) and non-irradiated (control mice) groups. Irradiation was performed three times per week for 10 weeks. In addition, 30-week-old HR-1 hairless mice were reared until 70 weeks of age without UV irradiation (aged mice). Histopathologies revealed that the flattening of dermal-epidermal junctions and epidermal thickening were observed only in UV-irradiated mice. Decreases in fine elastic fibers just beneath the epidermis, the thickening of elastic fibers in the reticular dermis, and the accumulation of glycosaminoglycans were more prominent in UV-irradiated mice as compared to non-irradiated aged mice. Quantitative PCR analyses revealed that UV-irradiated mice showed an increase in the expression of IFN-γ. In contrast, aged mice exhibited proportional up-regulation of both pro-inflammatory and anti-inflammatory cytokines. The IFN-γ/IL-4 ratio, an indicator for the balance of pro-inflammatory and anti-inflammatory cytokines, was significantly higher in UV-irradiated mice as compared to control and non-irradiated aged mice. An elevated IFN-γ/IL-4 ratio was also observed in aged senescence-accelerated mouse-prone 1 (SAMP1) mice, a spontaneous skin photoaging model we recently reported. Thus, an imbalance between pro-inflammatory and anti-inflammatory cytokines might be a key factor to differentiate photoaged skin from chronologically-aged skin.