Background:Fever is characterized by an upregulation of the thermoregulatory set-point after the body encounters any pathological challenge.It is accompanied by uncomfortable sickness behaviors and may be harmful in p...Background:Fever is characterized by an upregulation of the thermoregulatory set-point after the body encounters any pathological challenge.It is accompanied by uncomfortable sickness behaviors and may be harmful in patients with other comor-bidities.We have explored the impact of an Ayurvedic medicine,Fevogrit,in an endo-toxin(lipopolysaccharide)-induced fever model in Wistar rats.Methods:Active phytoconstituents of Fevogrit were identified and quantified using ultra-high-performance liquid chromatography(UHPLC)platform.For the in-vivo study,fever was induced in male Wistar rats by the intraperitoneal administration of lipopolysaccharide(LPS),obtained from Escherichia coli.The animals were allocated to normal control,disease control,Paracetamol treated and Fevogrit treated groups.The rectal temperature of animals was recorded at different time points using a digital thermometer.At the 6-h time point,levels of TNF-α,IL-1βand IL-6 cytokines were analyzed in serum.Additionally,the mRNA expression of these cytokines was deter-mined in hypothalamus,24 h post-LPS administration.Results:UHPLC analysis of Fevogrit revealed the presence of picroside I,picroside II,vanillic acid,cinnamic acid,magnoflorine and cordifolioside A,as bioactive constitu-ents with known anti-inflammatory properties.Fevogrit treatment efficiently reduces the LPS-induced rise in the rectal temperature of animals.The levels and gene ex-pression of TNF-α,IL-1βand IL-6 in serum and hypothalamus,respectively,was also significantly reduced by Fevogrit treatment.Conclusion:The findings of the study demonstrated that Fevogrit can suppress LPS-induced fever by inhibiting peripheral or central inflammatory signaling pathways and could well be a viable treatment for infection-induced increase in body temperatures.展开更多
BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnos...BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnosis.METHODS The study cohort comprised 50 patients diagnosed with GC and 50 healthy control subjects.A panel of 7 pro-inflammatory cytokines,including interleukin(IL)-1β,IL-2,IL-6,IL-8,IL-12,tumor necrosis factor-α,and interferon-γ(IFN-γ)were quantified using multiplex Luminex assays.Comparative analyses were conducted to evaluate cytokine levels between the GC patients and healthy controls.The diagnostic potential of serum pro-inflammatory cytokines in differentiating GC patients from healthy individuals was assessed through receiver operating characteristic(ROC)curve analysis.The correlation between serum cytokine levels and disease severity,as classified by the tumor-node-metastasis staging system,was analyzed using Spearman's rank correlation coefficient.RESULTS In comparison to the control group,patients with GC demonstrated significantly elevated serum levels of IL-1β(t=-4.089,P<0.001),IL-6(t=-3.983,P<0.001),IL8(t=-5.460,P<0.001),and IFN-γ(t=-2.856,P=0.005).ROC curve analysis indicated that the area under the curve values for IL-1β,IL-6,and IL-8 exceeded 0.7,effectively distinguishing GC patients from healthy controls.Additionally,serum levels of IL-1β(r=0.424,P=0.012)and IL-6(r=0.742,P<0.001)were positively correlated with the T stage in GC patients.Similarly,serum concentrations of IL-1β(r=0.356,P=0.039)and IL-6(r=0.441,P=0.008)exhibited a positive association with the N stage in these patients.CONCLUSION These findings suggest that circulating pro-inflammatory cytokines,such as IL-1β,IL-6,and IL-8,may serve as potential biomarkers for the diagnosis of GC.展开更多
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-infla...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.展开更多
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 form...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.展开更多
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（PPAR...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. ＋展开更多
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...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.展开更多
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 evi...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.展开更多
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 f...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.展开更多
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...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.展开更多
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 ...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.展开更多
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 natural...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.展开更多
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 diagn...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.展开更多
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 amo...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.展开更多
Older age is one of the leading risk indicators for advanced breast cancer.It is critical to extensively investigate how aging affects breast cancer,considering the increasing rate of population aging.Human body aging...Older age is one of the leading risk indicators for advanced breast cancer.It is critical to extensively investigate how aging affects breast cancer,considering the increasing rate of population aging.Human body aging and death are caused by cellular senescence and alterations in the aging microenvironment in vivo.Breast cancer cells may invade more easily with age due to the stiff extracellular matrix of the breast.Furthermore,growing evidence suggests that the massive release of inflammatory immune mediators,such as cytokines(interleukins)or CXC chemokines(CXCs),and their receptors(CXCRs),including interleukin(IL)-6,IL-8/CXCL8,tumor necrosis factor(TNF),interferon(INF),transforming growth factor(TGF),CXCL1,CXCL9,CXCL10,CXCL11/CXCR3,and CXCL12/CXCR4,plays a critical role in the development of breast cancer in elderly patients.Researchers are particularly interested in obesity-induced inflammation because it has been shown to raise the risk of breast cancer in postmenopausal women with higher body mass index.Obesity-triggered inflammation causes increased infiltration of proinflammatory cytokines,adipokines,immune cells,and tumor cells in the enlarged adipose tissue of postmenopausal women with breast cancer,thereby modulating the tumor's immune-mediated microenvironment.Therefore,in this review,we focus on the functional significance studies of proinflammatory cytokines,CXCs,and CXCRs and describe their roles in influencing breast cancer progression in older women and their factors,such as obesity in postmenopausal women.In addition,the current status and prospects of cytokine-and CXC-based theranostic interventions for breast cancer therapy in elderly and postmenopausal women are discussed.展开更多
Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and...Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and psoriasis. This review explores the underlying neuroimmune pathways that link stress to skin inflammation in children, focusing on the role of the hypothalamic-pituitary-adrenal (HPA) axis and stress-induced cytokine production. Studies have shown that chronic psychological stress leads to dysregulation of the HPA axis, resulting in elevated cortisol levels, which paradoxically impair skin barrier function and upregulate pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Specific stressors, such as bullying, have been associated with heightened immune responses, increasing inflammation in the skin. For example, research has demonstrated that children who experience social stressors show elevated levels of C-reactive protein (CRP) and other markers of systemic inflammation, which directly correlate with skin condition flare-ups. Furthermore, exposure to early life stress has been linked to long-term alterations in immune function, perpetuating chronic inflammation even in the absence of ongoing stress. Future research should focus on longitudinal studies assessing how the timing, duration, and type of stressors influence skin condition severity, alongside evaluating interventions like cognitive-behavioral therapy (CBT) and stress management techniques. By addressing these childhood stressors, there is potential to not only mitigate skin condition flares but also reduce the long-term health consequences of chronic inflammation leading to therapeutic strategies that emphasize mental health alongside traditional dermatological treatments.展开更多
Objective:To evaluate the anti-shigellosis activity of the hydroethanol extract of Diospyros gilletii(D.gilletii)stem bark in Shigella flexneri(S.flexneri)-induced diarrheal mice.Methods:The hydroethanolic extract was...Objective:To evaluate the anti-shigellosis activity of the hydroethanol extract of Diospyros gilletii(D.gilletii)stem bark in Shigella flexneri(S.flexneri)-induced diarrheal mice.Methods:The hydroethanolic extract was obtained by maceration of D.gilletii stem bark in 70%hydroethanol(water꞉ethanol;30꞉70,v/v)solution.Then,mice pretreated with cyclophosphamide for immunosuppression were administered orally with an inoculum containing S.flexneri,and subsequently treated with 100,200,and 400 mg/kg of the hydroethanol extracts for 10 days.The bacterial colonies were enumerated and hematological and biochemical parameters were determined.Serum pro-inflammatory mediators including IL-1β,IL-18,and TNF-α,and nitric oxide levels were quantified by ELISA.Histological analyses of the kidney,liver,and colon were also conducted.Results:Treatment with 200 and 400 mg/kg of the hydroethanolic extracts markedly inhibited the growth of S.flexneri.Moreover,treatment with D.gilletii extract downregulated the levels of IL-1β,IL-18,and TNF-α,and restored hematological and biochemical parameters as well as histological architecture of the colon,liver,and kidneys.Additionally,the oral administration of 2000 mg/kg D.gilletii extract did not induce any sign of toxicity,with a median lethal dose greater than 2000 mg/kg.Conclusions:D.gilletii extract demonstrates the anti-shigellosis effects in S.flexneri-induced diarrheal mice,supporting the traditional use of this plant in treating diarrhea.展开更多
Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability...Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.展开更多
Bone marrow edema syndrome (BMES), is a rare and self-limiting condition characterized by localized bone pain and transient marrow edema visible on MRI. BMES has been increasingly associated with specific cutaneous ma...Bone marrow edema syndrome (BMES), is a rare and self-limiting condition characterized by localized bone pain and transient marrow edema visible on MRI. BMES has been increasingly associated with specific cutaneous manifestations that may hold diagnostic and prognostic significance. Patients with BMES have reported localized erythema, dermal thickening, and induration overlying the affected joints, which are hypothesized to reflect microvascular compromise and inflammatory processes within the bone and adjacent soft tissues. Dermatologic signs are likely linked to regional hyperemia, venous stasis, and cytokine-mediated inflammation, paralleling the pathophysiological mechanisms underlying intraosseous edema. Elevated intraosseous pressure in BMES may disrupt local perfusion, resulting in ischemia-reperfusion injury and subsequent vascular leakage, which manifests in visible cutaneous changes. Pro-inflammatory mediators, such as interleukin-1β and vascular endothelial growth factor (VEGF), central to BMES pathogenesis, may exacerbate endothelial activation, and dermal involvement. Histopathologic studies of affected skin have revealed perivascular lymphocytic infiltration and increased dermal vascularity, further supporting the theory of a shared ischemic and inflammatory pathway between bone and skin. Although MRI remains the gold standard for BMES diagnosis, recognition of these cutaneous manifestations could expedite orthopedic referral and intervention, especially in cases where imaging is delayed or symptoms are ambiguous. Current treatment options, including bisphosphonates, prostacyclin analogs, and offloading of weight bearing, may benefit from integration with dermatologic strategies to alleviate localized cutaneous symptoms and improve patient comfort. Evaluating the molecular and vascular links between BMES and its cutaneous manifestations provides an opportunity to refine diagnostic protocols and therapeutic approaches, offering a comprehensive understanding of the systemic interplay between dermal and skeletal pathophysiology, and optimizing clinical outcomes for patients affected by BMES.展开更多
Objective To investigate the bone-protective potential of Nelumbo nucifera Gaertn.seed hydroalcoholic extract(NNHE)in an ovariectomized(OVX)rat model by modulating the estrogen receptor/osteoprotegerin/receptor activa...Objective To investigate the bone-protective potential of Nelumbo nucifera Gaertn.seed hydroalcoholic extract(NNHE)in an ovariectomized(OVX)rat model by modulating the estrogen receptor/osteoprotegerin/receptor activator of nuclear factor(NF)-κB(ER/OPG/RANKL)signaling pathway.Methods Network pharmacology was employed with the databases of PubChem,BindingDB,DisGeNET,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG),along with Cytoscape 3.10.2 for identifying the targets and pathways of NNHE relevant to OP.A total of 48 specific pathogen-free(SPF)grade female Wistar rats were randomly divided into six groups(n=8 per group):sham control,OVX control,OVX+NNHE[100,200,400 mg/(kg·d)],and OVX+alendronate[3 mg/(kg·week)].The treatment lasted for 16 weeks.Post-treatment assessment included bone parameters(weight,thickness,density,volume,and length),serum biochemical markers[parathyroid hormone(PTH),estrogen,OPG,RANKL,tartrate-resistant acid phosphatase(TRAP),osteocalcin(OC),calcitonin(CT),calcium(Ca),phosphorus(P),and alkaline phosphatase(ALP)],pro-inflammatory cytokines[tumour necrosis factor(TNF)-α,NF-κB,interleukin(IL)-1β,and IL-6],lipid profiles[total cholesterol(TC),triglycerides(TG),low density lipoprotein(LDL),and high density lipoprotein(HDL)],oxidative stress markers[superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH),and malondialdehyde(MDA)],and histopathological analyses of femur,uterus,and vaginal tissues.Results Network pharmacology analysis revealed 61 overlapping targets between NNHE and osteoporosis-related genes,including signal transducer and activator of transcription 3(STAT3),NF-κB subunit 1(NFKB1),dopamine receptor D2(DRD2),matrix metalloproteinase 9(MMP9),and caspase-3.GO and KEGG enrichment suggested involvement in the ER/OPG/RANKL signaling pathway.In vivo studies demonstrated that NNHE treatment(400 mg/kg)significantly reduced OVX-induced body weight gain and exhibited estrogenic activity in the vaginal cornification assay.NNHE at 200 and 400 mg/kg significantly increased serum estrogen levels compared with OVX control group,while uterine weight remained unaffected.NNHE significantly improved the lipid profile compared with OVX group,with TC,TG,and LDL decreased,while HDL levels were increased at 200 and 400 mg/kg.Bone metabolism markers were significantly improved compared with OVX group,with serum Ca and P levels restored at all NNHE doses and ALP activity reduced.NNHE effectively modulated bone turnover markers compared with OVX group by reducing levels of OC,TRAP,and PTH,and increasing level of CT.In addition,NNHE decreased RANKL level while increasing OPG level at 200 and 400 mg/kg.Bone mineral density(BMD)was significantly enhanced compared with OVX group.Serum oxidative stress was significantly mitigated compared with OVX group through increased levels of antioxidant enzymes(SOD,CAT,and GSH)and reduced MDA,with the most pronounced effects observed at 400 mg/kg.Pro-inflammatory cytokines(TNF-α,IL-6,IL-1β,and NF-κB)were significantly reduced in all NNHE treatment groups compared with OVX group.Histopathological analysis confirmed restoration of trabecular bone structure and normalization of reproductive tissue morphology in OVX rats after NNHE treatment.Conclusion NNHE demonstrated significant protective effects against OVX-induced osteoporosis through ER/OPG/RANKL signaling pathway modulation,oxidative stress,and inflammation suppression,resulting in improved BMD and structural integrity.These findings indicate that NNHE may represent a promising therapeutic candidate for postmenopausal osteoporosis management and merits further clinical investigation.展开更多
Due to the rapid development of obesity and related metabolic diseases in the world,it is particularly important to explore the ability of novel materials in regulating obesity.In this study,C57BL/6J obese mice were u...Due to the rapid development of obesity and related metabolic diseases in the world,it is particularly important to explore the ability of novel materials in regulating obesity.In this study,C57BL/6J obese mice were used as objects,and 16S rRNA gene sequencing and lipidomics techniques were used to explore the regulatory effect and mechanism of the Protaetia brevitarsis ethanol extract(50%,V/V)against obesity.Our r esults showed that P.brevitarsis extract could significantly reduce the body weight,triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and pro-inflammatory cytokines(tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),and interleukin-6(IL-6))levels of high-fat diet(HFD)-fed mice.Moreover,the P.brevitarsis extract changed the composition and relative abundance of its gut microbiota,especially increasing Akkermansia muciniphila.Meanwhile,the content of short-chain fatty acids(SCFAs)was increased,especially acetic acid and butyric acid,which leads to a decrease in the synthesis and accumulation of lipids in the liver.Furthermore,the P.brevitarsis extract also induced the difference in lipid synthesis in the liver by down-regulating the mRNA levels of sterol regulatory element binding protein-1C(SREBP-1C),fatty acid synthase(FAS),and acetyl-CoA carboxylase(ACC).Therefore,this research provided preliminary work and reference for the development of P.brevitarsis as a functional food for anti-obesity.展开更多
基金This study was supported by internal funds from Patanjali Research Foundation Trust,Haridwar,India。
文摘Background:Fever is characterized by an upregulation of the thermoregulatory set-point after the body encounters any pathological challenge.It is accompanied by uncomfortable sickness behaviors and may be harmful in patients with other comor-bidities.We have explored the impact of an Ayurvedic medicine,Fevogrit,in an endo-toxin(lipopolysaccharide)-induced fever model in Wistar rats.Methods:Active phytoconstituents of Fevogrit were identified and quantified using ultra-high-performance liquid chromatography(UHPLC)platform.For the in-vivo study,fever was induced in male Wistar rats by the intraperitoneal administration of lipopolysaccharide(LPS),obtained from Escherichia coli.The animals were allocated to normal control,disease control,Paracetamol treated and Fevogrit treated groups.The rectal temperature of animals was recorded at different time points using a digital thermometer.At the 6-h time point,levels of TNF-α,IL-1βand IL-6 cytokines were analyzed in serum.Additionally,the mRNA expression of these cytokines was deter-mined in hypothalamus,24 h post-LPS administration.Results:UHPLC analysis of Fevogrit revealed the presence of picroside I,picroside II,vanillic acid,cinnamic acid,magnoflorine and cordifolioside A,as bioactive constitu-ents with known anti-inflammatory properties.Fevogrit treatment efficiently reduces the LPS-induced rise in the rectal temperature of animals.The levels and gene ex-pression of TNF-α,IL-1βand IL-6 in serum and hypothalamus,respectively,was also significantly reduced by Fevogrit treatment.Conclusion:The findings of the study demonstrated that Fevogrit can suppress LPS-induced fever by inhibiting peripheral or central inflammatory signaling pathways and could well be a viable treatment for infection-induced increase in body temperatures.
文摘BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnosis.METHODS The study cohort comprised 50 patients diagnosed with GC and 50 healthy control subjects.A panel of 7 pro-inflammatory cytokines,including interleukin(IL)-1β,IL-2,IL-6,IL-8,IL-12,tumor necrosis factor-α,and interferon-γ(IFN-γ)were quantified using multiplex Luminex assays.Comparative analyses were conducted to evaluate cytokine levels between the GC patients and healthy controls.The diagnostic potential of serum pro-inflammatory cytokines in differentiating GC patients from healthy individuals was assessed through receiver operating characteristic(ROC)curve analysis.The correlation between serum cytokine levels and disease severity,as classified by the tumor-node-metastasis staging system,was analyzed using Spearman's rank correlation coefficient.RESULTS In comparison to the control group,patients with GC demonstrated significantly elevated serum levels of IL-1β(t=-4.089,P<0.001),IL-6(t=-3.983,P<0.001),IL8(t=-5.460,P<0.001),and IFN-γ(t=-2.856,P=0.005).ROC curve analysis indicated that the area under the curve values for IL-1β,IL-6,and IL-8 exceeded 0.7,effectively distinguishing GC patients from healthy controls.Additionally,serum levels of IL-1β(r=0.424,P=0.012)and IL-6(r=0.742,P<0.001)were positively correlated with the T stage in GC patients.Similarly,serum concentrations of IL-1β(r=0.356,P=0.039)and IL-6(r=0.441,P=0.008)exhibited a positive association with the N stage in these patients.CONCLUSION These findings suggest that circulating pro-inflammatory cytokines,such as IL-1β,IL-6,and IL-8,may serve as potential biomarkers for the diagnosis of GC.
文摘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.
基金supported by the Excellent Young Scientist Foundation of the National Natural Science Foundation of China(Grant No.81522012)the National Natural Science Foundation of China(Grant No.81670807,81600699,81702237,81701383,81400858)+8 种基金the Thousand Youth Talents Plan of China(Grant No.D1119003)the Hunan Youth Talent Project(Grant No.2016RS3021)the Innovation Driven Project of Central South University(2016CX028)the Youth Foundation of Xiangya Hospital in Central South University(Grant No.2016Q10)the Fundamental Research Funds for the Central Universities of Central South University(Grant No.2017zzts032,2017zzts014)the Hunan Province Natural Science Foundation of China(Grant No.2017JJ3501)the China Postdoctoral Science Foundation(Grant No.2017M612596)the Natural Science Foundation for Distinguished Yong Scholars of Guangdong Province(2016A030306051)the National Basic Research Program of China(973 Program,Grant no.2014CB942903)
文摘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.
文摘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. ＋
文摘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.
文摘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.
文摘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.
基金supported by the Jeju Sea-green Program for the Regional Innovation Systemthe Regional Technology Innovation Program (No RTI04-02-07) of the Ministry of Knowledge and Economy,Korea
文摘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.
基金funding support from Chinese Nature Science Foundation (No.81202705)The Effect of Long Dan Xie Gan Formula Granule on Toll Signaling Pathway in the Guinea pigs of Recurrent Genital Herpes Changsha Science and Technology Foundation (No.kh1601195)
文摘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.
基金supported by National Natural Science Foundation of China(81160222)the Foundation of Health Department of Jiangxi Province(20121044)
文摘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.
文摘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.
基金supported by Hospital Fundacion Nuestra Senora de la Luz,Private Assistance Institution.
文摘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.
基金supported by the National Natural Science Foundation of China(No.32070671,32270690)the COVID-19 research projects of West China Hospital Sichuan University(China)(No.HX-2019-nCoV-057)the regional innovation cooperation between Sichuan and Guangxi Provinces,China(No.2020YFQ0019).
文摘Older age is one of the leading risk indicators for advanced breast cancer.It is critical to extensively investigate how aging affects breast cancer,considering the increasing rate of population aging.Human body aging and death are caused by cellular senescence and alterations in the aging microenvironment in vivo.Breast cancer cells may invade more easily with age due to the stiff extracellular matrix of the breast.Furthermore,growing evidence suggests that the massive release of inflammatory immune mediators,such as cytokines(interleukins)or CXC chemokines(CXCs),and their receptors(CXCRs),including interleukin(IL)-6,IL-8/CXCL8,tumor necrosis factor(TNF),interferon(INF),transforming growth factor(TGF),CXCL1,CXCL9,CXCL10,CXCL11/CXCR3,and CXCL12/CXCR4,plays a critical role in the development of breast cancer in elderly patients.Researchers are particularly interested in obesity-induced inflammation because it has been shown to raise the risk of breast cancer in postmenopausal women with higher body mass index.Obesity-triggered inflammation causes increased infiltration of proinflammatory cytokines,adipokines,immune cells,and tumor cells in the enlarged adipose tissue of postmenopausal women with breast cancer,thereby modulating the tumor's immune-mediated microenvironment.Therefore,in this review,we focus on the functional significance studies of proinflammatory cytokines,CXCs,and CXCRs and describe their roles in influencing breast cancer progression in older women and their factors,such as obesity in postmenopausal women.In addition,the current status and prospects of cytokine-and CXC-based theranostic interventions for breast cancer therapy in elderly and postmenopausal women are discussed.
文摘Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and psoriasis. This review explores the underlying neuroimmune pathways that link stress to skin inflammation in children, focusing on the role of the hypothalamic-pituitary-adrenal (HPA) axis and stress-induced cytokine production. Studies have shown that chronic psychological stress leads to dysregulation of the HPA axis, resulting in elevated cortisol levels, which paradoxically impair skin barrier function and upregulate pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Specific stressors, such as bullying, have been associated with heightened immune responses, increasing inflammation in the skin. For example, research has demonstrated that children who experience social stressors show elevated levels of C-reactive protein (CRP) and other markers of systemic inflammation, which directly correlate with skin condition flare-ups. Furthermore, exposure to early life stress has been linked to long-term alterations in immune function, perpetuating chronic inflammation even in the absence of ongoing stress. Future research should focus on longitudinal studies assessing how the timing, duration, and type of stressors influence skin condition severity, alongside evaluating interventions like cognitive-behavioral therapy (CBT) and stress management techniques. By addressing these childhood stressors, there is potential to not only mitigate skin condition flares but also reduce the long-term health consequences of chronic inflammation leading to therapeutic strategies that emphasize mental health alongside traditional dermatological treatments.
基金funded by the Yaounde-Bielefeld Bilateral Graduate School for Natural Products with Anti-parasite and Antibacterial Activity(YaBiNaPA)(grant number:57316173).
文摘Objective:To evaluate the anti-shigellosis activity of the hydroethanol extract of Diospyros gilletii(D.gilletii)stem bark in Shigella flexneri(S.flexneri)-induced diarrheal mice.Methods:The hydroethanolic extract was obtained by maceration of D.gilletii stem bark in 70%hydroethanol(water꞉ethanol;30꞉70,v/v)solution.Then,mice pretreated with cyclophosphamide for immunosuppression were administered orally with an inoculum containing S.flexneri,and subsequently treated with 100,200,and 400 mg/kg of the hydroethanol extracts for 10 days.The bacterial colonies were enumerated and hematological and biochemical parameters were determined.Serum pro-inflammatory mediators including IL-1β,IL-18,and TNF-α,and nitric oxide levels were quantified by ELISA.Histological analyses of the kidney,liver,and colon were also conducted.Results:Treatment with 200 and 400 mg/kg of the hydroethanolic extracts markedly inhibited the growth of S.flexneri.Moreover,treatment with D.gilletii extract downregulated the levels of IL-1β,IL-18,and TNF-α,and restored hematological and biochemical parameters as well as histological architecture of the colon,liver,and kidneys.Additionally,the oral administration of 2000 mg/kg D.gilletii extract did not induce any sign of toxicity,with a median lethal dose greater than 2000 mg/kg.Conclusions:D.gilletii extract demonstrates the anti-shigellosis effects in S.flexneri-induced diarrheal mice,supporting the traditional use of this plant in treating diarrhea.
文摘Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.
文摘Bone marrow edema syndrome (BMES), is a rare and self-limiting condition characterized by localized bone pain and transient marrow edema visible on MRI. BMES has been increasingly associated with specific cutaneous manifestations that may hold diagnostic and prognostic significance. Patients with BMES have reported localized erythema, dermal thickening, and induration overlying the affected joints, which are hypothesized to reflect microvascular compromise and inflammatory processes within the bone and adjacent soft tissues. Dermatologic signs are likely linked to regional hyperemia, venous stasis, and cytokine-mediated inflammation, paralleling the pathophysiological mechanisms underlying intraosseous edema. Elevated intraosseous pressure in BMES may disrupt local perfusion, resulting in ischemia-reperfusion injury and subsequent vascular leakage, which manifests in visible cutaneous changes. Pro-inflammatory mediators, such as interleukin-1β and vascular endothelial growth factor (VEGF), central to BMES pathogenesis, may exacerbate endothelial activation, and dermal involvement. Histopathologic studies of affected skin have revealed perivascular lymphocytic infiltration and increased dermal vascularity, further supporting the theory of a shared ischemic and inflammatory pathway between bone and skin. Although MRI remains the gold standard for BMES diagnosis, recognition of these cutaneous manifestations could expedite orthopedic referral and intervention, especially in cases where imaging is delayed or symptoms are ambiguous. Current treatment options, including bisphosphonates, prostacyclin analogs, and offloading of weight bearing, may benefit from integration with dermatologic strategies to alleviate localized cutaneous symptoms and improve patient comfort. Evaluating the molecular and vascular links between BMES and its cutaneous manifestations provides an opportunity to refine diagnostic protocols and therapeutic approaches, offering a comprehensive understanding of the systemic interplay between dermal and skeletal pathophysiology, and optimizing clinical outcomes for patients affected by BMES.
文摘Objective To investigate the bone-protective potential of Nelumbo nucifera Gaertn.seed hydroalcoholic extract(NNHE)in an ovariectomized(OVX)rat model by modulating the estrogen receptor/osteoprotegerin/receptor activator of nuclear factor(NF)-κB(ER/OPG/RANKL)signaling pathway.Methods Network pharmacology was employed with the databases of PubChem,BindingDB,DisGeNET,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG),along with Cytoscape 3.10.2 for identifying the targets and pathways of NNHE relevant to OP.A total of 48 specific pathogen-free(SPF)grade female Wistar rats were randomly divided into six groups(n=8 per group):sham control,OVX control,OVX+NNHE[100,200,400 mg/(kg·d)],and OVX+alendronate[3 mg/(kg·week)].The treatment lasted for 16 weeks.Post-treatment assessment included bone parameters(weight,thickness,density,volume,and length),serum biochemical markers[parathyroid hormone(PTH),estrogen,OPG,RANKL,tartrate-resistant acid phosphatase(TRAP),osteocalcin(OC),calcitonin(CT),calcium(Ca),phosphorus(P),and alkaline phosphatase(ALP)],pro-inflammatory cytokines[tumour necrosis factor(TNF)-α,NF-κB,interleukin(IL)-1β,and IL-6],lipid profiles[total cholesterol(TC),triglycerides(TG),low density lipoprotein(LDL),and high density lipoprotein(HDL)],oxidative stress markers[superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH),and malondialdehyde(MDA)],and histopathological analyses of femur,uterus,and vaginal tissues.Results Network pharmacology analysis revealed 61 overlapping targets between NNHE and osteoporosis-related genes,including signal transducer and activator of transcription 3(STAT3),NF-κB subunit 1(NFKB1),dopamine receptor D2(DRD2),matrix metalloproteinase 9(MMP9),and caspase-3.GO and KEGG enrichment suggested involvement in the ER/OPG/RANKL signaling pathway.In vivo studies demonstrated that NNHE treatment(400 mg/kg)significantly reduced OVX-induced body weight gain and exhibited estrogenic activity in the vaginal cornification assay.NNHE at 200 and 400 mg/kg significantly increased serum estrogen levels compared with OVX control group,while uterine weight remained unaffected.NNHE significantly improved the lipid profile compared with OVX group,with TC,TG,and LDL decreased,while HDL levels were increased at 200 and 400 mg/kg.Bone metabolism markers were significantly improved compared with OVX group,with serum Ca and P levels restored at all NNHE doses and ALP activity reduced.NNHE effectively modulated bone turnover markers compared with OVX group by reducing levels of OC,TRAP,and PTH,and increasing level of CT.In addition,NNHE decreased RANKL level while increasing OPG level at 200 and 400 mg/kg.Bone mineral density(BMD)was significantly enhanced compared with OVX group.Serum oxidative stress was significantly mitigated compared with OVX group through increased levels of antioxidant enzymes(SOD,CAT,and GSH)and reduced MDA,with the most pronounced effects observed at 400 mg/kg.Pro-inflammatory cytokines(TNF-α,IL-6,IL-1β,and NF-κB)were significantly reduced in all NNHE treatment groups compared with OVX group.Histopathological analysis confirmed restoration of trabecular bone structure and normalization of reproductive tissue morphology in OVX rats after NNHE treatment.Conclusion NNHE demonstrated significant protective effects against OVX-induced osteoporosis through ER/OPG/RANKL signaling pathway modulation,oxidative stress,and inflammation suppression,resulting in improved BMD and structural integrity.These findings indicate that NNHE may represent a promising therapeutic candidate for postmenopausal osteoporosis management and merits further clinical investigation.
基金finally supported by the National Natural Science Foundation of China(31830084,31970440)the construction funds for the‘Double First-Class’initiative for Nankai University(96172158,96173250,91822294)。
文摘Due to the rapid development of obesity and related metabolic diseases in the world,it is particularly important to explore the ability of novel materials in regulating obesity.In this study,C57BL/6J obese mice were used as objects,and 16S rRNA gene sequencing and lipidomics techniques were used to explore the regulatory effect and mechanism of the Protaetia brevitarsis ethanol extract(50%,V/V)against obesity.Our r esults showed that P.brevitarsis extract could significantly reduce the body weight,triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and pro-inflammatory cytokines(tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),and interleukin-6(IL-6))levels of high-fat diet(HFD)-fed mice.Moreover,the P.brevitarsis extract changed the composition and relative abundance of its gut microbiota,especially increasing Akkermansia muciniphila.Meanwhile,the content of short-chain fatty acids(SCFAs)was increased,especially acetic acid and butyric acid,which leads to a decrease in the synthesis and accumulation of lipids in the liver.Furthermore,the P.brevitarsis extract also induced the difference in lipid synthesis in the liver by down-regulating the mRNA levels of sterol regulatory element binding protein-1C(SREBP-1C),fatty acid synthase(FAS),and acetyl-CoA carboxylase(ACC).Therefore,this research provided preliminary work and reference for the development of P.brevitarsis as a functional food for anti-obesity.
