AIM:To evaluate the predictive value of pan-immuneinflammation value(PIV)in the diagnosis of proliferative diabetic retinopathy(PDR)and its association with the stage of PDR.METHODS:This observational case-control stu...AIM:To evaluate the predictive value of pan-immuneinflammation value(PIV)in the diagnosis of proliferative diabetic retinopathy(PDR)and its association with the stage of PDR.METHODS:This observational case-control study included participants who underwent routine complete blood count testing.Inflammation-related indices,including neutrophil-to-lymphocyte ratio,systemic immune-inflammation index(SII),and PIV,were derived and analyzed.Receiver operating characteristic curve(ROC)analysis was applied to assess the diagnostic performance of these indices in distinguishing patients with PDR,with sensitivity,specificity,area under ROC,and optimal threshold values calculated.In addition,binary logistic regression analysis was performed to evaluate the association between inflammatory indices and PDR stage.RESULTS:This study included 205 patients:60 with diabetes without retinopathy(mean age:61.81±10.76y),80 with PDR(mean age:61.63±10.03y)and 65 healthy controls(mean age:59.52±5.88y).The PDR group had significantly higher white blood cell(WBC,P<0.001),monocyte(MONO,P=0.009)and neutrophil(NEU)counts(P<0.001).SII and PIV had the highest sensitivity and area under ROC for predicting patients with PDR(0.822,0.846,respectively).The optimal cut-off values for discriminating patients with PDR were determined to be>527.12 and>299.08 for SII and PIV,respectively.The logistic regression analysis demonstrated that a decrease in lymphocyte(LYM)count and an increase in platelet count(PLT),glycated haemoglobin(HbA1c),SII,and PIV were all significantly associated with the development of high-risk PDR(all P<0.05).PIV was more stable than independent MONO,LYM,PLT and NEU levels in predicting both the diagnosis and stage of PDR.The optimal cut-off value for PIV to discriminate patients with high-risk PDR was found to be>345.87 area under ROC=0.871,with sensitivity of 0.827 and specificity of 0.812.CONCLUSION:PIV is a reliable,valuable,and inexpensive blood index that can be used for early detection and staging of PDR.PIV may therefore be essential to be used for the follow-up of diabetic patients.展开更多
Dear Editor,Idiopathic orbital inflammation(IOI),also known as orbital inflammatory pseudotumor,is a relatively common orbital disorder[1].Its pathogenesis remains unclear,often regarded as a nonspecific immune-mediat...Dear Editor,Idiopathic orbital inflammation(IOI),also known as orbital inflammatory pseudotumor,is a relatively common orbital disorder[1].Its pathogenesis remains unclear,often regarded as a nonspecific immune-mediated response[2].IOI presents with symptoms such as pain,photophobia,proptosis,eyelid swelling,edema,conjunctival congestion,and diplopia,with possible vision loss occurring in some cases.Based on the soft tissue structures involved,IOI can be classified into subtypes such as myositis,optic neuritis,dacryoadenitis,diffuse orbital inflammation,and orbital inflammatory masses[2].展开更多
Neuroinflammation,the inflammatory response of the central nervous system(CNS),is a common feature of many neurological disorders such as sepsis-associated encephalopathy(SAE),multiple sclerosis(MS),and Parkinson'...Neuroinflammation,the inflammatory response of the central nervous system(CNS),is a common feature of many neurological disorders such as sepsis-associated encephalopathy(SAE),multiple sclerosis(MS),and Parkinson's disease(PD).Prior studies identified cytokines(e.g.,tumor necrosis factor[TNF],interleukin[IL]-1,and IL-6)delivered by resident glial cells and brain-invading peripheral immune cells as the major contributor to neuroinflammation(Becher et al.,2017).In addition to pro-inflammatory cytokines,elevated levels of extracellular purine molecules such as adenosine triphosphate(ATP)and adenosine can be detected upon any pathological insults(e.g.,injury,ischemia,and hypoxia),contributing to the progression of neurological disorders(Borea et al.,2017).展开更多
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
Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response pla...Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.展开更多
Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammat...Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.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
Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated ...Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.展开更多
The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evi...The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.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
Globally,glaucoma stands as a primary cause of irreversible blindness,marked by intricate pathophysiological processes in which neuroinflammation plays a pivotal role.As the principal immune cells within the central n...Globally,glaucoma stands as a primary cause of irreversible blindness,marked by intricate pathophysiological processes in which neuroinflammation plays a pivotal role.As the principal immune cells within the central nervous system,microglia play a dual function in the progression of glaucoma.Under standard physiological states,microglia safeguard the retina by offering neurotrophic support and removing cellular debris.In the pathological progression of glaucoma,microglia become activated and release significant levels of inflammatory factors,resulting in retinal ganglion cell injury,cell death,and impaired neuroregeneration.This review focuses on examining the dual functions of microglia in glaucoma,evaluating their influence on retinal neurodegeneration and repair,and suggesting that modulating microglial activity could serve as a promising therapeutic strategy.Understanding the mechanisms of microglial action in glaucoma is crucial for unveiling the complex pathophysiological processes of the disease and developing new therapeutic strategies.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
Inflammation plays a key role in driving the secondary brain injury that follows ischemic stroke.Melatonin is an endogenous neuroendocrine hormone that regulates mitochondrial homeostasis.However,the role and mechanis...Inflammation plays a key role in driving the secondary brain injury that follows ischemic stroke.Melatonin is an endogenous neuroendocrine hormone that regulates mitochondrial homeostasis.However,the role and mechanisms by which melatonin regulates microglial pyroptosis and the inflammatory cascade through double-stranded DNA(dsDNA)-sensing cyclic GMP-AMP synthase(cGAS)signaling warrant further study.Using middle cerebral artery occlusion mice,we investigated the effects of melatonin on cGAS-mediated pyroptosis and neuroinflammation.Middle cerebral artery occlusion model mice exhibited significantly increased DNA damage and cytoplasmic dsDNA release,as reflected byγH2AX staining,as well as heightened activation of the cytosolic dsDNA-sensing cGAS-STING pathway,both of which were notably suppressed by melatonin treatment.Melatonin also mitigated NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome activation and nuclear factor(NF)-κB/gasdermin D-mediated pyroptosis in microglia following ischemic stroke,while exhibiting the capacity to attenuate the immune response to ischemia in mice.This led to reduced infiltration of peripheral neutrophils and monocytes/macrophages in the ischemic brain.Specifically,melatonin administration resulted in reductions in the numbers of ionized calcium-binding adapter molecule 1-positive cells and production of interleukin-6 and tumor necrosis factor-αby microglia.Regarding neurological outcomes,melatonin significantly reduced cerebral infarct volume and ameliorated neurological deficits in mice.Notably,the neuroprotective effect of melatonin was correlated with the inhibition of cGAS activity.We also developed and tested melatonin co-loaded macrophage membrane-biomimetic reactive oxygen species-responsive nanoparticles(Mф-MLT@FNGs),which exhibited therapeutic properties in middle cerebral artery occlusion mice.Our findings suggest that melatonin acts on microglial pyroptosis to inhibit neuroinflammation and reshape the immune microenvironment through regulation of the cGAS-STING-NF-κB signaling pathway.By doing so,melatonin rescues damaged brain tissue and protects neurological function,highlighting its potential as a neuroprotective treatment for ischemic stroke.展开更多
AIM:To report and analyze cases of sterile intraocular inflammation(IOI)following intravitreal faricimab injections in patients treated for neovascular age-related macular degeneration(nAMD)and diabetic macular edema(...AIM:To report and analyze cases of sterile intraocular inflammation(IOI)following intravitreal faricimab injections in patients treated for neovascular age-related macular degeneration(nAMD)and diabetic macular edema(DME).METHODS:This double-center case series included nine eyes of six patients who developed uveitis after faricimab therapy.Comprehensive clinical evaluation was performed,including slit-lamp examination,intraocular pressure(IOP)measurement,fluorescein and indocyanine green angiography(ICGA),and laboratory tests.Inflammatory responses were treated with topical or systemic corticosteroids,and patients were monitored for visual acuity and inflammatory activity.RESULTS:The incidence of IOI was 0.8%per patient(Innsbruck)and 0.23%(Czechia),with inflammation typically occurring between the third and sixth injection(mean interval:10d post-injection).Inflammator y presentations ranged from anterior uveitis to posterior segment involvement.One notable case demonstrated novel choroidal hypofluorescent lesions on angiography,suggesting deeper ocular involvement.The mean patient age was 76y;five of six affected patients were female.All cases responded to local and systemic corticosteroids,with full recovery of initial visual acuity.CONCLUSION:Sterile IOI after faricimab appears to be a rare but relevant adverse event.Although the incidence falls within expected ranges for anti-vascular endothelial growth factor(anti-VEGF)agents,the observed choroidal involvement represents a potentially new safety signal.Prompt diagnosis and corticosteroid therapy are effective in all cases.Our findings support the need for vigilant post-marketing surveillance and further studies to better understand the underlying mechanisms and risk factors of faricimab-associated inflammation.展开更多
AIM:To investigate the impact of depression-like behavior on ocular surface homeostasis in a mouse model,with a focus on dry eye-like alterations.METHODS:Male C57BL/6J mice(10-12 weeks old)were randomly assigned to co...AIM:To investigate the impact of depression-like behavior on ocular surface homeostasis in a mouse model,with a focus on dry eye-like alterations.METHODS:Male C57BL/6J mice(10-12 weeks old)were randomly assigned to control or restraint stress(RS)groups.The RS group underwent three intermittent 24-hour restraint sessions to induce depressive-like behavior.Behavioral testing,tear secretion measurement,and corneal Oregon Green Dextran(OGD)staining were performed.Postmortem analyses included histological evaluation of lacrimal glands,goblet cell quantification using periodic acid-Schiff staining,and assessment of key inflammatory and apoptotic markers:interleukin(IL)-17,matrix metalloproteinases(MMP)-3,MMP-9,IL-13,interferon(IFN)-γ,and cleaved caspase-3 and-8.RESULTS:Repeated RS induced depression-like behavior and significant ocular surface changes.RStreated mice showed increased corneal OGD uptake and upregulation of gene/protein expression of IL-17,MMP-3,and MMP-9(P<0.05).Goblet cell density and IL-13 protein expression were reduced,while IFN-γprotein expression was elevated(P<0.05).Cleaved caspase-3 and-8 levels were significantly increased in both cornea and conjunctiva.Tear volume and lacrimal gland size were unchanged;however,mild inflammatory infiltration was observed in lacrimal glands.CONCLUSION:Repeated RS leads to ocular surface inflammation and dry eye-like pathology,including corneal barrier disruption,goblet cell loss,and epithelial apoptosis.These findings suggest that depression contributes to the pathogenesis of dry eye disease via immune-mediated mechanisms.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
Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and ...Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and systemic inflammation,as well as whether this association is modified by indoor particulate matter and the underlying mechanisms.In this prospective repeated-measure study among 66 participants,indoor airborne mi-crobiome was characterized using amplicon sequencing and qPCR.Indoor fine particulate matter(PM_(2.5))and inhalable particulate matter(PM10)were measured.Systemic inflammatory biomarkers were assessed,including white blood cell(WBC),neutrophil(NEUT),monocyte,eosinophil counts,and their proportions.Targeted serum amino acid metabolomics were conducted to explore the underlying mechanisms.Linear mixed-effect models re-vealed that bacterial and fungal Simpson diversity were significantly associated with decreased WBC and NEUT.For example,for each interquartile range increase in the bacterial Simpson diversity,WBC and NEUT changed by-4.53%(95%CI:-8.25%,-0.66%)and-5.95%(95%CI:-11.3%,-0.27%),respectively.Notably,increased inflammatory risks of airborne microbial exposure were observed when indoor PM_(2.5) and PM10 levels were below the WHO air quality guidelines.Mediation analyses indicated that dopamine metabolism partially mediated the anti-inflammatory effects of fungal diversity exposure.Overall,our study indicated protection from a diverse indoor microbial environment on cardiovascular health and proposed an underlying mechanism through amino acid metabolism.Additionally,health risks associated with microbial exposure deserve more attention in con-texts of low indoor particulate matter pollution.Further research is necessary to fully disentangle the complex relationships between indoor microbiome,air pollutants,and human health.展开更多
AIM:To define the prevalence and anatomical patterns of paranasal sinus abnormalities(PSA)in thyroid-associated ophthalmopathy(TAO)and to test the hypothesis that TAO is partially driven by contiguous orbital inflamma...AIM:To define the prevalence and anatomical patterns of paranasal sinus abnormalities(PSA)in thyroid-associated ophthalmopathy(TAO)and to test the hypothesis that TAO is partially driven by contiguous orbital inflammation rather than systemic autoimmunity or generalized orbital pressure.METHODS:Data included ophthalmic assessments and a panel of thyroid function and autoimmune biomarkers.Blinded radiological analysis of orbital computed tomography(CT)scans was performed to quantify sinus abnormalities and extraocular muscles(EOMs)involvement.Patients were categorized into two groups based on CT findings,those with no radiological evidence of sinus abnormalities(non-PSA control group)and those with identifiable PSA.Furthermore,ethmoid sinus mucosal biopsies from a subset of TAO patients and noninflammatory controls were subjected to histopathological analysis.RESULTS:Totally 121 TAO patients(mean age 42.4±12.8y,range 10-78y),male:female=42:79,were included.PSA was identified in 44.6%(n=54)of patients,with a distribution anatomically restricted to the maxillary(50.0%isolated)and ethmoid sinuses(18.5%isolated;29.6%combined).Compared to the non-PSA group(n=67),patients with PSA were significantly older(45.1±11.8 vs 40.3±13.2y;P=0.040)and were more likely to be male(55.6%vs 17.9%;P<0.001).They also had significantly higher proptosis(22.1±3.2 vs 20.7±2.9 mm;P<0.001).Medial/inferior rectus involvement was most frequent(88.4%vs 89.3%).Histopathological analysis of sinus mucosa from PSA patients provided direct evidence of pathology,revealing a dense,chronic lymphoplasmacytic infiltrate and submucosal edema,validating the radiological findings as a true inflammatory process.No significant correlation was found with systemic autoimmune markers,including thyroid-stimulating hormone(TSH)receptor antibodies(TRAb,median 4.86 vs 2.71 IU/L,P=0.104).CONCLUSION:TAO is associated with a high prevalence of PSA in a pattern consistent with the orbital anatomy.The correlation with ipsilateral muscle thickening combined with the lack of association with proptosis laterality or systemic biomarkers lend strong support to a model of contiguous inflammation over systemic autoimmunity,a hypothesis that warrants further validation through longitudinal and mechanistic studies.展开更多
Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,par...Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).展开更多
文摘AIM:To evaluate the predictive value of pan-immuneinflammation value(PIV)in the diagnosis of proliferative diabetic retinopathy(PDR)and its association with the stage of PDR.METHODS:This observational case-control study included participants who underwent routine complete blood count testing.Inflammation-related indices,including neutrophil-to-lymphocyte ratio,systemic immune-inflammation index(SII),and PIV,were derived and analyzed.Receiver operating characteristic curve(ROC)analysis was applied to assess the diagnostic performance of these indices in distinguishing patients with PDR,with sensitivity,specificity,area under ROC,and optimal threshold values calculated.In addition,binary logistic regression analysis was performed to evaluate the association between inflammatory indices and PDR stage.RESULTS:This study included 205 patients:60 with diabetes without retinopathy(mean age:61.81±10.76y),80 with PDR(mean age:61.63±10.03y)and 65 healthy controls(mean age:59.52±5.88y).The PDR group had significantly higher white blood cell(WBC,P<0.001),monocyte(MONO,P=0.009)and neutrophil(NEU)counts(P<0.001).SII and PIV had the highest sensitivity and area under ROC for predicting patients with PDR(0.822,0.846,respectively).The optimal cut-off values for discriminating patients with PDR were determined to be>527.12 and>299.08 for SII and PIV,respectively.The logistic regression analysis demonstrated that a decrease in lymphocyte(LYM)count and an increase in platelet count(PLT),glycated haemoglobin(HbA1c),SII,and PIV were all significantly associated with the development of high-risk PDR(all P<0.05).PIV was more stable than independent MONO,LYM,PLT and NEU levels in predicting both the diagnosis and stage of PDR.The optimal cut-off value for PIV to discriminate patients with high-risk PDR was found to be>345.87 area under ROC=0.871,with sensitivity of 0.827 and specificity of 0.812.CONCLUSION:PIV is a reliable,valuable,and inexpensive blood index that can be used for early detection and staging of PDR.PIV may therefore be essential to be used for the follow-up of diabetic patients.
基金Supported by the National Natural Science Foundation of China(No.82388101,No.81930024)the Science and Technology Commission of Shanghai(No.22YS1400400,No.20DZ2270800).
文摘Dear Editor,Idiopathic orbital inflammation(IOI),also known as orbital inflammatory pseudotumor,is a relatively common orbital disorder[1].Its pathogenesis remains unclear,often regarded as a nonspecific immune-mediated response[2].IOI presents with symptoms such as pain,photophobia,proptosis,eyelid swelling,edema,conjunctival congestion,and diplopia,with possible vision loss occurring in some cases.Based on the soft tissue structures involved,IOI can be classified into subtypes such as myositis,optic neuritis,dacryoadenitis,diffuse orbital inflammation,and orbital inflammatory masses[2].
基金supported by grants from the Deutsche Forschungsgemeinschaft(HU 2614/1-1(Project No.462650276))the Fritz Thyssen Foundation(10.21.1.021MN)the Medical faculty of the University of Saarland(HOMFOR2016,HOMFORexzellent2017,HOMFOR2024 Anschubfinanzierung)to WH。
文摘Neuroinflammation,the inflammatory response of the central nervous system(CNS),is a common feature of many neurological disorders such as sepsis-associated encephalopathy(SAE),multiple sclerosis(MS),and Parkinson's disease(PD).Prior studies identified cytokines(e.g.,tumor necrosis factor[TNF],interleukin[IL]-1,and IL-6)delivered by resident glial cells and brain-invading peripheral immune cells as the major contributor to neuroinflammation(Becher et al.,2017).In addition to pro-inflammatory cytokines,elevated levels of extracellular purine molecules such as adenosine triphosphate(ATP)and adenosine can be detected upon any pathological insults(e.g.,injury,ischemia,and hypoxia),contributing to the progression of neurological disorders(Borea et al.,2017).
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 European Union-NextGeneration EU under the Italian University and Research(MUR)National Innovation Ecosystem grant ECS00000041-VITALITY-CUP E13C22001060006(to MdA)。
文摘Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.
基金supported by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil(CAPES)[Finance Code 001](to MGS)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico(CNPq)fellowship[research grants 309840/2022-8]。
文摘Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.
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.
基金supported by FWO(Fonds voor Wetenschappelijk Onderzoek),grant number G07562NFWO(to BB)。
文摘Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC).
文摘The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.
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.
基金supported by the Deutsche Forschungsgemeinschaft(DFG)with grants PR1569/1-1 and PR 1569/1-3(to VP).
文摘Globally,glaucoma stands as a primary cause of irreversible blindness,marked by intricate pathophysiological processes in which neuroinflammation plays a pivotal role.As the principal immune cells within the central nervous system,microglia play a dual function in the progression of glaucoma.Under standard physiological states,microglia safeguard the retina by offering neurotrophic support and removing cellular debris.In the pathological progression of glaucoma,microglia become activated and release significant levels of inflammatory factors,resulting in retinal ganglion cell injury,cell death,and impaired neuroregeneration.This review focuses on examining the dual functions of microglia in glaucoma,evaluating their influence on retinal neurodegeneration and repair,and suggesting that modulating microglial activity could serve as a promising therapeutic strategy.Understanding the mechanisms of microglial action in glaucoma is crucial for unveiling the complex pathophysiological processes of the disease and developing new therapeutic strategies.
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 the Natural Science Foundation of Heilongjiang Province,No.YQ2021H011(to QL)China Postdoctoral Science Foundation,Nos.2020M670925,2022T150172(to QL)+2 种基金Postdoctoral Foundation of Heilongjiang Province,Nos.LBH‐Z19027,LBH‐TZ2019(to QL)Institute Cultivation Fund,No.PYMS2023-1(to QL)Natural Science Foundation of Jiangsu Province,No.BK20241233(to YL).
文摘Inflammation plays a key role in driving the secondary brain injury that follows ischemic stroke.Melatonin is an endogenous neuroendocrine hormone that regulates mitochondrial homeostasis.However,the role and mechanisms by which melatonin regulates microglial pyroptosis and the inflammatory cascade through double-stranded DNA(dsDNA)-sensing cyclic GMP-AMP synthase(cGAS)signaling warrant further study.Using middle cerebral artery occlusion mice,we investigated the effects of melatonin on cGAS-mediated pyroptosis and neuroinflammation.Middle cerebral artery occlusion model mice exhibited significantly increased DNA damage and cytoplasmic dsDNA release,as reflected byγH2AX staining,as well as heightened activation of the cytosolic dsDNA-sensing cGAS-STING pathway,both of which were notably suppressed by melatonin treatment.Melatonin also mitigated NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome activation and nuclear factor(NF)-κB/gasdermin D-mediated pyroptosis in microglia following ischemic stroke,while exhibiting the capacity to attenuate the immune response to ischemia in mice.This led to reduced infiltration of peripheral neutrophils and monocytes/macrophages in the ischemic brain.Specifically,melatonin administration resulted in reductions in the numbers of ionized calcium-binding adapter molecule 1-positive cells and production of interleukin-6 and tumor necrosis factor-αby microglia.Regarding neurological outcomes,melatonin significantly reduced cerebral infarct volume and ameliorated neurological deficits in mice.Notably,the neuroprotective effect of melatonin was correlated with the inhibition of cGAS activity.We also developed and tested melatonin co-loaded macrophage membrane-biomimetic reactive oxygen species-responsive nanoparticles(Mф-MLT@FNGs),which exhibited therapeutic properties in middle cerebral artery occlusion mice.Our findings suggest that melatonin acts on microglial pyroptosis to inhibit neuroinflammation and reshape the immune microenvironment through regulation of the cGAS-STING-NF-κB signaling pathway.By doing so,melatonin rescues damaged brain tissue and protects neurological function,highlighting its potential as a neuroprotective treatment for ischemic stroke.
文摘AIM:To report and analyze cases of sterile intraocular inflammation(IOI)following intravitreal faricimab injections in patients treated for neovascular age-related macular degeneration(nAMD)and diabetic macular edema(DME).METHODS:This double-center case series included nine eyes of six patients who developed uveitis after faricimab therapy.Comprehensive clinical evaluation was performed,including slit-lamp examination,intraocular pressure(IOP)measurement,fluorescein and indocyanine green angiography(ICGA),and laboratory tests.Inflammatory responses were treated with topical or systemic corticosteroids,and patients were monitored for visual acuity and inflammatory activity.RESULTS:The incidence of IOI was 0.8%per patient(Innsbruck)and 0.23%(Czechia),with inflammation typically occurring between the third and sixth injection(mean interval:10d post-injection).Inflammator y presentations ranged from anterior uveitis to posterior segment involvement.One notable case demonstrated novel choroidal hypofluorescent lesions on angiography,suggesting deeper ocular involvement.The mean patient age was 76y;five of six affected patients were female.All cases responded to local and systemic corticosteroids,with full recovery of initial visual acuity.CONCLUSION:Sterile IOI after faricimab appears to be a rare but relevant adverse event.Although the incidence falls within expected ranges for anti-vascular endothelial growth factor(anti-VEGF)agents,the observed choroidal involvement represents a potentially new safety signal.Prompt diagnosis and corticosteroid therapy are effective in all cases.Our findings support the need for vigilant post-marketing surveillance and further studies to better understand the underlying mechanisms and risk factors of faricimab-associated inflammation.
基金Supported by the Key Program of the National Natural Science Foundation of China(No.82530034)the National Natural Science Foundation of China(No.82271054)the Nature Science Foundation of Xiamen,China(No.3502Z20227121).
文摘AIM:To investigate the impact of depression-like behavior on ocular surface homeostasis in a mouse model,with a focus on dry eye-like alterations.METHODS:Male C57BL/6J mice(10-12 weeks old)were randomly assigned to control or restraint stress(RS)groups.The RS group underwent three intermittent 24-hour restraint sessions to induce depressive-like behavior.Behavioral testing,tear secretion measurement,and corneal Oregon Green Dextran(OGD)staining were performed.Postmortem analyses included histological evaluation of lacrimal glands,goblet cell quantification using periodic acid-Schiff staining,and assessment of key inflammatory and apoptotic markers:interleukin(IL)-17,matrix metalloproteinases(MMP)-3,MMP-9,IL-13,interferon(IFN)-γ,and cleaved caspase-3 and-8.RESULTS:Repeated RS induced depression-like behavior and significant ocular surface changes.RStreated mice showed increased corneal OGD uptake and upregulation of gene/protein expression of IL-17,MMP-3,and MMP-9(P<0.05).Goblet cell density and IL-13 protein expression were reduced,while IFN-γprotein expression was elevated(P<0.05).Cleaved caspase-3 and-8 levels were significantly increased in both cornea and conjunctiva.Tear volume and lacrimal gland size were unchanged;however,mild inflammatory infiltration was observed in lacrimal glands.CONCLUSION:Repeated RS leads to ocular surface inflammation and dry eye-like pathology,including corneal barrier disruption,goblet cell loss,and epithelial apoptosis.These findings suggest that depression contributes to the pathogenesis of dry eye disease via immune-mediated mechanisms.
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.
基金supported by the National Key Research and Development Program of China(No.2022YFC3702704)the National Natural Science Foundation of China(Nos.22376005,22076006 and 82073506).
文摘Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and systemic inflammation,as well as whether this association is modified by indoor particulate matter and the underlying mechanisms.In this prospective repeated-measure study among 66 participants,indoor airborne mi-crobiome was characterized using amplicon sequencing and qPCR.Indoor fine particulate matter(PM_(2.5))and inhalable particulate matter(PM10)were measured.Systemic inflammatory biomarkers were assessed,including white blood cell(WBC),neutrophil(NEUT),monocyte,eosinophil counts,and their proportions.Targeted serum amino acid metabolomics were conducted to explore the underlying mechanisms.Linear mixed-effect models re-vealed that bacterial and fungal Simpson diversity were significantly associated with decreased WBC and NEUT.For example,for each interquartile range increase in the bacterial Simpson diversity,WBC and NEUT changed by-4.53%(95%CI:-8.25%,-0.66%)and-5.95%(95%CI:-11.3%,-0.27%),respectively.Notably,increased inflammatory risks of airborne microbial exposure were observed when indoor PM_(2.5) and PM10 levels were below the WHO air quality guidelines.Mediation analyses indicated that dopamine metabolism partially mediated the anti-inflammatory effects of fungal diversity exposure.Overall,our study indicated protection from a diverse indoor microbial environment on cardiovascular health and proposed an underlying mechanism through amino acid metabolism.Additionally,health risks associated with microbial exposure deserve more attention in con-texts of low indoor particulate matter pollution.Further research is necessary to fully disentangle the complex relationships between indoor microbiome,air pollutants,and human health.
基金Supported by The National Natural Science Foundation of China(No.82101180)the Fund for Beijing Science&Technology Development of TCM(No.BJZYYB-2023-17)the Beijing Municipal Natural Science Foundation grant(No.7252093).
文摘AIM:To define the prevalence and anatomical patterns of paranasal sinus abnormalities(PSA)in thyroid-associated ophthalmopathy(TAO)and to test the hypothesis that TAO is partially driven by contiguous orbital inflammation rather than systemic autoimmunity or generalized orbital pressure.METHODS:Data included ophthalmic assessments and a panel of thyroid function and autoimmune biomarkers.Blinded radiological analysis of orbital computed tomography(CT)scans was performed to quantify sinus abnormalities and extraocular muscles(EOMs)involvement.Patients were categorized into two groups based on CT findings,those with no radiological evidence of sinus abnormalities(non-PSA control group)and those with identifiable PSA.Furthermore,ethmoid sinus mucosal biopsies from a subset of TAO patients and noninflammatory controls were subjected to histopathological analysis.RESULTS:Totally 121 TAO patients(mean age 42.4±12.8y,range 10-78y),male:female=42:79,were included.PSA was identified in 44.6%(n=54)of patients,with a distribution anatomically restricted to the maxillary(50.0%isolated)and ethmoid sinuses(18.5%isolated;29.6%combined).Compared to the non-PSA group(n=67),patients with PSA were significantly older(45.1±11.8 vs 40.3±13.2y;P=0.040)and were more likely to be male(55.6%vs 17.9%;P<0.001).They also had significantly higher proptosis(22.1±3.2 vs 20.7±2.9 mm;P<0.001).Medial/inferior rectus involvement was most frequent(88.4%vs 89.3%).Histopathological analysis of sinus mucosa from PSA patients provided direct evidence of pathology,revealing a dense,chronic lymphoplasmacytic infiltrate and submucosal edema,validating the radiological findings as a true inflammatory process.No significant correlation was found with systemic autoimmune markers,including thyroid-stimulating hormone(TSH)receptor antibodies(TRAb,median 4.86 vs 2.71 IU/L,P=0.104).CONCLUSION:TAO is associated with a high prevalence of PSA in a pattern consistent with the orbital anatomy.The correlation with ipsilateral muscle thickening combined with the lack of association with proptosis laterality or systemic biomarkers lend strong support to a model of contiguous inflammation over systemic autoimmunity,a hypothesis that warrants further validation through longitudinal and mechanistic studies.
文摘Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).
