Omentin-1 prevents inflammation-induced osteoporosis by downregulating the pro-inflammatory cytokines

Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout（omentin-1^-/-） mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α（TNF-α）, we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.

Pro-inflammatory cytokines profiles in Nigerian pregnant women infected with Plasmodium falciparum malaria

Objective:To investigate the pro-inflammatory cytokines profiles in in Nigerian pregnant women infected with Plasmodium falciparum(P.falciparum) malaria.Methods:Peripheral, and placental blood samples were collected from 96 consenting volunteers comprising 76 P.falciparium infected pregnant women and 20 healthy uninfected pregnant women in Ekpoma.Nigeria,and subjected to ELISA for cytokines evaluation.Results:Increased serum concentrations of interferon-gamma(IFN-γ) was observed in infected pregnant women than their uninfected counterparts[(31.2±20.9) pg/mL vs(1.8±0.9) pg/mL]and these differences were statistically significant(χ~2= 26.18,P【0.05).The depressed levels of interleukin-12(IL- 12) seen in peripheral blood of the infected pregnant women than the uninfected women[(13.9±3.6) pg/mL vs(28.4±5.28) pg/mL]respectively was not statistically significant(χ~2= 4.96,P】0.05). The interleukin-6(IL-6) was significantly elevated in infected pregnant women(81.0±26.1 pg/mL) than in the uninfected pregnant women[(25.0±5.0) pg/mL](χ~2 = 29.58,P【0.05).In all, mean cytokines concentration of IL-6,IL-12 and IFN-γin the placental blood from infected pregnant women were(53.5±23.4) pg/mL,(8.7±6.9) pg/mL and(16.4±4.0) pg/mL,respectively. The multigravidae had a higher haemoglobin level of 10.2 g/dL and birth weight of 3 000 g than the primigrivadae with lower haemoglobin level of 7.5 g/dL and birth weight of 2 430 g. Conclusions:The elevated IFN-γamong the malarous pregnant women implicates it as the major cytokine mediator in the host responses to systematic P.falciparum malaria in our locality.

Reduction of pro-inflammatory cytokines in rats following 7-day oral supplementation with a proprietary eggshell membrane-derived product

NEM®?brand eggshell membrane is a novel dietary supplement that has been clinically shown to alleviate arthritis joint pain and stiffness;however the mechanism of action is not well understood. Preliminary evidence from an?in vitro?study of?NEM®?indicated that the mechanism of action may be based on the reduction of pro-inflammatory cytokines.?In vivo?studies were therefore initiated to evaluate the effects of?NEM®?on pro-inflammatory and anti-inflammatory cytokines following oral administration in rats.?NEM®?was administered daily at doses of 6.13 mg/kg bw/day (Study 1), 10.0 mg/kg bw/day (Study 2), or at doses of 0 (control), 26.0 or 52.0 mg/kg bw/day (Study 3) by oral gavage for 7 consecutive days. Inflammation was induced in the Study 3 rats by intraperitoneal injection of lipopolysaccharide. Changes in plasma cytokine levels from baseline following 7 days of oral supplementation with?NEM®?at 6.13 mg/kg bw/ day (Study 1) were statistically significant at Day 8 for IL-2, TIMP-1 and VEGF, at Day 21 for IL-10, and at Day 35 for MCP-1, MCP-3 and TIMP-1, and at 10.0 mg/kg bw/day (Study 2) were statistically significant at Day 8 for VEGF, at Day 21 for MIP-1β, MIP-2 and VEGF, and at Day 35 for MCP-3, MIP-1β, MIP-2 and VEGF. Changes in serum cytokine levels versus control at 26.0 mg/kg bw/day (Study 3) were statistically significant at all time-points for IL-1β?and at 1.5 hours for IL-10, and at 52.0 mg/kg bw/day (Study 3) were statistically significant at 1.5 hours for IFN-γ, IL-1β?and IL-10, and at 3 hours for IL-1β, and at 24 hours for IL-10. Taken together, these studies demonstrate that oral supplementation with?NEM®?can influence both early-phase pro-inflammatory cytokines like IL-1β?and TNF-α?(Study 3), as well as later-phase cytokines like MCP-1, MIP-1α?&?β, RANTES and VEGF (Study 1 & 2). These studies provide a possible basis for the mechanism of action of?NEM®?in vivo.

Long Dan Xie Gan Formula Granule Promotes Pro-Inflammatory Cytokine Expression in Female Guinea Pigs with Recurrent Genital Herpes

Objective To explore the effects of Long Dan Xie Gan formula granule(LDXGFG)on regulation of pro-inflammatory cytokines in female guinea pigs with recurrent genital herpes(herpes simplex virus 2,HSV-2).Methods Levels of pro-inflammatory cytokines in blood of HSV-2-infected guinea pigs,including IL-6,IL-8,IL-10,IL-12,IFN-α,IFN-β,IFN-γ,and TNF-α,were detected by ELISA;corresponding gene expression levels in tissues were detected by real-time PCR.Results IL-6,IL-10,IL-12,IFN-α,IFN-γand TNF-αdecreased significantly in both blood and diseased tissues after infection with recurrent genital herpes.Upon feeding LDXGFG to HSV-2-infected guinea pigs,IL-6,IL-10,IL-12,IFN-α,IFN-γand TNF-αdemonstrated significant increases,similar to the effects of acyclovir(ACV).LDXGFG promoted the expression of pro-inflammatory cytokines in blood and tissue,with a stronger effect than ACV.Moreover,LDXGFG demonstrated broader effects than ACV.Conclusion The present results suggest that LDXGFG can serve as an alternative,inexpensive,and long-term treatment for HSV-2 infection.

Pro-inflammatory cytokines levels in tears and dry eye disease in Parkinson’s disease

Background:Neuroinflammation is an essential event in Parkinson’s disease(PD).Identifying affordable and less invasive biomarkers to make an early diagnosis and monitor therapeutic strategies should be a priority among researchers.The study’s objective was to measure tear levels of cytokines in subjects with PD and their association with motor features and the presence of dry eye symptoms.Methods:A total of 16 subjects with PD and 16 age-and sex-matched controls were included.Movement Disorders Society-Unified Parkinson’s Disease Rating Scale(MDS-UPDRS),Hoehn and Yahr(HY)stage scale,Montreal Cognitive Assessment(MoCA),tear break-up time(TBUT),blink rate(BR),Dry Eye Questionnaire 5(DEQ-5)were examined,and pro-inflammatory cytokines[interleukin(IL)-1β,IL-6,IL-8,IL-10,IL-12p70 and tumor necrosis factor-alpha(TNF-α)]were quantified in tears using the BD Cytometric Bead Array Human Inflammatory Cytokine Kit.Results:Higher tear TNF-αwere quantified in PD compared to controls(2.94±3.95 vs.0.33±0.49 pg/mL,P=0.008).According to DEQ-5,50.0%(n=8)of PD subjects and 12.5%(n=2)controls had dry eye disease(DED).No differences were found in cytokines concentrations between PD patients with DED compared to those without DED.IL-8 was associated with the HY stage,TBUT,DEQ-5,and a better MoCA score.A higher BR correlated moderately with a lower HY stage(r=−0.645,P=0.007),and DED patients have lower BR in PD(12.14±2.54 vs.9.0±2.06 blinks/minute,P=0.031).Conclusions:PD patients have higher levels of TNF-αin tears than age-and sex-matched HC.IL-8 in tears may be both involved in the severity of the disease and in the development of DED in PD.In addition,our findings suggest that as HY stage increases,indicating a more advanced stage,BR decreases,indicating greater motor impairment.Conversely,the presence of DED is associated with higher levels of bradykinesia in PD patients,suggesting a potential relationship between DED and motor impairment severity.

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.

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.

Distinct Cytokine Profiles in Patients with Oligoarticular Juvenile Idiopathic Arthritis after <i>in</i><i>Vitro</i>Blockade of Interleukin (IL)-1 and Tumor Necrosis Factor (TNF)-α

Oligoarticular juvenile idiopathic arthritis (oJIA) is an antigen-driven and lymphocyte-mediated autoimmune disorder with irregularity in the adaptive immune system. Auto reactive T cells, activated by cartilage-derived auto antigens, produce pro-inflammatory cytokines as IFN-γ and IL-17. Failure of regulatory T cells leads to decreased anti-inflammatory cytokine IL-10 production and results in the loss of immune tolerance. This activation of innate and adaptive immunity stimulates the release of pro-inflammatory cytokines IL-1, IL-6 and TNF-α. Thus, inhibition of these cytokines is considered as an appropriate therapeutic strategy for oJIA. The aim of this study was to investigate whether the blockade of a single cytokine pathway in the present cytokine setting causes an unfavourable imbalance in the cytokine system or whether the blockade is sufficient to suppress the inflammatory condition. We examined the cytokine secretion after in vitro inhibition of IL-1 and TNF-α of patients with oJIA and healthy subjects. This single center cohort study consisted of oJIA affected children and control subjects. Cytokine profiles from cell culture supernatants were examined with multiplex fluorescent bead immunoassay by flow cytometry. Adalimumab prevents highly effective and very selective effect of the cytokine TNF-α. Due to its structure, the mode of action of etanercept is difficult to display. In addition, adalimumab and etanercept appear in vitro suppressive to IFN-γ. The efficiency of both substances is particularly supported by the increased secretion of anti-inflammatory cytokine IL-4. In contrast, anakinra unselectively inhibits the pro-inflammatory macrophage cytokines. To conclude, our observations suggest that inhibition of IL-1 or TNF-α may contribute to the unselective decline of other pro-inflammatory cytokines in oJIA patients. The selective anti-inflammatory effect of cytokine inhibitors is most likely supported by an increase of IL-4 or IL-10. It still remains to be elucidated whether the reduced IFN-γ secretion is maybe causative for the increased susceptibility to infections with opportunistic pathogens.

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.

Correlation of serum Hcy metabolism with pro-inflammatory factors, chemokines and oxidative stress response in patients with senile dementia

Objective: To investigate the correlation of serum Hcy metabolism with pro-inflammatory factors, chemokines and oxidative stress response in patients with senile dementia. Methods:A total of 50 patients who were diagnosed with senile dementia in our hospital between August 2012 and June 2016 were selected as the senile dementia group, and 50 elderly patients who underwent physical examination in this hospital during the same period were selected as normal control group. The differences in serum levels of Hcy, pro-inflammatory cytokines, chemokines and oxidative stress indexes were compared between the two groups, and Pearson test was adopted to assess the correlation between serum Hcy level and illness. Results: Serum Hcy level of senile dementia group was higher than that of control group;serum pro-inflammatory cytokines IL-1, IL-6, TNF-α and CRP levels were higher than those of control group;serum chemokines MCP-1, CCL2 and RANTES levels were higher than those of control group;serum oxidative stress indexes ROS, MDA and 4-HNE contents were higher than those of control group. Pearson test showed that the serum Hcy level in patients with senile dementia was positively correlated with the levels of pro-inflammatory factors, chemokines and oxidative stress indexes. Conclusions: The serum Hcy metabolism disorder in patients with senile dementia is closely related to the inflammatory response and oxidative stress response.

Involvement of pro-inflammatory and anti-inflammatory cytokines in the anti-inflammatory activity of Rubus idaeus L.on LPS-treated RAW 264.7 cells

Anti-inflammatory activity ofRubus idaeus L. and possible mechanisms involved were explored in lipopolysaccharide （LPS）-treated RAW 264.7 cells. The effects of ethanol extract of R. idaeus on the levels of pro-inflammatory cytokines, including tumor necrosis factor-alfa （TNF-α）, interleukin-6 （IL-6） and interleukin-1 beta （IL-1β）, as well as pro-inflammatory mediators, such as nitric oxide （NO）, inducible nitric oxide synthase （iNOS） and cyclooxygenase-2 （COX-2） were studied by Sandwich ELISA, real-time PCR, and Western blot analysis. Moreover, the effects of ethanol extract of R. idaeus on anti-inflammatory cytokine interleukin-10 （IL-10） and anti-inflammatory mediator heme oxygenase-1 （HO-1） were also investigated using the same methods. Furthermore, nuclear factor-gB （NF-κB） level was assayed by immunocytochemistry. The results showed that the production of IL-1β, IL-6, NO, TNF-α and COX-2 in LPS-treated cells could be significantly inhibited （P〈0.01 or P〈0.05） by ethanol extract ofR. idaeus compared with that in the cells treated with LPS only. Meanwhile, the production of NF-r,B was also inhibited by the extract. Based on these results, the anti-inflammatory activity ofR. idaeus was attributed to the down-regulation of IL-6, IL-1β and TNF-α levels as well as gene expression of iNOS and COX-2 through the suppression of NF-κB activation, and induction of anti-inflammatory cytokine IL- 10 and anti-inflammatory mediator HO- 1.

Salmeterol attenuates the inflammatory response in asthma and decreases the pro-inflammatory cytokine secretion of dendritic cells

Salmeterol is a long-acting β2-agonist that activates adenylate cyclase, causing long-lasting bronchodilation and has been used for many years to control asthma. However, little information is available about the immunoregulatory effects of salmeterol. We found that salmeterol decreases the production of pro-inflammatory cytokines in a model of allergen-challenged mice that expressed tumor-necrosis factor-alpha, interleukin-1 and interleukin-6. Dendritic cells （DCs） are antigen-presenting cells and act as sentinels in the airway. We found that salmeterol （10-s mol/I） reduced the inflammation caused by lipopolysaccharide （0.1 pg/ml） in activated murine bone marrow-derived DCs. Moreover, western blots demonstrated that this protective effect was mediated partially by inhibiting signaling through the nuclear factor-kappa B （NF-κB）, mitogen-activated protein kinase （MAPK） pathways and dramatically decreased levels of p-ERK. We suggest that salmeterol regulates the inflammation of allergen-induced asthma by modulating DCs. In conclusion, we provide evidence that DCs are the target immune cells responsible for the action of salmeterol against asthma.

Neutralization of interleukin-17A alleviates burn-induced intestinal barrier disruption via reducing pro-inflammatory cytokines in a mouse model

Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage.Interleukin-17A(IL-17A)plays a critical role in inflammatory diseases.However,the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood.In this study,we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury,and furthermore,we sought to determine the early source of IL-17A in the intestine.Methods:Mouse burn model was successfully established with infliction of 30%total body surface area scald burn.The histopathological manifestation,intestinal permeability,zonula occludens-1 expression,pro-inflammatory cytokines were determined with or without IL-17A-neutralization.Flow cytometry was used to detect the major source of IL-17A^(+)cells in the intestine.Results:Burn caused intestinal barrier damage,increase of intestinal permeability,alteration of zonula occludens-1 expressions,elevation of IL-17A,IL-6,IL-1βand tumor necrosis factor-α(TNF-α),whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption,maintained zonula occludens-1 expression,and noticeably,inhibited pro-inflammatory cytokines elevation.In addition,we observed that the proportion of intestinal IL-17A^(+)Vγ4^(+)T subtype cells(but not IL-17A^(+)Vγ1^(+)T subtype cells)were increased in burn group,and neutralization of IL-17A suppressed this increase.Conclusions:The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines,and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined.Furthermore,Vγ4^(+)T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model.These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.

SCN1A rs6732655A/T polymorphism:Diagnostic and therapeutic insights for drug-resistant epilepsy

BACKGROUND A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs,resulting in heightened mortality rates,psychosocial challenges,and a diminished quality of life.Genetic factors,particularly within the SCN1A gene,and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases.In this extended study,we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response.AIM To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response.METHODS The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases.We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique.The diagnostic performance of interleukin(IL)-1β,IL-6,and high mobility group box 1(HMGB1)protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis.RESULTS AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy.Serum biomarkers IL-6,IL1βand HMGB1 demonstrated diagnostic potential,with cutoff values of 4.63 pg/mL,59.52 pg/mL and 7.99 ng/mL,respectively,offering valuable tools for epilepsy management.Moreover,specific genotypes(AA and AT)were found to be linked to the elevated levels of IL-1βand IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy.CONCLUSION SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk.These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance.

Wear particle-mediated expressions of pro-inflammatory cytokines, NF-κB and RANK were impacted by lanthanum chloride in RAW264.7 cells

To explore the impact of different concentrations of lanthanum chloride （LaC13） on critical components of wear particle-mediated signaling pathways in inflammation and osteoclastogenesis, RAW264.7 cells were naturally divided into eight groups and analyzed by CCK-8 assay, flow cytometry, ELISA, RT-PCR and western blot after treatments. The results showed that three concentrations of LaCI3 had no influence on viability of RAW264.7 cells and down-regulated receptor activator of nuclear factor rd3 （RANK） instead of macrophage colony-stimulating factor receptor （M-CSFR）. Additionally, 2.5 and 10 pmol/L LaC13 could signifi- cantly inhibit gene and protein levels of pro-inflammatory cytokines （tumor necrosis factor-or and interleukin-113, i.e., TNF-ct and IL-113） and NF-r,B/p65, but 100 pmol/L LaC13 did not exert an obvious inflammation-inhibiting effect, and even induced inflamma- tion. In conclusion, these findings demonstrated that LaC13 was able to suppress wear particle-induced inflammation and activation of NF-rd3 in a certain range of concentrations in vitro and mainly decrease the expression of RANK, but not M-CSFR, all of which were generally recognized to play a pivotal role in osteoclastogenesis.

老年抑郁症病人免疫功能及其心理状况的对照研究

目的 探讨老年抑郁症病人的免疫功能变化及与心理因素的相关性。方法 对 2 4例 6 0岁以上首次发作的抑郁症患者 (抑郁组 ) ,2 6名健康老年人 (对照组 ) ,作细胞因子测定 ,并以HAMD、HAMA、EPQ和LES量表进行评定。结果 与对照组比较 ,抑郁组细胞因子IL 1β和IL 6显著高于对照组 ,抑郁组HAMD ,HAMA总分及因子分EPQ的神经质分 ,负性生活事件总分和社交问题的因子分显著高于对照组。IL 6与HAMD总分、HAMA总分及认知障碍和躯体性焦虑因子分呈正相关。结论 老年抑郁症病人存在免疫功能改变 ,心理健康状况较正常老年人差。

硫酸氨基葡萄糖联合参麦注射液治疗膝骨性关节炎的疗效研究

目的:探讨硫酸氨基葡萄糖联合参麦注射液治疗膝骨性关节炎的疗效。方法:取膝骨性关节炎患者120例作为研究对象,随机分为联合组和对照组,每组各60例。对照组单纯给予硫酸氨基葡萄糖治疗,联合组给予硫酸氨基葡萄糖(0.5g/次,3次/天)联合参麦注射液(每次每膝5 m L,每周注射1次)治疗,连续治疗6周,观察两组患者临床疗效。结果:联合组临床治疗总有效率为91.67%,对照组为78.33%,两组差异有统计学意义(P<0.05);治疗后,联合组患者膝关节骨性关节炎自评量表(WOMAC)改善较对照组明显,差异有统计学意义(P<0.05);联合组和对照患者治疗不良反应发生率无显著差异;治疗后,两组患者血清IL-17、IL-18浓度水平明显下降,转化生长因子β(TGF-β)、胰岛素样生长因子1(IGF-1)、成纤维细胞生长因子2(FGF-2)浓度水平明显上升;联合组患者血清IL-17、IL-18浓度水平下降明显优于对照组,TGF-β、IGF-1、FGF-2浓度水平上升明显优于对照组,差异均有统计学意义(P<0.05)。结论:联合组治疗膝骨性关节炎的疗效显著增加,不良反应发生率较低,其作用机制可能与降低血清IL-17、IL-18浓度水平和提高TGF-β、IGF-1、FGF-2浓度水平有关。

肝损伤模型小鼠高迁移率族蛋白-1的表达

将刀豆蛋白A(Con A)经尾静脉注射入雄性Balb/C小鼠,建立T细胞介导的Con A急性肝损伤小鼠模型,检测模型小鼠不同时间点血清中高迁移率族蛋白1(HMGB1)及肝组织HMGB1mRNA的表达水平,并与血清中TNF-α进行对比.实验显示:在Con A注射后0～3h,小鼠血清中的未能检测出HMGB1蛋白特异带;但在4h后,检测出一条微弱的HMGB1蛋白特异带;在6～36h,均检测出一条清晰的HMGB1蛋白特异带,在8￣12h处于一个高水平状态.而正常对照组小鼠血清中未能检测HMGB1蛋白.与HMGB1动力学曲线不同,血清中TNF-α水平在Con A注射后2h就达到峰值,4h后迅速下降,8h恢复到正常范围.Con A小鼠肝细胞中HMGB1mRNA的表达在Con A注射1h后即达到峰值,是对照组的2.4倍,之后迅速回落,3～12h均低于对照组水平(0.5～0.8倍),24h后逐渐恢复正常水平.初步揭示HMGB1在Con A小鼠急性肝损伤中可能发挥重要作用,血清中HMGB1蛋白与TNF-α相比,呈现出迟发与长效的特点,HMGB1给肝细胞造成损伤有足够强度和效应时间.

益气解毒方对中晚期鼻咽癌患者CD4^+CD25^+调节性T细胞和Th17细胞的影响

目的探讨益气解毒方对中晚期鼻咽癌患者外周血CD4+CD25+调节性T细胞和Th17细胞的影响。方法用流式细胞仪检测18例经益气解毒方加常规治疗的中晚期鼻咽癌患者(观察组)及l5例常规治疗的中晚期鼻咽癌患者(对照组)外周血CD4+CD25+调节性T细胞和Th17细胞比例,RT-PCR法检测Foxp3 mRNA和ROR-γt mRNA转录水平,ELISA法检测血清白细胞介素-6(IL-6)和转化生长因子-β(TGF-β)水平。结果观察组患者外周血中CD4+CD25+调节性T细胞占CD4+T细胞的比例和Foxp3 mRNA的相对表达量均低于对照组(P<0.05),而Th17细胞占CD4+T细胞的数量比例和ROR-γt mRNA的相对表达量均高于对照组(P<0.05);观察组患者血清IL-6水平高于对照组(P<0.05),而TGF-β水平低于对照组(P<0.05)。结论益气解毒方可影响中晚期鼻咽癌CD4+CD25+调节性T细胞的比例与功能,增强Th17细胞的分化,其机制可能是通过调节IL-6和TGF-β水平而逆转鼻咽癌免疫耐受。

益气健脾解毒方联合FOLFOX4方案治疗中晚期胃癌疗效观察

目的观察益气健脾解毒方联合FOLFOX4方案治疗中晚期胃癌患者的临床效果及安全性。方法将76例中晚期胃癌患者随机分为观察组和对照组。2组均接受FOLFOX4治疗方案,观察组在此基础上给予益气健脾解毒方治疗,以2周为1个疗程,共治疗4个疗程。观察2组肿瘤病灶变化以及血清肿瘤标记物、细胞因子及细胞免疫功能变化情况,并统计患者不良反应发生情况。结果观察组总有效率为63.2%,对照组为42.1%,观察组总有效率显著高于对照组(P<0.05);治疗后2组血清CEA、CA72-4、TSGF、IL-4和IL-10含量均较治疗前显著降低(P均<0.05),血清TNF-α和IFN含量均较治疗前显著升高(P均<0.05),且观察组各指标改善情况均显著优于对照组(P均<0.05);观察组CD3^+、CD4^+、CD4^+/CD8^+及NK细胞比率均显著升高(P均<0.05),对照组CD3^+、CD4^+、CD4^+/CD8^+及NK细胞比率均无明显变化(P均>0.05),且观察组均显著高于对照组(P均<0.05);2组治疗后不良反应比较差异无统计学意义(P>0.05)。结论益气健脾解毒方联合FOLFOX4方案治疗中晚期胃癌,能够有效促进患者免疫功能恢复,改善肿瘤病变的预后与转归,且安全。