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.

Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis

Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous system.Macrophage polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple sclerosis.This study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune encephalomyelitis.We found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6.Crucially,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified macrophages.In addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced inflammation.These findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for multiple sclerosis.

Dietary inflammatory index and its impact on severity and recurrence of Tourette syndrome in children

BACKGROUND Tourette syndrome(TS)is a neurodevelopmental disorder characterized by the presence of motor and vocal tics,typically beginning in childhood.Despite signifi-cant research efforts,the exact pathophysiology of TS remains incompletely understood.Recent studies suggest that inflammation may play a role in the severity and progression of TS,pointing to the potential influence of dietary and lifestyle factors on the condition.Currently,research on the specific connection between dietary inflammatory index(DII)and TS is still in its early stages,requir-ing additional clinical and epidemiological studies to validate the strength and specific mechanisms of this connection.METHODS A total of 207 children diagnosed with TS in the pediatric department of Qingdao Chengyang People’s Hospital from January 2022 to January 2023 were selected.They were divided into stable and unstable groups based on follow-up condi-tions.Before enrollment,general information of the children[age,gender,body mass index(BMI),guardian’s education level,DII score,medical history,family history,academic stress,electronic device usage,medication,and disease progression]was assessed,and serum inflammatory levels were measured during follow-up visits.DII scores and Yale Global Tic Severity Scale(YGTSS)scores were calculated.Furthermore,based on YGTSS scores,the children were classified into mild,moderate,and severe groups.The DII,interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-alpha(TNF-α)levels in each group were compared.RESULTS Follow-up surveys were completed by 207 children and their guardians.Among them,117 children were in the stable group,and 90 were in the recurrent group.We found no statistically significant differences in age,gender,comorbidities,BMI,and disease duration between the two groups(P>0.05).However,academic stress,electronic device usage,medication,guardian’s education level,and DII scores showed statistically significant differences between the groups(P<0.05).Multifactorial regression analysis revealed that guardian’s anxiety level,DII score,medication,academic stress,and family history were statistically significant factors(P<0.05)affecting the recurrence of TS in children.Therefore,anxiety level,DII score,medication status,electronic device usage,and academic stress were identified as factors influencing the recurrence of TS in children.Among them,DII score,academic stress,and family history had odds ratios(OR)greater than 1,indicating risk factors,whereas medication status and guardian’s education level had OR values less than 1,indicating protective factors.According to the YGTSS scores,children were categorized into mild,moderate,and severe groups.Comparative analysis of DII and inflammatory levels in children with different degrees of tic disorders revealed that the severe group had the highest DII and inflammatory levels,followed by the moderate group,and the mild group had the lowest levels.The trend of TS progression was consistent with the DII results.Receiver operating characteristic curves were plotted to predict disease progression in patients with TS via inflammatory markers.The areas under the curve for IL-6,CRP,and TNF-αwere 0.894(95%CI:0.817-0.969),0.793(95%CI:0.694-0.893),and 0.728(95%CI:0.614-0.843)respectively,with statistically significant differences(P<0.05).According to the Youden index,the optimal cutoff values were IL-6=3.775 ng/L(sensitivity 68.1%and specificity 68.4%),CRP=6.650 mg/L(sensitivity 60.6%and specificity 68.4%),and TNF-α=0.666(sensitivity 60.6%and specificity 71.1%).CONCLUSION We found a certain correlation between DII and the severity,recurrence,and inflammatory levels of TS in children.Reasonable reduction in the intake of pro-inflammatory foods may be beneficial in reducing the risk of disease progression in children with TS.

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.

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.

Advanced Glycation End Products Promote Differentiation of CD4^+ T Helper Cells toward Pro-inflammatory Response

This study investigated the effect of advanced glycation end products（AGEs） on differentiation of na ve CD4＋T cells and the role of the receptor of AGEs（RAGE） and peroxisome proliferator-activated receptors（PPARs） activity in the process in order to gain insight into the mechanism of immunological disorders in diabetes. AGEs were prepared by the reaction of bovine serum albumin（BSA） with glucose. Human na ve CD4＋T cells, enriched from blood of healthy adult volunteers with negative selection assay, were cultured in vitro and treated with various agents including AGEs, BSA, high glucose, PGJ2 and PD68235 for indicated time. In short hairpin（sh） RNA knock-down experiment, na ve CD4＋T cells were transduced with media containing shRNA-lentivirus generated from lentiviral packaging cell line, Lent-XTM293 T cells. Surface and intracellular cytokine stainings were used for examination of CD4＋T cell phenotypes, and real-time PCR and Western blotting for detection of transcription factor mRNA and protein expression, respectively. The suppressive function of regulatory T（Treg） cells was determined by a [3H]-thymidine incorporation assay. The results showed that AGEs induced higher pro-inflammatory Th1/Th17 cells differentiated from na ve CD4＋T cells than the controls, whereas did not affect anti-inflammatory Treg cells. However, AGEs eliminated suppressive function of Treg cells. In addition, AGEs increased RAGE mRNA expression in na ve CD4＋T cells, and RAGE knock-down by shRNA eliminated the effect of AGEs on the differentiation of CD4＋T cells and the reduction of suppressive function of Treg cells. Furthermore, AGEs inhibited the mRNA expression of PPARγ, not PPARα; PPARγ agonist, PGJ2, inhibited the effect of AGEs on na ve CD4＋T cell differentiation and reversed the AGE-reduced suppressive function of Treg cells; on the other hand, PPARγ antagonist, PD68235, attenuated the blocking effect of RAGE shRNA on the role of AGEs. It was concluded that AGEs may promote CD4＋T cells development toward pro-inflammatory state, which is associated with increased RAGE mRNA expression and reduced PPARγ activity. ＋

<i>Ratanasampil</i>(Tibetan Medicine, RNSP) Reduces <i>β</i>-Amyloid Protein (Aβ) and Pro-Inflammatory Factor Levels and Improves Cognitive Functions in Mild-to-Moderate Alzheimer’s Disease (AD) Patients Living at High Altitude

Ratanasampil (RNSP) is a traditional Tibetan medicine used for the treatment of stroke and cerebrovascular diseases. Previous discoveries that RNSP can reduce β-amyloid protein levels and increase learning and memory in Alzheimer’s mouse models (Tg2576) led us to investigate whether RNSP can improve cognitive functions in Alzheimer’s patients. In this study, 146 AD patients living in Qinghai province received either one gram or 0.33 gram daily of RNSP for 16 weeks. Placebo patients received Piracetam. Serum Aβ40 and Aβ42 levels were measured at the beginning of the study and after 4 and 16 weeks of treatment. Compared to the same group before treatment, MMSE scores, ADAS-cog scores and ADL scores were significantly improved (p 0.05, p > 0.05). After 16-week treatment, serum TNF-α, IL-1β, IL-6 and Aβ42 levels were significantly decreased (p < 0. 01) in the high-dose RNSP group, whereas no significant differences were found in the low-dose and placebo groups. The Aβ42/Aβ40 ratio was significantly decreased after 4-week and 16-week treatment in the high-dose RNSP group (p < 0. 05, p < 0.01). Furthermore, serum Aβ42 concentrations had a strong positive correlation with TNF-α, IL-1β and IL-6 levels. There were no observable adverse effects in either treatment or control groups. We conclude that further clinical trials of RNSP in Alzheimer disease are warranted.

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&reg;?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&REG;?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&REG;?on pro-inflammatory and anti-inflammatory cytokines following oral administration in rats.?NEM&REG;?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&REG;?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&REG;?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&REG;?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.

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.

Vagus nerve stimulation is a potential treatment for ischemic stroke

Microglia are the brain’s primary innate immune cells,and they are activated and affect pro-inflammatory phenotype or regulatory phenotype after ischemic stroke.Vagus nerve stimulation was shown to activate microglial phenotypic changes and exhibit neuroprotective effects in ischemia/reperfusion injury.In this study,we established rat models of ischemic stroke by occlusion of the middle cerebral artery and performed vagus nerve stimulation 30 minutes after modeling.We found that vagus nerve stimulation caused a shift from a pro-inflammatory phenotype to a regulatory phenotype in microglia in the ischemic penumbra.Vagus nerve stimulation decreased the levels of pro-inflammatory phenotype markers inducible nitric oxide synthase and tumor necrosis factorαand increased the expression of regulatory phenotype markers arginase 1 and transforming growth factorβthrough activatingα7 nicotinic acetylcholine receptor expression.Additionally,α7 nicotinic acetylcholine receptor blockade reduced the inhibition of Toll-like receptor 4/nuclear factor kappa-B pathwayassociated proteins,including Toll-like receptor 4,myeloid differentiation factor 88,I kappa B alpha,and phosphorylated-I kappa B alpha,and also weakened the neuroprotective effects of vagus nerve stimulation in ischemic stroke.Vagus nerve stimulation inhibited Toll-like receptor 4/nuclear factor kappa-B expression through activatingα7 nicotinic acetylcholine receptor and regulated microglial polarization after ischemic stroke,thereby playing a role in the treatment of ischemic stroke.Findings from this study confirm the mechanism underlying vagus nerve stimulation against ischemic stroke.

Different priming strategies improve distinct therapeutic capabilities of mesenchymal stromal/stem cells:Potential implications for their clinical use

Mesenchymal stromal/stem cells(MSCs)have shown significant therapeutic potential,and have therefore been extensively investigated in preclinical studies of regenerative medicine.However,while MSCs have been shown to be safe as a cellular treatment,they have usually been therapeutically ineffective in human diseases.In fact,in many clinical trials it has been shown that MSCs have moderate or poor efficacy.This inefficacy appears to be ascribable primarily to the heterogeneity of MSCs.Recently,specific priming strategies have been used to improve the therapeutic properties of MSCs.In this review,we explore the literature on the principal priming approaches used to enhance the preclinical inefficacy of MSCs.We found that different priming strategies have been used to direct the therapeutic effects of MSCs toward specific pathological processes.Particularly,while hypoxic priming can be used primarily for the treatment of acute diseases,inflammatory cytokines can be used mainly to prime MSCs in order to treat chronic immune-related disorders.The shift in approach from regeneration to inflammation implies,in MSCs,a shift in the production of functional factors that stimulate regenerative or anti-inflammatory pathways.The opportunity to fine-tune the therapeutic properties of MSCs through different priming strategies could conceivably pave the way for optimizing their therapeutic potential.

Effect of Astragalus-hawthorn on ovarian reproductive function and inflammatory mechanism of action in rats with polycystic ovary syndrome

Objective:To investigate the effects of prophylactic administration of Astragalus-Hawthorn on ovarian reproductive function and inflammatory mechanism in rats with polycystic ovary syndrome(PCOS).Methods:Fifty 21-day-old female rats were randomly divided into five groups of 10 rats each:Normal group,Model group,Astragalus group,Hawthorn group and Astragalus-Hawthorn group.All groups,except the normal group,were fed a high-fat model diet.Each treatment group received astragalus,hawthorn and an astragalus-hawthorn solution orally during the molding period for an intervention period of 15 weeks.The estrous cycle of the rats in each group was observed under the microscope from week 8,the interference rate was calculated,changes in ovarian tissues were observed by HE staining and the levels of sex hormones,proinflammatory and anti-inflammatory factors in the serum of the rats were measured by ELISA.Results:Rate of estrous cycle disorders were more frequent in the model group than in the normal group.(P<0.01);ovarian tissue was polycystic,with few corpora lutea and sinusoids and numerous follicular ovarian cysts;Luteinising hormone/follicle-stimulating hormone(LH/FSH),testosterone(T),interleukin 6(IL-6),interleukin 17A(IL-17A)and tumour necrosis factor(TNF-α)levels were significantly higher in the model group than in the normal group;interleukin 10(IL-10)was significantly lower than in the normal group(P<0.05).Compared to the model group,rats in the Astragalus and hawthorn groups had a lower rate of estrous cycle disorders(P<0.01);the number of cystic follicles in the ovarian tissue decreased;the number of mature follicles and corpus luteum increased;LH/FSH,T,IL-6 and IL-17A levels were significantly lower in the Astragalus group,hawthorn group and the Astragalus and hawthorn groups;TNF-αlevels were significantly lower in the astragalus and hawthorn groups;IL-10 levels were significantly higher in the hawthorn and astragalus hawthorn groups(P<0.05).IL-10 levels were significantly higher in the astragalus and hawthorn groups(P<0.05).Compared to the astragalus group,T levels were significantly lower in the astragalus and hawthorn groups and IL-10 levels were significantly higher in the astragalus and hawthorn groups(P<0.05).Compared to the hawthorn group,levels of T and IL-17A were significantly lower in the astragalus-hawthorn group(P<0.05).Conclusion:Astragalus-Hawthorn prophylactic administration can improve ovarian reproductive function in rats with PCOS,and the mechanism of action may be related to reducing the levels of pro-inflammatory factors IL-6,IL-17A and TNF-α,increasing the levels of anti-inflammatory factor IL-10,and reducing the inflammatory state.

The role of microglia in depression

According to studies,neuroinflammation is increasingly being linked to the development of major depressive disorder(MDD).In response to inflammatory stimuli,brain microglia,which are immune cells,can change into reactive states.Because of this,microglia play an essentiall role in the early stages of neuroinflammation.Experiments have shown that microglia are able to detect infected or damaged cells,which then activates a cytotoxic response that further exacerbates the harm to brain cells.It has been proven that microglia are quite good at recognizing infections and damaged cells.Microglia,on the other hand,have been found to respond in a number of ways to injury and may even help regenerate damaged tissues.Chronic activation of microglia has been observed in persons with MDD.Deficits in neuroplasticity have been linked to depression,and recent studies show that this may be related to changes in microglia shape and function brought on by either excessive inflammatory activity or the natural aging process.Changing the phenotype of microglia by regulation of inflammatory pathways may be necessary for harnessing neuroinflammation in MDD.Recent research has linked several microglial phenotypes to individual metabolic pathways,showing that energy metabolism plays a pivotal role in coordinating microglial activity.In this study,we investigate whether or not traditional pro-inflammatory,anti-inflammatory,and metabolic pathways in microglia can be used as novel therapeutic routes for regulating neuroinflammation in brain diseases.The focus of this essay is on MDD,although we will also discuss related mental health issues.

Alcohol,inflammation,and gut-liver-brain interactions in tissue damage and disease development

Chronic inflammation is often associated with alcoholrelated medical conditions. The key inducer of such inflammation, and also the best understood, is gut microflora-derived lipopolysaccharide (LPS). Alcohol can significantly increase the translocation of LPS from the gut. In healthy individuals, the adverse effects of LPS are kept in check by the actions and interactions of multiple organs. The liver plays a central role in detoxifying LPS and producing a balanced cytokine milieu. The central nervous system contributes to anti-inflammatory regulation through neuroimmunoendocrine actions. Chronic alcohol use impairs not only gut and liver functions, but also multi-organ interactions, leading to persistent systemic inflammation and ultimately, to organ damage. The study of these interactions may provide potential new targets for therapeutic intervention.

Effects of interventions on oxidative stress and inflammation of cardiovascular diseases

Excessive oxidative stress and low-grade chronic inflammation are major pathophysiological factors contributing to the development of cardiovascular diseases (CVD) such as hypertension, diabetes and atherosclerosis. Accumulating evidence suggests that a compromised antioxidant system can lead to excessive oxidative stress in cardiovascular related organs, resulting in cell damage and death. In addition, increased circulating levels of pro-inflammatory cytokines, such as tumor necrosis factor α, interleukin-6 and C-reactive protein, are closely related to morbidity and mortality of cardiovascular complications. Emerging evidence suggests that interventions including nutrition, pharmacology and exercise may activate expression of cellular anti-oxidant systems via the nuclear factor erythroid 2-related factor 2-Kelchlike ECH-associated protein 1 signaling pathway and play a role in preventing inflammatory processes in CVD. The focus of the present review is to summarize recent evidence showing the role of these anti-oxidant and anti-inflammatory interventions in cardiovascular disease. We believe that these findings may prompt new effective pathogenesis-oriented interventions, based on the exercise-induced protection from disease in the cardiovascular system, aimed at targeting oxidant stress and inflammation.

Role of soluble triggering receptor expressed on myeloid cells in inflammatory bowel disease

AIM： To investigate the probable role of soluble triggering receptor expressed on myeloid cells-1 （sTREM-1） in the pathogenesis of inflammatory bowel disease （IBD）.METHODS： Fifty-eight patients were enrolled; nineteen healthy volunteers served as controls; 8 patients were diagnosed with Crohn＇s disease, and 31 with ulcerative colitis, Clinical and endoscopic activity indexes of patients with Crohn＇s disease and ulcerative colitis respectively were estimated, Upon admission blood was sampled; sTREM-1 and TNFα were measured by an immunoassay and malondialdehyde （IDA） by the thiobarbitourate assay, after passage through an HPLC system,RESULTS： Median ± SE of TNFα of controls, patients with Crohn＇s disease and patients with ulcerative colitis were 6.02 ± 3.94, 7.98 ± 5.08 （P = NS vs controls）, and 8.45 ± 4.15 ng/L （P = 0.018 vs controls） respectively. Respective values of sTREM-1 were 53.31 ± 32.93, 735.10 ± 197.17 （P = 0.008 vs controls） and 435.82 ± 279.71 ng/L （P = 0.049 vs controls）, sTREM-1 was positively correlated with Crohn＇s disease activity index and clinical and endoscopic activity indexes of ulcerative colitis （P = 0.002, 0.001 and 0.009, respectively）, sTREM-1 of patients with ulcerative colitis was positively correlated with TNFα （P = 0.001）.CONCLUSION： sTREM-1 seems to behave as a novel mediator in IBD in correlation with the degree of the intlammatory reaction of the intestinal mucosa.

Study on the antiulcer effects of Veronicastrum axillare on gastric ulcer in rats induced by ethanol based on tumor necrosis factor-α(TNF-α)and endothelin-1(ET-1)

Objective:To assess whether Veronicastrum axillare(V.axillare)can ameliorate ethanol-induced gastric mucosal lesions in rats,reduce the production of pro-inflammatory cytokines,suppress apoptosis and improve local microcirculation disturbances.Methods:Totally 48 male Sprague-Dawley rats were randomly divided into six groups,eight rats in each group.Rats in the normal group and the model group were administered with 0.9%normal saline respectively.Rats in the positive group and ranitidine group were administered with 0.18%ranitidine suspension by intragastric administration respectively.Those in the high dose V.axillare group,the medium dose V.axillare group and the low dose V.axillare group were administrated with V.axillare at the daily dose of 2.8 g/kg,1.4 g/kg and 0.7 g/kg by intragastric administration.Gastric mucosal lesions were produced by intragastric administration of absolute ethanol.Water extract of V.axillare was successively injected for 14 d and last day was injected 1 h before ethanol administration.Gastric mucosal ulcer index and ulcer inhibitory rate were counted by improved Guth methods.The tissue sections were made for pathological histology analysis.Also,we measured the concentrations of tumor necrosis factor-α(TNF-α)and endothelin-1(ET-1)in gastric mucosal,as an index of the pro-inflammatory cytokines,apoptosis and local microcirculation.Besides,the mRNA contents of TNF-αand ET-1 were measured to verify effects on gene expression by real-time fluorescent quantitative PCR.Results:Water extract of V.axillare significantly ameliorated the gastric mucosal lesions induced by ethanol administration(P【0.01).Pro-inflammatory cytokines,TNF-a and ET-1 were increased after ethanol administration and significantly reduced by water extract of V.axillare.The expressions of TNF-αand ET-1 mRNA were also be inhibited by water extract of V.axillare.Conclusion:Current evidences show water extract of V.axillare is effective for defending against ethanol-induced gastric mucosal lesions,significantly inhibiting the production of proinflammatory cytokines and the expressions of TNF-αand ET-1 mRNA,which may be useful for inhibiting apoptosis and improving local microcirculation.

Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer:The role of inflammation

Chemotherapy-induced diarrhea(CID)is a common and often severe side effect experienced by colorectal cancer(CRC)patients during their treatment.As chemotherapy regimens evolve to include more efficacious agents,CID is increasingly becoming a major cause of dose limiting toxicity and merits further investigation.Inflammation is a key factor behind gastrointestinal(GI)toxicity of chemotherapy.Different chemotherapeutic agents activate a diverse range of pro-inflammatory pathways culminating in distinct histopathological changes in the small intestine and colonic mucosa.Here we review the current understanding of the mechanisms behind GI toxicity and the mucositis associated with systemic treatment of CRC.Insights into the inflammatory response activated during this process gained from various models of GI toxicity are discussed.The inflammatory processes contributing to the GI toxicity of chemotherapeutic agents are increasingly being recognised as having an important role in the development of anti-tumor immunity,thus conferring added benefit against tumor recurrence and improving patient survival.We review the basic mechanisms involved in the promotion of immunogenic cell death and its relevance in the treatment of colorectal cancer.Finally,the impact of CID on patient outcomes and therapeutic strategies to prevent or minimise the effect of GI toxicity and mucositis are discussed.