Three-dimensional(3D)-printed hydrogel scaffolds are widely used in spinal cord injury repair,with gelatin methacrylate being particularly favored owing to its excellent biocompatibility.However,traditional scaffolds ...Three-dimensional(3D)-printed hydrogel scaffolds are widely used in spinal cord injury repair,with gelatin methacrylate being particularly favored owing to its excellent biocompatibility.However,traditional scaffolds have a small contact area with tissues and lack the ability to regulate the inflammatory microenvironment.Therefore,there is a need to develop smart scaffolds with drug delivery and immune regulation functions.In this study,a 3D-printed gelatin methacrylate scaffold was developed to deliver interferon regulatory factor 4 in a targeted and sustained manner.The scaffold showed good mechanical properties,biocompatibility,and sustained interferon regulatory factor 4 release.The sustained-release interferon regulatory factor 4 competitively bound to myeloid differentiation factor 88 to inhibit the pro-inflammatory effects of interferon regulatory factor 5,and activated the signal transducer and activator of transcription 6 pathway to promote M2 macrophage polarization,thereby facilitating neural regeneration and recovery of spinal cord function.This indicates that the constructed interferon regulatory factor 4-loaded 3D-printed methyl acrylate-modified gelatin scaffold can regulate macrophage polarization through the interferon regulatory factor 4/5 axis,improve the inflammatory microenvironment after spinal cord injury,and thus provide a new target for promoting neural regeneration.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
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
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
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
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
AIM:To investigate the expression of interferon regulatory factors(IRFs)in peripheral blood mononuclear cells(PBMCs)of patients with Sjögren’s syndrome-related dry eye(SSDE)and to explore their correlation with ...AIM:To investigate the expression of interferon regulatory factors(IRFs)in peripheral blood mononuclear cells(PBMCs)of patients with Sjögren’s syndrome-related dry eye(SSDE)and to explore their correlation with clinical features,dendritic cell activation,and serological indicators.METHODS:A total of 53 SSDE patients and 62 non-Sjögren’s syndrome dry eye(NSSDE)patients were enrolled.Demographic and clinical data were collected,and comprehensive ophthalmic examinations were performed,including the ocular surface disease index(OSDI)questionnaires,Schirmer I test(SIT),tear break-up time(TBUT),corneal fluorescein staining score(CFS),and in vivo confocal microscopy(IVCM).PBMCs were isolated,and IRFs expression levels were analyzed using Western blotting(WB)and quantitative real-time polymerase chain reaction(qRT-PCR).Serological indicators,including antinuclear antibodies(ANA)and anti-Ro60,anti-Ro52,and anti-La autoantibodies,were detected.Statistical analyses evaluated correlations between IRFs expression and clinical parameters.RESULTS:Compared to NSSDE,the relative mRNA and protein expression of the IRF-8 was significantly upregulated in patients with SSDE(P<0.001),whereas no significant differences were observed in IRF-1,IRF-3,IRF-5,and IRF-7(P=0.12,P=0.10,P=0.66,P=0.96).Correlation analysis revealed that IRF-8 expression was positively associated with CFS and OSDI scores(r=0.57,r=0.38,both P<0.05).Moreover,IRF-8 expression correlated with corneal dendritic cell(DC)density and size,and the number of dendrites(r=0.43,r=0.40,r=0.65,all P<0.05).IRF-8 expression was significantly elevated in patients positive for anti-Ro60,anti-Ro52 and anti-La autoantibodies(P<0.05).CONCLUSION:In SSDE,IRF-8 is upregulated and associated with clinical features,DC activation,and serological indicators.These findings suggest that IRF-8 plays a critical role in SSDE pathogenesis and may serve as a potential therapeutic target for diagnosis and treatment.展开更多
BACKGROUND Chronic hepatitis B(CHB)patients rarely achieve functional cure with initial pegylated interferon alpha-2b(Peg-IFNα-2b)therapy.Validated tools to guide retreatment candidates are lacking.We hypothesized th...BACKGROUND Chronic hepatitis B(CHB)patients rarely achieve functional cure with initial pegylated interferon alpha-2b(Peg-IFNα-2b)therapy.Validated tools to guide retreatment candidates are lacking.We hypothesized that clinical indicators predict hepatitis B surface antigen(HBsAg)clearance during retreatment.AIM To develop a prediction model for HBsAg clearance in Peg-IFNα-2b retreatment.METHODS In this retrospective cohort study,we enrolled 135 CHB/compensated cirrhosis patients receiving Peg-IFNα-2b retreatment after initial non-clearance at Tianjin University Central Hospital(2017-2025).Predictors were identified through univariate Cox,least absolute shrinkage and selection operator,and multivariate Cox regression.Model performance was assessed via receiver operating characteristic analysis and Harrell’s C-index,with risk stratification by X-tile optimization.RESULTS HBsAg clearance rate was 20.74%(28/135).Independent predictors included:Combination nucleos(t)ide analogue(NA)therapy during initial treatment[hazard ratio(HR)=0.276,95%confidence interval(CI):0.092-0.833],baseline HBsAg at retreatment(HR=0.571,95%CI:0.410-0.795),HBsAg decline after initial treatment(HR=2.050,95%CI:1.108-3.793),and treatment interval(HR=1.013/week,95%CI:1.008-1.018).The retreatment HBsAg clearance prediction score(RHCP-S)demonstrated area under the curve of 0.920(95%CI:0.863-0.946),sensitivity of 92.3%,specificity of 79.3%.Clearance rates differed significantly:RHCP-S challenge group(≤74 points):3.45%,RHCP-S probable group(74-110 points):29.63%,RHCP-S dominant group(≥110 points):80.95%(P<0.001).CONCLUSION The overall HBsAg clearance rate with Peg-IFNα-2b retreatment was 20.74%(28/135).The RHCP-S model identifies optimal retreatment candidates(≥110 points)with 80.95%clearance probability,associated with the absence of combination NA therapy during initial treatment,greater initial HBsAg decline,longer intervals,and lower retreatment HBsAg.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
干扰素-γ诱导蛋白16(interferon gamma-inducible protein 16,IFI16)是含pyrin和造血表达、干扰素诱导特性和核定位(hematopoietic expression,interferon-inducible nature,and nuclear localization,HIN)结构域的蛋白质(pyrin and HI...干扰素-γ诱导蛋白16(interferon gamma-inducible protein 16,IFI16)是含pyrin和造血表达、干扰素诱导特性和核定位(hematopoietic expression,interferon-inducible nature,and nuclear localization,HIN)结构域的蛋白质(pyrin and HIN domain-containing protein,PYHIN)家族的重要成员,其独特的分子结构使其能够识别细胞内的多种核酸分子。作为一种关键的免疫调节因子,IFI16可通过多种途径参与天然免疫信号转导,在宿主抗病毒防御中发挥重要作用。本文综述了IFI16的分子特征及其在天然免疫和病毒感染中的调控机制,为抗病毒感染的治疗靶点及药物开发提供理论依据。展开更多
基金supported by the National Natural Science Foundation of China,Nos.81930070(to SF),82002309(to ZS)the Tianjin Key Medical Discipline(Specialty)Construct Project,No.TJYXZDXK-027A(to SF)a grant from Tianjin Institute of Orthopedic Innovation and Transformation(to SF).
文摘Three-dimensional(3D)-printed hydrogel scaffolds are widely used in spinal cord injury repair,with gelatin methacrylate being particularly favored owing to its excellent biocompatibility.However,traditional scaffolds have a small contact area with tissues and lack the ability to regulate the inflammatory microenvironment.Therefore,there is a need to develop smart scaffolds with drug delivery and immune regulation functions.In this study,a 3D-printed gelatin methacrylate scaffold was developed to deliver interferon regulatory factor 4 in a targeted and sustained manner.The scaffold showed good mechanical properties,biocompatibility,and sustained interferon regulatory factor 4 release.The sustained-release interferon regulatory factor 4 competitively bound to myeloid differentiation factor 88 to inhibit the pro-inflammatory effects of interferon regulatory factor 5,and activated the signal transducer and activator of transcription 6 pathway to promote M2 macrophage polarization,thereby facilitating neural regeneration and recovery of spinal cord function.This indicates that the constructed interferon regulatory factor 4-loaded 3D-printed methyl acrylate-modified gelatin scaffold can regulate macrophage polarization through the interferon regulatory factor 4/5 axis,improve the inflammatory microenvironment after spinal cord injury,and thus provide a new target for promoting neural regeneration.
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,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 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.
基金Supported by National Natural Science Foundation of China(No.82471046)the Joint Medical Research Project of Chongqing Health Commission and Science and Technology Bureau(No.2023GDRC004)the Program for Youth Innovation in Future Medicine of Chongqing Medical University(No.W0185).
文摘AIM:To investigate the expression of interferon regulatory factors(IRFs)in peripheral blood mononuclear cells(PBMCs)of patients with Sjögren’s syndrome-related dry eye(SSDE)and to explore their correlation with clinical features,dendritic cell activation,and serological indicators.METHODS:A total of 53 SSDE patients and 62 non-Sjögren’s syndrome dry eye(NSSDE)patients were enrolled.Demographic and clinical data were collected,and comprehensive ophthalmic examinations were performed,including the ocular surface disease index(OSDI)questionnaires,Schirmer I test(SIT),tear break-up time(TBUT),corneal fluorescein staining score(CFS),and in vivo confocal microscopy(IVCM).PBMCs were isolated,and IRFs expression levels were analyzed using Western blotting(WB)and quantitative real-time polymerase chain reaction(qRT-PCR).Serological indicators,including antinuclear antibodies(ANA)and anti-Ro60,anti-Ro52,and anti-La autoantibodies,were detected.Statistical analyses evaluated correlations between IRFs expression and clinical parameters.RESULTS:Compared to NSSDE,the relative mRNA and protein expression of the IRF-8 was significantly upregulated in patients with SSDE(P<0.001),whereas no significant differences were observed in IRF-1,IRF-3,IRF-5,and IRF-7(P=0.12,P=0.10,P=0.66,P=0.96).Correlation analysis revealed that IRF-8 expression was positively associated with CFS and OSDI scores(r=0.57,r=0.38,both P<0.05).Moreover,IRF-8 expression correlated with corneal dendritic cell(DC)density and size,and the number of dendrites(r=0.43,r=0.40,r=0.65,all P<0.05).IRF-8 expression was significantly elevated in patients positive for anti-Ro60,anti-Ro52 and anti-La autoantibodies(P<0.05).CONCLUSION:In SSDE,IRF-8 is upregulated and associated with clinical features,DC activation,and serological indicators.These findings suggest that IRF-8 plays a critical role in SSDE pathogenesis and may serve as a potential therapeutic target for diagnosis and treatment.
基金Supported by the Tianjin Health Research Project(Key Project),No.TJWJ2024ZD004Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-034A.
文摘BACKGROUND Chronic hepatitis B(CHB)patients rarely achieve functional cure with initial pegylated interferon alpha-2b(Peg-IFNα-2b)therapy.Validated tools to guide retreatment candidates are lacking.We hypothesized that clinical indicators predict hepatitis B surface antigen(HBsAg)clearance during retreatment.AIM To develop a prediction model for HBsAg clearance in Peg-IFNα-2b retreatment.METHODS In this retrospective cohort study,we enrolled 135 CHB/compensated cirrhosis patients receiving Peg-IFNα-2b retreatment after initial non-clearance at Tianjin University Central Hospital(2017-2025).Predictors were identified through univariate Cox,least absolute shrinkage and selection operator,and multivariate Cox regression.Model performance was assessed via receiver operating characteristic analysis and Harrell’s C-index,with risk stratification by X-tile optimization.RESULTS HBsAg clearance rate was 20.74%(28/135).Independent predictors included:Combination nucleos(t)ide analogue(NA)therapy during initial treatment[hazard ratio(HR)=0.276,95%confidence interval(CI):0.092-0.833],baseline HBsAg at retreatment(HR=0.571,95%CI:0.410-0.795),HBsAg decline after initial treatment(HR=2.050,95%CI:1.108-3.793),and treatment interval(HR=1.013/week,95%CI:1.008-1.018).The retreatment HBsAg clearance prediction score(RHCP-S)demonstrated area under the curve of 0.920(95%CI:0.863-0.946),sensitivity of 92.3%,specificity of 79.3%.Clearance rates differed significantly:RHCP-S challenge group(≤74 points):3.45%,RHCP-S probable group(74-110 points):29.63%,RHCP-S dominant group(≥110 points):80.95%(P<0.001).CONCLUSION The overall HBsAg clearance rate with Peg-IFNα-2b retreatment was 20.74%(28/135).The RHCP-S model identifies optimal retreatment candidates(≥110 points)with 80.95%clearance probability,associated with the absence of combination NA therapy during initial treatment,greater initial HBsAg decline,longer intervals,and lower retreatment HBsAg.
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.
文摘干扰素-γ诱导蛋白16(interferon gamma-inducible protein 16,IFI16)是含pyrin和造血表达、干扰素诱导特性和核定位(hematopoietic expression,interferon-inducible nature,and nuclear localization,HIN)结构域的蛋白质(pyrin and HIN domain-containing protein,PYHIN)家族的重要成员,其独特的分子结构使其能够识别细胞内的多种核酸分子。作为一种关键的免疫调节因子,IFI16可通过多种途径参与天然免疫信号转导,在宿主抗病毒防御中发挥重要作用。本文综述了IFI16的分子特征及其在天然免疫和病毒感染中的调控机制,为抗病毒感染的治疗靶点及药物开发提供理论依据。
