Abstract AIM To investigate whether PMN from patients with IBD or infectious colitis, respectively, secrete increased amounts of pro inflammatory cytokines and can be regulated by IL 10. METHODS Secretion (E...Abstract AIM To investigate whether PMN from patients with IBD or infectious colitis, respectively, secrete increased amounts of pro inflammatory cytokines and can be regulated by IL 10. METHODS Secretion (ELISA) as well as corresponding mRNA levels (semiquantitative RT PCR) of pro inflammatory cytokines (IL 1β, TNF α) and of IL 1 receptor antagonist were assessed in peripheral PMN. RESULTS PMN from patients with IBD are primed to secrete enhanced amounts of pro inflammatory cytokines accompanied by detection of corresponding mRNAs in comparison with normal controls. This finding is not specific for IBD but rather reflects intestinal inflammation in general. IL 10 markedly inhibited proinflammatory cytokine secretion as well as corresponding mRNA concentrations. CONCLUSION PMN are an important source of pro inflammatory cytokines in patients with intestinal inflammation and can be downregulated by IL 10.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
Objective:To evaluate the anti-inflammatory potential of peptide/polypeptide fraction of Aloe vera through in vitro and in vivo studies.Methods:The peptide/polypeptide fraction from Aloe vera was obtained through tric...Objective:To evaluate the anti-inflammatory potential of peptide/polypeptide fraction of Aloe vera through in vitro and in vivo studies.Methods:The peptide/polypeptide fraction from Aloe vera was obtained through trichloroacetic acid precipitation.The anti-inflammatory property of the peptide/polypeptide fraction was tested by protein denaturation,membrane stabilization assays.The effect of the fraction on RAW 264.7 cell viability was examined by MTT assays.The nitric oxide level was determined through Griess reagent.TNF-αand IL-6 levels were estimated using ELISA kits.In vivo studies were carried out in male Wistar rats through injection of Freund’s adjuvant in the hind paw.Paw edema was measured through the Vernier scale and levels of alanine aminotransferase,aspartate transaminase,TNF-α,IL-6,and secretory phospholipase A2 were estimated through their respective kits after fourteen days of treatment.Graph Pad Prism6 was used for analyzing the results.Results:The peptide/polypeptide extract inhibited protein denaturation with an IC50 value of(218.9±15.6)μg/m L and stabilized the membrane of red blood cells with an IC50 value of(275.9±19.1)μg/m L.The extract showed no changes in cell morphology or cytotoxicity up to the concentration of 20μg/mL in MTT assays.The peptide/polypeptide fraction markedly reduced the levels of proinflammatory markers and mediators in both in vitro and in vivo studies.Conclusions:The results indicate that the peptide/polypeptide fraction of Aloe vera has antiinflammatory property through inhibition of inflammatory markers and mediators responsible for NF-κB and mitogen-activated protein kinase pathways.展开更多
Cytokines play an important role in the pathological process of atherosclerosis(AS),affecting the progression and prognosis of cerebrovascular diseases concerned with AS.Cytokines mainly include C-reactive protein,int...Cytokines play an important role in the pathological process of atherosclerosis(AS),affecting the progression and prognosis of cerebrovascular diseases concerned with AS.Cytokines mainly include C-reactive protein,interleukin,tumor necrosis factor,chemotactic cytokines,matrix metalloproteinases,etc.These These cytokines promote or inhibit the inflammatory response and plaque formation during AS process through different targets and mechanisms.A comprehensive understanding of the cytokines in the occurrence and development of AS is conducive to search for new therapeutic targets and drugs.展开更多
The main pathological change in post-traumatic osteoarthritis (PTOA) is cartilage degeneration, which is closely related to inflammation and oxidative stress. Inflammation can cause degeneration of articular cartil...The main pathological change in post-traumatic osteoarthritis (PTOA) is cartilage degeneration, which is closely related to inflammation and oxidative stress. Inflammation can cause degeneration of articular cartilage. Cartilage degeneration can also stimulate the progression of inflammation. It has been found that inflammatory cytokines can participate in the pathological process of cartilage degeneration through multiple signaling pathways, mainly mitogen-activated protein kinase, nuclear transcription factor kappa B, and Wnt-p-catenin signal transduction pathways. This review aimed at exploring the relationship between PTOA and inflammation-related cytokines by introducing the role of proinflammatory cytokines in chondrocyte destruction and extracellular matrix degradation.展开更多
Idiopathic pulmonary fibrosis(IPF)is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function...Idiopathic pulmonary fibrosis(IPF)is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function.Chronic inflammation has been demonstrated to be the pathological basis of fibrosis.Emerging studies have revealed that most interleukin-17(IL-17)isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity.Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes,including the initiation and exacerbation of IPF.Here,we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.展开更多
Objective: To determine whether balloon catheter denudation can induce vascular smooth muscle cells (VSMCs) to senescence, and whether this senescence can result in inflammation activity. Methods: Twelve male Chin...Objective: To determine whether balloon catheter denudation can induce vascular smooth muscle cells (VSMCs) to senescence, and whether this senescence can result in inflammation activity. Methods: Twelve male Chinese white rabbits were denuded of the carotid arteries or VSMCs. Acidic β-galactosidase activity of carotid arteries or VSMCs was detected. Transfection and chloramphenicol acetyltransferase (CAT) assay for iNOS gene and nitrite (NO2^-) assay were undertaken. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate inflammation cytokines mRNA expression. Measurement of NF-kB activity was detected by electrophoretic mobility shift assay (EMSA). MMP-9, ICAM-1, P-p65, and IkBα expressions were analyzed by Western blotting. Results: After denudation VSMCs from denuded arteries showed an accumulation of significantly more senescence-associated β-galactosidase (SA-β-Gal) positive ceils and greater iNOS activity. Transcriptional activity of iNOS was highly expressed. The mRNA expressions of IL-1β, ICAM-1,MMP-9, TNF-α and the iNOS enzyme were significantly increased in injuring-induced senescence SMCs. However, the TNF-α or IL-1β-induced the protein production (ICAM-1 and MMP-9) was prevented by PDTC and MG132, which are inhibitors of NF-kB activation. Also, activation of NF-kB and cytokine-induced degradation of IKBα in the denuded VSMC were significantly affected. Conclusion: Intraluminal injury to the artery may lead to the emergence of senescent VSMC. Inflammation activity in SMCs is closely related to the senescence and the activation of NF-kB is involved.展开更多
This editorial refers to the article“Comparative analysis of Nε-carboxymethyllysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients”,published in the recent issue of the World...This editorial refers to the article“Comparative analysis of Nε-carboxymethyllysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients”,published in the recent issue of the World Journal of Diabetes 2023 is based on glucose metabolism,advanced glycation end products(AGEs),inflammation and adiposity on diabetes and coronary artery disease(CAD).This study has included CAD patients who were stratified according to glycosylated hemoglobin higher than 6.5 and sex-matched.A higher prevalence of hypertension,dyslipidemia,and non-vegetarian diet were found in the diabetic group.These risk factors might influence body weight and adiposity and explain the increment of the left atrium.Although this data was not supported by the study.The diet can also explain the non-enzymatic reactions on lipids,proteins,or nucleic acids and consequently an increment of AGEs.These molecules can emit fluorescence.However,one of the non-fluorescent and most abundant AGEs is Nε-carboxymethyl-lysine(CML).Its association with coronary artery stenosis and severity in the diabetic group might suggest its role as a player in CAD progression.Thus,CML,after binding with its receptor(RAGE),can induce calcification cascade through reactive oxygen species and mitogen-activated protein kinase.Moreover,this interaction AGE-RAGE can cause activation of the transcription nuclear factor-kb and induce inflammatory cytokines.It might explain the relationship between CML and pro-inflammatory cytokines in diabetic and CAD patients.Although this is a population from one center,the determination of CML and inflammatory cytokines might improve the diagnosis of severe and progressive CAD.Future and comparative studies among glycosylated hemoglobin,CML,and other AGE levels according to diagnosis and prognosis value might modify the clinical practice.Although these molecules are irreversible,they can act through a specific receptor inducing a signal transduction that might be modulated by inhibitors,antibodies,or siRNA.Further mechanistic studies might improve the development of future preventive therapies for diabetic patients.展开更多
Objective:To investigate the underlying mechanism of anti-inflammatory action of coumarin and eugenol in lipopolysaccharide(LPS)-stimulated RAW 264.7 cells.Methods:RAW 264.7 cells were treated with 2.5μg/mL of LPS,50...Objective:To investigate the underlying mechanism of anti-inflammatory action of coumarin and eugenol in lipopolysaccharide(LPS)-stimulated RAW 264.7 cells.Methods:RAW 264.7 cells were treated with 2.5μg/mL of LPS,50μM of coumarin,and 50μM eugenol for 24 h.The viability of the cells was assessed using MTT assay.The production of nitric oxide was determined using Griess reagent and DCFH-DA was used to measure the production of reactive oxygen species.The protein expression of NLRP3,IL-1β,NF-κB,and cyclooxygenase 2 was assessed using Western blot analysis.Results:Coumarin and eugenol showed anti-inflammatory effects against LPS-induced inflammatory response by ameliorating the expression of NLRP3 inflammasome and NF-κB,which further led to a subsequent reduction in IL-1β,nitric oxide,and reactive oxygen species.Conclusions:Coumarin and eugenol exert their anti-inflammatory activities by modulating the NLRP3 inflammasome pathway and NF-κB.These compounds may have promising therapeutic applications for the treatment of various inflammatory diseases.展开更多
Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was c...Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.展开更多
BACKGROUND Generalized anxiety disorder(GAD)is a relatively common mental disorder.Recently,inflammation,an important factor for the development of depression,has attracted increasing attention.Several studies have sh...BACKGROUND Generalized anxiety disorder(GAD)is a relatively common mental disorder.Recently,inflammation,an important factor for the development of depression,has attracted increasing attention.Several studies have shown that inflammatory cytokines can affect the pathophysiological processes of several nervous system diseases.We hypothesized that there is a correlation between the levels of lipopolysaccharide(LPS)-stimulated inflammatory cytokines and the clinical symptoms of GAD.AIM To investigate the predictive effect of LPS-stimulated inflammatory cytokines on symptoms of GAD.METHODS This was a cross-sectional study in which 89 patients with GAD diagnosed at The First Hospital of Hebei Medical University from January 2022 to December 2022 and 70 individuals without anxiety and depression(controls)during the same period were included.Fasting venous blood was collected from all the subjects in heparin tubes,and another 3 ml of blood was supplemented with LPS(10 ng/ml).The plasma levels of 12 cytokines[Interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,tumor necrosis factor(TNF)-α,interferon(IFN)-γ,IL-17A,IL-12p70,and IFN-α]were detected.RESULTS Post-LPS stimulation,the levels of IL-1β,IL-6,IL-8,IL-10,and TNF-αin both the control and GAD groups were significantly elevated above those in the nonstimulated groups,with IL-6 and IL-8 showing marked increases.Increases in IL-8 and TNF-αwere statistically significant in the GAD group(P<0.05).IL-1β,IL-6,IL-8,IL-10,and TNF-αwere found to be significantly correlated with Hamilton Anxiety Rating Scale(HAMA)scores(P<0.05).A negative correlation was observed between IL-10 levels and HAMA scores.Further analysis revealed that TNF-αwas associated with mental anxiety,whereas IL-1β,IL-8,and IL-10 were associated with physical anxiety symptoms,with IL-10 showing a negative correlation with physical anxiety.IL-6 was associated with both mental and physical aspects of anxiety.CONCLUSION The physical symptoms of GAD are related to inflammatory factors.IL-1β,IL-8,IL-10,and TNF-a can be used as predictors of physical or mental anxiety in patients with GAD.展开更多
BACKGROUND Sepsis,which is characterized by acute systemic inflammation and is associated with high rates of morbidity and mortality,presents a significant challenge in health care.Some scholars have found that the se...BACKGROUND Sepsis,which is characterized by acute systemic inflammation and is associated with high rates of morbidity and mortality,presents a significant challenge in health care.Some scholars have found that the sequential organ failure assessment(SOFA)and quick SOFA scores are not ideal for predicting severe sepsis and mortality.Microbial culture takes a long time(2-3 d)and provides no information for early diagnosis and treatment.Therefore,new diagnostic methods for sepsis need to be explored.AIM To assess cytokine levels in the plasma of sepsis patients and identify potential biomarkers for diagnosing sepsis.METHODS Ten sepsis patients admitted to the emergency department within 24 h of onset were enrolled as the observation group,whereas ten noninfected patients served as the control group.Of the 10 noninfected patients,9 hypertension combined with cerebral infarction,1 patients with vertiginous syndrome.Plasma Cytokines were measured using the Bio-Plex Pro^(TM)Human Chemokine Panel 40-plex.Differentially expressed cytokines in plasma of sepsis and nonsepsis patients were analyzed using Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses.RESULTS Interleukin(IL)-16,granulocyte-macrophage granulocyte-macrophage colony-stimulating factor(GM-CSF),CX3CL1,CXCL9,CXCL16,CCL25,and CCL23 plasma levels were significantly increased in sepsis patients.GO analysis revealed that these cytokines were mainly associated with cellular structures such as intermediates,nuclear plaques,adhesion plaques,lateral plasma membranes,and cell matrix junctions.These genes were involved in various molecular functions,such as cytokine activity,receptor ligand activity,and signal receptor activator activity,contributing to various biological functions,such as leukocyte chemotaxis,migration,and chemotaxis.KEGG analysis indicated involvement in cytokine cytokine receptor interactions,chemokine signaling pathways,virus–protein interactions with cytokines and cytokine receptors,and the tumor necrosis factor signaling pathway.CONCLUSION Elevated serum levels of IL-16,GM-CSF,CX3CL1,CXCL9,CXCL16,CCL25,and CCL23 in sepsis patients suggest their potential as diagnostic biomarkers for sepsis.展开更多
Bats,notable as the only flying mammals,serve as natural reservoir hosts for various highly pathogenic viruses in humans(e.g.,SARS-CoV and Ebola virus).Furthermore,bats exhibit an unparalleled longevity among mammals ...Bats,notable as the only flying mammals,serve as natural reservoir hosts for various highly pathogenic viruses in humans(e.g.,SARS-CoV and Ebola virus).Furthermore,bats exhibit an unparalleled longevity among mammals relative to their size,particularly the Myotis bats,which can live up to 40 years.However,the mechanisms underlying these distinctive traits remain incompletely understood.In our prior research,we demonstrated that bats exhibit dampened STING-interferon activation,potentially conferring upon them the capacity to mitigate virus-or aging-induced inflammation.To substantiate this hypothesis,we established the first in vivo bat-mouse model for aging studies by integrating Myotis davidii bat STING(MdSTING)into the mouse genome.We monitored the genotypes of these mice and performed a longitudinal comparative transcriptomic analysis on MdSTING and wild-type mice over a 3-year aging process.Blood transcriptomic analysis indicated a reduction in aging-related inflammation in female MdSTING mice,as evidenced by significantly lower levels of pro-inflammatory cytokines and chemokines,immunopathology,and neutrophil recruitment in aged female MdSTING mice compared to aged wild-type mice in vivo.These results indicated that MdSTING knock-in attenuates the aging-related inflammatory response and may also improve the healthspan in mice in a sex-dependent manner.Although the underlying mechanism awaits further study,this research has critical implications for bat longevity research,potentially contributing to our comprehension of healthy aging in humans.展开更多
The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.Obesity-related conditions like type 2 d...The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.Obesity-related conditions like type 2 diabetes and non-alcoholic fatty liver disease exacerbate this relationship.Peripheral lipid accumulation,particularly in the liver,initiates a cascade of inflammatory processes that extend to the brain,influencing critical metabolic regulatory regions.Ceramide and palmitate,key lipid components,along with lipid transporters lipocalin-2 and apolipoprotein E,contribute to neuroinflammation by disrupting blood–brain barrier integrity and promoting gliosis.Peripheral insulin resistance further exacerbates brain insulin resistance and neuroinflammation.Preclinical interventions targeting peripheral lipid metabolism and insulin signaling pathways have shown promise in reducing neuroinflammation in animal models.However,translating these findings to clinical practice requires further investigation into human subjects.In conclusion,metabolic dysfunction,peripheral inflammation,and insulin resistance are integral to neuroinflammation and neurodegeneration.Understanding these complex mechanisms holds potential for identifying novel therapeutic targets and improving outcomes for neurodegenerative diseases.展开更多
Non-specific orbital inflammation(NSOI)is a noninfectious orbital inflammation.Although it is often considered the most common diagnosis in orbital biopsies,it is an exclusionary diagnosis that requires ruling out sys...Non-specific orbital inflammation(NSOI)is a noninfectious orbital inflammation.Although it is often considered the most common diagnosis in orbital biopsies,it is an exclusionary diagnosis that requires ruling out systemic disease or other possible causes.Its characteristics include acute orbital signs and symptoms,including pain,proptosis,periorbital edema,chemosis,diplopia,and visual impairment.The clinical manifestations and histological findings of NSOI are heterogeneous,without specific diagnostic criteria or treatment guidelines,which poses significant challenges for diagnosis and treatment.This guideline provides a detailed description of the definition,classification,diagnosis,and treatment of NSOI.展开更多
DNA damage occurs across tumorigenesis and tumor development.Tumor intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orch...DNA damage occurs across tumorigenesis and tumor development.Tumor intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment(TIME)and dominate tumor progression.Accumulating evidence documents that multiple signaling pathways,including cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein(ATM/ATR),are activated downstream of DNA damage and they are associated with the secretion of diverse cytokines.These cytokines possess multifaced functions in the anti-tumor immune response.Thus,it is necessary to deeply interpret the complex TIME reshaped by damaged DNA and tumor-derived cytokines,critical for the development of effective tumor therapies.This manuscript comprehensively reviews the relationship between the DNA damage response and related cytokines in tumors and depicts the dual immunoregulatory roles of these cytokines.We also summarize clinical trials targeting signaling pathways and cytokines associated with DNA damage and provide future perspectives on emerging technologies.展开更多
Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlyi...Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlying mechanisms are not clear.This study was to find out whether systemic inflammation plays an important role.Methods:A total of 103 patients with early-stage HCC under liver resection were enrolled(LLR group,n=53;OLR group,n=50).The expression of 9 inflammatory cytokines in patients at preoperation,postoperative day 1(POD1)and POD7 was quantified by Luminex Multiplex assay.The relationships of the cytokines and the postoperative outcomes were compared between LLR and OLR.Results:Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative levels.Compared to OLR,the POD1 levels of granulocytemacrophage colony-stimulating factor(GM-CSF),interleukin-6(IL-6),IL-8,and monocyte chemoattractant protein-1(MCP-1)in the LLR group were significantly lower.Higher POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during operation.The levels of these cytokines were positively associated with postoperative liver injury,and the length of hospital stay.Importantly,a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver resection.Conclusions:Significantly lower level of GM-CSF,IL-6,IL-8,and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.展开更多
Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lyci...Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.展开更多
AIM:To investigate the causal effect of inflammatory bowel disease(IBD)on ocular inflammation using Mendelian randomization(MR)analysis.METHODS:Genetic instruments associated with inflammatory bowel disease(IBD),ulcer...AIM:To investigate the causal effect of inflammatory bowel disease(IBD)on ocular inflammation using Mendelian randomization(MR)analysis.METHODS:Genetic instruments associated with inflammatory bowel disease(IBD),ulcerative colitis(UC),and Crohn’s disease(CD)were derived from the largest genome-wide association studies(GWAS)published to date.The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis,keratitis,iridocyclitis,chorioretinitis,episcleritis,and optic neuritis.All participants were of European ancestry.Three methods which included inverse variance weighting(IVW),weighted median(WM),and MR-Egger regression were performed to estimate the causal association in this study.IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes,to summarize the effect sizes of multiple independent studies,which could provide the most precise estimated results.IVW was used as the primary outcome,while WM and MR-Egger were used to improve the estimation of IVW.RESULTS:A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis,keratitis,iridocyclitis,and optic neuritis,but not on chorioretinitis or episcleritis.After Bonferroni correction,the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis(IVW:OR,1.17;95%CI,1.10-1.24,P=2.54×10^(-7)).CD was significantly associated with conjunctivitis(IVW:OR,1.05;95%CI,1.03-1.08,P=3.20×10^(-5)),keratitis(IVW:OR,1.06;95%CI,1.02-1.09;P=1.13×10^(-3)),and iridocyclitis(IVW:OR,1.09;95%CI,1.04-1.14;P=1.43×10^(-4)).CONCLUSION:IBD causally poses a risk of inflammation of conjunctiva,cornea,Iris-ciliary body complex,and optic neuritis.CD is more closely associated with the eye inflammation than UC.These impliy that the relationship of IBD and different parts of the eye structure are different,and provide novel evidence linking based on the association of the gut-eye axis.展开更多
BACKGROUND Conventional five-port laparoscopic surgery,the current standard treatment for colorectal carcinoma(CRC),has many disadvantages.AIM To assess the influence of reduced-port laparoscopic surgery(RPLS)on perio...BACKGROUND Conventional five-port laparoscopic surgery,the current standard treatment for colorectal carcinoma(CRC),has many disadvantages.AIM To assess the influence of reduced-port laparoscopic surgery(RPLS)on perioperative indicators,postoperative recovery,and serum inflammation indexes in patients with CRC.METHODS The study included 115 patients with CRC admitted between December 2019 and May 2023,52 of whom underwent conventional five-port laparoscopic surgery(control group)and 63 of whom underwent RPLS(research group).Comparative analyses were performed on the following dimensions:Perioperative indicators[operation time(OT),incision length,intraoperative blood loss(IBL),and rate of conversion to laparotomy],postoperative recovery(first postoperative exhaust,bowel movement and oral food intake,and bowel sound recovery time),serum inflammation indexes[high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)],postoperative complications(anastomotic leakage,incisional infection,bleeding,ileus),and therapeutic efficacy.RESULTS The two groups had comparable OTs and IBL volumes.However,the research group had a smaller incision length;lower rates of conversion to laparotomy and postoperative total complication;and shorter time of first postoperative exhaust,bowel movement,oral food intake,and bowel sound recovery;all of which were significant.Furthermore,hs-CRP,IL-6,and TNF-αlevels in the research group were significantly lower than the baseline and those of the control group,and the total effective rate was higher.CONCLUSION RPLS exhibited significant therapeutic efficacy in CRC,resulting in a shorter incision length and a lower conversion rate to laparotomy,while also promoting postoperative recovery,effectively inhibiting the inflammatory response,and reducing the risk of postoperative complications.展开更多
文摘Abstract AIM To investigate whether PMN from patients with IBD or infectious colitis, respectively, secrete increased amounts of pro inflammatory cytokines and can be regulated by IL 10. METHODS Secretion (ELISA) as well as corresponding mRNA levels (semiquantitative RT PCR) of pro inflammatory cytokines (IL 1β, TNF α) and of IL 1 receptor antagonist were assessed in peripheral PMN. RESULTS PMN from patients with IBD are primed to secrete enhanced amounts of pro inflammatory cytokines accompanied by detection of corresponding mRNAs in comparison with normal controls. This finding is not specific for IBD but rather reflects intestinal inflammation in general. IL 10 markedly inhibited proinflammatory cytokine secretion as well as corresponding mRNA concentrations. CONCLUSION PMN are an important source of pro inflammatory cytokines in patients with intestinal inflammation and can be downregulated by IL 10.
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Objective:To evaluate the anti-inflammatory potential of peptide/polypeptide fraction of Aloe vera through in vitro and in vivo studies.Methods:The peptide/polypeptide fraction from Aloe vera was obtained through trichloroacetic acid precipitation.The anti-inflammatory property of the peptide/polypeptide fraction was tested by protein denaturation,membrane stabilization assays.The effect of the fraction on RAW 264.7 cell viability was examined by MTT assays.The nitric oxide level was determined through Griess reagent.TNF-αand IL-6 levels were estimated using ELISA kits.In vivo studies were carried out in male Wistar rats through injection of Freund’s adjuvant in the hind paw.Paw edema was measured through the Vernier scale and levels of alanine aminotransferase,aspartate transaminase,TNF-α,IL-6,and secretory phospholipase A2 were estimated through their respective kits after fourteen days of treatment.Graph Pad Prism6 was used for analyzing the results.Results:The peptide/polypeptide extract inhibited protein denaturation with an IC50 value of(218.9±15.6)μg/m L and stabilized the membrane of red blood cells with an IC50 value of(275.9±19.1)μg/m L.The extract showed no changes in cell morphology or cytotoxicity up to the concentration of 20μg/mL in MTT assays.The peptide/polypeptide fraction markedly reduced the levels of proinflammatory markers and mediators in both in vitro and in vivo studies.Conclusions:The results indicate that the peptide/polypeptide fraction of Aloe vera has antiinflammatory property through inhibition of inflammatory markers and mediators responsible for NF-κB and mitogen-activated protein kinase pathways.
基金National Natural Foundation(No.81873117)Subproject of Threeyear Planning for Traditional Chinese Medicine of Shanghai(2018-2020)[No.ZY(2018-2020)-CCCX-2002-04]。
文摘Cytokines play an important role in the pathological process of atherosclerosis(AS),affecting the progression and prognosis of cerebrovascular diseases concerned with AS.Cytokines mainly include C-reactive protein,interleukin,tumor necrosis factor,chemotactic cytokines,matrix metalloproteinases,etc.These These cytokines promote or inhibit the inflammatory response and plaque formation during AS process through different targets and mechanisms.A comprehensive understanding of the cytokines in the occurrence and development of AS is conducive to search for new therapeutic targets and drugs.
基金supported by Shanxi Province Returned Overseas Students Research Funding Project(No.2016-118)
文摘The main pathological change in post-traumatic osteoarthritis (PTOA) is cartilage degeneration, which is closely related to inflammation and oxidative stress. Inflammation can cause degeneration of articular cartilage. Cartilage degeneration can also stimulate the progression of inflammation. It has been found that inflammatory cytokines can participate in the pathological process of cartilage degeneration through multiple signaling pathways, mainly mitogen-activated protein kinase, nuclear transcription factor kappa B, and Wnt-p-catenin signal transduction pathways. This review aimed at exploring the relationship between PTOA and inflammation-related cytokines by introducing the role of proinflammatory cytokines in chondrocyte destruction and extracellular matrix degradation.
基金Natural Science Foundation of Jiangsu Province(BK20180616)the Joint Funds for the Health and Education of Fujian Province(2019-WJ-31)the Institute of Respiratory Diseases,Xiamen Medical College(HXJB-15).
文摘Idiopathic pulmonary fibrosis(IPF)is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function.Chronic inflammation has been demonstrated to be the pathological basis of fibrosis.Emerging studies have revealed that most interleukin-17(IL-17)isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity.Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes,including the initiation and exacerbation of IPF.Here,we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.
文摘Objective: To determine whether balloon catheter denudation can induce vascular smooth muscle cells (VSMCs) to senescence, and whether this senescence can result in inflammation activity. Methods: Twelve male Chinese white rabbits were denuded of the carotid arteries or VSMCs. Acidic β-galactosidase activity of carotid arteries or VSMCs was detected. Transfection and chloramphenicol acetyltransferase (CAT) assay for iNOS gene and nitrite (NO2^-) assay were undertaken. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate inflammation cytokines mRNA expression. Measurement of NF-kB activity was detected by electrophoretic mobility shift assay (EMSA). MMP-9, ICAM-1, P-p65, and IkBα expressions were analyzed by Western blotting. Results: After denudation VSMCs from denuded arteries showed an accumulation of significantly more senescence-associated β-galactosidase (SA-β-Gal) positive ceils and greater iNOS activity. Transcriptional activity of iNOS was highly expressed. The mRNA expressions of IL-1β, ICAM-1,MMP-9, TNF-α and the iNOS enzyme were significantly increased in injuring-induced senescence SMCs. However, the TNF-α or IL-1β-induced the protein production (ICAM-1 and MMP-9) was prevented by PDTC and MG132, which are inhibitors of NF-kB activation. Also, activation of NF-kB and cytokine-induced degradation of IKBα in the denuded VSMC were significantly affected. Conclusion: Intraluminal injury to the artery may lead to the emergence of senescent VSMC. Inflammation activity in SMCs is closely related to the senescence and the activation of NF-kB is involved.
文摘This editorial refers to the article“Comparative analysis of Nε-carboxymethyllysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients”,published in the recent issue of the World Journal of Diabetes 2023 is based on glucose metabolism,advanced glycation end products(AGEs),inflammation and adiposity on diabetes and coronary artery disease(CAD).This study has included CAD patients who were stratified according to glycosylated hemoglobin higher than 6.5 and sex-matched.A higher prevalence of hypertension,dyslipidemia,and non-vegetarian diet were found in the diabetic group.These risk factors might influence body weight and adiposity and explain the increment of the left atrium.Although this data was not supported by the study.The diet can also explain the non-enzymatic reactions on lipids,proteins,or nucleic acids and consequently an increment of AGEs.These molecules can emit fluorescence.However,one of the non-fluorescent and most abundant AGEs is Nε-carboxymethyl-lysine(CML).Its association with coronary artery stenosis and severity in the diabetic group might suggest its role as a player in CAD progression.Thus,CML,after binding with its receptor(RAGE),can induce calcification cascade through reactive oxygen species and mitogen-activated protein kinase.Moreover,this interaction AGE-RAGE can cause activation of the transcription nuclear factor-kb and induce inflammatory cytokines.It might explain the relationship between CML and pro-inflammatory cytokines in diabetic and CAD patients.Although this is a population from one center,the determination of CML and inflammatory cytokines might improve the diagnosis of severe and progressive CAD.Future and comparative studies among glycosylated hemoglobin,CML,and other AGE levels according to diagnosis and prognosis value might modify the clinical practice.Although these molecules are irreversible,they can act through a specific receptor inducing a signal transduction that might be modulated by inhibitors,antibodies,or siRNA.Further mechanistic studies might improve the development of future preventive therapies for diabetic patients.
基金supported by the Defence Institute of Physiology and Allied Sciences.
文摘Objective:To investigate the underlying mechanism of anti-inflammatory action of coumarin and eugenol in lipopolysaccharide(LPS)-stimulated RAW 264.7 cells.Methods:RAW 264.7 cells were treated with 2.5μg/mL of LPS,50μM of coumarin,and 50μM eugenol for 24 h.The viability of the cells was assessed using MTT assay.The production of nitric oxide was determined using Griess reagent and DCFH-DA was used to measure the production of reactive oxygen species.The protein expression of NLRP3,IL-1β,NF-κB,and cyclooxygenase 2 was assessed using Western blot analysis.Results:Coumarin and eugenol showed anti-inflammatory effects against LPS-induced inflammatory response by ameliorating the expression of NLRP3 inflammasome and NF-κB,which further led to a subsequent reduction in IL-1β,nitric oxide,and reactive oxygen species.Conclusions:Coumarin and eugenol exert their anti-inflammatory activities by modulating the NLRP3 inflammasome pathway and NF-κB.These compounds may have promising therapeutic applications for the treatment of various inflammatory diseases.
基金funded by The National Key Research and Development Program(2022YFC2603500,2022YFC2603505)Beijing Municipal Health Commission high-level public health technical personnel construction project,discipline leader-03-26+2 种基金Beijing Hospitals Authority Clinical medicine Development of special funding support(XMLX202127)The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority(XXZ0302)The capital health research and development of special(2022-1-2172)。
文摘Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.
基金The 2023 Scientific Research Fund Project of Hebei Provincial Health and Family Planning Commission,No.20231081The"Spark"Youth Research Project,The First Hospital of Hebei Medical University,No.XH202302.
文摘BACKGROUND Generalized anxiety disorder(GAD)is a relatively common mental disorder.Recently,inflammation,an important factor for the development of depression,has attracted increasing attention.Several studies have shown that inflammatory cytokines can affect the pathophysiological processes of several nervous system diseases.We hypothesized that there is a correlation between the levels of lipopolysaccharide(LPS)-stimulated inflammatory cytokines and the clinical symptoms of GAD.AIM To investigate the predictive effect of LPS-stimulated inflammatory cytokines on symptoms of GAD.METHODS This was a cross-sectional study in which 89 patients with GAD diagnosed at The First Hospital of Hebei Medical University from January 2022 to December 2022 and 70 individuals without anxiety and depression(controls)during the same period were included.Fasting venous blood was collected from all the subjects in heparin tubes,and another 3 ml of blood was supplemented with LPS(10 ng/ml).The plasma levels of 12 cytokines[Interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,tumor necrosis factor(TNF)-α,interferon(IFN)-γ,IL-17A,IL-12p70,and IFN-α]were detected.RESULTS Post-LPS stimulation,the levels of IL-1β,IL-6,IL-8,IL-10,and TNF-αin both the control and GAD groups were significantly elevated above those in the nonstimulated groups,with IL-6 and IL-8 showing marked increases.Increases in IL-8 and TNF-αwere statistically significant in the GAD group(P<0.05).IL-1β,IL-6,IL-8,IL-10,and TNF-αwere found to be significantly correlated with Hamilton Anxiety Rating Scale(HAMA)scores(P<0.05).A negative correlation was observed between IL-10 levels and HAMA scores.Further analysis revealed that TNF-αwas associated with mental anxiety,whereas IL-1β,IL-8,and IL-10 were associated with physical anxiety symptoms,with IL-10 showing a negative correlation with physical anxiety.IL-6 was associated with both mental and physical aspects of anxiety.CONCLUSION The physical symptoms of GAD are related to inflammatory factors.IL-1β,IL-8,IL-10,and TNF-a can be used as predictors of physical or mental anxiety in patients with GAD.
基金Supported by The Project of Hengyang Science and Technology Bureau,No.202222035602.
文摘BACKGROUND Sepsis,which is characterized by acute systemic inflammation and is associated with high rates of morbidity and mortality,presents a significant challenge in health care.Some scholars have found that the sequential organ failure assessment(SOFA)and quick SOFA scores are not ideal for predicting severe sepsis and mortality.Microbial culture takes a long time(2-3 d)and provides no information for early diagnosis and treatment.Therefore,new diagnostic methods for sepsis need to be explored.AIM To assess cytokine levels in the plasma of sepsis patients and identify potential biomarkers for diagnosing sepsis.METHODS Ten sepsis patients admitted to the emergency department within 24 h of onset were enrolled as the observation group,whereas ten noninfected patients served as the control group.Of the 10 noninfected patients,9 hypertension combined with cerebral infarction,1 patients with vertiginous syndrome.Plasma Cytokines were measured using the Bio-Plex Pro^(TM)Human Chemokine Panel 40-plex.Differentially expressed cytokines in plasma of sepsis and nonsepsis patients were analyzed using Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses.RESULTS Interleukin(IL)-16,granulocyte-macrophage granulocyte-macrophage colony-stimulating factor(GM-CSF),CX3CL1,CXCL9,CXCL16,CCL25,and CCL23 plasma levels were significantly increased in sepsis patients.GO analysis revealed that these cytokines were mainly associated with cellular structures such as intermediates,nuclear plaques,adhesion plaques,lateral plasma membranes,and cell matrix junctions.These genes were involved in various molecular functions,such as cytokine activity,receptor ligand activity,and signal receptor activator activity,contributing to various biological functions,such as leukocyte chemotaxis,migration,and chemotaxis.KEGG analysis indicated involvement in cytokine cytokine receptor interactions,chemokine signaling pathways,virus–protein interactions with cytokines and cytokine receptors,and the tumor necrosis factor signaling pathway.CONCLUSION Elevated serum levels of IL-16,GM-CSF,CX3CL1,CXCL9,CXCL16,CCL25,and CCL23 in sepsis patients suggest their potential as diagnostic biomarkers for sepsis.
基金supported by the China Natural Science Foundation for Outstanding Scholars(82325032)Self-Supporting Program of Guangzhou Laboratory(SRPG22-001)。
文摘Bats,notable as the only flying mammals,serve as natural reservoir hosts for various highly pathogenic viruses in humans(e.g.,SARS-CoV and Ebola virus).Furthermore,bats exhibit an unparalleled longevity among mammals relative to their size,particularly the Myotis bats,which can live up to 40 years.However,the mechanisms underlying these distinctive traits remain incompletely understood.In our prior research,we demonstrated that bats exhibit dampened STING-interferon activation,potentially conferring upon them the capacity to mitigate virus-or aging-induced inflammation.To substantiate this hypothesis,we established the first in vivo bat-mouse model for aging studies by integrating Myotis davidii bat STING(MdSTING)into the mouse genome.We monitored the genotypes of these mice and performed a longitudinal comparative transcriptomic analysis on MdSTING and wild-type mice over a 3-year aging process.Blood transcriptomic analysis indicated a reduction in aging-related inflammation in female MdSTING mice,as evidenced by significantly lower levels of pro-inflammatory cytokines and chemokines,immunopathology,and neutrophil recruitment in aged female MdSTING mice compared to aged wild-type mice in vivo.These results indicated that MdSTING knock-in attenuates the aging-related inflammatory response and may also improve the healthspan in mice in a sex-dependent manner.Although the underlying mechanism awaits further study,this research has critical implications for bat longevity research,potentially contributing to our comprehension of healthy aging in humans.
基金supported by a Presidential Postdoctoral Fellowship (021229-00001) from Nanyang Technological University,Singapore (to JZ)a Lee Kong Chian School of Medicine Dean’s Postdoctoral Fellowship (021207-00001) from NTU Singaporea Mistletoe Research Fellowship (022522-00001) from the Momental Foundaton,USA (to CHL)
文摘The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.Obesity-related conditions like type 2 diabetes and non-alcoholic fatty liver disease exacerbate this relationship.Peripheral lipid accumulation,particularly in the liver,initiates a cascade of inflammatory processes that extend to the brain,influencing critical metabolic regulatory regions.Ceramide and palmitate,key lipid components,along with lipid transporters lipocalin-2 and apolipoprotein E,contribute to neuroinflammation by disrupting blood–brain barrier integrity and promoting gliosis.Peripheral insulin resistance further exacerbates brain insulin resistance and neuroinflammation.Preclinical interventions targeting peripheral lipid metabolism and insulin signaling pathways have shown promise in reducing neuroinflammation in animal models.However,translating these findings to clinical practice requires further investigation into human subjects.In conclusion,metabolic dysfunction,peripheral inflammation,and insulin resistance are integral to neuroinflammation and neurodegeneration.Understanding these complex mechanisms holds potential for identifying novel therapeutic targets and improving outcomes for neurodegenerative diseases.
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)Jiangxi Double-Thousand Plan High-Level Talent Project of Science and Technology Innovation(No.jxsq2023201036)Key R&D Program of Jiangxi Province(No.20223BBH80014).
文摘Non-specific orbital inflammation(NSOI)is a noninfectious orbital inflammation.Although it is often considered the most common diagnosis in orbital biopsies,it is an exclusionary diagnosis that requires ruling out systemic disease or other possible causes.Its characteristics include acute orbital signs and symptoms,including pain,proptosis,periorbital edema,chemosis,diplopia,and visual impairment.The clinical manifestations and histological findings of NSOI are heterogeneous,without specific diagnostic criteria or treatment guidelines,which poses significant challenges for diagnosis and treatment.This guideline provides a detailed description of the definition,classification,diagnosis,and treatment of NSOI.
文摘DNA damage occurs across tumorigenesis and tumor development.Tumor intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment(TIME)and dominate tumor progression.Accumulating evidence documents that multiple signaling pathways,including cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein(ATM/ATR),are activated downstream of DNA damage and they are associated with the secretion of diverse cytokines.These cytokines possess multifaced functions in the anti-tumor immune response.Thus,it is necessary to deeply interpret the complex TIME reshaped by damaged DNA and tumor-derived cytokines,critical for the development of effective tumor therapies.This manuscript comprehensively reviews the relationship between the DNA damage response and related cytokines in tumors and depicts the dual immunoregulatory roles of these cytokines.We also summarize clinical trials targeting signaling pathways and cytokines associated with DNA damage and provide future perspectives on emerging technologies.
基金This study was supported by Shenzhen Fundamental Research Program-General Program(No.JCYJ20210324114403010).
文摘Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlying mechanisms are not clear.This study was to find out whether systemic inflammation plays an important role.Methods:A total of 103 patients with early-stage HCC under liver resection were enrolled(LLR group,n=53;OLR group,n=50).The expression of 9 inflammatory cytokines in patients at preoperation,postoperative day 1(POD1)and POD7 was quantified by Luminex Multiplex assay.The relationships of the cytokines and the postoperative outcomes were compared between LLR and OLR.Results:Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative levels.Compared to OLR,the POD1 levels of granulocytemacrophage colony-stimulating factor(GM-CSF),interleukin-6(IL-6),IL-8,and monocyte chemoattractant protein-1(MCP-1)in the LLR group were significantly lower.Higher POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during operation.The levels of these cytokines were positively associated with postoperative liver injury,and the length of hospital stay.Importantly,a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver resection.Conclusions:Significantly lower level of GM-CSF,IL-6,IL-8,and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.
基金supported by the National Natural Science Foundation of China,No.81671347(to KL)the Science and Technology Program of Guangzhou of China,No.202007030012(to KFS and KL)the Science and Technology Program of Guangzhou of China,No 202102020735(to RW).
文摘Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.
基金Supported by National Natural Science Foundation of China(No.82171085).
文摘AIM:To investigate the causal effect of inflammatory bowel disease(IBD)on ocular inflammation using Mendelian randomization(MR)analysis.METHODS:Genetic instruments associated with inflammatory bowel disease(IBD),ulcerative colitis(UC),and Crohn’s disease(CD)were derived from the largest genome-wide association studies(GWAS)published to date.The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis,keratitis,iridocyclitis,chorioretinitis,episcleritis,and optic neuritis.All participants were of European ancestry.Three methods which included inverse variance weighting(IVW),weighted median(WM),and MR-Egger regression were performed to estimate the causal association in this study.IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes,to summarize the effect sizes of multiple independent studies,which could provide the most precise estimated results.IVW was used as the primary outcome,while WM and MR-Egger were used to improve the estimation of IVW.RESULTS:A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis,keratitis,iridocyclitis,and optic neuritis,but not on chorioretinitis or episcleritis.After Bonferroni correction,the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis(IVW:OR,1.17;95%CI,1.10-1.24,P=2.54×10^(-7)).CD was significantly associated with conjunctivitis(IVW:OR,1.05;95%CI,1.03-1.08,P=3.20×10^(-5)),keratitis(IVW:OR,1.06;95%CI,1.02-1.09;P=1.13×10^(-3)),and iridocyclitis(IVW:OR,1.09;95%CI,1.04-1.14;P=1.43×10^(-4)).CONCLUSION:IBD causally poses a risk of inflammation of conjunctiva,cornea,Iris-ciliary body complex,and optic neuritis.CD is more closely associated with the eye inflammation than UC.These impliy that the relationship of IBD and different parts of the eye structure are different,and provide novel evidence linking based on the association of the gut-eye axis.
文摘BACKGROUND Conventional five-port laparoscopic surgery,the current standard treatment for colorectal carcinoma(CRC),has many disadvantages.AIM To assess the influence of reduced-port laparoscopic surgery(RPLS)on perioperative indicators,postoperative recovery,and serum inflammation indexes in patients with CRC.METHODS The study included 115 patients with CRC admitted between December 2019 and May 2023,52 of whom underwent conventional five-port laparoscopic surgery(control group)and 63 of whom underwent RPLS(research group).Comparative analyses were performed on the following dimensions:Perioperative indicators[operation time(OT),incision length,intraoperative blood loss(IBL),and rate of conversion to laparotomy],postoperative recovery(first postoperative exhaust,bowel movement and oral food intake,and bowel sound recovery time),serum inflammation indexes[high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)],postoperative complications(anastomotic leakage,incisional infection,bleeding,ileus),and therapeutic efficacy.RESULTS The two groups had comparable OTs and IBL volumes.However,the research group had a smaller incision length;lower rates of conversion to laparotomy and postoperative total complication;and shorter time of first postoperative exhaust,bowel movement,oral food intake,and bowel sound recovery;all of which were significant.Furthermore,hs-CRP,IL-6,and TNF-αlevels in the research group were significantly lower than the baseline and those of the control group,and the total effective rate was higher.CONCLUSION RPLS exhibited significant therapeutic efficacy in CRC,resulting in a shorter incision length and a lower conversion rate to laparotomy,while also promoting postoperative recovery,effectively inhibiting the inflammatory response,and reducing the risk of postoperative complications.