Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune respons...Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune responses and promote tissue repair.This review thoroughly examines the dynamic changes in the number and function of regulatory T cells and highlights their distinct roles at various stages of stroke progression.In the acute phase(within 5-7 days),regulatory T cells exert neuroprotective effects primarily by reducing inflammation.In the chronic phase(7 days post-onset),these cells support neuroregeneration and functional recovery.The review also explores the emerging role of regulatory T cells in the brain-gut axis,a key mediator of the systemic immune responses following stroke,and discusses its relevance in modulating post-stroke inflammation and repair.Various strategies aimed at enhancing regulatory T cell responses include adoptive transfer of regulatory T cells,administration of pharmacological agents,and induction of mucosal tolerance.All these approaches can potentially enhance the immunomodulatory and repair functions of regulatory T cells.Nevertheless,despite the promising preclinical results,the translation of regulatory T cell-based therapies into clinical practice is associated with challenges related to optimal timing,dosage,and long-term efficacy.Overall,targeting regulatory T cells is a novel and promising immunoregulatory approach for mitigating stroke-induced injury and promoting neural repair.展开更多
Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
Tobacco(Nicotiana tabacum,2n=48)is a key non-food economic crop,yet its stress response and gene regulatory mechanisms remain poorly understood.By analyzing 603 transcriptome datasets,this study identified 1405 tissue...Tobacco(Nicotiana tabacum,2n=48)is a key non-food economic crop,yet its stress response and gene regulatory mechanisms remain poorly understood.By analyzing 603 transcriptome datasets,this study identified 1405 tissue-specific genes,revealing tissue-specific synthesis of terpenoids and other ecologically important secondary metabolites in sepals and other tissues.Comparative stress-response analysis highlighted distinct gene expression patterns in leaves and roots under biotic and abiotic stresses.Additionally,28,396 expression quantitative trait loci(eQTLs)were mapped in leaves,offering valuable genetic regulatory markers.These findings provide crucial insights into tobacco’s gene expression characteristics and their functional implications,serving as a foundation for future research.展开更多
Rice production is increasingly challenged by flooding stress because of global warming and rising sea levels.As the world’s most important staple crop,rice is highly vulnerable to anaerobic and submergence condition...Rice production is increasingly challenged by flooding stress because of global warming and rising sea levels.As the world’s most important staple crop,rice is highly vulnerable to anaerobic and submergence conditions that occur during flooding,particularly at the germination and vegetative stages.Anaerobic environments hinder seedling establishment during germination,while prolonged submergence during the vegetative stage impairs growth,ultimately reducing yield and grain quality.These stresses,driven by extended inundation,trigger a cascade of detrimental physiological responses and represent a major barrier to stable rice production and global food security.In this review,we examine the effects of flooding on rice growth at both the germination and vegetative stages.We further summarize recent advances in the identification of flooding-tolerant germplasm,QTL mapping,genome-wide association study,transcriptomic and proteomic analyses,and other molecular studies.Subsequently,we highlight potential cultivation and regulatory strategies,including genetic,morphological,physiological,and endogenous hormone-related approaches,aimed at enhancing tolerance to anaerobic and submergence stress.Together,these approaches underscore the promise of integrating molecular insights with agronomic practices to mitigate flooding damage and support sustainable rice production.展开更多
Small RNAs(sRNAs)are important non-coding RNAs that usually play crucial roles in gene expression at the post-transcriptional level.The sRNAs have mostly been investigated in model microorganisms such as Escherichia c...Small RNAs(sRNAs)are important non-coding RNAs that usually play crucial roles in gene expression at the post-transcriptional level.The sRNAs have mostly been investigated in model microorganisms such as Escherichia coli and some pathogens.Nevertheless,microbial sRNAs from extreme environments such as the polar regions and deep sea have recently been discovered and analyzed for their unique roles in stress response,metabolic regulation and adaptation to extreme environments.These sRNAs fine-tune gene expression during oxidative and radiation stress,and modulate temperature and osmotic pressure responses.Representative sRNAs and their functions in thermophilic,psychrophilic,halophilic and radiation-tolerant bacteria are summarized in this review.Despite challenges in sample collection,RNA isolation,and functional annotation,the study of sRNAs in extreme environments provides opportunities for discovering novel regulatory mechanisms,applying them to biotechnology,and advancing our understanding of evolutionary adaptations.Looking ahead,high-throughput sequencing,synthetic biology,and multi-omics integration will bring new breakthroughs in discovering novel sRNAs and their functions and regulatory mechanisms.Such advancements are poised to enable comprehensive characterization of sRNA-mediated regulatory networks in extremophiles and unlock their biotechnological potential through mechanism-driven applications.展开更多
OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted...OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted from previously published databases.The autoimmune hepatitis(AIH)-related regulatory genes were obtained from the Dis Ge NET database.Intersections were taken,and enrichment analyses were performed on the extracted data.Concanavalin A(Con A)-induced AIH model mice were treated with CGGD via gavage.The results of network pharmacological analysis were experimentally validated.RESULTS:Network pharmacology revealed 228 genes at the intersection of AIH and CGGD.Kyoto Encyclopedia of Genes and Genomes analysis revealed that CGGD primarily regulates the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and cellular metabolism in AIH.Gene Ontology enrichment analysis revealed that CGGD modulates inflammation through transcription factor-mediated signaling pathways.As predicted,CGGD attenuated Con A-induced AIH in a dose-dependent manner by activating the PI3K/AKT signaling pathway.Histopathological assessment confirmed the protective effects of CGGD against Con Ainduced AIH.Further investigation revealed that CGGD regulated the T helper cell 17(Th17)/regulatory T cell(Treg)balance by modulating the PI3K/Akt/nuclear factor kappa-B(NF-κB)pathway.CONCLUSIONS:This study demonstrated the therapeutic effect of CGGD on AIH through a combination of network pharmacological prediction and experimental validation.Its mechanism of action involves PI3K/Akt/NF-κB-mediated regulation of Th17/Treg cells.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
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
Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and trans...Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and transcriptional regulatory networks(TRN)inherent in TNBC samples.Methods:We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas(TCGA)to compare triple-positive breast cancer(TPBC)with TNBC.TRN algorithms and virtual inference of protein-enriched regulon(VIPER)were used to identify master regulators and their target genes.Utilizing TNBC cells(MDA-MB-231 and MDA-MB-468),we validated the relationship of nuclear factor erythroid 2-like 3(NFE2L3)and basic helix-loop-helix family member E 40(BHLHE40)by performing a luciferase assay.The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots.The effect of these genes on cell proliferation and migration was studied using phenotypic assays.Results:Using computational approaches,we identified NFE2L3 as a master regulator with BHLHE40 as its target gene.NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity.Additionally,silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels.We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC.Conclusion:These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC,highlighting NFE2L3’s role in regulating the oncogenic activity of BHLHE40 in TNBC cells.展开更多
Rice(Oryza sativa)is a staple food for more than half of the world's population and a critical crop for global agriculture.Understanding the regulatory mechanisms that control gene expression in the rice genome is...Rice(Oryza sativa)is a staple food for more than half of the world's population and a critical crop for global agriculture.Understanding the regulatory mechanisms that control gene expression in the rice genome is fundamental for advancing agricultural productivity and food security.In mechanism,cis-regulatory elements(including promoters,enhancers,silencers,and insulators)are key DNA sequences whose activities determine the spatial and temporal expression patterns of nearby genes(Yocca and Edger,2022;Schmitz et al.,2022).展开更多
Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are ne...Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.展开更多
This paper explores the expansion from fintech-based regulatory sandboxes to those that include medical artificial intelligence(AI)by examining their potential to foster innovation and accelerate market access while e...This paper explores the expansion from fintech-based regulatory sandboxes to those that include medical artificial intelligence(AI)by examining their potential to foster innovation and accelerate market access while ensuring safety and compliance,especially considering how they provide a flexible framework for medical AI companies to develop and test new technologies.This work also highlights the key risks involved,including data privacy,ethical concerns,real-world validation,and regulatory consistency,and proposes strategies for mitigation.Using case studies from the United States,the United Kingdom,the European Union,Indonesia,Japan,and China,this paper illustrates how regulatory sandboxes can support AI-driven healthcare innovation.Overall,although regulatory sandboxes present several risks,they are valuable for advancing medical AI,granted that they balance innovation with robust oversight to ensure patient safety and long-term benefits.展开更多
Intercropping has been widely used in arid and semi-arid regions because of its high yield,stable productivity,and efficient utilization of resources.However,in recent years,the high yield of traditional intercropping...Intercropping has been widely used in arid and semi-arid regions because of its high yield,stable productivity,and efficient utilization of resources.However,in recent years,the high yield of traditional intercropping is mainly attributed to the large amount of purchased resources such as water and fertilizer,plastic film,and mechanical power.These lead to a decline in cultivated land quality and exacerbate intercrops'premature root and canopy senescence.So,the application of traditional intercropping faces major challenges in crop production.This paper analyzes the manifestations,occurrence mechanisms,and agronomic regulatory pathways of crop senescence.The physiological and ecological characteristics of intercropping to delay root and canopy senescence of crops are reviewed in this paper.The main agronomic regulatory pathways of intercropping to delay root and canopy senescence of crops are based on above-and blow-ground interactions,including collocation of crop varieties,spatial arrangement,water and fertilizer management,and tillage and mulch practices.Future research fields of intercropping to delay root and canopy senescence should focus on the aspects of selecting and breeding special varieties,application of molecular biology techniques,and developing or applying models to predict and evaluate the root and canopy senescence process of intercrops.Comprehensive analysis and evaluation of different research results could provide a basis for enhancing intercropping delay root and canopy senescence through adopting innovative technologies for regulating the physio-ecological characteristics of intercrops.This would support developing and adopting high-yield,efficient,and sustainable intercropping systems in arid and semi-arid areas with high population density,limited land,and abundant light and heat resources.展开更多
Cell cultured meat has been extensively studied as an environmentally friendly,energy-saving and more effective technology.However,there are many technical bottlenecks,especially the regulatory mechanism and manufactu...Cell cultured meat has been extensively studied as an environmentally friendly,energy-saving and more effective technology.However,there are many technical bottlenecks,especially the regulatory mechanism and manufacturing method of in vitro myogenesis.Based on an edible modified silk protein scaffold,with 3D culturing,in situ differentiated and transcriptome analysis,this study describes novel scaffolds and fabrication methods for cell cultured meat.The results showed that the effective space and utilization efficiency for cell culture of the scaffold is 26–1000 that of the traditional culture dish;it could form a tissue-like structure.Transcriptomics revealed the regulatory pathways and key factors of different cycles.It clarifies that the multi-cycle process of myoblast myogenesis in vitro is different from the single feedback regulation in vivo.More importantly,a novel scaffold-based cell cultured meat manufacturing method was developed,further develop a new tissue culture solution that is different from existing cell culture meat production.For manufacturing processes,it provides a new cell culture meat technology system,provides a theoretical basis for the regulation of cell proliferation and muscle growth,and lays the technical foundation for in situ tissue culture of cell cultured meat in vitro.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
Regulatory T cells(Treg cells)are a specialized subset of CD4+T cells defined by expression of the lineage-specifying transcription factor FOXP3 and a potent capacity to maintain peripheral immune tolerance.The modern...Regulatory T cells(Treg cells)are a specialized subset of CD4+T cells defined by expression of the lineage-specifying transcription factor FOXP3 and a potent capacity to maintain peripheral immune tolerance.The modern concept of Tregs was catalyzed by Shimon Sakaguchi's identification of CD4+CD25+suppressive T cells and subsequent work establishing FOXP3 as a central determinant of Treg cell development and function;together with landmark FOXP3 genetic discoveries by Mary E.Brunkow and Fred Ramsdell,these advances transformed understanding of immune homeostasis and were recognized by the 2025 Nobel Prize in Physiology or Medicine.Under normal physiological conditions,FOXP3+Treg cells restrain autoreactive lymphocytes,prevent excessive inflammation,and shape antigen-presenting cell activity through contact-dependent pathways and suppressive cytokines,thereby protecting tissues from immune-mediated damage.Disruption of Treg abundance,stability,or suppressive capacity can therefore lead to immune dysregulation and disease.Over the past two decades,Treg cells have become a major focus of immunology because their roles are highly context-dependent.In autoimmune and chronic inflammatory diseases,impaired Treg cell function or insufficient Treg activity contributes to loss of tolerance and persistent tissue injury,supporting therapeutic approaches designed to enhance Treg cell number,stability,and suppressive potency.In contrast,many cancers exploit Treg cells by promoting their expansion,activation,and recruitment into the tumor microenvironment(TME),where they blunt antitumor immunity by suppressing cytotoxic T-cell priming and effector function,limiting dendritic cell activation,and fostering immune escape.In both settings,immune checkpoint pathways critically influence Treg cell biology.Beyond PD-1/PD-L1 and CTLA-4,emerging checkpoints and costimulatory receptors,including TIGIT,TIM-3,LAG-3,and OX40,modulate Treg cell generation,stability,and suppressive functions,thereby shaping the balance between tolerance and immunity.Meanwhile,immunometabolic adaptations further tune Treg cell fitness and function in inflamed tissues and tumors;lipid utilization and mitochondrial programs,among other metabolic axes,enable Treg cells to persist in nutrient-and oxygen-restricted microenvironments,while microenvironmental stress can drive functional remodeling or fragility in a subset-dependent manner.In this review,we summarize the discovery and defining biological features of Treg cells,highlight core suppressive mechanisms and regulatory circuits,and synthesize evidence for the dual roles of Treg cells in preventing autoimmunity yet enabling tumor immune evasion.We further outline current and emerging therapeutic strategies aimed at augmenting Treg cell activity to restore tolerance in autoimmune disease,or selectively depleting,functionally inhibiting,and reprogramming tumor-resident Treg cells to enhance cancer immunotherapy.Overall we discuss how deeper insight into Treg heterogeneity,checkpoint control,and immunometabolic regulation may enable more precise Treg celldirected interventions and inform next-generation immunotherapeutic combinations across immune-mediated and malignant diseases.展开更多
Kang et al.published a research article on the treatment of ischemic stroke using engineered Treg cells(Kang et al.,Prog Biochem Biophys,2025,52(4):946-956.DOI:10.16476/j.pibb.2025.0019).Their study mainly explores th...Kang et al.published a research article on the treatment of ischemic stroke using engineered Treg cells(Kang et al.,Prog Biochem Biophys,2025,52(4):946-956.DOI:10.16476/j.pibb.2025.0019).Their study mainly explores the immunoregulatory role of regulatory T(Treg)cells in ischemic stroke,providing an innovative therapeutic strategy.Neuroinflammation is a major driver of secondary injury after stroke.Existing treatments focus on vascular recanalization while neglecting immune regulation.Their study proposes to modulate neuroinflammation through in vitro-induced Treg cells,offering a novel approach distinct from traditional thrombolysis and endovascular interventions.展开更多
Systemic lupus erythematosus(SLE)is a chronic autoimmune disease.Defects in the regulatory T cells(Treg cells)play a key role in breaking immune tolerance in SLE patients.This study investigates the causes of impaired...Systemic lupus erythematosus(SLE)is a chronic autoimmune disease.Defects in the regulatory T cells(Treg cells)play a key role in breaking immune tolerance in SLE patients.This study investigates the causes of impaired Treg cell function in SLE patients.Peripheral blood from 56 SLE patients and 33 healthy donors was used to assess Treg cell proportions among CD4^(+)T cells and plasma cytokine levels.Treg cells and naïve CD4^(+)T cells from healthy individuals were isolated,cultured under various conditions,and analyzed for phenotype and signal transduction mechanisms using flow cytometry,RT-qPCR,Western blotting,and calcium signaling assays.In SLE patients,the proportion of CD4^(+)CD25^(+)Foxp3^(+)and CD4^(+)Foxp3^(+)Treg cells decreased.Plasma CXCL11 levels were elevated in lupus patients.CXCL11 expression inversely correlated with Treg cell proportions and positively correlated with disease severity.CXCL11 impaired immune function and inhibited Treg cell differentiation.We present a novel pathological pathway in SLE,wherein CXCL11 impedes the immunosuppressive functions of Treg cells.展开更多
OBJECTIVE:To examine the T helper 17(Th17)/regulatory T(Treg)immune balance in passive Heymann nephritis(PHN)rats with dampness syndrome(DS).METHODS:Rats were divided into four groups:normal control(NC),PHN model,PHN+...OBJECTIVE:To examine the T helper 17(Th17)/regulatory T(Treg)immune balance in passive Heymann nephritis(PHN)rats with dampness syndrome(DS).METHODS:Rats were divided into four groups:normal control(NC),PHN model,PHN+DS model,and DS model.The DS model was created by administering lard,a 60%cold sucrose solution,and Chinese Baijiu viagavage.In contrast,PHN was induced in male Sprague-Dawley rats by injecting anti-Fx1A serum into the tail vein.The general condition of the rats was assessed,while the levels of urine protein,albumin,and serum creatinine were measured using commercially available kits.Pathological renal damage was evaluated using hematoxylin and eosin,periodic acid-schiff,and periodic acid-silver methenamine staining,while podocyte damage was assessed through immunohistochemistry.The proportions of Th17 cells and Treg cells in peripheral blood mononuclear cells were quantified by flow cytometry.Plasma cytokine levels of interleukin 17,transforming growth factor-β1,and interleukin 6 were determined by enzyme-linked immunosorbent assay.RESULTS:This study demonstrated a significant increase in proteinuria and total cholesterol levels in PHN rats with DS,along with more severe histopathological kidney damage.DS exacerbated podocyte damage in PHN rats.Additionally,the number of Treg cells was significantly reduced,while the ratio of Th17/Treg cells was significantly elevated in PHN rats with DS.CONCLUSION:In conclusion,the findings of our study indicate that the presence of DS exacerbates renal injury in PHN,a rat model used to simulate experimental membranous nephropathy.This observation may be closely linked to the exacerbation of the Th17/Treg imbalance and podocyte injury in PHN rats induced by DS.展开更多
基金supported by National Key R&D Program:Key Special Project on Research for the Prevention and Treatment of Common Diseases-2022 Annual Project,Nos.2022YFC2504900,2022YFC2504902(both to ZL).
文摘Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune responses and promote tissue repair.This review thoroughly examines the dynamic changes in the number and function of regulatory T cells and highlights their distinct roles at various stages of stroke progression.In the acute phase(within 5-7 days),regulatory T cells exert neuroprotective effects primarily by reducing inflammation.In the chronic phase(7 days post-onset),these cells support neuroregeneration and functional recovery.The review also explores the emerging role of regulatory T cells in the brain-gut axis,a key mediator of the systemic immune responses following stroke,and discusses its relevance in modulating post-stroke inflammation and repair.Various strategies aimed at enhancing regulatory T cell responses include adoptive transfer of regulatory T cells,administration of pharmacological agents,and induction of mucosal tolerance.All these approaches can potentially enhance the immunomodulatory and repair functions of regulatory T cells.Nevertheless,despite the promising preclinical results,the translation of regulatory T cell-based therapies into clinical practice is associated with challenges related to optimal timing,dosage,and long-term efficacy.Overall,targeting regulatory T cells is a novel and promising immunoregulatory approach for mitigating stroke-induced injury and promoting neural repair.
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
基金supported by the Guizhou Provincial Basic Research Program(Natural Science)[(2024)648]the Program of China National Tobacco Corporation(110202101032(JY-09),110202201003(JY-03))+2 种基金the Program of Guizhou Branch of China National Tobacco Corporation(2023XM02,2022XM05 and 2024XM01)the Qiankehe Platform Project(ZSYS[2025]028)the Program of China National Tobacco Corporation(110202102034).
文摘Tobacco(Nicotiana tabacum,2n=48)is a key non-food economic crop,yet its stress response and gene regulatory mechanisms remain poorly understood.By analyzing 603 transcriptome datasets,this study identified 1405 tissue-specific genes,revealing tissue-specific synthesis of terpenoids and other ecologically important secondary metabolites in sepals and other tissues.Comparative stress-response analysis highlighted distinct gene expression patterns in leaves and roots under biotic and abiotic stresses.Additionally,28,396 expression quantitative trait loci(eQTLs)were mapped in leaves,offering valuable genetic regulatory markers.These findings provide crucial insights into tobacco’s gene expression characteristics and their functional implications,serving as a foundation for future research.
基金supported by the National Natural Science Foundation of China(Grant Nos.32160501 and 32201901)the Accelerated Breeding Initiative of the Consultative Group on International Agricultural Research(Grant No.INIT-01)+2 种基金the Natural Science Foundation of Guangxi,China(Grant No.2021GXNSFAA220026)the Program on National Modern Agricultural Technology System Guangxi Innovation Team,China(Grant No.nycytxgxcxtd-2021-01-04)the Advantage Team Project of Guangxi Academy of Agricultural Sciences,China(Grant No.2026YT070).
文摘Rice production is increasingly challenged by flooding stress because of global warming and rising sea levels.As the world’s most important staple crop,rice is highly vulnerable to anaerobic and submergence conditions that occur during flooding,particularly at the germination and vegetative stages.Anaerobic environments hinder seedling establishment during germination,while prolonged submergence during the vegetative stage impairs growth,ultimately reducing yield and grain quality.These stresses,driven by extended inundation,trigger a cascade of detrimental physiological responses and represent a major barrier to stable rice production and global food security.In this review,we examine the effects of flooding on rice growth at both the germination and vegetative stages.We further summarize recent advances in the identification of flooding-tolerant germplasm,QTL mapping,genome-wide association study,transcriptomic and proteomic analyses,and other molecular studies.Subsequently,we highlight potential cultivation and regulatory strategies,including genetic,morphological,physiological,and endogenous hormone-related approaches,aimed at enhancing tolerance to anaerobic and submergence stress.Together,these approaches underscore the promise of integrating molecular insights with agronomic practices to mitigate flooding damage and support sustainable rice production.
基金supported by the National Natural Science Foundation of China(Grant nos.42476264,41976224).
文摘Small RNAs(sRNAs)are important non-coding RNAs that usually play crucial roles in gene expression at the post-transcriptional level.The sRNAs have mostly been investigated in model microorganisms such as Escherichia coli and some pathogens.Nevertheless,microbial sRNAs from extreme environments such as the polar regions and deep sea have recently been discovered and analyzed for their unique roles in stress response,metabolic regulation and adaptation to extreme environments.These sRNAs fine-tune gene expression during oxidative and radiation stress,and modulate temperature and osmotic pressure responses.Representative sRNAs and their functions in thermophilic,psychrophilic,halophilic and radiation-tolerant bacteria are summarized in this review.Despite challenges in sample collection,RNA isolation,and functional annotation,the study of sRNAs in extreme environments provides opportunities for discovering novel regulatory mechanisms,applying them to biotechnology,and advancing our understanding of evolutionary adaptations.Looking ahead,high-throughput sequencing,synthetic biology,and multi-omics integration will bring new breakthroughs in discovering novel sRNAs and their functions and regulatory mechanisms.Such advancements are poised to enable comprehensive characterization of sRNA-mediated regulatory networks in extremophiles and unlock their biotechnological potential through mechanism-driven applications.
基金Supported by the Nanjing Health Science and Technology Key Medical Science and Technology Development Program:Mechanism of Action of the Modified Si-Miao Powder with Sanguisorba Carbonisata in Regulating Microbiota and Microecology for the Treatment of Recurrent Vulvovaginal Candidiasis(ZKX22039)。
文摘OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted from previously published databases.The autoimmune hepatitis(AIH)-related regulatory genes were obtained from the Dis Ge NET database.Intersections were taken,and enrichment analyses were performed on the extracted data.Concanavalin A(Con A)-induced AIH model mice were treated with CGGD via gavage.The results of network pharmacological analysis were experimentally validated.RESULTS:Network pharmacology revealed 228 genes at the intersection of AIH and CGGD.Kyoto Encyclopedia of Genes and Genomes analysis revealed that CGGD primarily regulates the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and cellular metabolism in AIH.Gene Ontology enrichment analysis revealed that CGGD modulates inflammation through transcription factor-mediated signaling pathways.As predicted,CGGD attenuated Con A-induced AIH in a dose-dependent manner by activating the PI3K/AKT signaling pathway.Histopathological assessment confirmed the protective effects of CGGD against Con Ainduced AIH.Further investigation revealed that CGGD regulated the T helper cell 17(Th17)/regulatory T cell(Treg)balance by modulating the PI3K/Akt/nuclear factor kappa-B(NF-κB)pathway.CONCLUSIONS:This study demonstrated the therapeutic effect of CGGD on AIH through a combination of network pharmacological prediction and experimental validation.Its mechanism of action involves PI3K/Akt/NF-κB-mediated regulation of Th17/Treg cells.
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.
文摘Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and transcriptional regulatory networks(TRN)inherent in TNBC samples.Methods:We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas(TCGA)to compare triple-positive breast cancer(TPBC)with TNBC.TRN algorithms and virtual inference of protein-enriched regulon(VIPER)were used to identify master regulators and their target genes.Utilizing TNBC cells(MDA-MB-231 and MDA-MB-468),we validated the relationship of nuclear factor erythroid 2-like 3(NFE2L3)and basic helix-loop-helix family member E 40(BHLHE40)by performing a luciferase assay.The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots.The effect of these genes on cell proliferation and migration was studied using phenotypic assays.Results:Using computational approaches,we identified NFE2L3 as a master regulator with BHLHE40 as its target gene.NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity.Additionally,silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels.We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC.Conclusion:These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC,highlighting NFE2L3’s role in regulating the oncogenic activity of BHLHE40 in TNBC cells.
基金supported by the National Natural Science Foundation of China(32070656)。
文摘Rice(Oryza sativa)is a staple food for more than half of the world's population and a critical crop for global agriculture.Understanding the regulatory mechanisms that control gene expression in the rice genome is fundamental for advancing agricultural productivity and food security.In mechanism,cis-regulatory elements(including promoters,enhancers,silencers,and insulators)are key DNA sequences whose activities determine the spatial and temporal expression patterns of nearby genes(Yocca and Edger,2022;Schmitz et al.,2022).
基金supported by the Natural Science Foundation of Fujian Province,No.2021J02035(to WX).
文摘Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.
基金National Science and Technology Major Project(2020AAA0105000)Beijing Science and Technology Plan(Z241100007724003).
文摘This paper explores the expansion from fintech-based regulatory sandboxes to those that include medical artificial intelligence(AI)by examining their potential to foster innovation and accelerate market access while ensuring safety and compliance,especially considering how they provide a flexible framework for medical AI companies to develop and test new technologies.This work also highlights the key risks involved,including data privacy,ethical concerns,real-world validation,and regulatory consistency,and proposes strategies for mitigation.Using case studies from the United States,the United Kingdom,the European Union,Indonesia,Japan,and China,this paper illustrates how regulatory sandboxes can support AI-driven healthcare innovation.Overall,although regulatory sandboxes present several risks,they are valuable for advancing medical AI,granted that they balance innovation with robust oversight to ensure patient safety and long-term benefits.
基金supported by the National Natural Science Foundation of China(32101857 and U21A20218)the China Agricultural University Corresponding Support Research Joint Fund(GSAU-DKZY-2024-001)+1 种基金the Science and Technology Program in Gansu Province,China(24ZDNA008and23JRRA1407)the Fuxi Young Talents Fund of Gansu Agricultural University,China(Gaufx-03Y10).
文摘Intercropping has been widely used in arid and semi-arid regions because of its high yield,stable productivity,and efficient utilization of resources.However,in recent years,the high yield of traditional intercropping is mainly attributed to the large amount of purchased resources such as water and fertilizer,plastic film,and mechanical power.These lead to a decline in cultivated land quality and exacerbate intercrops'premature root and canopy senescence.So,the application of traditional intercropping faces major challenges in crop production.This paper analyzes the manifestations,occurrence mechanisms,and agronomic regulatory pathways of crop senescence.The physiological and ecological characteristics of intercropping to delay root and canopy senescence of crops are reviewed in this paper.The main agronomic regulatory pathways of intercropping to delay root and canopy senescence of crops are based on above-and blow-ground interactions,including collocation of crop varieties,spatial arrangement,water and fertilizer management,and tillage and mulch practices.Future research fields of intercropping to delay root and canopy senescence should focus on the aspects of selecting and breeding special varieties,application of molecular biology techniques,and developing or applying models to predict and evaluate the root and canopy senescence process of intercrops.Comprehensive analysis and evaluation of different research results could provide a basis for enhancing intercropping delay root and canopy senescence through adopting innovative technologies for regulating the physio-ecological characteristics of intercrops.This would support developing and adopting high-yield,efficient,and sustainable intercropping systems in arid and semi-arid areas with high population density,limited land,and abundant light and heat resources.
基金funded under the National key research and development plan(2021YFC2101404)Chinese Academy of Engineering Strategic Research and Consulting Project(2023-XZ-79,2022-30-19).
文摘Cell cultured meat has been extensively studied as an environmentally friendly,energy-saving and more effective technology.However,there are many technical bottlenecks,especially the regulatory mechanism and manufacturing method of in vitro myogenesis.Based on an edible modified silk protein scaffold,with 3D culturing,in situ differentiated and transcriptome analysis,this study describes novel scaffolds and fabrication methods for cell cultured meat.The results showed that the effective space and utilization efficiency for cell culture of the scaffold is 26–1000 that of the traditional culture dish;it could form a tissue-like structure.Transcriptomics revealed the regulatory pathways and key factors of different cycles.It clarifies that the multi-cycle process of myoblast myogenesis in vitro is different from the single feedback regulation in vivo.More importantly,a novel scaffold-based cell cultured meat manufacturing method was developed,further develop a new tissue culture solution that is different from existing cell culture meat production.For manufacturing processes,it provides a new cell culture meat technology system,provides a theoretical basis for the regulation of cell proliferation and muscle growth,and lays the technical foundation for in situ tissue culture of cell cultured meat in vitro.
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.
文摘Regulatory T cells(Treg cells)are a specialized subset of CD4+T cells defined by expression of the lineage-specifying transcription factor FOXP3 and a potent capacity to maintain peripheral immune tolerance.The modern concept of Tregs was catalyzed by Shimon Sakaguchi's identification of CD4+CD25+suppressive T cells and subsequent work establishing FOXP3 as a central determinant of Treg cell development and function;together with landmark FOXP3 genetic discoveries by Mary E.Brunkow and Fred Ramsdell,these advances transformed understanding of immune homeostasis and were recognized by the 2025 Nobel Prize in Physiology or Medicine.Under normal physiological conditions,FOXP3+Treg cells restrain autoreactive lymphocytes,prevent excessive inflammation,and shape antigen-presenting cell activity through contact-dependent pathways and suppressive cytokines,thereby protecting tissues from immune-mediated damage.Disruption of Treg abundance,stability,or suppressive capacity can therefore lead to immune dysregulation and disease.Over the past two decades,Treg cells have become a major focus of immunology because their roles are highly context-dependent.In autoimmune and chronic inflammatory diseases,impaired Treg cell function or insufficient Treg activity contributes to loss of tolerance and persistent tissue injury,supporting therapeutic approaches designed to enhance Treg cell number,stability,and suppressive potency.In contrast,many cancers exploit Treg cells by promoting their expansion,activation,and recruitment into the tumor microenvironment(TME),where they blunt antitumor immunity by suppressing cytotoxic T-cell priming and effector function,limiting dendritic cell activation,and fostering immune escape.In both settings,immune checkpoint pathways critically influence Treg cell biology.Beyond PD-1/PD-L1 and CTLA-4,emerging checkpoints and costimulatory receptors,including TIGIT,TIM-3,LAG-3,and OX40,modulate Treg cell generation,stability,and suppressive functions,thereby shaping the balance between tolerance and immunity.Meanwhile,immunometabolic adaptations further tune Treg cell fitness and function in inflamed tissues and tumors;lipid utilization and mitochondrial programs,among other metabolic axes,enable Treg cells to persist in nutrient-and oxygen-restricted microenvironments,while microenvironmental stress can drive functional remodeling or fragility in a subset-dependent manner.In this review,we summarize the discovery and defining biological features of Treg cells,highlight core suppressive mechanisms and regulatory circuits,and synthesize evidence for the dual roles of Treg cells in preventing autoimmunity yet enabling tumor immune evasion.We further outline current and emerging therapeutic strategies aimed at augmenting Treg cell activity to restore tolerance in autoimmune disease,or selectively depleting,functionally inhibiting,and reprogramming tumor-resident Treg cells to enhance cancer immunotherapy.Overall we discuss how deeper insight into Treg heterogeneity,checkpoint control,and immunometabolic regulation may enable more precise Treg celldirected interventions and inform next-generation immunotherapeutic combinations across immune-mediated and malignant diseases.
文摘Kang et al.published a research article on the treatment of ischemic stroke using engineered Treg cells(Kang et al.,Prog Biochem Biophys,2025,52(4):946-956.DOI:10.16476/j.pibb.2025.0019).Their study mainly explores the immunoregulatory role of regulatory T(Treg)cells in ischemic stroke,providing an innovative therapeutic strategy.Neuroinflammation is a major driver of secondary injury after stroke.Existing treatments focus on vascular recanalization while neglecting immune regulation.Their study proposes to modulate neuroinflammation through in vitro-induced Treg cells,offering a novel approach distinct from traditional thrombolysis and endovascular interventions.
基金supported by the National Natural Science Foundation of China(No.82071838)the Key Medical Discipline Construction Unit of Jiangsu Province(No.JSDW202205)+1 种基金the Research Hospital of Jiangsu Province(No.YJXYY202204)Natural Science Foundation of Nantong City(No.JC2023053).
文摘Systemic lupus erythematosus(SLE)is a chronic autoimmune disease.Defects in the regulatory T cells(Treg cells)play a key role in breaking immune tolerance in SLE patients.This study investigates the causes of impaired Treg cell function in SLE patients.Peripheral blood from 56 SLE patients and 33 healthy donors was used to assess Treg cell proportions among CD4^(+)T cells and plasma cytokine levels.Treg cells and naïve CD4^(+)T cells from healthy individuals were isolated,cultured under various conditions,and analyzed for phenotype and signal transduction mechanisms using flow cytometry,RT-qPCR,Western blotting,and calcium signaling assays.In SLE patients,the proportion of CD4^(+)CD25^(+)Foxp3^(+)and CD4^(+)Foxp3^(+)Treg cells decreased.Plasma CXCL11 levels were elevated in lupus patients.CXCL11 expression inversely correlated with Treg cell proportions and positively correlated with disease severity.CXCL11 impaired immune function and inhibited Treg cell differentiation.We present a novel pathological pathway in SLE,wherein CXCL11 impedes the immunosuppressive functions of Treg cells.
基金Supported by the Special Project of State Key Laboratory of Dampness Syndrome of Chinese Medicine: a Randomized Controlled Clinical Study of Sanqi Qushi Granules in the Treatment of Membranous Nephropathy (No. SZ2021ZZ36)a Cohort Study on the Pathogenesis and Evolution of Dampness Syndrome in Idiopathic Membranous Nephropathy and Its Material Basis (No. SZ2021ZZ09)+8 种基金the National Natural Science Foundation of China: Research on the Role of Damp Nephropathy based on the Metabolic Disorders-T helper 17/Regulatory T Imbalance Evil in the Progression of Membranous (No. 81974565)the Guangzhou Science and Technology Plan Project: Exploring the Mechanism of Treating Membranous Nephropathy based on Dampness from the Perspective of Regulating Amino Acid Metabolism Disorders (No. 2023A03J0746)Multi-omics Study to Explore the Material Basis of Dampness Syndrome in Membranous Nephropathy and the Intervention Mechanism of Sanqi Qushi Decoction (No. 2024A03J0117)a Multimodal Machine Learning Prediction Model based on Pathological Images, Transcriptomics and Traditional Chinese Medicine Syndromes to Explore the Prognosis-related lncRNA Molecules of Membranous Nephropathy and the Intervention Mechanism of Sanqi Qushi Decoction (No. 2025A03J4062)Research Project of Guangdong Provincial Hospital of Traditional Chinese Medicine: Construction of a Risk Management Prediction Model for Membranous Nephropathy Based on Artificial Intelligence Technology (No. YN2023HL03)Study on the Pathogenesis Evolution and Microbiological Mechanism of Membranous Nephropathy with Dampness Syndrome Based on the Changes of Tongue Coating Microecology (No. YN2023MB10)Post-doctoral Research Project of Guangdong Provincial Hospital of Chinese Medicine:Study on the Mechanism of Yinyang Shengmai Method in Regulating Myocardial Infarction in Diabetic Rats based on Ang/Vascular Endothelial Growth Factor-Mediated Angiogenesis (No. 10814)Funding Project of Guangdong Provincial Administration of Traditional Chinese Medicine:Study on the Mechanism of"Dampness Stagnation in Blood Collaterals"inducing Vascular Aging Based on Oxidative Stress-inflammation Crosstalk and Intervention of Traditional Chinese Medicine (No. 20233021)China Postdoctoral Science Foundation Funded Project:Study on the Mechanism of Shenmai Injection in Promoting Angiogenesis after Myocardial Infarction in Rats with Qi and Yin Deficiency Type Diabetic Nephropathy (No. 2023M730810)
文摘OBJECTIVE:To examine the T helper 17(Th17)/regulatory T(Treg)immune balance in passive Heymann nephritis(PHN)rats with dampness syndrome(DS).METHODS:Rats were divided into four groups:normal control(NC),PHN model,PHN+DS model,and DS model.The DS model was created by administering lard,a 60%cold sucrose solution,and Chinese Baijiu viagavage.In contrast,PHN was induced in male Sprague-Dawley rats by injecting anti-Fx1A serum into the tail vein.The general condition of the rats was assessed,while the levels of urine protein,albumin,and serum creatinine were measured using commercially available kits.Pathological renal damage was evaluated using hematoxylin and eosin,periodic acid-schiff,and periodic acid-silver methenamine staining,while podocyte damage was assessed through immunohistochemistry.The proportions of Th17 cells and Treg cells in peripheral blood mononuclear cells were quantified by flow cytometry.Plasma cytokine levels of interleukin 17,transforming growth factor-β1,and interleukin 6 were determined by enzyme-linked immunosorbent assay.RESULTS:This study demonstrated a significant increase in proteinuria and total cholesterol levels in PHN rats with DS,along with more severe histopathological kidney damage.DS exacerbated podocyte damage in PHN rats.Additionally,the number of Treg cells was significantly reduced,while the ratio of Th17/Treg cells was significantly elevated in PHN rats with DS.CONCLUSION:In conclusion,the findings of our study indicate that the presence of DS exacerbates renal injury in PHN,a rat model used to simulate experimental membranous nephropathy.This observation may be closely linked to the exacerbation of the Th17/Treg imbalance and podocyte injury in PHN rats induced by DS.
