Background:The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.Methods:We analyzed the DNA of an index patient with early-onset systemic inflammation,cuta...Background:The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.Methods:We analyzed the DNA of an index patient with early-onset systemic inflammation,cutaneous vasculopathy,and pulmonary inflammation.We sequenced a candidate gene,TMEM173,encoding the stimulator of interferon genes(STING),in this patient and in five unrelated children with similar clinical phenotypes.Four children were evaluated clinically and immunologically.With the STING ligand cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),we stimulated peripheral-blood mononuclear cells and fibroblasts from patients and controls,as well as commercially obtained endothelial cells,and then assayed transcription of IFNB1,the gene encoding interferon-β,in the stimulated cells.We analyzed IFNB1 reporter levels in HEK293T cells cotransfected with mutant or nonmutant STING constructs.Mutant STING leads to increased phosphorylation of signal transducer and activator of transcription 1(STAT1),so we tested the effect of Janus kinase(JAK)inhibitors on STAT1 phosphorylation in lymphocytes from the affected children and controls.展开更多
Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genoty...Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.展开更多
Background:The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.Methods:We analyzed the DNA of an index patient with early-onset systemic inflammation,cuta...Background:The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.Methods:We analyzed the DNA of an index patient with early-onset systemic inflammation,cutaneous vasculopathy,and pulmonary inflammation.We sequenced a candidate gene,TMEM173,encoding the stimulator of interferon genes(STING),in this patient and in five unrelated children with similar clinical phenotypes.展开更多
Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever...Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever using interferon type I(IFN-I)or combined IFN-I/II receptor knockout mice infected with dengue virus(DENV).However,this model requires further optimization to better support related studies.Methods:This study aimed to establish a stable dengue infection model by evaluating the effects of different genetic backgrounds and injection routes on DENV infection in interferon receptor knockout mice.We first infected various strains of interferon receptor-deficient mice with DENV and compared their susceptibility based on clini-cal symptoms,viremia levels,organ indices,histopathological findings,and vascular leakage markers.Subsequently,we selected the most susceptible strain to further investigate the impact of different injection methods on infection outcomes.Results:We found that BALB/c background mice with type 1 interferon recep-tor knockout(IFNAR)had the most obvious symptoms.Subsequently,we selected IFNAR−/−BALB/c mice to further explore the effects of different injection methods on dengue virus infection.The results showed that the intraperitoneal injection group had the most severe clinical symptoms,the longest duration of viremia,and the most obvious degree of organ damage.Conclusion:Through systematic screening and optimization,we established a robust animal model of dengue virus infection via intraperitoneal injection in IFNAR−/−BALB/c mice.This model offers a valuable tool for future dengue research.展开更多
Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of a...Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of all the autoimmune rheumatic diseases,SSc has the highest all-cause mortality rate,and the underlying pathogenic processes that mediate disease are still obscure,with wide diff erences in presentation and progression[2,3].展开更多
Interferon regulatory factor 1 is involved in many autoimmune conditions and is increased in patients with myasthenia gravis.However,its function in myasthenia gravis remains unclear.Herein,we explored the function of...Interferon regulatory factor 1 is involved in many autoimmune conditions and is increased in patients with myasthenia gravis.However,its function in myasthenia gravis remains unclear.Herein,we explored the function of interferon regulatory factor 1 in myasthenia gravis,with an aim to understand the underlying mechanisms.Patients with myasthenia gravis who had acetylcholine receptor antibodies were included in the study.Peripheral blood lymphocytes were extracted from the included patients,and B lymphocyte subsets were isolated.Next,T and B cells from peripheral blood were co-cultured to explore the interferon regulatory factor 1-related mechanisms in myasthenia gravis.Chromatin immunoprecipitation experiments confirmed an interaction between interferon regulatory factor 1 and the CD180 promoter region.Dual-luciferase reporter gene confirmed the transcriptional activity of interferon regulatory factor 1 on CD180 promoter.In vitro results further indicated that interferon regulatory factor 1 promoted B cell activation and T cell differentiation via the inhibition of CD180.Interferon regulatory factor 1 recruited histone deacetylase 1 to inhibit CD180 transcription.Additionally,histone deacetylase 1 promoted B cell activation and T cell differentiation.Finally,in vitro experiments demonstrated that CD180 inhibited B cell activation and T cell differentiation by inhibiting the Toll-like receptor 4/mitogen-activated protein kinases/nuclear factor-kappa B pathway.Collectively,our results suggest that interferon regulatory factor 1 enhances T cell differentiation by recruiting histone deacetylase 1 to block B cell CD180 transcription in myasthenia gravis via the Toll-like receptor 4/mitogen-activated protein kinases/nuclear factor-kappa B pathway.Together,these findings indicate the important role of interferon regulatory factor 1 in myasthenia gravis and suggest its molecular mechanisms.They also provide new ideas and targets for diagnosing and treating myasthenia gravis,which will be both scientifically and clinically valuable.展开更多
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
Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway has emerged as a key mediator of neuroinflammation.While current studies primarily attribute its effects to neurons and glial ce...The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway has emerged as a key mediator of neuroinflammation.While current studies primarily attribute its effects to neurons and glial cells,emerging research suggests that cGAS-STING signaling may play a critical role in cerebral vasculature,particularly in brain endothelial cells.Therefore,studying the role 7of inflammation caused by the cGAS-STING pathway in brain endothelial cells could provide a more comprehensive understanding of neuroinflammatory disease and new avenues for therapeutic interventions.Here,we review the multifaceted role of global cGAS-STING signaling in various neurological and neuroinflammatory diseases and the potential contribution of cGAS-STING in brain endothelial cells.展开更多
Background:Colorectal cancer(CRC)holds the third position in global cancer prevalence mortality.Although chemotherapy is a conventional treatment,recent investigations have shed light on the therapeutic potential of t...Background:Colorectal cancer(CRC)holds the third position in global cancer prevalence mortality.Although chemotherapy is a conventional treatment,recent investigations have shed light on the therapeutic potential of the cGAS cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)pathway in CRC management.Despite the primary role of the death domain-associated protein(Daxx)in cellular apoptosis,its influence on the regulation of cGAS-STING activation remains elusive.Methods:The Daxx degradation and speck formation were conducted using immunofluorescence and Western blotting.The Daxx knock-down and over-expression in CRC cells were performed to detect in vivo and in vitro migration,proliferation,cGAS-STING activation,and immune responses.Results:Our study reveals that treatment with irinotecan(CPT-11)and oxaliplatin(OXA)significantly accelerated the Daxx degradation and diminished the formation of Daxx specks within the nucleus of CRC cells.Genetic elimination of Daxx enhanced the irinotecan and oxaliplatin-induced suppression of proliferation and migration in CRC cells,and overexpression of Daxx resulted in similar results.Mechanistically,Daxx overexpression reduced DNA damage repair by restraining homologous recombination(HR)over non-homologous end-joining(NHEJ),which suppressed TBK1 and IRF3 phosphorylation downstream of the cGAS-STING signal.In a murine model of CT-26 tumors,Daxx knockdown amplified the OXA-mediated tumor growth inhibition by promoting STING activation and immune responses.Conclusions:Our findings show that the degradation of nuclear Daxx potentiates the cGAS-STING pathway,thereby bolstering the efficacy of chemotherapy.展开更多
Humans and other vertebrates are safeguarded from invading pathogenic microbes by the immune system.Black seed,scientifically known as Nigella sativa,has garnered attention for its potential immunomodulatory effects i...Humans and other vertebrates are safeguarded from invading pathogenic microbes by the immune system.Black seed,scientifically known as Nigella sativa,has garnered attention for its potential immunomodulatory effects in both clinical and preclinical studies.This comprehensive review aims to consolidate and analyze the existing body of evidence surrounding the immunological impact of black seeds.In this review,we analyze the immunomodulatory potentials of black seeds(N.sativa).For the purpose of finding pertinent publications,the literatures was searched in web-based databases,including Web of Science,Medline/PMC/PubMed,Embase,EBSCO,Google Scholar,Science Direct,and reference lists.Several clinical,in vivo,and in vitro studies have demonstrated that supplementation with black seeds(N.sativa)has potential immunomodulatory activity.Black seeds(N.sativa)may influence immune responses through a variety of mechanisms.By synthesizing and critically assessing the current state of knowledge on the immunomodulatory effects of black seeds,this review aims to provide valuable insights into the potential therapeutic uses and future research directions for harnessing the immunological benefits of this natural remedy.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)ranks as the fourth leading cause of cancerrelated deaths in China,and the treatment options are limited.The cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS...BACKGROUND Hepatocellular carcinoma(HCC)ranks as the fourth leading cause of cancerrelated deaths in China,and the treatment options are limited.The cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)activates the stimulator of interferon gene(STING)signaling pathway as a crucial immune response pathway in the cytoplasm,which detects cytoplasmic DNA to regulate innate and adaptive immune responses.As a potential therapeutic target,cGASSTING pathway markedly inhibits tumor cell proliferation and metastasis,with its activation being particularly relevant in HCC.However,prolonged pathway activation may lead to an immunosuppressive tumor microenvironment,which fostering the invasion or metastasis of liver tumor cells.AIM To investigate the dual-regulation mechanism of cGAS-STING in HCC.METHODS This review was conducted according to the PRISMA guidelines.The study conducted a comprehensive search for articles related to HCC on PubMed and Web of Science databases.Through rigorous screening and meticulous analysis of the retrieved literature,the research aimed to summarize and elucidate the impact of the cGAS-STING pathway on HCC tumors.RESULTS All authors collaboratively selected studies for inclusion,extracted data,and the initial search of online databases yielded 1445 studies.After removing duplicates,remaining 964 records were screened.Ultimately,55 articles met the inclusion criteria and were included in this review.CONCLUSION Acute inflammation can have a few inhibitory effects on cancer,while chronic inflammation generally promotes its progression.Extended cGAS-STING pathway activation will result in a suppressive tumor microenvironment.展开更多
Ring finger protein 122(RNF122),an E3 ubiquitin ligase,orchestrates antiviral immune responses in mammals by targeting retinoic acid-inducible gene 1 and melanoma differentiation-associated gene 5 for ubiquitination.H...Ring finger protein 122(RNF122),an E3 ubiquitin ligase,orchestrates antiviral immune responses in mammals by targeting retinoic acid-inducible gene 1 and melanoma differentiation-associated gene 5 for ubiquitination.However,its functional relevance in teleosts has yet to be clearly defined,particularly regarding the identification of substrate-specific regulatory sites.This study characterized RNF122 from mandarin fish(Siniperca chuatsi),termed scRNF122,and investigated its regulatory impact on stimulator of interferon genes(STING)-mediated antiviral signaling.Results showed that scRNF122 expression was up-regulated in response to mandarin fish ranavirus(MRV)infection,and its overexpression suppressed scSTING-mediated interferon(IFN)production and enhanced MRV replication.Co-immunoprecipitation confirmed a direct interaction between scRNF122 and scSTING.Functional assays demonstrated that scRNF122 facilitated scSTING degradation through the ubiquitin-proteasome pathway,a process impeded by MG132 treatment.Ubiquitination analyses of various scSTING mutants revealed that scRNF122 catalyzed scSTING ubiquitination at K95,K117,and K155 residues.Moreover,scRNF122 significantly impaired scSTING-dependent antiviral responses by engaging negative regulatory elements within the signaling cascade.Overall,scRNF122 was identified as a negative modulator of STING-mediated IFN signaling in mandarin fish,diminishing STING-dependent antiviral activity and promoting its degradation via the ubiquitin-proteasome pathway at lysine residues K95,K117,and K155.These findings provide mechanistic insight into the post-translational control of STING in teleosts and establish a foundation for future investigations into antiviral immune regulation.展开更多
Chronic hepatitis delta virus(HDV)represents a rare but important co-infection in approximately 5%of patients with chronic hepatitis B virus(HBV)infection,and is associated with significant morbidity and mortality due...Chronic hepatitis delta virus(HDV)represents a rare but important co-infection in approximately 5%of patients with chronic hepatitis B virus(HBV)infection,and is associated with significant morbidity and mortality due to an increased risk for liver cirrhosis,liver failure,and hepatocellular carcinoma relative to HBV monoinfected individuals.The current treatment of chronic HDV infection includes the off-label use of pegylated interferon(IFN),which is limited by poor safety,tolerability,and efficacy.Guidelines of the major international liver organizations such as the American Association for the Study of Liver Diseases,European Association for the Study of the Liver,and Asian Pacific Association for the Study of the Liver provide recommendations for contemporary diagnosis and management of chronic HDV infection,including the incorporation of bulevirtide,a newly licensed antiviral agent in Europe.Significant unmet medical needs remain in the treatment of HDV,and recent advances in drug development offer hope for meaningful advances in drug therapy which may improve virologic response rates and clinical outcomes.This review summarizes trial design and available efficacy data from key phase 2 and 3 trials for investigational therapies including entry inhibitors(bulevirtide),prenylation inhibitors(lonafarnib),novel IFNs(peginterferon lambda),RNA interference molecules(JNJ-3989,elebsiran),monoclonal antibodies(tobevibart),and nucleic acid polymers(REP2139),and addresses future directions in HDV pharmacotherapy.展开更多
The canonical signaling of interferon gamma(IFN-γ)through the Janus kinase 1 and 2–signal transducer and activator of transcription 1(STAT1)axis leads to the expression of several interferon-stimulated genes(ISGs),w...The canonical signaling of interferon gamma(IFN-γ)through the Janus kinase 1 and 2–signal transducer and activator of transcription 1(STAT1)axis leads to the expression of several interferon-stimulated genes(ISGs),which have diverse effects depending on the cellular context.In glioblastoma,a highly aggressive primary brain tumor in adults,elements of IFN-γcanonical signaling are deregulated,resulting in the overexpression of STAT1-target ISGs associated with tumor progression.This mini-review highlights key ISGs,including STAT1,interferon regulatory factor 1,programmed death-ligand 1,indoleamine 2,3-dioxygenase 1,and interferon-stimulated gene 15,involved in the pathology of glioblastoma.These genes may serve as valuable biomarkers and have therapeutic potential for targeting IFN-γsignaling in this malignancy.展开更多
Current treatment options for hepatitis D are limited,with pegylated interferonalpha(PEG-IFNα)being the only therapy available in the Asia-Pacific region.However,PEG-IFNαhas limited efficacy and significant side eff...Current treatment options for hepatitis D are limited,with pegylated interferonalpha(PEG-IFNα)being the only therapy available in the Asia-Pacific region.However,PEG-IFNαhas limited efficacy and significant side effects.Pegylated interferon lambda acts on interferon-lambda(Type III)receptors predominantly expressed in hepatocytes.In 2023,bulevirtide was approved in the European Union and Russia for treating chronic hepatitis D.This drug works by binding to and inhibiting the sodium taurocholate co-transporting polypeptide receptor on liver cells,which is the primary entry point for the virus.Recently,several new drugs have entered various stages of development,offering hope for improved hepatitis D virus(HDV)management.Two more viral entry inhibitors are HH003 and tobevibart.Other agents include nucleic acid polymers(REP 2139-Mg),prenylation inhibitors(lonafarnib),and RNA interference-based therapies(elebsiran).Emerging trials are now considering combination therapies,such as SOLSTICE,a Phase 2 clinical trial evaluating tobevibart alone or combined with elebsiran.The combination dosed monthly achieved>50%virologic and biochemical response at 24 weeks of therapy.The efficacy and safety of these drugs will further be evaluated in ECLIPSE 1,2,and 3 trials.With these new treatments on the horizon,the prospects for improved HDV patient outcomes are promising.展开更多
To investigate the risk and influencing factors of long-term liver adverse events in chronic hepatitis B patients achieving hepatitis B surface antigen(HBsAg)clearance after pegylated interferonα(Peg-IFNα)treatment,...To investigate the risk and influencing factors of long-term liver adverse events in chronic hepatitis B patients achieving hepatitis B surface antigen(HBsAg)clearance after pegylated interferonα(Peg-IFNα)treatment,a retrospective analysis was conducted on 456 patients at Beijing Ditan Hospital from 2008 to 2023 who achieved HBsAg clearance and discontinued Peg-IFNαtreatment.The baseline was defined as the time of HBsAg clearance and treatment cessation.The endpoint was the first occurrence of liver adverse events(hepatocellular carcinoma or ascites)or last follow-up.Subsequently,we evaluated the incidence and risk factors of liver adverse events,along with changes in liver fibrosis,cirrhosis,and liver function indicators.During a median follow-up of 70 months,the incidence of liver adverse events was 2.30%,hepatocellular carcinoma 1.76%,and ascites 0.55%.Older age and cirrhosis were significant risk factors(HR 1.075 and 41.393,both P<0.01).The APRI score significantly improved at follow-up compared to baseline(0.53 vs.0.25,P<0.001),and cirrhosis prevalence decreased from 5.70%to 0.88%(P<0.001).In conclusion,patients who achieved HBsAg clearance and discontinued Peg-IFNαtreatment have a low risk of liver adverse events,while advanced age and cirrhosis remain major risk factors.展开更多
Peyronie’s disease(PD)presents a multifaceted challenge in contemporary urological practice,marked by penile deformity,pain,and the potential for erectile dysfunction.We meticulously explored the existing literature ...Peyronie’s disease(PD)presents a multifaceted challenge in contemporary urological practice,marked by penile deformity,pain,and the potential for erectile dysfunction.We meticulously explored the existing literature of intralesional/topical interventions,aiming to provide clinicians with a nuanced understanding of available options for comprehensive PD management.To conduct this review,we performed a systematic search using the PubMed,Scopus,and ScienceDirect databases,including the keywords of combination of the“Peyronie’s disease/plastic induration of the penis(PIP)and intralesional/topical treatments”.The study selection was based on adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,resulting in the inclusion of 16 articles.We delve into the effectiveness and safety profiles of collagenase Clostridium histolyticum(CCH),interferon,platelet-rich plasma(PRP),hyaluronic acid,botulinum toxin,stem cell,extracorporeal shock wave therapy(ESWT),and traction therapy,assessing their impact on penile curvature,length improvement,and patient-reported symptoms and outcomes.The best options evaluated are intralesional injections of CCH and penile traction devices,alone or in combination.Despite PD remains a challenge for urologists,the objective of this review is to contribute to the evolving landscape of PD management,fostering informed decision-making,and personalized care for individuals grappling with this challenging condition.展开更多
OBJECTIVE:To examine the effects of the Jianpi Yifei Tongluo recipe(健脾益肺通络方剂,JYTR)on chronic obstructive pulmonary disease(COPD)within an animal model and to elucidate its anti-inflammatory mechanisms.METHODS:...OBJECTIVE:To examine the effects of the Jianpi Yifei Tongluo recipe(健脾益肺通络方剂,JYTR)on chronic obstructive pulmonary disease(COPD)within an animal model and to elucidate its anti-inflammatory mechanisms.METHODS:In this study,we utilized cigarette smoke(CS)exposure and lipopolysaccharide(LPS)-induced models of COPD in rats to evaluate the effects of the JYTR on airway inflammation.Sprague-Dawley rats were randomly assigned to various groups:control,model,budesonide,synbiotics,and low,medium,and high JYTR.Pulmonary function was gauged using an animal volumetric tracer.Pathological alterations in lung tissue were examined under a light microscope.To ascertain cytokine production,we conducted enzyme-linked immunosorbent assay tests,and we employed Western blotting to measure the expression levels of interferon regulatory factor 4(IRF4),arginase 1(Arg1),inducible nitric oxide synthase(iNOS),nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor,alpha(IKB-α),and P65.RESULTS:Compared to the control group,rats in the COPD model group exhibited significantly compromised pulmonary function and severe inflammatory pathology in the lungs.Treatment with budesonide,synbiotics,and the JYTR markedly improved pulmonary function and diminished the production of inflammatory cytokines transforming growth factor-beta(TGF-β),tumor necrosis factor-alpha(TNF-α),and interleukin-6(IL-6).These improvements were particularly notable in the budesonide group and the high-dose JYTR group.Additionally,the JYTR increased the expression of IRF4 and upregulated the protein expression of Arg1,while concurrently downregulating the protein expression of iNOS,phosphorylated IKB-α,and phosphorylated P65.CONCLUSION:Our current study reveals that JYTR can mitigate inflammatory lung injury,enhance lung function,and lower levels of inflammatory cytokines induced by CS or LPS exposure in COPD model rats.The mechanism behind its anti-inflammatory effect likely involves the regulation of IRF4 expression and M2 polarization through the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway.展开更多
Topical chemotherapy is increasingly used to treat ocular surface tumors as a primary therapy and an adjuvant treatment after surgical excision.The most employed topical agents include mitomycin C(MMC),5-fluorouracil(...Topical chemotherapy is increasingly used to treat ocular surface tumors as a primary therapy and an adjuvant treatment after surgical excision.The most employed topical agents include mitomycin C(MMC),5-fluorouracil(5-FU),and interferon alpha-2b(IFNα2b),each with distinctmechanisms of action,efficacy profiles,and toxicity risks.Although these agents offer effective tumor control and allow for a non-invasive approach in many cases,ocular surface complications requiring medical or surgical management can occur.This summarizes the adverse effect and outilines practical strategies for their prevention and treatment.MMC is the most potent agent but also the most toxic,with reported complications such as limbal stemcell deficiency,punctal stenosis,and persistent epithelial defects.5-FU demonstrates a more favorable safety profile,although rare cases of corneal ulceration have been described.IFNα2b is well tolerated and associated primarily with mild,reversible reactions.The choice of the proper agent should be tailored according to patient’s clinical presentation,ocular surface status,and ability to adhere to therapy and followup.Timely recognition and management of complications are essential to minimize long-term sequelae.Reliance on compounded formulations highlights the need for stable,standardized,and commercially available topical agents specifically designed for ocular use to ensure safety,reproducibility,and global accessibility.展开更多
文摘Background:The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.Methods:We analyzed the DNA of an index patient with early-onset systemic inflammation,cutaneous vasculopathy,and pulmonary inflammation.We sequenced a candidate gene,TMEM173,encoding the stimulator of interferon genes(STING),in this patient and in five unrelated children with similar clinical phenotypes.Four children were evaluated clinically and immunologically.With the STING ligand cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),we stimulated peripheral-blood mononuclear cells and fibroblasts from patients and controls,as well as commercially obtained endothelial cells,and then assayed transcription of IFNB1,the gene encoding interferon-β,in the stimulated cells.We analyzed IFNB1 reporter levels in HEK293T cells cotransfected with mutant or nonmutant STING constructs.Mutant STING leads to increased phosphorylation of signal transducer and activator of transcription 1(STAT1),so we tested the effect of Janus kinase(JAK)inhibitors on STAT1 phosphorylation in lymphocytes from the affected children and controls.
基金supported by the National Natural Science Foundation of China(Grant No.82220108002 to F.C.and Grant No.82273737 to R.Z.)the U.S.National Institutes of Health(Grant Nos.CA209414,HL060710,and ES000002 to D.C.C.,Grant Nos.CA209414 and CA249096 to Y.L.)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)supported by the Qing Lan Project of the Higher Education Institutions of Jiangsu Province and the Outstanding Young Level Academic Leadership Training Program of Nanjing Medical University.
文摘Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.
文摘Background:The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.Methods:We analyzed the DNA of an index patient with early-onset systemic inflammation,cutaneous vasculopathy,and pulmonary inflammation.We sequenced a candidate gene,TMEM173,encoding the stimulator of interferon genes(STING),in this patient and in five unrelated children with similar clinical phenotypes.
基金Guangdong Province Medical Research Fund Project,Grant/Award Number:B2024112The Scientific Research Special Project of the Joint Construction Project of High-level Hospitals between Guangzhou University of Chinese Medicine and the Scientific Research Fund Project,Grant/Award Number:GZYZS2024G09+2 种基金Special Project of the Research Platform of Guangdong Provincial Department of Traditional Chinese Medicine,Grant/Award Number:20254040the Project of the Incubation Program for the Science and Technology Development of Chinese Medicine Guangdong Laboratory/Hengqin Laboratory,Grant/Award Number:HQL2024PZ043Guangdong Province Natural Science Foundation-Guangzhou-South China Joint Youth Fund Project,Grant/Award Number:2023A1515110849。
文摘Background:In recent decades,the global incidence of dengue fever has been stead-ily increasing,with continuous geographical expansion.Researchers have successfully modeled most clinical symptoms of human dengue fever using interferon type I(IFN-I)or combined IFN-I/II receptor knockout mice infected with dengue virus(DENV).However,this model requires further optimization to better support related studies.Methods:This study aimed to establish a stable dengue infection model by evaluating the effects of different genetic backgrounds and injection routes on DENV infection in interferon receptor knockout mice.We first infected various strains of interferon receptor-deficient mice with DENV and compared their susceptibility based on clini-cal symptoms,viremia levels,organ indices,histopathological findings,and vascular leakage markers.Subsequently,we selected the most susceptible strain to further investigate the impact of different injection methods on infection outcomes.Results:We found that BALB/c background mice with type 1 interferon recep-tor knockout(IFNAR)had the most obvious symptoms.Subsequently,we selected IFNAR−/−BALB/c mice to further explore the effects of different injection methods on dengue virus infection.The results showed that the intraperitoneal injection group had the most severe clinical symptoms,the longest duration of viremia,and the most obvious degree of organ damage.Conclusion:Through systematic screening and optimization,we established a robust animal model of dengue virus infection via intraperitoneal injection in IFNAR−/−BALB/c mice.This model offers a valuable tool for future dengue research.
文摘Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of all the autoimmune rheumatic diseases,SSc has the highest all-cause mortality rate,and the underlying pathogenic processes that mediate disease are still obscure,with wide diff erences in presentation and progression[2,3].
基金National Natural Science Foundation of China,No.82271440Jiangxi Provincial Health Technology Project,No.202510009(both to LX).
文摘Interferon regulatory factor 1 is involved in many autoimmune conditions and is increased in patients with myasthenia gravis.However,its function in myasthenia gravis remains unclear.Herein,we explored the function of interferon regulatory factor 1 in myasthenia gravis,with an aim to understand the underlying mechanisms.Patients with myasthenia gravis who had acetylcholine receptor antibodies were included in the study.Peripheral blood lymphocytes were extracted from the included patients,and B lymphocyte subsets were isolated.Next,T and B cells from peripheral blood were co-cultured to explore the interferon regulatory factor 1-related mechanisms in myasthenia gravis.Chromatin immunoprecipitation experiments confirmed an interaction between interferon regulatory factor 1 and the CD180 promoter region.Dual-luciferase reporter gene confirmed the transcriptional activity of interferon regulatory factor 1 on CD180 promoter.In vitro results further indicated that interferon regulatory factor 1 promoted B cell activation and T cell differentiation via the inhibition of CD180.Interferon regulatory factor 1 recruited histone deacetylase 1 to inhibit CD180 transcription.Additionally,histone deacetylase 1 promoted B cell activation and T cell differentiation.Finally,in vitro experiments demonstrated that CD180 inhibited B cell activation and T cell differentiation by inhibiting the Toll-like receptor 4/mitogen-activated protein kinases/nuclear factor-kappa B pathway.Collectively,our results suggest that interferon regulatory factor 1 enhances T cell differentiation by recruiting histone deacetylase 1 to block B cell CD180 transcription in myasthenia gravis via the Toll-like receptor 4/mitogen-activated protein kinases/nuclear factor-kappa B pathway.Together,these findings indicate the important role of interferon regulatory factor 1 in myasthenia gravis and suggest its molecular mechanisms.They also provide new ideas and targets for diagnosing and treating myasthenia gravis,which will be both scientifically and clinically valuable.
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 the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
基金partially supported by a grant(RF1AG059694)from the U.S.National Institutes of Healthby Polytrauma System of Care,VAPAHCS(to JL)。
文摘The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway has emerged as a key mediator of neuroinflammation.While current studies primarily attribute its effects to neurons and glial cells,emerging research suggests that cGAS-STING signaling may play a critical role in cerebral vasculature,particularly in brain endothelial cells.Therefore,studying the role 7of inflammation caused by the cGAS-STING pathway in brain endothelial cells could provide a more comprehensive understanding of neuroinflammatory disease and new avenues for therapeutic interventions.Here,we review the multifaceted role of global cGAS-STING signaling in various neurological and neuroinflammatory diseases and the potential contribution of cGAS-STING in brain endothelial cells.
基金supported by the National Natural Science Foundation of China(82202956)。
文摘Background:Colorectal cancer(CRC)holds the third position in global cancer prevalence mortality.Although chemotherapy is a conventional treatment,recent investigations have shed light on the therapeutic potential of the cGAS cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)pathway in CRC management.Despite the primary role of the death domain-associated protein(Daxx)in cellular apoptosis,its influence on the regulation of cGAS-STING activation remains elusive.Methods:The Daxx degradation and speck formation were conducted using immunofluorescence and Western blotting.The Daxx knock-down and over-expression in CRC cells were performed to detect in vivo and in vitro migration,proliferation,cGAS-STING activation,and immune responses.Results:Our study reveals that treatment with irinotecan(CPT-11)and oxaliplatin(OXA)significantly accelerated the Daxx degradation and diminished the formation of Daxx specks within the nucleus of CRC cells.Genetic elimination of Daxx enhanced the irinotecan and oxaliplatin-induced suppression of proliferation and migration in CRC cells,and overexpression of Daxx resulted in similar results.Mechanistically,Daxx overexpression reduced DNA damage repair by restraining homologous recombination(HR)over non-homologous end-joining(NHEJ),which suppressed TBK1 and IRF3 phosphorylation downstream of the cGAS-STING signal.In a murine model of CT-26 tumors,Daxx knockdown amplified the OXA-mediated tumor growth inhibition by promoting STING activation and immune responses.Conclusions:Our findings show that the degradation of nuclear Daxx potentiates the cGAS-STING pathway,thereby bolstering the efficacy of chemotherapy.
文摘Humans and other vertebrates are safeguarded from invading pathogenic microbes by the immune system.Black seed,scientifically known as Nigella sativa,has garnered attention for its potential immunomodulatory effects in both clinical and preclinical studies.This comprehensive review aims to consolidate and analyze the existing body of evidence surrounding the immunological impact of black seeds.In this review,we analyze the immunomodulatory potentials of black seeds(N.sativa).For the purpose of finding pertinent publications,the literatures was searched in web-based databases,including Web of Science,Medline/PMC/PubMed,Embase,EBSCO,Google Scholar,Science Direct,and reference lists.Several clinical,in vivo,and in vitro studies have demonstrated that supplementation with black seeds(N.sativa)has potential immunomodulatory activity.Black seeds(N.sativa)may influence immune responses through a variety of mechanisms.By synthesizing and critically assessing the current state of knowledge on the immunomodulatory effects of black seeds,this review aims to provide valuable insights into the potential therapeutic uses and future research directions for harnessing the immunological benefits of this natural remedy.
基金Supported by the National Natural Science Foundation of China,No.81973840the Sichuan Provincial Administration of Traditional Chinese Medicine Major Science and Technology projects,No.2021XYCZ004。
文摘BACKGROUND Hepatocellular carcinoma(HCC)ranks as the fourth leading cause of cancerrelated deaths in China,and the treatment options are limited.The cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)activates the stimulator of interferon gene(STING)signaling pathway as a crucial immune response pathway in the cytoplasm,which detects cytoplasmic DNA to regulate innate and adaptive immune responses.As a potential therapeutic target,cGASSTING pathway markedly inhibits tumor cell proliferation and metastasis,with its activation being particularly relevant in HCC.However,prolonged pathway activation may lead to an immunosuppressive tumor microenvironment,which fostering the invasion or metastasis of liver tumor cells.AIM To investigate the dual-regulation mechanism of cGAS-STING in HCC.METHODS This review was conducted according to the PRISMA guidelines.The study conducted a comprehensive search for articles related to HCC on PubMed and Web of Science databases.Through rigorous screening and meticulous analysis of the retrieved literature,the research aimed to summarize and elucidate the impact of the cGAS-STING pathway on HCC tumors.RESULTS All authors collaboratively selected studies for inclusion,extracted data,and the initial search of online databases yielded 1445 studies.After removing duplicates,remaining 964 records were screened.Ultimately,55 articles met the inclusion criteria and were included in this review.CONCLUSION Acute inflammation can have a few inhibitory effects on cancer,while chronic inflammation generally promotes its progression.Extended cGAS-STING pathway activation will result in a suppressive tumor microenvironment.
基金supported by the National Key Research and Development Program of China(2022YFE0203900,2024YFD2401101)China Agriculture Research System(CARS-46)+1 种基金National Natural Science Foundation of China(32473201)Guangdong S&T Program(2022B1111030001,2024B1212040007)。
文摘Ring finger protein 122(RNF122),an E3 ubiquitin ligase,orchestrates antiviral immune responses in mammals by targeting retinoic acid-inducible gene 1 and melanoma differentiation-associated gene 5 for ubiquitination.However,its functional relevance in teleosts has yet to be clearly defined,particularly regarding the identification of substrate-specific regulatory sites.This study characterized RNF122 from mandarin fish(Siniperca chuatsi),termed scRNF122,and investigated its regulatory impact on stimulator of interferon genes(STING)-mediated antiviral signaling.Results showed that scRNF122 expression was up-regulated in response to mandarin fish ranavirus(MRV)infection,and its overexpression suppressed scSTING-mediated interferon(IFN)production and enhanced MRV replication.Co-immunoprecipitation confirmed a direct interaction between scRNF122 and scSTING.Functional assays demonstrated that scRNF122 facilitated scSTING degradation through the ubiquitin-proteasome pathway,a process impeded by MG132 treatment.Ubiquitination analyses of various scSTING mutants revealed that scRNF122 catalyzed scSTING ubiquitination at K95,K117,and K155 residues.Moreover,scRNF122 significantly impaired scSTING-dependent antiviral responses by engaging negative regulatory elements within the signaling cascade.Overall,scRNF122 was identified as a negative modulator of STING-mediated IFN signaling in mandarin fish,diminishing STING-dependent antiviral activity and promoting its degradation via the ubiquitin-proteasome pathway at lysine residues K95,K117,and K155.These findings provide mechanistic insight into the post-translational control of STING in teleosts and establish a foundation for future investigations into antiviral immune regulation.
文摘Chronic hepatitis delta virus(HDV)represents a rare but important co-infection in approximately 5%of patients with chronic hepatitis B virus(HBV)infection,and is associated with significant morbidity and mortality due to an increased risk for liver cirrhosis,liver failure,and hepatocellular carcinoma relative to HBV monoinfected individuals.The current treatment of chronic HDV infection includes the off-label use of pegylated interferon(IFN),which is limited by poor safety,tolerability,and efficacy.Guidelines of the major international liver organizations such as the American Association for the Study of Liver Diseases,European Association for the Study of the Liver,and Asian Pacific Association for the Study of the Liver provide recommendations for contemporary diagnosis and management of chronic HDV infection,including the incorporation of bulevirtide,a newly licensed antiviral agent in Europe.Significant unmet medical needs remain in the treatment of HDV,and recent advances in drug development offer hope for meaningful advances in drug therapy which may improve virologic response rates and clinical outcomes.This review summarizes trial design and available efficacy data from key phase 2 and 3 trials for investigational therapies including entry inhibitors(bulevirtide),prenylation inhibitors(lonafarnib),novel IFNs(peginterferon lambda),RNA interference molecules(JNJ-3989,elebsiran),monoclonal antibodies(tobevibart),and nucleic acid polymers(REP2139),and addresses future directions in HDV pharmacotherapy.
基金Supported by Colegio de Ciencia y Tecnología de la Universidad Autónoma de la Ciudad de México,No.CCYT-2025-CON-11.
文摘The canonical signaling of interferon gamma(IFN-γ)through the Janus kinase 1 and 2–signal transducer and activator of transcription 1(STAT1)axis leads to the expression of several interferon-stimulated genes(ISGs),which have diverse effects depending on the cellular context.In glioblastoma,a highly aggressive primary brain tumor in adults,elements of IFN-γcanonical signaling are deregulated,resulting in the overexpression of STAT1-target ISGs associated with tumor progression.This mini-review highlights key ISGs,including STAT1,interferon regulatory factor 1,programmed death-ligand 1,indoleamine 2,3-dioxygenase 1,and interferon-stimulated gene 15,involved in the pathology of glioblastoma.These genes may serve as valuable biomarkers and have therapeutic potential for targeting IFN-γsignaling in this malignancy.
文摘Current treatment options for hepatitis D are limited,with pegylated interferonalpha(PEG-IFNα)being the only therapy available in the Asia-Pacific region.However,PEG-IFNαhas limited efficacy and significant side effects.Pegylated interferon lambda acts on interferon-lambda(Type III)receptors predominantly expressed in hepatocytes.In 2023,bulevirtide was approved in the European Union and Russia for treating chronic hepatitis D.This drug works by binding to and inhibiting the sodium taurocholate co-transporting polypeptide receptor on liver cells,which is the primary entry point for the virus.Recently,several new drugs have entered various stages of development,offering hope for improved hepatitis D virus(HDV)management.Two more viral entry inhibitors are HH003 and tobevibart.Other agents include nucleic acid polymers(REP 2139-Mg),prenylation inhibitors(lonafarnib),and RNA interference-based therapies(elebsiran).Emerging trials are now considering combination therapies,such as SOLSTICE,a Phase 2 clinical trial evaluating tobevibart alone or combined with elebsiran.The combination dosed monthly achieved>50%virologic and biochemical response at 24 weeks of therapy.The efficacy and safety of these drugs will further be evaluated in ECLIPSE 1,2,and 3 trials.With these new treatments on the horizon,the prospects for improved HDV patient outcomes are promising.
基金funded by the Beijing Research Ward Ecxellence Program,BRWEP(BRWEP2024W102170101)the capital health research and development of special public health project(2022-1-2172)+3 种基金the National Key Research and Development Program(2022YFC2603500,2022YFC2603505,2023YFC2306901,2023YFC2308105,2023YFC2308105)the Beijing Municipal Health Commission high-level public health technical personnel construction project,discipline leader-03-26Beijing Hospitals Authority"peak"talent training program(DFL20241803)the Beijing Hospitals Authority Clinical medicine Development of special funding support(ZLRK202301).
文摘To investigate the risk and influencing factors of long-term liver adverse events in chronic hepatitis B patients achieving hepatitis B surface antigen(HBsAg)clearance after pegylated interferonα(Peg-IFNα)treatment,a retrospective analysis was conducted on 456 patients at Beijing Ditan Hospital from 2008 to 2023 who achieved HBsAg clearance and discontinued Peg-IFNαtreatment.The baseline was defined as the time of HBsAg clearance and treatment cessation.The endpoint was the first occurrence of liver adverse events(hepatocellular carcinoma or ascites)or last follow-up.Subsequently,we evaluated the incidence and risk factors of liver adverse events,along with changes in liver fibrosis,cirrhosis,and liver function indicators.During a median follow-up of 70 months,the incidence of liver adverse events was 2.30%,hepatocellular carcinoma 1.76%,and ascites 0.55%.Older age and cirrhosis were significant risk factors(HR 1.075 and 41.393,both P<0.01).The APRI score significantly improved at follow-up compared to baseline(0.53 vs.0.25,P<0.001),and cirrhosis prevalence decreased from 5.70%to 0.88%(P<0.001).In conclusion,patients who achieved HBsAg clearance and discontinued Peg-IFNαtreatment have a low risk of liver adverse events,while advanced age and cirrhosis remain major risk factors.
文摘Peyronie’s disease(PD)presents a multifaceted challenge in contemporary urological practice,marked by penile deformity,pain,and the potential for erectile dysfunction.We meticulously explored the existing literature of intralesional/topical interventions,aiming to provide clinicians with a nuanced understanding of available options for comprehensive PD management.To conduct this review,we performed a systematic search using the PubMed,Scopus,and ScienceDirect databases,including the keywords of combination of the“Peyronie’s disease/plastic induration of the penis(PIP)and intralesional/topical treatments”.The study selection was based on adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,resulting in the inclusion of 16 articles.We delve into the effectiveness and safety profiles of collagenase Clostridium histolyticum(CCH),interferon,platelet-rich plasma(PRP),hyaluronic acid,botulinum toxin,stem cell,extracorporeal shock wave therapy(ESWT),and traction therapy,assessing their impact on penile curvature,length improvement,and patient-reported symptoms and outcomes.The best options evaluated are intralesional injections of CCH and penile traction devices,alone or in combination.Despite PD remains a challenge for urologists,the objective of this review is to contribute to the evolving landscape of PD management,fostering informed decision-making,and personalized care for individuals grappling with this challenging condition.
基金Supported by the National Science Foundation for Distinguished Young Scholars of China to Intestinal Microflora-Mediated Regulation of Breast Regression Protein 39/chitinase-3-like Protein 1 Signaling pathway in the Intervention of Chronic Obstructive Pulmonary Disease by Invigorating Spleen Supplementing Lung and Relaxing Collaterals Method (No. 81804074)
文摘OBJECTIVE:To examine the effects of the Jianpi Yifei Tongluo recipe(健脾益肺通络方剂,JYTR)on chronic obstructive pulmonary disease(COPD)within an animal model and to elucidate its anti-inflammatory mechanisms.METHODS:In this study,we utilized cigarette smoke(CS)exposure and lipopolysaccharide(LPS)-induced models of COPD in rats to evaluate the effects of the JYTR on airway inflammation.Sprague-Dawley rats were randomly assigned to various groups:control,model,budesonide,synbiotics,and low,medium,and high JYTR.Pulmonary function was gauged using an animal volumetric tracer.Pathological alterations in lung tissue were examined under a light microscope.To ascertain cytokine production,we conducted enzyme-linked immunosorbent assay tests,and we employed Western blotting to measure the expression levels of interferon regulatory factor 4(IRF4),arginase 1(Arg1),inducible nitric oxide synthase(iNOS),nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor,alpha(IKB-α),and P65.RESULTS:Compared to the control group,rats in the COPD model group exhibited significantly compromised pulmonary function and severe inflammatory pathology in the lungs.Treatment with budesonide,synbiotics,and the JYTR markedly improved pulmonary function and diminished the production of inflammatory cytokines transforming growth factor-beta(TGF-β),tumor necrosis factor-alpha(TNF-α),and interleukin-6(IL-6).These improvements were particularly notable in the budesonide group and the high-dose JYTR group.Additionally,the JYTR increased the expression of IRF4 and upregulated the protein expression of Arg1,while concurrently downregulating the protein expression of iNOS,phosphorylated IKB-α,and phosphorylated P65.CONCLUSION:Our current study reveals that JYTR can mitigate inflammatory lung injury,enhance lung function,and lower levels of inflammatory cytokines induced by CS or LPS exposure in COPD model rats.The mechanism behind its anti-inflammatory effect likely involves the regulation of IRF4 expression and M2 polarization through the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway.
文摘Topical chemotherapy is increasingly used to treat ocular surface tumors as a primary therapy and an adjuvant treatment after surgical excision.The most employed topical agents include mitomycin C(MMC),5-fluorouracil(5-FU),and interferon alpha-2b(IFNα2b),each with distinctmechanisms of action,efficacy profiles,and toxicity risks.Although these agents offer effective tumor control and allow for a non-invasive approach in many cases,ocular surface complications requiring medical or surgical management can occur.This summarizes the adverse effect and outilines practical strategies for their prevention and treatment.MMC is the most potent agent but also the most toxic,with reported complications such as limbal stemcell deficiency,punctal stenosis,and persistent epithelial defects.5-FU demonstrates a more favorable safety profile,although rare cases of corneal ulceration have been described.IFNα2b is well tolerated and associated primarily with mild,reversible reactions.The choice of the proper agent should be tailored according to patient’s clinical presentation,ocular surface status,and ability to adhere to therapy and followup.Timely recognition and management of complications are essential to minimize long-term sequelae.Reliance on compounded formulations highlights the need for stable,standardized,and commercially available topical agents specifically designed for ocular use to ensure safety,reproducibility,and global accessibility.
