Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has...Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.展开更多
High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the ex...High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.展开更多
Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune system.This exploration is particularly significant in understanding micro...Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune system.This exploration is particularly significant in understanding microglia,the CNS’s innate immune cells,beyond the conventional conflation of“neuroinflammation”and“microglial activation.”This conflation has clouded the true complexity of these processes,potentially stalling scientific progress and the development of new therapies.We challenge the long-standing perspectives that have oversimplified these interactions,advocating for a deeper exploration of the dynamic relationship between neuroinflammation and microglial activation.By dissecting specific molecular pathways,we aim to illuminate their elaborate roles in neuroinflammatory responses,especially in the context of Alzheimer’s disease(AD).Here,neuroinflammation is not merely a passive observer or a direct antagonist but a complex agent in the disease’s progression.This article calls for a significant paradigm shift towards an integrative,multi-omics approach to neuroimmunology.Adopting such a comprehensive framework is crucial for advancing our understanding of neuroinflammatory conditions and paving the way for targeted therapeutic strategies for brain diseases.展开更多
Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and...Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.展开更多
In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, n...In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.展开更多
Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
Multiple sclerosis(MS),which is characterized by inflammatory demyelination in the central nervous system(CNS),is the most common neurological disease in the young adult population.Experimental autoimmune encephalomye...Multiple sclerosis(MS),which is characterized by inflammatory demyelination in the central nervous system(CNS),is the most common neurological disease in the young adult population.Experimental autoimmune encephalomyelitis(EAE),an animal model of MS,is often used in preclinical studies.Accumulating data indicate that in addition to immune cells such as T cells and dendritic cells,CNS resident microglia and astrocytes play important roles in demyelinating neuroinflammation(Healy et al.,2022).In particular,microglia are key immune-competent cells that can respond to environmental changes.Conditional depletion of transforming growth factor-β-activated kinase 1,a mitogen-associated protein kinase kinase kinase,in microglia is reported to reduce CNS inflammation and diminish axonal and myelin damage significantly.This suggests that elucidating the mechanisms of microglia-specific responses during pathologies may help in the development of treatments that reduce EAE/MS disease severity(Goldmann et al.,2013).展开更多
Neuroinflammation has been identified as a crucial element in several neurological disorders. Glial cells play a critical role in directing neuroinflammation, both in deleterious and beneficial ways.
Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most seve...Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most severe form of sepsis which leads to distributive shock and high mortality rates.There have been significant advances in sepsis management mainly focusing on early identification and therapy.However,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick SOFA.These limitations have underscored the modest progress in reducing sepsis-related mortality.This review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.展开更多
To the Editor:Distinguishing ocular adnexal lymphoma(OAL)from idiopathic orbital inflammation(IOI)is challenging owing to their similar clinical symptoms and imaging features.Previous research has demonstrated that ma...To the Editor:Distinguishing ocular adnexal lymphoma(OAL)from idiopathic orbital inflammation(IOI)is challenging owing to their similar clinical symptoms and imaging features.Previous research has demonstrated that magnetic resonance imaging(MRI)-based radiological characteristics can offer valuable insights for distinguishing between OAL and IOI.However,the diagnostic accuracy of these imaging findings relies largely on subjective interpretation,leading to inconsistent and sometimes controversial conclusions.The integration of MRI-based radiomics with machine learning(ML)is expected to provide quantitative features in a more objective manner,thereby further establishing diagnostic models and enhancing diagnostic accuracy.展开更多
Atrial fibrillation(AF)is the most common arrhythmia in humans,affecting more than 40 million people worldwide.Radiofrequency catheter ablation(RFCA)was first introduced as a treatment for AF by Haïssaguerre M in...Atrial fibrillation(AF)is the most common arrhythmia in humans,affecting more than 40 million people worldwide.Radiofrequency catheter ablation(RFCA)was first introduced as a treatment for AF by Haïssaguerre M in the late 1990s.This procedure quickly became the treatment of choice,especially for symptomatic patients with AF refractory to medication.However,up to 45%of patients may experience AF recurrence within 12 months after RFCA.In this setting,AF recurrence is likely multifactorial,including atrial remodeling,local fibrosis or incomplete ablation due to failure in locating the trigger.Additionally,patients with obesity,sleep apnea,hypertension,or diabetes are at an increased risk of AF recurrence after RFCA.Inflammation is increasingly recognized as a potential key factor in AF recurrence and may arise both from the healing response of heart tissue post-ablation or from chronic low-grade inflammation,as observed in many risk factors.Here,we present an original study by Wang et al,which investigated the combination of the systemic immune-inflammation index-a marker developed to assess overall inflammatory status-and the APPLE score,designed to predict AF recurrence following RFCA.The study found that using both indicators together improved the accuracy of AF recurrence prediction.These findings underscore the significant role of inflammation in cardiovascular disease and demonstrated its impact on AF recurrence after RFCA.Further research is warranted to validate the combined use of these two scores in clinical settings for predicting AF recurrence following catheter ablation.展开更多
Atrial fibrillation(Afib)is a common arrhythmia with significant public health implications,affecting millions of individuals worldwide.Catheter ablation(CA)is an established treatment for drug-resistant Afib,yet recu...Atrial fibrillation(Afib)is a common arrhythmia with significant public health implications,affecting millions of individuals worldwide.Catheter ablation(CA)is an established treatment for drug-resistant Afib,yet recurrence remains a major concern,impacting quality of life in a significant portion of patients.Inflammation plays a critical role in the recurrence of Afib after ablation,with systemic inflammatory markers such as C-reactive protein being linked to higher recurrence rates.In this editorial,we discuss the study by Wang et al,published in the latest issue,which investigates the predictive role of the systemic immune inflammation index(SII)in Afib recurrence following radiofrequency CA.Elevated pre-ablation SII levels are identified as an independent predictor of recurrence,significantly enhancing the predictive power of the APPLE score.Integration of SII improved the APPLE score’s predictive performance,as shown by enhanced area under the curve,net reclassification improvement,and integrated discrimination improvement.This combined model highlights the importance of both structural and inflammatory factors in Afib recurrence,offering a more personalized approach to patient management.Additionally,the affordability and accessibility of SII enhance its practicality in clinical workflows.The study by Wang et al underscores the potential of integrating SII with existing scoring systems to refine risk stratification and optimize treatment strategies.Future research should validate these findings across diverse populations,explore limitations such as the potential influence of comorbidities on SII reliability,and investigate additional biomarkers to enhance predictive accuracy.展开更多
Inflammatory bowel disease(IBD)is a chronic inflammatory disorder of the gastrointestinal tract,which increases the incidence of colorectal cancer(CRC).In the pathophysiology of IBD,ubiquitination/deubiquitination pla...Inflammatory bowel disease(IBD)is a chronic inflammatory disorder of the gastrointestinal tract,which increases the incidence of colorectal cancer(CRC).In the pathophysiology of IBD,ubiquitination/deubiquitination plays a critical regulatory function.Josephin domain containing 2(JOSD2),a deubiquitinating enzyme,controls cell proliferation and carcinogenesis.However,its role in IBD remains unknown.Colitis mice model developed by dextran sodium sulfate(DSS)or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages.JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation.DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation.Mechanistically,JOSD2 binds to the C-terminal of inosine-5′-monophosphate dehydrogenase 2(IMPDH2)and preferentially cleaves K63-linked polyubiquitin chains at the K134 site,suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B(NF-κB)and inflammation in macrophages.It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane(AOM)/DSS-induced CRC,and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice.These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2,suggesting that targeting JOSD2 is a potential strategy for treating IBD.展开更多
Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal a...Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal anti-inflammatory drugs(NSAIDs),and corticosteroids,frequently result in unintended adverse effects.Dexamethasone(DEX)is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties.Liposomal delivery of DEX,particu-larly when liposomes are surface-modified with targeting ligands like peptides or sialic acid,can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity.This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA.Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models,reduces joint inflammation and damage,and alleviates cartilage destruction compared to free DEX.The liposomal formulation also shows better hemocompatibility,fewer adverse effects on body weight and immune organ index,and a longer circulation time with higher bioavailability.The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α(TNF-α)and B-cell-activating factor(BAFF),which are key players in the pathogenesis of RA.Additionally,liposomal DEX can induce the expres-sion of anti-inflammatory cytokines like interleukin-10(IL-10),which has significant anti-inflammatory and immunoregulatory properties.The findings suggest that lipo-somal DEX represents a promising candidate for effective and safe RA therapy,with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.展开更多
Atopic dermatitis(AD)is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching.The colonization of Staphylococcus aureus(S.aureus)is correlated with the se...Atopic dermatitis(AD)is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching.The colonization of Staphylococcus aureus(S.aureus)is correlated with the severity of the disease,but its role in AD development remains elusive.Using single-cell RNA sequencing,we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S.aureus(MRSA).Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology.Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march.Mechanistically,IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33,which in turn aggravated type 2 immunity and AD-like skin conditions.Overall,these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.展开更多
Objective Emerging evidence suggests that exposure to ultrafine particulate matter(UPM,aerodynamic diameter<0.1μm)is associated with adverse cardiovascular events.Previous studies have found that Shenlian(SL)extra...Objective Emerging evidence suggests that exposure to ultrafine particulate matter(UPM,aerodynamic diameter<0.1μm)is associated with adverse cardiovascular events.Previous studies have found that Shenlian(SL)extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process.In this study,we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis.Methods We established a mouse model of MI+UPM.Echocardiographic measurement,measurement of myocardialinfarct size,biochemical analysis,enzyme-linked immunosorbent assay(ELISA),histopathological analysis,Transferase dUTP Nick End Labeling(TUNEL),Western blotting(WB),Polymerase Chain Reaction(PCR)and so on were used to explore the anti-inflammatory and antiapoptotic effects of SL in vivo and in vitro.Results SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction,fractional shortening,and decreasing cardiac infarction area.SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations.Moreover,SL significantly reduced expression levels of the inflammatory cytokines IL-6,TNF-α,and MCP-1.UPM further increased the infiltration of macrophages in myocardial tissue,whereas SL intervention reversed this phenomenon.UPM also triggered myocardial apoptosis,which was markedly attenuated by SL treatment.The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells.Conclusion Overall,both in vivo and in vitro experiments demonstrated that SL attenuated UPMaggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis.The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.展开更多
Most Aloe species are used as new food or functional food ingredient.Even though widely known for its health benefits,the anti-inflammatory effects and underlying mechanisms of Aloin(Alo),an anthraquinone compound iso...Most Aloe species are used as new food or functional food ingredient.Even though widely known for its health benefits,the anti-inflammatory effects and underlying mechanisms of Aloin(Alo),an anthraquinone compound isolated from plant species of the genus Aloe,remain unidentified.Here,we investigated the protective effects of Alo against cecal ligation and puncture(CLP)-induced sepsis and microflora in mice.Alo significantly improved CLP-induced sepsis and the survival rate of septic mice,downregulated the expression of proinflammatory factors,and decreased the infiltration of inflammatory cells in tissues.Alo upregulated the proportion of peritoneal macrophages,reduced the number of peritoneal bacteria,decreased the content of short-chain fatty acids and bile acids in the abdominal cavity,and suppressed Toll-like receptor(TLR)-2/4/nuclear factor kappa-B(NF-κB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)/Caspase-1/3/8 signaling.Furthermore,Alo altered the composition of the microbiome and promoted the growth of Lactobacillus,which showed a stronger anti-inflammatory effect.Whole-genome analysis identified the genes Saa3,Il10,Fpr1,and Eif4a1 associated with the protective effects of Alo in mice with CLP-induced sepsis.Overall,our results provide novel insights into the therapeutic potential and mechanism of action of Alo in the treatment of sepsis.展开更多
The recurrence of atrial fibrillation(AF)in patients after successful radiofrequency catheter ablation(RFCA)appears to be an unresolved clinical issue and needs to be clearly elucidated.There are many factors associat...The recurrence of atrial fibrillation(AF)in patients after successful radiofrequency catheter ablation(RFCA)appears to be an unresolved clinical issue and needs to be clearly elucidated.There are many factors associated with AF recurrence,such as duration of AF,male sex,concomitant heart failure,hemodynamic parameters,chronic obstructive pulmonary disease,hypertension,obstructive sleep apnea,hyperthyroidism,smoking and obesity.However,the inflammatory changes are strongly associated with electrical and structural cardiac remodeling,cardiac damage,myocardial fibrotic changes,microvascular dysfunction and altered reparative response.In this context,biomarkers reflecting the different stages of AF pathogenesis deserve thorough investigation.The authors of the retrospective study revealed that one-year recurrence rate of non-valvular AF in the high systemic immune inflammation(SII)index group was significantly increased compared to that of the low SII index group and provided additional predictive value to the APPLE.Furthermore,the authors suggest that this biomarker may help physicians to optimize the selection of AF patients and to develop a personalized treatment approach.In conclusion,the SII index may serve as a valuable indicator of recurrent AF in patients after RFCA and may be a biomarker with plausible predictive value for poor clinical outcomes.展开更多
BACKGROUND Laparoscopic surgery,with the advantage of less trauma,has been predominantly performed to treat pediatric inguinal hernia.However,the traditional three-port laparoscopic surgery remains extremely traumatic...BACKGROUND Laparoscopic surgery,with the advantage of less trauma,has been predominantly performed to treat pediatric inguinal hernia.However,the traditional three-port laparoscopic surgery remains extremely traumatic for children,whereas singleport laparoscopic surgery causes less damage to children than traditional laparoscopy.However,single-port laparoscopic surgery is more challenging;thus,studies on the effect of its application in pediatric inguinal hernia remain relatively limited.AIM To analyze the association of single-incision laparoscopic herniorrhaphy needle treatment with surgical outcomes,postoperative complications,and serum inflammation in pediatric inguinal hernia.METHODS This retrospective study included 113 pediatric patients with inguinal hernia who underwent surgery at the Children’s Hospital,Capital Institute of Pediatrics,from April 2022 to May 2023.Participants were categorized into the observation group(single-incision laparoscopic herniorrhaphy needle,n=60)and the control group(two-port laparoscopic surgery,n=53).Comparative analyses involved surgical duration,intraoperative blood loss,and length of hospital stay.C-reactive protein(CRP)and white blood cell count(WBC)levels were measured preoperatively and 24 hours postoperatively.Postoperative pain was evaluated with the face,legs,activity,cry,and Consolability scale.Further,the incidence of complications,recurrence,and reoperation rates was assessed.Logistic regression was employed to determine independent risk factors related to poor prognosis.RESULTS The observation group demonstrated significantly reduced intraoperative blood loss and shorter hospitalization compared to the control group(P<0.05).Both groups demonstrated increased CRP and WBC levels postoperatively,but the observation group exhibited significantly lower levels(P<0.05).Further,pain scores at 24 hours postoperatively were significantly lower in the observation group(P<0.05).Additionally,the observation group experienced fewer adverse events,recurrence rates,and reoperations compared to the control group(P<0.05).Logistic regression analysis determined increased postoperative stress markers and surgical technique as independent predictors of recurrence(P<0.05).CONCLUSION Single-incision laparoscopic herniorrhaphy needle treatment for pediatric inguinal hernia exhibits significant efficacy,effectively reduces postoperative complications,ensures a more concealed surgical incision,and promotes faster postoperative recovery than conventional two-port laparoscopy.This approach merits wider application.展开更多
Background:Adenoid hypertrophy(AH)is a common pediatric disease that signifi-cantly impacts the growth and quality of life of children.However,there is no replica-ble and valid model for AH.Methods:An AH rat model was...Background:Adenoid hypertrophy(AH)is a common pediatric disease that signifi-cantly impacts the growth and quality of life of children.However,there is no replica-ble and valid model for AH.Methods:An AH rat model was developed via comprehensive allergic sensitization,chronic inflammation induction,and chronic intermittent hypoxia(CIH).The modeling process involved three steps:female Sprague-Dawley rats(aged 4-5 weeks)were used for modeling.Allergen sensitization was induced via intraperitoneal administra-tion and intranasal provocation using ovalbumin(OVA);chronic nasal inflammation was induced through intranasal lipopolysaccharide(LPS)administration for sustained nasal irritation;CIH akin to obstructive sleep apnea/hypopnea syndrome was induced using an animal hypoxia chamber.Postmodel establishment,behaviors,and histologi-cal changes in nasopharynx-associated lymphoid tissue(NALT)and nasal mucosa were assessed.Arterial blood gas analysis and quantification of serum and tissue levels of(interleukin)IL-4 and IL-13,OVA-specific immunoglobulin E(sIgE),eosinophil cationic protein(ECP),tumor necrosis factor(TNF-α),IL-17,and transforming growth factor(TGF)-βwere conducted for assessment.The treatment group received a combination of mometasone furoate and montelukast sodium for a week and then was evaluated.Results:Rats exhibited notable nasal symptoms and hypoxia after modeling.Histopathological analysis revealed NALT follicle hypertrophy and nasal mucosa in-flammatory cell infiltration.Elevated IL-4,IL-13,IL-17,OVA-sIgE,ECP,and TNF-αlev-els and reduced TGF-βlevels were observed in the serum and tissue of model-group rats.After a week of treatment,the treatment group exhibited symptom and inflam-matory factor improvement.Conclusion:The model effectively simulates AH symptoms and pathological changes.But it should be further validated for genetic,immunological,and hormonal back-grounds in the currently used and other strains and species.展开更多
基金funded by FEDER/Ministerio de Ciencia,Innovación y Universidades Agencia Estatal de Investigación/Project(PID2020-119729GB-100,REF/AEI/10.13039/501100011033)(to EP)a predoctoral fellowship from the Spanish Ministry of Universities(FPU)and Amigos de la Universidad de Navarra(to NSS)“Programa MRR Investigo 2023”(to MGB and MMD)。
文摘Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.
基金supported by a grant of the M.D.-Ph.D./Medical Scientist Training Program through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(to HK)+3 种基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean government(MSITMinistry of Science and ICT)(NRF2019R1A5A2026045 and NRF-2021R1F1A1061819)a grant from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(HR21C1003)New Faculty Research Fund of Ajou University School of Medicine(to JYC)。
文摘High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.
基金funded by Portuguese funds through FCT——Funda??o para a Ciência e a Tecnologia/Ministério da Ciência,Tecnologia e Ensino Superior in the framework of the project PTDC/MEDNEU/1677/2021(to JBR)。
文摘Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune system.This exploration is particularly significant in understanding microglia,the CNS’s innate immune cells,beyond the conventional conflation of“neuroinflammation”and“microglial activation.”This conflation has clouded the true complexity of these processes,potentially stalling scientific progress and the development of new therapies.We challenge the long-standing perspectives that have oversimplified these interactions,advocating for a deeper exploration of the dynamic relationship between neuroinflammation and microglial activation.By dissecting specific molecular pathways,we aim to illuminate their elaborate roles in neuroinflammatory responses,especially in the context of Alzheimer’s disease(AD).Here,neuroinflammation is not merely a passive observer or a direct antagonist but a complex agent in the disease’s progression.This article calls for a significant paradigm shift towards an integrative,multi-omics approach to neuroimmunology.Adopting such a comprehensive framework is crucial for advancing our understanding of neuroinflammatory conditions and paving the way for targeted therapeutic strategies for brain diseases.
基金supported by NIH funding(RF1NS110637,2RF1NS094527,R01NS110635)to JW.
文摘Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.
文摘In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.
基金supported by the Christiane and Claudia Hempel Foundation for Regenerative Medicineby the James and Elisabeth Cloppenburg, Peek and Cloppenburg Düsseldorf Stiftung(to PK)。
文摘Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
基金supported by Japan Society for the Promotion of Science(JSPS)KAKENHI Grants-in-Aid for Scientific Research(JP21K09688 and JP24K12795 to XGJP22K09804 to CHJP19KK0229,JP21H02819,JP21K18279,and JP24H00583 to TH),Shiseido Female Researcher Science Grant(to XG)and the Takeda Science Foundation(to TH).
文摘Multiple sclerosis(MS),which is characterized by inflammatory demyelination in the central nervous system(CNS),is the most common neurological disease in the young adult population.Experimental autoimmune encephalomyelitis(EAE),an animal model of MS,is often used in preclinical studies.Accumulating data indicate that in addition to immune cells such as T cells and dendritic cells,CNS resident microglia and astrocytes play important roles in demyelinating neuroinflammation(Healy et al.,2022).In particular,microglia are key immune-competent cells that can respond to environmental changes.Conditional depletion of transforming growth factor-β-activated kinase 1,a mitogen-associated protein kinase kinase kinase,in microglia is reported to reduce CNS inflammation and diminish axonal and myelin damage significantly.This suggests that elucidating the mechanisms of microglia-specific responses during pathologies may help in the development of treatments that reduce EAE/MS disease severity(Goldmann et al.,2013).
基金supported by a grant from the Basic Science Research Program through the National Research Foundation(NRF),which is funded by the Korean government(MSIP)(NRF-2020M3E5D9079764)(to KS)。
文摘Neuroinflammation has been identified as a crucial element in several neurological disorders. Glial cells play a critical role in directing neuroinflammation, both in deleterious and beneficial ways.
文摘Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most severe form of sepsis which leads to distributive shock and high mortality rates.There have been significant advances in sepsis management mainly focusing on early identification and therapy.However,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick SOFA.These limitations have underscored the modest progress in reducing sepsis-related mortality.This review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.
基金supported by National Health Commission’s Capacity Building and Continuing Education Center(No.YXFSC2022JJSJ009)Beijing Municipal Administration of Hospitals’Ascent Plan(No.DFL20190203)+1 种基金Beijing Postdoctoral Research Foundation(No.2023-ZZ-027)National Key Research and Development Program of China(No.2022YFC2404005).
文摘To the Editor:Distinguishing ocular adnexal lymphoma(OAL)from idiopathic orbital inflammation(IOI)is challenging owing to their similar clinical symptoms and imaging features.Previous research has demonstrated that magnetic resonance imaging(MRI)-based radiological characteristics can offer valuable insights for distinguishing between OAL and IOI.However,the diagnostic accuracy of these imaging findings relies largely on subjective interpretation,leading to inconsistent and sometimes controversial conclusions.The integration of MRI-based radiomics with machine learning(ML)is expected to provide quantitative features in a more objective manner,thereby further establishing diagnostic models and enhancing diagnostic accuracy.
文摘Atrial fibrillation(AF)is the most common arrhythmia in humans,affecting more than 40 million people worldwide.Radiofrequency catheter ablation(RFCA)was first introduced as a treatment for AF by Haïssaguerre M in the late 1990s.This procedure quickly became the treatment of choice,especially for symptomatic patients with AF refractory to medication.However,up to 45%of patients may experience AF recurrence within 12 months after RFCA.In this setting,AF recurrence is likely multifactorial,including atrial remodeling,local fibrosis or incomplete ablation due to failure in locating the trigger.Additionally,patients with obesity,sleep apnea,hypertension,or diabetes are at an increased risk of AF recurrence after RFCA.Inflammation is increasingly recognized as a potential key factor in AF recurrence and may arise both from the healing response of heart tissue post-ablation or from chronic low-grade inflammation,as observed in many risk factors.Here,we present an original study by Wang et al,which investigated the combination of the systemic immune-inflammation index-a marker developed to assess overall inflammatory status-and the APPLE score,designed to predict AF recurrence following RFCA.The study found that using both indicators together improved the accuracy of AF recurrence prediction.These findings underscore the significant role of inflammation in cardiovascular disease and demonstrated its impact on AF recurrence after RFCA.Further research is warranted to validate the combined use of these two scores in clinical settings for predicting AF recurrence following catheter ablation.
文摘Atrial fibrillation(Afib)is a common arrhythmia with significant public health implications,affecting millions of individuals worldwide.Catheter ablation(CA)is an established treatment for drug-resistant Afib,yet recurrence remains a major concern,impacting quality of life in a significant portion of patients.Inflammation plays a critical role in the recurrence of Afib after ablation,with systemic inflammatory markers such as C-reactive protein being linked to higher recurrence rates.In this editorial,we discuss the study by Wang et al,published in the latest issue,which investigates the predictive role of the systemic immune inflammation index(SII)in Afib recurrence following radiofrequency CA.Elevated pre-ablation SII levels are identified as an independent predictor of recurrence,significantly enhancing the predictive power of the APPLE score.Integration of SII improved the APPLE score’s predictive performance,as shown by enhanced area under the curve,net reclassification improvement,and integrated discrimination improvement.This combined model highlights the importance of both structural and inflammatory factors in Afib recurrence,offering a more personalized approach to patient management.Additionally,the affordability and accessibility of SII enhance its practicality in clinical workflows.The study by Wang et al underscores the potential of integrating SII with existing scoring systems to refine risk stratification and optimize treatment strategies.Future research should validate these findings across diverse populations,explore limitations such as the potential influence of comorbidities on SII reliability,and investigate additional biomarkers to enhance predictive accuracy.
基金supported by the National Natural Science Foundation of China(82300589 to Xin Liu,82004042 to Mincong Huang,and 82370244 to Yi Wang)the Zhejiang Provincial Key Scientific Project(2021C03041 to Guang Liang,China).
文摘Inflammatory bowel disease(IBD)is a chronic inflammatory disorder of the gastrointestinal tract,which increases the incidence of colorectal cancer(CRC).In the pathophysiology of IBD,ubiquitination/deubiquitination plays a critical regulatory function.Josephin domain containing 2(JOSD2),a deubiquitinating enzyme,controls cell proliferation and carcinogenesis.However,its role in IBD remains unknown.Colitis mice model developed by dextran sodium sulfate(DSS)or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages.JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation.DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation.Mechanistically,JOSD2 binds to the C-terminal of inosine-5′-monophosphate dehydrogenase 2(IMPDH2)and preferentially cleaves K63-linked polyubiquitin chains at the K134 site,suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B(NF-κB)and inflammation in macrophages.It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane(AOM)/DSS-induced CRC,and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice.These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2,suggesting that targeting JOSD2 is a potential strategy for treating IBD.
文摘Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal anti-inflammatory drugs(NSAIDs),and corticosteroids,frequently result in unintended adverse effects.Dexamethasone(DEX)is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties.Liposomal delivery of DEX,particu-larly when liposomes are surface-modified with targeting ligands like peptides or sialic acid,can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity.This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA.Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models,reduces joint inflammation and damage,and alleviates cartilage destruction compared to free DEX.The liposomal formulation also shows better hemocompatibility,fewer adverse effects on body weight and immune organ index,and a longer circulation time with higher bioavailability.The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α(TNF-α)and B-cell-activating factor(BAFF),which are key players in the pathogenesis of RA.Additionally,liposomal DEX can induce the expres-sion of anti-inflammatory cytokines like interleukin-10(IL-10),which has significant anti-inflammatory and immunoregulatory properties.The findings suggest that lipo-somal DEX represents a promising candidate for effective and safe RA therapy,with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.
基金supported by the National Key R&D Program of China(2023YFC2306300)the National Natural Science Foundation of China(Grant Nos.32225019,92357304,and 32394003)supported by the Center for Life Sciences,the Institute for Immunology,and School of Basic Medical Sciences at Tsinghua University.
文摘Atopic dermatitis(AD)is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching.The colonization of Staphylococcus aureus(S.aureus)is correlated with the severity of the disease,but its role in AD development remains elusive.Using single-cell RNA sequencing,we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S.aureus(MRSA).Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology.Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march.Mechanistically,IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33,which in turn aggravated type 2 immunity and AD-like skin conditions.Overall,these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
基金supported by CACMS Innovation Fund(No CI2021A04611,CI2021A05106)Scientific and technological innovation project of China Academy of Chinese Medical Sciences(CI2021B015)+1 种基金Scientific and technological innovation project of China Academy of Chinese Medical Sciences(CI2023E001TS01)Fundamental research funds for the central public welfare research institutes(L2022035).
文摘Objective Emerging evidence suggests that exposure to ultrafine particulate matter(UPM,aerodynamic diameter<0.1μm)is associated with adverse cardiovascular events.Previous studies have found that Shenlian(SL)extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process.In this study,we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis.Methods We established a mouse model of MI+UPM.Echocardiographic measurement,measurement of myocardialinfarct size,biochemical analysis,enzyme-linked immunosorbent assay(ELISA),histopathological analysis,Transferase dUTP Nick End Labeling(TUNEL),Western blotting(WB),Polymerase Chain Reaction(PCR)and so on were used to explore the anti-inflammatory and antiapoptotic effects of SL in vivo and in vitro.Results SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction,fractional shortening,and decreasing cardiac infarction area.SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations.Moreover,SL significantly reduced expression levels of the inflammatory cytokines IL-6,TNF-α,and MCP-1.UPM further increased the infiltration of macrophages in myocardial tissue,whereas SL intervention reversed this phenomenon.UPM also triggered myocardial apoptosis,which was markedly attenuated by SL treatment.The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells.Conclusion Overall,both in vivo and in vitro experiments demonstrated that SL attenuated UPMaggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis.The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
基金supported by the National Natural Science Foundation of China(81803547)the Natural Science Foundation of Fujian Province,China(2021J01204)Fujian Provincial Regional Development Project(2021N3005)。
文摘Most Aloe species are used as new food or functional food ingredient.Even though widely known for its health benefits,the anti-inflammatory effects and underlying mechanisms of Aloin(Alo),an anthraquinone compound isolated from plant species of the genus Aloe,remain unidentified.Here,we investigated the protective effects of Alo against cecal ligation and puncture(CLP)-induced sepsis and microflora in mice.Alo significantly improved CLP-induced sepsis and the survival rate of septic mice,downregulated the expression of proinflammatory factors,and decreased the infiltration of inflammatory cells in tissues.Alo upregulated the proportion of peritoneal macrophages,reduced the number of peritoneal bacteria,decreased the content of short-chain fatty acids and bile acids in the abdominal cavity,and suppressed Toll-like receptor(TLR)-2/4/nuclear factor kappa-B(NF-κB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)/Caspase-1/3/8 signaling.Furthermore,Alo altered the composition of the microbiome and promoted the growth of Lactobacillus,which showed a stronger anti-inflammatory effect.Whole-genome analysis identified the genes Saa3,Il10,Fpr1,and Eif4a1 associated with the protective effects of Alo in mice with CLP-induced sepsis.Overall,our results provide novel insights into the therapeutic potential and mechanism of action of Alo in the treatment of sepsis.
文摘The recurrence of atrial fibrillation(AF)in patients after successful radiofrequency catheter ablation(RFCA)appears to be an unresolved clinical issue and needs to be clearly elucidated.There are many factors associated with AF recurrence,such as duration of AF,male sex,concomitant heart failure,hemodynamic parameters,chronic obstructive pulmonary disease,hypertension,obstructive sleep apnea,hyperthyroidism,smoking and obesity.However,the inflammatory changes are strongly associated with electrical and structural cardiac remodeling,cardiac damage,myocardial fibrotic changes,microvascular dysfunction and altered reparative response.In this context,biomarkers reflecting the different stages of AF pathogenesis deserve thorough investigation.The authors of the retrospective study revealed that one-year recurrence rate of non-valvular AF in the high systemic immune inflammation(SII)index group was significantly increased compared to that of the low SII index group and provided additional predictive value to the APPLE.Furthermore,the authors suggest that this biomarker may help physicians to optimize the selection of AF patients and to develop a personalized treatment approach.In conclusion,the SII index may serve as a valuable indicator of recurrent AF in patients after RFCA and may be a biomarker with plausible predictive value for poor clinical outcomes.
基金Supported by Research Unit of Minimally Invasive Pediatric Surgery on Diagnosis and Treatment,Chinese Academy of Medical Sciences,No.2021RU016.
文摘BACKGROUND Laparoscopic surgery,with the advantage of less trauma,has been predominantly performed to treat pediatric inguinal hernia.However,the traditional three-port laparoscopic surgery remains extremely traumatic for children,whereas singleport laparoscopic surgery causes less damage to children than traditional laparoscopy.However,single-port laparoscopic surgery is more challenging;thus,studies on the effect of its application in pediatric inguinal hernia remain relatively limited.AIM To analyze the association of single-incision laparoscopic herniorrhaphy needle treatment with surgical outcomes,postoperative complications,and serum inflammation in pediatric inguinal hernia.METHODS This retrospective study included 113 pediatric patients with inguinal hernia who underwent surgery at the Children’s Hospital,Capital Institute of Pediatrics,from April 2022 to May 2023.Participants were categorized into the observation group(single-incision laparoscopic herniorrhaphy needle,n=60)and the control group(two-port laparoscopic surgery,n=53).Comparative analyses involved surgical duration,intraoperative blood loss,and length of hospital stay.C-reactive protein(CRP)and white blood cell count(WBC)levels were measured preoperatively and 24 hours postoperatively.Postoperative pain was evaluated with the face,legs,activity,cry,and Consolability scale.Further,the incidence of complications,recurrence,and reoperation rates was assessed.Logistic regression was employed to determine independent risk factors related to poor prognosis.RESULTS The observation group demonstrated significantly reduced intraoperative blood loss and shorter hospitalization compared to the control group(P<0.05).Both groups demonstrated increased CRP and WBC levels postoperatively,but the observation group exhibited significantly lower levels(P<0.05).Further,pain scores at 24 hours postoperatively were significantly lower in the observation group(P<0.05).Additionally,the observation group experienced fewer adverse events,recurrence rates,and reoperations compared to the control group(P<0.05).Logistic regression analysis determined increased postoperative stress markers and surgical technique as independent predictors of recurrence(P<0.05).CONCLUSION Single-incision laparoscopic herniorrhaphy needle treatment for pediatric inguinal hernia exhibits significant efficacy,effectively reduces postoperative complications,ensures a more concealed surgical incision,and promotes faster postoperative recovery than conventional two-port laparoscopy.This approach merits wider application.
基金This work was financially supported by the National Natural Science Foundation of China(grant number:8217150152)the Clinical Science and Technology Innovation Project of Shanghai Shenkang Hospital Development Center(grant number:SHDC12021102)the Shanghai Three-Year Action Plan to Further Accelerate the Development of Traditional Chinese Medicine Inheritance and Innovation(grant number:ZY(2021-2023)-0209-05).
文摘Background:Adenoid hypertrophy(AH)is a common pediatric disease that signifi-cantly impacts the growth and quality of life of children.However,there is no replica-ble and valid model for AH.Methods:An AH rat model was developed via comprehensive allergic sensitization,chronic inflammation induction,and chronic intermittent hypoxia(CIH).The modeling process involved three steps:female Sprague-Dawley rats(aged 4-5 weeks)were used for modeling.Allergen sensitization was induced via intraperitoneal administra-tion and intranasal provocation using ovalbumin(OVA);chronic nasal inflammation was induced through intranasal lipopolysaccharide(LPS)administration for sustained nasal irritation;CIH akin to obstructive sleep apnea/hypopnea syndrome was induced using an animal hypoxia chamber.Postmodel establishment,behaviors,and histologi-cal changes in nasopharynx-associated lymphoid tissue(NALT)and nasal mucosa were assessed.Arterial blood gas analysis and quantification of serum and tissue levels of(interleukin)IL-4 and IL-13,OVA-specific immunoglobulin E(sIgE),eosinophil cationic protein(ECP),tumor necrosis factor(TNF-α),IL-17,and transforming growth factor(TGF)-βwere conducted for assessment.The treatment group received a combination of mometasone furoate and montelukast sodium for a week and then was evaluated.Results:Rats exhibited notable nasal symptoms and hypoxia after modeling.Histopathological analysis revealed NALT follicle hypertrophy and nasal mucosa in-flammatory cell infiltration.Elevated IL-4,IL-13,IL-17,OVA-sIgE,ECP,and TNF-αlev-els and reduced TGF-βlevels were observed in the serum and tissue of model-group rats.After a week of treatment,the treatment group exhibited symptom and inflam-matory factor improvement.Conclusion:The model effectively simulates AH symptoms and pathological changes.But it should be further validated for genetic,immunological,and hormonal back-grounds in the currently used and other strains and species.
