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.

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.

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.

Inhibitory effect of Jeju endemic seaweeds on the production of pro-inflammatory mediators in mouse macrophage cell line RAW 264.7

Seaweed has been used in traditional cosmetics and as a herbal medicine in treatments for cough,boils,goiters,stomach ailments,and urinary diseases,and for reducing the incidence of tumors,ulcers,and headaches.Despite the fact that seaweeds are frequently used in the practice of human health,little is known about the role of seaweed in the context of inflammation.This study aimed to investigate the influence of Jeju endemic seaweed on a mouse macrophage cell line(RAW 264.7) under the stimulation of lipopolysaccharide(LPS).Ethyl acetate extracts obtained from 14 different kinds of Jeju seaweeds were screened for inhibitory effects on pro-inflammatory mediators.Our results revealed that extracts from five seaweeds,Laurencia okamurae,Grateloupia elliptica,Sargassum thun-bergii,Gloiopeltis furcata,and Hizikia fusiformis,were potent inhibitors of the production of pro-inflammatory mediators such as nitric oxide(NO),prostaglandin E2(PGE2),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α).Based on these results,the anti-inflammatory effects and low cell toxicity of these seaweed extracts suggest potential thera-peutic applications in the regulation of the inflammatory response.

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.

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.

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.