Background:Neonatal-onset multisystem inflammatory disease is characterized by fever,urticarial rash,aseptic meningitis,deforming arthropathy,hearing loss,and mental retardation.Many patients have mutations in the col...Background:Neonatal-onset multisystem inflammatory disease is characterized by fever,urticarial rash,aseptic meningitis,deforming arthropathy,hearing loss,and mental retardation.Many patients have mutations in the cold-induced autoinflammatory syndrome 1(CIAS1)gene,encoding cryopyrin,a protein that regulates inflammation.展开更多
Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen...Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen et al systematically evaluated six complete blood count-derived inflammatory indices:Neutrophil-tolymphocyte ratio,monocyte-to-lymphocyte ratio,platelet-to-lymphocyte ratio,systemic immune-inflammation index,systemic inflammatory response index(SIRI),and aggregate index of systemic inflammation and demonstrated their positive associations with GU prevalence,identifying SIRI as the strongest predictor.This editorial contextualizes these findings within the broader literature,clarifies that these indices reflect systemic rather than GU-specific inflammation,highlights methodological strengths and major limitations,and proposes a conceptual clinical algorithm for integrating SIRI into GU risk assessment.Future multicenter studies incorporating Helicobacter pylori infection,non-steroidal antiinflammatory drug exposure,and prospective design are essential to validate and translate these findings into clinical practice.展开更多
To explore the material basis and mechanisms of the anti-inflammatory effects of Hibiscus mutabilis L..The active ingredients and potential targets of Hibiscus mutabilis L.were obtained through the literature review a...To explore the material basis and mechanisms of the anti-inflammatory effects of Hibiscus mutabilis L..The active ingredients and potential targets of Hibiscus mutabilis L.were obtained through the literature review and SwissADME platform.Genes related to the inflammation were collected using Genecards and OMIM databases,and the intersection genes were submitted on STRING and DAVID websites.Then,the protein interaction network(PPI),gene ontology(GO)and pathway(KEGG)were analyzed.Cytoscape 3.7.2 software was used to construct the“Hibiscus mutabilis L.-active ingredient-target-inflammation”network diagram,and AutoDockTools-1.5.6 software was used for the molecular docking verification.The antiinflammatory effect of Hibiscus mutabilis L.active ingredient was verified by the RAW264.7 inflammatory cell model.The results showed that 11 active components and 94 potential targets,1029 inflammatory targets and 24 intersection targets were obtained from Hibiscus mutabilis L..The key anti-inflammatory active ingredients of Hibiscus mutabilis L.are quercetin,apigenin and luteolin.Its action pathway is mainly related to NF-κB,cancer pathway and TNF signaling pathway.Cell experiments showed that total flavonoids of Hibiscus mutabilis L.could effectively inhibit the expression of tumor necrosis factor(TNF-α),interleukin 8(IL-8)and epidermal growth factor receptor(EGFR)in LPS-induced RAW 264.7 inflammatory cells.It also downregulates the phosphorylation of human nuclear factor ĸB inhibitory protein α(IĸBα)and NF-κB p65 subunit protein(p65).Overall,the anti-inflammatory effect of Hibiscus mutabilis L.is related to many active components,many signal pathways and targets,which provides a theoretical basis for its further development and application.展开更多
Moringa oleifera(MO)is traditionally used to mitigate inflammatory-mediated disorders;however,the influence of ecotypic variation on its anti-inflammatory activity remains poorly understood.In this study,we compared t...Moringa oleifera(MO)is traditionally used to mitigate inflammatory-mediated disorders;however,the influence of ecotypic variation on its anti-inflammatory activity remains poorly understood.In this study,we compared the phytochemical composition and anti-inflammatory activity of ethanolic extracts obtained from fresh and dried leaves of four MO ecotypes(India,Paraguay,Mozambique,and Pakistan),all grown under the same outdoor conditions,as well as two commercial powders(Just Moringa and WISSA),using LPS-stimulated RAW 264.7 macrophages.Extracts from fresh leaves were 19-43%more cytotoxic than those from dried leaves,depending on the ecotype,likely due to higher cyanogenic glycoside content.Extracts from the India and Paraguay ecotypes,characterized by high levels of quercetin derivatives and caffeic acids,as well as Just Moringa,enriched in kaempferol derivatives,significantly inhibited LPS-induced nitric oxide(NO)production(p<0.05).Just Moringa and Paraguay extracts also reduced iNOS gene expression(p<0.05 and p<0.01,respectively),whereas only the Paraguay extract decreased iNOS protein levels(p<0.05).In contrast,quercetin-3-O-glucoside and rutin showed significant effects only at concentrations approximately 100-fold higher than those present in the extracts,indicating that the phytocomplex displays greater bioactivity than individual compounds.Overall,these results demonstrate that ecotypic variation strongly affects the polyphenolic composition and anti-inflammatory properties of MO leaves,highlighting the importance of reporting both origin and phytochemical composition in MO-based products.展开更多
Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually wit...Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually with>20%mortality.Its progression involves metabolic imbalances,toxin accumulation,and multiorgan failure,often culminating in chronic kidney disease.Current therapies(fluid resuscitation,diuretics,renal replacement therapy)remain limited.Inflammation drives AKI pathogenesis:renal insults(ischemia,toxins)trigger tubular cell release of pro-inflammatory mediators(TNF-α,IL-1β,IL-6),activating neutrophil gelatinase-associated lipocalin(NGAL)and dysregulating P38 MAPK/ERK pathways.This cascade promotes leukocyte infiltration,oxidative stress,and apoptosis,exacerbating renal damage.Ononin,a flavonoid from Astragali Radix,shows multi-target potential by suppressing pro-inflammatory cytokines,modulating signaling,and mitigating oxidative stress.Its dual anti-inflammatory/antioxidant properties position it as a promising candidate for AKI intervention.Exploring the ameliorative effect of ononin on the inflammatory response Ameliorative effect of ononin on the inflammatory response in doxorubicin-induced AKI mice.Methods:We used network pharmacology to explore ononin’s target molecules and AKI-related disease molecules,identified their intersections,and predicted potential mechanisms via enrichment analysis,followed by molecular docking verification.For in-vivo validation,50 mice were randomly divided into five groups(n=10/group):Control,Model,Ononin-L(15 mg/kg),Ononin-H(60 mg/kg),and Dexamethasone(2.6 mg/kg).An AKI model was established by intravenous tail-vein injection of Doxorubicin(15 mg/kg).Samples were collected 12 h post-induction.We calculated the renal coefficient,examined renal histopathology using hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and Masson’s trichrome(MASSON)staining,and observed mitochondrial morphology by electron microscopy(EM).ELISA was used to measure NGAL,serum creatinine(Scr),and blood urea nitrogen(BUN)levels in serum.Immunofluorescence(IF)evaluated the expression of P-P38,P-ERK,NGAL,and KIM-1 in renal tissues.RT-qPCR assessed the gene expression of pro-inflammatory cytokines,MAPK pathway components,and renal injury markers in kidney tissues.Western Blot(WB)quantified P-P38,P38 MAPK,P-ERK,ERK,NGAL,and KIM-1 in renal tissues.Results:Network pharmacology analysis suggested that ononin could attenuate AKI through its anti-inflammatory properties and regulation of the MAPK signaling pathway.The Model group exhibited a significantly elevated renal coefficient(P<0.05),severe histopathological damage,and mitochondrial dysfunction compared to controls.Serum levels of NGAL,Scr,and BUN were markedly increased(P<0.05),indicating impaired renal function.Enhanced fluorescence signals of P-P38 MAPK,P-ERK,NGAL,and KIM-1 suggested activation of MAPK pathways and renal injury.Upregulation of pro-inflammatory cytokines(IL-1β,IL-6,TNF-α)and MAPK-related genes(P38 MAPK,ERK)alongside injury markers(NGAL,KIM-1)(P<0.05).Increased ratios of phosphorylated-to-total proteins(P-P38/P38,P-ERK/ERK)and elevated NGAL/KIM-1 protein levels confirmed pathway dysregulation.Treatment significantly reduced the renal coefficient(P<0.05),attenuated histological damage,and restored mitochondrial integrity.NGAL,Scr,and BUN levels were lowered,reflecting functional recovery.Diminished fluorescence intensities of P-P38,P-ERK,NGAL,and KIM-1 indicated suppression of injury pathways.Downregulation of inflammatory cytokines(IL-1β,IL-6,TNF-α),MAPK components(P38 MAPK,ERK),and injury markers(NGAL,KIM-1)(P<0.05).Reduced phosphorylation ratios(P-P38/P38,P-ERK/ERK)and decreased NGAL/KIM-1 protein expression demonstrated therapeutic efficacy.Conclusion:Ononin ameliorates inflammatory responses in AKI mice via the P38 MAPK/ERK pathway.展开更多
Cardiovascular diseases(CVDs)are the leading cause of global mortality,with chronic inflammation playing an important role in their pathogenesis[1].Inflammatory bowel disease(IBD)has been associated with an increased ...Cardiovascular diseases(CVDs)are the leading cause of global mortality,with chronic inflammation playing an important role in their pathogenesis[1].Inflammatory bowel disease(IBD)has been associated with an increased risk of CVDs,including arrhythmias and atherosclerotic disease,potentially mediated by persistent systemic inflammation[2,3].展开更多
BACKGROUND Gastric ulcer(GU),a common gastrointestinal condition,is influenced by multiple factors,particularly inflammatory and immune responses.Complete blood count(CBC)-derived inflammatory biomarkers represent a n...BACKGROUND Gastric ulcer(GU),a common gastrointestinal condition,is influenced by multiple factors,particularly inflammatory and immune responses.Complete blood count(CBC)-derived inflammatory biomarkers represent a novel indicator of systemic inflammation and immune status;however,their association with GU remains unclear.AIM To investigate the association between CBC-derived inflammatory markers and GU.METHODS The study sample included individuals admitted to the Gastroenterology Unit of the Second Affiliated Hospital of Nanchang University from 2023 to 2024.We explored how each CBC-based inflammation indicator correlated with GU occurrence through logistic models,and assessed their predictive ability using receiver operating characteristic curve analysis.Additionally,we applied the least absolute shrinkage and selection operator method along with stepwise regression techniques to determine which inflammatory indicators were most significantly linked to GU.RESULTS Higher levels of log2 neutrophil-to-lymphocyte ratio,log2 monocyte-to-lymphocyte ratio,log2 systemic immuneinflammation index,log2 systemic inflammatory response index(SIRI),and log2 aggregate index of systemic inflammation were significantly associated with increased GU prevalence across all models,while log2 platelet-tolymphocyte ratio was significant only in the fully adjusted model.SIRI demonstrated the highest discriminative ability,with an area under the curve of 0.868.CONCLUSION Hematological indicators derived from CBC tests show a significant correlation with the prevalence of GU.Among them,SIRI demonstrated the most prominent association.These markers could act as practical tools in recognizing individuals more likely to develop GU.展开更多
Inflammatory bone diseases constitute a category of chronic inflammatory disorders,with the primary pathological characteristic being the impact of chronic inflammation on bone metabolism and remodeling.It leads to pa...Inflammatory bone diseases constitute a category of chronic inflammatory disorders,with the primary pathological characteristic being the impact of chronic inflammation on bone metabolism and remodeling.It leads to pain,spinal joint deformities,and functional impairments.Common clinical types of inflammatory bone diseases include rheumatoid arthritis,ankylosing spondylitis,and osteoarthritis.However,there is a paucity of effective clinical treatments for inflammatory bone diseases,and pharmacological interventions are frequently associated with intolerable side effects.Traditional Chinese medicine(TCM)has a long-standing history and proven efficacy in managing inflammatory bone diseases.In recent years,an increasing number of studies have highlighted the potential of TCM in this context.This article systematically evaluates the application of TCM in treating inflammatory bone diseases,emphasizing the underlying molecular mechanisms of its anti-inflammatory effects.By elucidating the specific targets of TCM in the treatment of rheumatoid arthritis,ankylosing spondylitis,and osteoarthritis,we aim to provide novel insights into the further exploration of TCM’s role in clinical application for inflammatory bone diseases.展开更多
The oral microbiome is the second largest microbial community in the human body after the gut microbiome.It includes an array of fungi,bacteria,amoebae,flagellates,archaea,and viruses,all of which are potential pathog...The oral microbiome is the second largest microbial community in the human body after the gut microbiome.It includes an array of fungi,bacteria,amoebae,flagellates,archaea,and viruses,all of which are potential pathogens.This microbiome can act as a facilitator not only for protection but also for aggravation when dysbiosis occurs.Although conventional thought is this is primarily in terms of oral health issues,such as dental caries and gingival disease.The systemic effects of the oral microbiome however,are relevant to both gastrointestinal(GI)disease and non-GI disease.These systemic risks occur for several reasons,including upregulation of cytokines,adhesion cell-like processes,toll-like receptors,reactive oxidative species or generation of mutation inducing DNA changes.Additionally,there is translocation risk of potential active pathogens or their metabolic byproducts.There is a substantial and growing body of evidence that the oral microbiome influences diseases including Barrett’s esophagus,metabolicassociated steatosis liver disease,and GI cancers.Additionally,there is burgeoning evidence of a causal association with systemic inflammatory diseases,including inflammatory bowel disease.This report discusses the most recent evidence of this association and highlights new approaches to potentially enhance our“best practice”strategies for optimal care of patients with inflammatory bowel disease.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)and inflam-matory bowel disease(IBD)are chronic conditions with complex aetiologies,in which environmental factors and interactions between the gut and li...Metabolic dysfunction-associated steatotic liver disease(MASLD)and inflam-matory bowel disease(IBD)are chronic conditions with complex aetiologies,in which environmental factors and interactions between the gut and liver play a key role.Both conditions are characterised by disturbances in the gut microbiota,which can affect local and systemic inflammatory responses.In particular,inc-reased intestinal permeability promotes the translocation of bacterial components into the portal circulation,contributing to the development of inflammation in the liver.There is growing evidence that modulation of the gut microbiota and imp-roved intestinal barrier function may be of therapeutic importance.The purpose of this review is to discuss the pathogenetic mechanisms that link MASLD and IBD,with a particular emphasis on the influence of the microbiota and environ-mental factors on the development of these diseases.展开更多
BACKGROUND Although thoracotomy has been the conventional treatment for patients with early esophageal cancer(EEC),its drawbacks underscore the demand for more effective therapeutic strategies to improve surgical outc...BACKGROUND Although thoracotomy has been the conventional treatment for patients with early esophageal cancer(EEC),its drawbacks underscore the demand for more effective therapeutic strategies to improve surgical outcomes.AIM To comprehensively analyze the effect of totally thoracoscopic esophagectomy(TTE)on postoperative complications and serum inflammatory factors in patients diagnosed with EEC.METHODS A total of 113 patients with EEC,who were admitted to our hospital between September 2022 and December 2024,were recruited for this study.Specifically,55 patients were assigned to the control group and underwent conventional surgical procedures,whereas 58 patients formed the research group and underwent TTE.Subsequently,a series of comparisons and analyses were conducted between the two groups.These comparisons included surgery-related parameters,such as incision length,operation duration,and the number and extent of lymph node dissection;postoperative complications,namely,empyema,pulmonary infection,incision infection,anastomotic fistula,and delayed gastric emptying;postoperative pain,which was quantitatively evaluated by the Numerical Rating Scale;postoperative hospitalization duration;serum inflammatory factors,including interleukin(IL)-6,IL-8,and tumor necrosis factor-α;and stress response-associated indicators,such as C-reactive protein,cortisol,and adrenaline.RESULTS Statistical data demonstrated that compared with the control group,the research group exhibited substantially shorter incision length and postoperative hospitalization duration.The two groups had comparable number and extent of lymph node dissection.Notably,both the overall incidence of postoperative complications and the Numerical Rating Scale score on postoperative day 3 were remarkably lower in the research group.Although the levels of IL-6,IL-8,tumor necrosis factor-α,C-reactive protein,cortisol,and adrenaline in the research group increased statistically postoperatively,they were still considerably lower than those in the control group.CONCLUSION In patients with EEC,TTE not only reduces the risk of postoperative complications but also effectively alleviates the body’s inflammatory and stress responses associated with surgery.展开更多
BACKGROUND Inflammatory bowel diseases(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD),are chronic gastrointestinal disorders with an increasing global prevalence and significant healthcare impact.The ex...BACKGROUND Inflammatory bowel diseases(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD),are chronic gastrointestinal disorders with an increasing global prevalence and significant healthcare impact.The exact etiology of this condition remains unclear.Neutrophils play a critical role in IBD pathogenesis.Translocator protein(TSPO),a mitochondrial protein linked to immune responses,has demonstrated potential as an inflammatory marker.However,its role in IBD remains underexplored.AIM To investigate the role of TSPO in IBD pathogenesis,particularly in neutrophils.METHODS Bioinformatics analyses of Gene Expression Omnibus datasets(GE75214,GSE94648,GSE156776)assessed TSPO expression in IBD patients.TSPO expression was evaluated in human IBD samples,neutrophiles and a chronic colitis mouse model.Neutrophil function was examined in 18 samples using reactive oxygen species(ROS)production and neutrophil extracellular trap(NET)formation assays.Positron emission tomography-computed tomography(PET-CT)imaging and histology from 12 mice revealed TSPO expression in colitis.PET-CT and immunofluorescence staining assessed TSPO expression in brain under neuroinflammation condition.RESULTS Bioinformatics analysis revealed elevated TSPO expression in the intestinal mucosa and peripheral blood of patients with IBD,especially in neutrophils.This was confirmed by quantitative real-time polymerase chain reaction and immunohistochemical staining,which showed a significant upregulation of TSPO in active IBD.Neutrophils from patients with UC and CD exhibited higher TSPO expression,which correlated with increased ROS production and NET formation.In a mouse model of dextran sodium sulfate-induced chronic colitis,TSPO was upregulated in the colonic neutrophils and brain tissues,indicating its systemic involvement.PET-CT imaging showed enhanced TSPO uptake in the inflamed colon and brain regions,particularly in the microglia,highlighting neuroinflammation.CONCLUSION TSPO is significantly upregulated in neutrophils in IBD and contributes to intestinal inflammation.Its elevated expression in gut highlights its potential as a promising therapeutic target for IBD.展开更多
Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its glo...Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its global prevalence is rising,largely driven by urbanization,sedentary lifestyles,and dietary changes.These same factors are also associated with the increasing incidence of inflammatory bowel diseases(IBD),including Crohn’s disease and ulcerative colitis.Emerging evidence supports a potential biological link between chronic gastrointestinal inflammation and the later development of cardiometabolic disorders;a con-nection that is particularly relevant for patients with IBD.Comparative studies examining cardiometabolic risk associated with Crohn’s disease versus ulcerative colitis have reported inconsistent findings,likely due to confounding factors such as age,lifestyle,and comorbidities.This review summarizes current evidence linking IBD and cardiometabolic disorders,and highlights the need for clinicians to recognize cardiometabolic risk in patients with IBD.Future research should investigate whether treat-to-target strategies focused on controlling intestinal inflammation can simultaneously improve both long-term IBD and cardiometabolic outcomes.展开更多
BACKGROUND Systemic immunoinflammatory diseases can affect multiple systems and organs.They have a severe course and severe complications,causing multiple organ failure and death.Quite often these patients are require...BACKGROUND Systemic immunoinflammatory diseases can affect multiple systems and organs.They have a severe course and severe complications,causing multiple organ failure and death.Quite often these patients are required to be hospitalized in the intensive care unit(ICU).Approximately 50% of patients with multisystem inflammatory syndrome associated with coronavirus disease 2019 in children and systemic lupus erythematosus need admission to the ICU.AIM To find early predictors of death in patients with immunoinflammatory diseases who are hospitalized in the ICU.METHODS The retrospective continuous cohort study included 51 patients(23 males,28 females)with immunoinflammatory diseases,including multisystem inflammatory syndrome associated with coronavirus disease 2019(n=18),systemic rheumatic diseases(n=24),and generalized infections(n=9).The patients ranged in age from 7 months to 17 years old and were admitted to the ICU of the clinic of Saint Petersburg State Pediatric Medical University from 2007 to 2023.RESULTS Thirteen patients(25.5%)died within 39(17;62)days after ICU admission.Patients with an unfavorable outcome were significantly older and were admitted to the ICU later than patients who survived(30 days vs 7 days,P=0.013)and had a longer stay in the ICU(30 days vs 6 days,P=0.003).The main predictors of the fatal outcome were age>162 months[odds ratio(OR)=10.7;95%confidence interval(CI):2.4-47.2,P=0.0006],time to ICU admission>26 days from the disease onset(OR=12.0;95%CI:2.6-55.3,P=0.008),preceding immune suppression treatment(OR=6.2;95%CI:1.6-24.0,P=0.013),invasive mycosis during the ICU stay(OR=18.8;95%CI:1.9-184.1,P=0.0005),systemic rheumatic diseases(OR=7.2;95%CI:1.7-31.1,P=0.004),and ICU stay over 15 days(OR=19.1;95%CI:4.0-91.8,P=0.00003).Multiple regression analysis(r^(2)=0.422,P<0.000002)identified two predictors of the fatal outcomes:Systemic rheumatic diseases(P=0.015)and ICU stay over 15 days(P=0.00002).CONCLUSION Identifying patients at high risk of an unfavorable outcome is the subject of the most careful monitoring and appropriate treatment program.Avoiding ICU stays for patients with systemic rheumatic diseases,close monitoring,and preventing invasive mycosis might improve the outcome in children with systemic immunemediated diseases.展开更多
The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first i...The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflammatory progression,mainly by secreting inflammatory factors.In the future,a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells,along with the activation of M2-type microglia.These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.展开更多
Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19...Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19 is important for its function in osteoclast differentiation,and LEL-Fc,a competitive inhibitor of Tm4sf19,effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis.This study aimed to investigate the role of Tm4sf19 in RA,an inflammatory and abnormal osteoclast disease,using a mouse model of collagen-induced arthritis(CIA).Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium,and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group.Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model,reducing the CIA score,swelling,inflammation,cartilage damage,and bone damage.Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages.LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2,but also the interaction between TLR4 and MD2.μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice.Taken together,these findings suggest that LELFc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.展开更多
Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously...Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously confined to military and/or professional astronauts only.This new evidence offers additional opportunities for better characterizing the impact that the transition from Earth’s 1G to microgravity in space could have on the astronauts’health while comparing well-trained subjects such as the latt er to space newcomers[1].展开更多
Objective:The occurrence and development of atrial fibrillation(AF)are influenced by the autonomic nervous system and inflammation.Acupuncture is an effective treatment for AF.This study explored the protective effect...Objective:The occurrence and development of atrial fibrillation(AF)are influenced by the autonomic nervous system and inflammation.Acupuncture is an effective treatment for AF.This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms.Methods:Male Sprague-Dawley rats(n=130)were randomly divided into blank control(Con),sham operation(Sham),AF,and acupuncture treatment(Acu)groups.A paroxysmal AF model was established by rapid atrial pacing through the jugular vein.Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint(PC6)for 20 min daily for seven days.The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture.The AF induction rate,AF duration,cardiac electrophysiological parameters,and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals.After the intervention,the rats were euthanized,and atrial morphology was assessed using haematoxylin and eosin staining.The expression of macrophage F4/80 antigen(F4/80)and cluster of differentiation(CD)86 in atrial myocardial tissue was detected using immunohistochemistry,immunofluorescence and flow cytometry.The expression levels or contents of interleukin(IL)-1β,IL-6,tumor necrosis factor-a(TNF-a),a7 nicotinic acetylcholine receptor(a7nAChR),phosphorylated Janus kinase 2(p-JAK2),and phosphorylated signal transducer and activator of transcription 3(p-STAT3)in atrial myocardial tissue were detected using Western blotting,reverse transcription-quantitative polymerase chain reaction,or enzyme-linked immunosorbent assay.The role of a7nAChR in acupuncture treatment was verified by intraperitoneal injection of the a7nAChR antagonist methyllycaconitine(MLA).Results:Compared with the AF group,acupuncture significantly reduced AF duration and induction rate,improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance.It also decreased the pro-inflammatory M1 macrophage proportion,alleviating myocardial injury and infiltration.MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect.Results suggest that acupuncture triggers the a7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation.Conclusion:Acupuncture significantly reduced the AF induction rate,shortened AF duration,improved cardiac electrophysiological parameters,enhanced vagus nerve activity,and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF.展开更多
Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss o...Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons.Neuroinflammation has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be determined.Human leukocyte antigen.展开更多
FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways ...FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain unclear.In this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function recovery.These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.展开更多
文摘Background:Neonatal-onset multisystem inflammatory disease is characterized by fever,urticarial rash,aseptic meningitis,deforming arthropathy,hearing loss,and mental retardation.Many patients have mutations in the cold-induced autoinflammatory syndrome 1(CIAS1)gene,encoding cryopyrin,a protein that regulates inflammation.
基金Supported by the National Natural Science Foundation of China,No.82170406 and No.81970238.
文摘Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen et al systematically evaluated six complete blood count-derived inflammatory indices:Neutrophil-tolymphocyte ratio,monocyte-to-lymphocyte ratio,platelet-to-lymphocyte ratio,systemic immune-inflammation index,systemic inflammatory response index(SIRI),and aggregate index of systemic inflammation and demonstrated their positive associations with GU prevalence,identifying SIRI as the strongest predictor.This editorial contextualizes these findings within the broader literature,clarifies that these indices reflect systemic rather than GU-specific inflammation,highlights methodological strengths and major limitations,and proposes a conceptual clinical algorithm for integrating SIRI into GU risk assessment.Future multicenter studies incorporating Helicobacter pylori infection,non-steroidal antiinflammatory drug exposure,and prospective design are essential to validate and translate these findings into clinical practice.
文摘To explore the material basis and mechanisms of the anti-inflammatory effects of Hibiscus mutabilis L..The active ingredients and potential targets of Hibiscus mutabilis L.were obtained through the literature review and SwissADME platform.Genes related to the inflammation were collected using Genecards and OMIM databases,and the intersection genes were submitted on STRING and DAVID websites.Then,the protein interaction network(PPI),gene ontology(GO)and pathway(KEGG)were analyzed.Cytoscape 3.7.2 software was used to construct the“Hibiscus mutabilis L.-active ingredient-target-inflammation”network diagram,and AutoDockTools-1.5.6 software was used for the molecular docking verification.The antiinflammatory effect of Hibiscus mutabilis L.active ingredient was verified by the RAW264.7 inflammatory cell model.The results showed that 11 active components and 94 potential targets,1029 inflammatory targets and 24 intersection targets were obtained from Hibiscus mutabilis L..The key anti-inflammatory active ingredients of Hibiscus mutabilis L.are quercetin,apigenin and luteolin.Its action pathway is mainly related to NF-κB,cancer pathway and TNF signaling pathway.Cell experiments showed that total flavonoids of Hibiscus mutabilis L.could effectively inhibit the expression of tumor necrosis factor(TNF-α),interleukin 8(IL-8)and epidermal growth factor receptor(EGFR)in LPS-induced RAW 264.7 inflammatory cells.It also downregulates the phosphorylation of human nuclear factor ĸB inhibitory protein α(IĸBα)and NF-κB p65 subunit protein(p65).Overall,the anti-inflammatory effect of Hibiscus mutabilis L.is related to many active components,many signal pathways and targets,which provides a theoretical basis for its further development and application.
文摘Moringa oleifera(MO)is traditionally used to mitigate inflammatory-mediated disorders;however,the influence of ecotypic variation on its anti-inflammatory activity remains poorly understood.In this study,we compared the phytochemical composition and anti-inflammatory activity of ethanolic extracts obtained from fresh and dried leaves of four MO ecotypes(India,Paraguay,Mozambique,and Pakistan),all grown under the same outdoor conditions,as well as two commercial powders(Just Moringa and WISSA),using LPS-stimulated RAW 264.7 macrophages.Extracts from fresh leaves were 19-43%more cytotoxic than those from dried leaves,depending on the ecotype,likely due to higher cyanogenic glycoside content.Extracts from the India and Paraguay ecotypes,characterized by high levels of quercetin derivatives and caffeic acids,as well as Just Moringa,enriched in kaempferol derivatives,significantly inhibited LPS-induced nitric oxide(NO)production(p<0.05).Just Moringa and Paraguay extracts also reduced iNOS gene expression(p<0.05 and p<0.01,respectively),whereas only the Paraguay extract decreased iNOS protein levels(p<0.05).In contrast,quercetin-3-O-glucoside and rutin showed significant effects only at concentrations approximately 100-fold higher than those present in the extracts,indicating that the phytocomplex displays greater bioactivity than individual compounds.Overall,these results demonstrate that ecotypic variation strongly affects the polyphenolic composition and anti-inflammatory properties of MO leaves,highlighting the importance of reporting both origin and phytochemical composition in MO-based products.
基金supported by Hebei Province Natural Science Foundation(H2023423037)The Government Funded Clinical Program of Hebei Province(No.ZF2025287)+1 种基金Special Project of Hebei Industrial Technology Institute for Traditional Chinese Medicine Preparation(No.YJY2024001)Chinese Medicine Scientific Research Program of Hebei Province(No.2025222).
文摘Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually with>20%mortality.Its progression involves metabolic imbalances,toxin accumulation,and multiorgan failure,often culminating in chronic kidney disease.Current therapies(fluid resuscitation,diuretics,renal replacement therapy)remain limited.Inflammation drives AKI pathogenesis:renal insults(ischemia,toxins)trigger tubular cell release of pro-inflammatory mediators(TNF-α,IL-1β,IL-6),activating neutrophil gelatinase-associated lipocalin(NGAL)and dysregulating P38 MAPK/ERK pathways.This cascade promotes leukocyte infiltration,oxidative stress,and apoptosis,exacerbating renal damage.Ononin,a flavonoid from Astragali Radix,shows multi-target potential by suppressing pro-inflammatory cytokines,modulating signaling,and mitigating oxidative stress.Its dual anti-inflammatory/antioxidant properties position it as a promising candidate for AKI intervention.Exploring the ameliorative effect of ononin on the inflammatory response Ameliorative effect of ononin on the inflammatory response in doxorubicin-induced AKI mice.Methods:We used network pharmacology to explore ononin’s target molecules and AKI-related disease molecules,identified their intersections,and predicted potential mechanisms via enrichment analysis,followed by molecular docking verification.For in-vivo validation,50 mice were randomly divided into five groups(n=10/group):Control,Model,Ononin-L(15 mg/kg),Ononin-H(60 mg/kg),and Dexamethasone(2.6 mg/kg).An AKI model was established by intravenous tail-vein injection of Doxorubicin(15 mg/kg).Samples were collected 12 h post-induction.We calculated the renal coefficient,examined renal histopathology using hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and Masson’s trichrome(MASSON)staining,and observed mitochondrial morphology by electron microscopy(EM).ELISA was used to measure NGAL,serum creatinine(Scr),and blood urea nitrogen(BUN)levels in serum.Immunofluorescence(IF)evaluated the expression of P-P38,P-ERK,NGAL,and KIM-1 in renal tissues.RT-qPCR assessed the gene expression of pro-inflammatory cytokines,MAPK pathway components,and renal injury markers in kidney tissues.Western Blot(WB)quantified P-P38,P38 MAPK,P-ERK,ERK,NGAL,and KIM-1 in renal tissues.Results:Network pharmacology analysis suggested that ononin could attenuate AKI through its anti-inflammatory properties and regulation of the MAPK signaling pathway.The Model group exhibited a significantly elevated renal coefficient(P<0.05),severe histopathological damage,and mitochondrial dysfunction compared to controls.Serum levels of NGAL,Scr,and BUN were markedly increased(P<0.05),indicating impaired renal function.Enhanced fluorescence signals of P-P38 MAPK,P-ERK,NGAL,and KIM-1 suggested activation of MAPK pathways and renal injury.Upregulation of pro-inflammatory cytokines(IL-1β,IL-6,TNF-α)and MAPK-related genes(P38 MAPK,ERK)alongside injury markers(NGAL,KIM-1)(P<0.05).Increased ratios of phosphorylated-to-total proteins(P-P38/P38,P-ERK/ERK)and elevated NGAL/KIM-1 protein levels confirmed pathway dysregulation.Treatment significantly reduced the renal coefficient(P<0.05),attenuated histological damage,and restored mitochondrial integrity.NGAL,Scr,and BUN levels were lowered,reflecting functional recovery.Diminished fluorescence intensities of P-P38,P-ERK,NGAL,and KIM-1 indicated suppression of injury pathways.Downregulation of inflammatory cytokines(IL-1β,IL-6,TNF-α),MAPK components(P38 MAPK,ERK),and injury markers(NGAL,KIM-1)(P<0.05).Reduced phosphorylation ratios(P-P38/P38,P-ERK/ERK)and decreased NGAL/KIM-1 protein expression demonstrated therapeutic efficacy.Conclusion:Ononin ameliorates inflammatory responses in AKI mice via the P38 MAPK/ERK pathway.
文摘Cardiovascular diseases(CVDs)are the leading cause of global mortality,with chronic inflammation playing an important role in their pathogenesis[1].Inflammatory bowel disease(IBD)has been associated with an increased risk of CVDs,including arrhythmias and atherosclerotic disease,potentially mediated by persistent systemic inflammation[2,3].
文摘BACKGROUND Gastric ulcer(GU),a common gastrointestinal condition,is influenced by multiple factors,particularly inflammatory and immune responses.Complete blood count(CBC)-derived inflammatory biomarkers represent a novel indicator of systemic inflammation and immune status;however,their association with GU remains unclear.AIM To investigate the association between CBC-derived inflammatory markers and GU.METHODS The study sample included individuals admitted to the Gastroenterology Unit of the Second Affiliated Hospital of Nanchang University from 2023 to 2024.We explored how each CBC-based inflammation indicator correlated with GU occurrence through logistic models,and assessed their predictive ability using receiver operating characteristic curve analysis.Additionally,we applied the least absolute shrinkage and selection operator method along with stepwise regression techniques to determine which inflammatory indicators were most significantly linked to GU.RESULTS Higher levels of log2 neutrophil-to-lymphocyte ratio,log2 monocyte-to-lymphocyte ratio,log2 systemic immuneinflammation index,log2 systemic inflammatory response index(SIRI),and log2 aggregate index of systemic inflammation were significantly associated with increased GU prevalence across all models,while log2 platelet-tolymphocyte ratio was significant only in the fully adjusted model.SIRI demonstrated the highest discriminative ability,with an area under the curve of 0.868.CONCLUSION Hematological indicators derived from CBC tests show a significant correlation with the prevalence of GU.Among them,SIRI demonstrated the most prominent association.These markers could act as practical tools in recognizing individuals more likely to develop GU.
文摘Inflammatory bone diseases constitute a category of chronic inflammatory disorders,with the primary pathological characteristic being the impact of chronic inflammation on bone metabolism and remodeling.It leads to pain,spinal joint deformities,and functional impairments.Common clinical types of inflammatory bone diseases include rheumatoid arthritis,ankylosing spondylitis,and osteoarthritis.However,there is a paucity of effective clinical treatments for inflammatory bone diseases,and pharmacological interventions are frequently associated with intolerable side effects.Traditional Chinese medicine(TCM)has a long-standing history and proven efficacy in managing inflammatory bone diseases.In recent years,an increasing number of studies have highlighted the potential of TCM in this context.This article systematically evaluates the application of TCM in treating inflammatory bone diseases,emphasizing the underlying molecular mechanisms of its anti-inflammatory effects.By elucidating the specific targets of TCM in the treatment of rheumatoid arthritis,ankylosing spondylitis,and osteoarthritis,we aim to provide novel insights into the further exploration of TCM’s role in clinical application for inflammatory bone diseases.
文摘The oral microbiome is the second largest microbial community in the human body after the gut microbiome.It includes an array of fungi,bacteria,amoebae,flagellates,archaea,and viruses,all of which are potential pathogens.This microbiome can act as a facilitator not only for protection but also for aggravation when dysbiosis occurs.Although conventional thought is this is primarily in terms of oral health issues,such as dental caries and gingival disease.The systemic effects of the oral microbiome however,are relevant to both gastrointestinal(GI)disease and non-GI disease.These systemic risks occur for several reasons,including upregulation of cytokines,adhesion cell-like processes,toll-like receptors,reactive oxidative species or generation of mutation inducing DNA changes.Additionally,there is translocation risk of potential active pathogens or their metabolic byproducts.There is a substantial and growing body of evidence that the oral microbiome influences diseases including Barrett’s esophagus,metabolicassociated steatosis liver disease,and GI cancers.Additionally,there is burgeoning evidence of a causal association with systemic inflammatory diseases,including inflammatory bowel disease.This report discusses the most recent evidence of this association and highlights new approaches to potentially enhance our“best practice”strategies for optimal care of patients with inflammatory bowel disease.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)and inflam-matory bowel disease(IBD)are chronic conditions with complex aetiologies,in which environmental factors and interactions between the gut and liver play a key role.Both conditions are characterised by disturbances in the gut microbiota,which can affect local and systemic inflammatory responses.In particular,inc-reased intestinal permeability promotes the translocation of bacterial components into the portal circulation,contributing to the development of inflammation in the liver.There is growing evidence that modulation of the gut microbiota and imp-roved intestinal barrier function may be of therapeutic importance.The purpose of this review is to discuss the pathogenetic mechanisms that link MASLD and IBD,with a particular emphasis on the influence of the microbiota and environ-mental factors on the development of these diseases.
基金Supported by Zhejiang Provincial Traditional Chinese Medicine Science and Technology Plan Project,No.2023ZL424.
文摘BACKGROUND Although thoracotomy has been the conventional treatment for patients with early esophageal cancer(EEC),its drawbacks underscore the demand for more effective therapeutic strategies to improve surgical outcomes.AIM To comprehensively analyze the effect of totally thoracoscopic esophagectomy(TTE)on postoperative complications and serum inflammatory factors in patients diagnosed with EEC.METHODS A total of 113 patients with EEC,who were admitted to our hospital between September 2022 and December 2024,were recruited for this study.Specifically,55 patients were assigned to the control group and underwent conventional surgical procedures,whereas 58 patients formed the research group and underwent TTE.Subsequently,a series of comparisons and analyses were conducted between the two groups.These comparisons included surgery-related parameters,such as incision length,operation duration,and the number and extent of lymph node dissection;postoperative complications,namely,empyema,pulmonary infection,incision infection,anastomotic fistula,and delayed gastric emptying;postoperative pain,which was quantitatively evaluated by the Numerical Rating Scale;postoperative hospitalization duration;serum inflammatory factors,including interleukin(IL)-6,IL-8,and tumor necrosis factor-α;and stress response-associated indicators,such as C-reactive protein,cortisol,and adrenaline.RESULTS Statistical data demonstrated that compared with the control group,the research group exhibited substantially shorter incision length and postoperative hospitalization duration.The two groups had comparable number and extent of lymph node dissection.Notably,both the overall incidence of postoperative complications and the Numerical Rating Scale score on postoperative day 3 were remarkably lower in the research group.Although the levels of IL-6,IL-8,tumor necrosis factor-α,C-reactive protein,cortisol,and adrenaline in the research group increased statistically postoperatively,they were still considerably lower than those in the control group.CONCLUSION In patients with EEC,TTE not only reduces the risk of postoperative complications but also effectively alleviates the body’s inflammatory and stress responses associated with surgery.
基金Supported by National Natural Science Foundation of China,No.82300604Science and Technology Innovation Action Plan Star Project Application Guide/Star Project Incubation(Yangfan Special Program)of Shanghai,No.24YF2727600.
文摘BACKGROUND Inflammatory bowel diseases(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD),are chronic gastrointestinal disorders with an increasing global prevalence and significant healthcare impact.The exact etiology of this condition remains unclear.Neutrophils play a critical role in IBD pathogenesis.Translocator protein(TSPO),a mitochondrial protein linked to immune responses,has demonstrated potential as an inflammatory marker.However,its role in IBD remains underexplored.AIM To investigate the role of TSPO in IBD pathogenesis,particularly in neutrophils.METHODS Bioinformatics analyses of Gene Expression Omnibus datasets(GE75214,GSE94648,GSE156776)assessed TSPO expression in IBD patients.TSPO expression was evaluated in human IBD samples,neutrophiles and a chronic colitis mouse model.Neutrophil function was examined in 18 samples using reactive oxygen species(ROS)production and neutrophil extracellular trap(NET)formation assays.Positron emission tomography-computed tomography(PET-CT)imaging and histology from 12 mice revealed TSPO expression in colitis.PET-CT and immunofluorescence staining assessed TSPO expression in brain under neuroinflammation condition.RESULTS Bioinformatics analysis revealed elevated TSPO expression in the intestinal mucosa and peripheral blood of patients with IBD,especially in neutrophils.This was confirmed by quantitative real-time polymerase chain reaction and immunohistochemical staining,which showed a significant upregulation of TSPO in active IBD.Neutrophils from patients with UC and CD exhibited higher TSPO expression,which correlated with increased ROS production and NET formation.In a mouse model of dextran sodium sulfate-induced chronic colitis,TSPO was upregulated in the colonic neutrophils and brain tissues,indicating its systemic involvement.PET-CT imaging showed enhanced TSPO uptake in the inflamed colon and brain regions,particularly in the microglia,highlighting neuroinflammation.CONCLUSION TSPO is significantly upregulated in neutrophils in IBD and contributes to intestinal inflammation.Its elevated expression in gut highlights its potential as a promising therapeutic target for IBD.
文摘Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its global prevalence is rising,largely driven by urbanization,sedentary lifestyles,and dietary changes.These same factors are also associated with the increasing incidence of inflammatory bowel diseases(IBD),including Crohn’s disease and ulcerative colitis.Emerging evidence supports a potential biological link between chronic gastrointestinal inflammation and the later development of cardiometabolic disorders;a con-nection that is particularly relevant for patients with IBD.Comparative studies examining cardiometabolic risk associated with Crohn’s disease versus ulcerative colitis have reported inconsistent findings,likely due to confounding factors such as age,lifestyle,and comorbidities.This review summarizes current evidence linking IBD and cardiometabolic disorders,and highlights the need for clinicians to recognize cardiometabolic risk in patients with IBD.Future research should investigate whether treat-to-target strategies focused on controlling intestinal inflammation can simultaneously improve both long-term IBD and cardiometabolic outcomes.
文摘BACKGROUND Systemic immunoinflammatory diseases can affect multiple systems and organs.They have a severe course and severe complications,causing multiple organ failure and death.Quite often these patients are required to be hospitalized in the intensive care unit(ICU).Approximately 50% of patients with multisystem inflammatory syndrome associated with coronavirus disease 2019 in children and systemic lupus erythematosus need admission to the ICU.AIM To find early predictors of death in patients with immunoinflammatory diseases who are hospitalized in the ICU.METHODS The retrospective continuous cohort study included 51 patients(23 males,28 females)with immunoinflammatory diseases,including multisystem inflammatory syndrome associated with coronavirus disease 2019(n=18),systemic rheumatic diseases(n=24),and generalized infections(n=9).The patients ranged in age from 7 months to 17 years old and were admitted to the ICU of the clinic of Saint Petersburg State Pediatric Medical University from 2007 to 2023.RESULTS Thirteen patients(25.5%)died within 39(17;62)days after ICU admission.Patients with an unfavorable outcome were significantly older and were admitted to the ICU later than patients who survived(30 days vs 7 days,P=0.013)and had a longer stay in the ICU(30 days vs 6 days,P=0.003).The main predictors of the fatal outcome were age>162 months[odds ratio(OR)=10.7;95%confidence interval(CI):2.4-47.2,P=0.0006],time to ICU admission>26 days from the disease onset(OR=12.0;95%CI:2.6-55.3,P=0.008),preceding immune suppression treatment(OR=6.2;95%CI:1.6-24.0,P=0.013),invasive mycosis during the ICU stay(OR=18.8;95%CI:1.9-184.1,P=0.0005),systemic rheumatic diseases(OR=7.2;95%CI:1.7-31.1,P=0.004),and ICU stay over 15 days(OR=19.1;95%CI:4.0-91.8,P=0.00003).Multiple regression analysis(r^(2)=0.422,P<0.000002)identified two predictors of the fatal outcomes:Systemic rheumatic diseases(P=0.015)and ICU stay over 15 days(P=0.00002).CONCLUSION Identifying patients at high risk of an unfavorable outcome is the subject of the most careful monitoring and appropriate treatment program.Avoiding ICU stays for patients with systemic rheumatic diseases,close monitoring,and preventing invasive mycosis might improve the outcome in children with systemic immunemediated diseases.
基金supported by the National Natural Science Foundation of China,Nos.82104560(to CL),U21A20400(to QW)the Natural Science Foundation of Beijing,No.7232279(to XW)the Project of Beijing University of Chinese Medicine,No.2022-JYB-JBZR-004(to XW)。
文摘The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflammatory progression,mainly by secreting inflammatory factors.In the future,a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells,along with the activation of M2-type microglia.These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.
基金supported by GILO Foundation.This research is in part supported by Korea Drug Development Fund funded by Ministry of Science and ICT,Ministry of Trade,Industry,and Energy,and Ministry of Health and Welfare(RS-2023-00282595,Republic of Korea).
文摘Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19 is important for its function in osteoclast differentiation,and LEL-Fc,a competitive inhibitor of Tm4sf19,effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis.This study aimed to investigate the role of Tm4sf19 in RA,an inflammatory and abnormal osteoclast disease,using a mouse model of collagen-induced arthritis(CIA).Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium,and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group.Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model,reducing the CIA score,swelling,inflammation,cartilage damage,and bone damage.Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages.LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2,but also the interaction between TLR4 and MD2.μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice.Taken together,these findings suggest that LELFc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.
基金supported by the Hyperbaric Med School of the Department of Biomedical Sciences at the University of Padova,the Italian Air Force,and the Institute of Clinical Physiology(Milan)-National Research Council(IFC-CNR).
文摘Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously confined to military and/or professional astronauts only.This new evidence offers additional opportunities for better characterizing the impact that the transition from Earth’s 1G to microgravity in space could have on the astronauts’health while comparing well-trained subjects such as the latt er to space newcomers[1].
基金supported by the National Key Research and Development Program of China(No.2019YFC1712100)the National Natural Science Foundation of China(No.82105017)。
文摘Objective:The occurrence and development of atrial fibrillation(AF)are influenced by the autonomic nervous system and inflammation.Acupuncture is an effective treatment for AF.This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms.Methods:Male Sprague-Dawley rats(n=130)were randomly divided into blank control(Con),sham operation(Sham),AF,and acupuncture treatment(Acu)groups.A paroxysmal AF model was established by rapid atrial pacing through the jugular vein.Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint(PC6)for 20 min daily for seven days.The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture.The AF induction rate,AF duration,cardiac electrophysiological parameters,and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals.After the intervention,the rats were euthanized,and atrial morphology was assessed using haematoxylin and eosin staining.The expression of macrophage F4/80 antigen(F4/80)and cluster of differentiation(CD)86 in atrial myocardial tissue was detected using immunohistochemistry,immunofluorescence and flow cytometry.The expression levels or contents of interleukin(IL)-1β,IL-6,tumor necrosis factor-a(TNF-a),a7 nicotinic acetylcholine receptor(a7nAChR),phosphorylated Janus kinase 2(p-JAK2),and phosphorylated signal transducer and activator of transcription 3(p-STAT3)in atrial myocardial tissue were detected using Western blotting,reverse transcription-quantitative polymerase chain reaction,or enzyme-linked immunosorbent assay.The role of a7nAChR in acupuncture treatment was verified by intraperitoneal injection of the a7nAChR antagonist methyllycaconitine(MLA).Results:Compared with the AF group,acupuncture significantly reduced AF duration and induction rate,improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance.It also decreased the pro-inflammatory M1 macrophage proportion,alleviating myocardial injury and infiltration.MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect.Results suggest that acupuncture triggers the a7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation.Conclusion:Acupuncture significantly reduced the AF induction rate,shortened AF duration,improved cardiac electrophysiological parameters,enhanced vagus nerve activity,and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF.
基金supported by the Spanish Government(ISCIII-FEDER)PI20/01063by Navarra Government(PC 060-061 and PC 192-193)Fundación Gangoiti(to MSA).LA was funded by FPU19/03255.
文摘Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons.Neuroinflammation has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be determined.Human leukocyte antigen.
基金supported by the National Natural Science Foundation of China,No.81971177(to YK)the Natural Science Foundation of Beijing,No.7222198(to NH)the Peking University People's Hospital Research and Development Fund,No.RDX2021-01(to YK)。
文摘FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain unclear.In this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function recovery.These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.
