The red imported fire ant,Solenopsis invicta Buren,is a highly invasive eusocial insect pest that threatens native biodiversity,agriculture,and human health.The innate immune system and intricate social immune respons...The red imported fire ant,Solenopsis invicta Buren,is a highly invasive eusocial insect pest that threatens native biodiversity,agriculture,and human health.The innate immune system and intricate social immune responses of S.invicta pose challenges to the development of effective control strategies.Micro RNAs(mi RNAs)play critical roles in the post-transcriptional regulation of gene expression,which influences various biological processes,including immunity and host-pathogen interactions.While the mi RNA-mediated response of insects to pathogens has been extensively studied in solitary insects,little is known about the innate immune responses of individual members within a colony.To address this gap,we constructed small RNA libraries from Metarhizium anisopliae-infected S.invicta workers and investigated the temporal dynamics of mi RNA-mediated immune responses to the entomopathogen.Several differentially expressed mi RNAs were identified,and they were found to regulate genes involved in the Toll,IMD,and melanization immune pathways.Quantitative real-time PCR(q RT-PCR)was employed to analyze the spatiotemporal dynamics of key mi RNAs/target genes,specifically mi R-71/Mod SP1-Relish and mi R-7/Lysozyme2-Serine protease7.A dual luciferase assay(in vitro)was performed to validate the interactions between mi RNAs and their target genes.Overexpression of mi R-71 and mi R-7(via mi RNA mimics)efficiently suppressed their target genes,impaired the antifungal immune response of S.invicta and increased the susceptibility to M.anisopliae infection compared to controls.Furthermore,RNA interference-based gene silencing elucidated the roles of these immune genes in regulating fungal susceptibility,thus providing vital clues for developing virulent and effective mycoinsecticides using modern genetic engineering tools.展开更多
Objectives:Postmenopausal osteoporosis is the most common form of osteoporosis in clinical practice,affecting millions of postmenopausal women worldwide.Postmenopausal osteoporosis demands safe and effective therapies...Objectives:Postmenopausal osteoporosis is the most common form of osteoporosis in clinical practice,affecting millions of postmenopausal women worldwide.Postmenopausal osteoporosis demands safe and effective therapies.This study aimed to evaluate the potential of hederagenin(Hed)for treating osteoporosis and to elucidate its underlying mechanisms of action.Methods:The anti-osteoporotic potential of Hed was assessed by investigating its effects on ovariectomy(OVX)-induced bone loss in mice and on receptor activator of NF-kappaB ligand(RANKL)-induced osteoclast differentiation in RAW264.7 cells.Network pharmacology analysis and molecular docking were employed to identify key targets,which were subsequently validated experimentally.Results:In vitro,Hed suppressed osteoclastogenesis by inhibiting the formation of osteoclasts and F-actin rings and by down-regulating osteoclastspecific genes(Atp6v0d2 and Acp5).In vivo,Hed significantly amelioratedOVX-induced bone loss,restoring trabecular bone volume fraction(BV/TV)and trabecular number(Tb.N),while reducing trabecular separation(Tb.Sp).Network pharmacology analysis identified 142 overlapping targets linking Hed to osteoporosis,including tumor necrosis factor alpha(TNF-α),interleukin-6(IL-6),and IL-1β,with enrichment in innate immune signaling and osteoclast differentiation.Molecular docking analysis indicated strong binding affinities between Hed and targets such as TNF-α,IL-6,and IL-1β.Experimentally,Hed was found to decrease RANKL,elevate osteoprotegerin(OPG),and suppress intestinalmRNA levels of pro-inflammatory cytokines such as IL-1β,IL-6,IL-17A,and TNF-α.Conclusion:Hed exerts significant anti-osteoporotic effects inOVX-induced osteoporosis through a dualmechanism involving the suppression of both osteoclastogenesis and innate immune signaling pathways.These findings highlighted Hed’s novel role in modulating immune-bone crosstalk,offering a promising strategy for treating osteolytic diseases without estrogenic side effects.展开更多
The cerebellum is receiving increasing attention for its cognitive,emotional,and social functions,as well as its unique metabolic profiles.Cerebellar microglia exhibit specialized and highly immunogenic phenotypes und...The cerebellum is receiving increasing attention for its cognitive,emotional,and social functions,as well as its unique metabolic profiles.Cerebellar microglia exhibit specialized and highly immunogenic phenotypes under both physiological and pathological conditions.These immune cells communicate with intrinsic and systemic factors and contribute to the structural and functional compartmentalization of the cerebellum.In this review,we discuss the roles of microglia in the cerebellar microenvironment,neuroinflammation,cerebellar adaptation,and neuronal activity,the associated molecular and cellular mechanisms,and potential therapeutic strategies targeting cerebellar microglia in the context of neuroinflammation.Future directions and unresolved questions in this field are further highlighted,particularly regarding therapeutic interventions targeting cerebellar microglia,functional mechanisms and activities of microglia in the cerebellar circuitry,neuronal connectivity,and neurofunctional outcomes of their activity.Cerebellar morphology and neuronal performance are influenced by both intrinsic and systemic factors that are actively monitored by microglia in both healthy and diseased states.Under pathological conditions,local subsets of microglia exhibit diverse responses to the altered microenvironment that contribute to the structural and functional compartmentalization of the cerebellum.Microglia in the cerebellum undergo early maturation during the embryonic stage and display specialized,highly immunogenic phenotypes.In summary,cerebellar microglia have the capacity to serve as regulatory tools that influence outcomes across a wide range of neurological and systemic conditions,including neurodevelopmental,neurodegenerative,metabolic,and stress-related disorders.展开更多
Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reti...Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reticulum that contributes toward its unique adaptability.It is now recognized that mitochondrial perturbations can activate various innate immune pathways,such as the nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome complex by propagating inflammatory signaling in response to damage-associated molecular patterns(DAMPs).The NLRP3 inflammasome is a multimeric protein complex and is a prominent regulator of innate immunity and cell death by mediating the activation of caspase-1,pro-inflammatory cytokines interleukin-1βand interleukin-18 and pro-pyroptotic protein gasdermin-D.While several studies have begun to demonstrate the relationship between various mitochondrial DAMPs(mtDAMPs)and NLRP3 inflammasome activation,the influence of various metabolic states on the production of these DAMPs and subsequent inflammatory profile remains poorly understood.This narrative review aimed to address this by highlighting the effects of skeletal muscle use and disuse on mitochondrial quality mechanisms including mitochondrial biogenesis,fusion,fission and mitophagy.Secondly,this review summarized the impact of alterations in mitochondrial quality control mechanisms following muscle denervation,aging,and exercise training in relation to NLRP3 inflammasome activation.By consolidating the current body of literature,this work aimed to further the understanding of innate immune signaling within skeletal muscle,which can highlight areas for future research and therapeutic strategies to regulate NLRP3 inflammasome activation during divergent metabolic conditions.展开更多
Innate immunity is the primary defense against viral infections,with Toll-like receptors(TLRs) playing a crucial role in this process.This study aims to highlight the effectiveness of a pyrrolo[3,2-d]pyrimidine deriva...Innate immunity is the primary defense against viral infections,with Toll-like receptors(TLRs) playing a crucial role in this process.This study aims to highlight the effectiveness of a pyrrolo[3,2-d]pyrimidine derivative(named TLR713),a potential TLR7 agonist,in inhibiting pseudorabies virus(PRV) replication both in vitro and in vivo.Tests on PK-15 cells demonstrated that TLR713 had no significant impact on cell viability,cell cycle progression,or apoptosis at concentrations of 0–3 μmol L^(–1).TLR713 could promote the phosphorylation of IκBα,p38,and JNK through TLR7,and increase the expression of inflammatory cytokines.In vitro,when cells were treated with TLR713,PRV proliferation was inhibited via TLR7 pathway.Analysis of the viral life cycle indicated that TLR713 could inhibit the replication of PRV,but not affect viral attachment,entry,assembly,or release.In vivo,TLR713 showed no side effects on mice at a concentration of 25 mg kg^(–1).It improved the survival rate of PRV-infected mice,reduced tissue viral load,and alleviated the inflammatory response.In summary,this study highlights the potential of TLR713 as a novel TLR7 agonist capable of inhibiting PRV replication and may offer new opportunities for developing antiviral therapies.展开更多
Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily...Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily involving abnormal development and damage of the dopaminergic system,pose significant public health challenges.Microglia,as the primary immune cells in the brain,are crucial in regulating neuronal circuit development and survival.From the embryonic stage to adulthood,microglia exhibit stage-specific gene expression profiles,transcriptome characteristics,and functional phenotypes,enhancing the susceptibility to early life stress.However,the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood.This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia,leading to dopaminergic system disorders,along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions.Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support(e.g.,insulin-like growth factor-1)and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning.Furthermore,blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission.Furthermore,inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress–induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic–pituitary–adrenal axis,the gut–brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.展开更多
Traumatic brain injury is a global health crisis,causing significant death and disability worldwide.Neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive im...Traumatic brain injury is a global health crisis,causing significant death and disability worldwide.Neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this response.Following traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain regions.Homeostatic astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are overexpressed.This altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive recovery.In addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional recovery.Current therapeutic strategies for traumatic brain injury are focused on preventing acute complications.Statins,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of astrocytes.In this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.展开更多
Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive imm...Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.展开更多
Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary e...Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary effects rather than reversing its pathogenic mechanisms(Jeong et al.,2019).The pathogenesis of IBD involves intestinal barrier dysfunction,tissue damage,and dysregulated innate and adaptive immune responses(de Souza et al.,2017).Elevated neutrophil activity has been reported in IBD(Danne et al.,2024),yet the precise roles and mechanisms of neutrophils in disease progression remain to be elucidated.展开更多
Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-i...Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.展开更多
The cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)pathway has significantly deepened our knowledge about innate immune sensing.The cGAS-STING pathway was originally identified as having a role in d...The cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)pathway has significantly deepened our knowledge about innate immune sensing.The cGAS-STING pathway was originally identified as having a role in detecting cytosolic deoxyribonucleic acid(DNA)for stimulating antiviral responses.Recently,the cGAS-STING pathway has increasingly been acknowledged to be important in tumor immunology with deterministic roles in cancer progression and therapeutic responses.This review will discuss the molecular mechanisms underlying cGAS-STING signaling,the paradoxical roles in cancer progression and suppression,and the relevance and translational potential of targeting this pathway,especially in the context of hepatocellular carcinoma(HCC).Emerging research directions and therapeutic strategies that leverage cGAS-STING activation to enhance anti-tumor immunity will also be highlighted.展开更多
BACKGROUND In the context of hepatobiliary and liver transplant surgery,ischemia-reperfusion(I/R)injury can occur due to temporary interruption of blood flow to the organ followed by a potentially damaging inflammator...BACKGROUND In the context of hepatobiliary and liver transplant surgery,ischemia-reperfusion(I/R)injury can occur due to temporary interruption of blood flow to the organ followed by a potentially damaging inflammatory response to reperfusion.Ma-crophages can drive inflammation in response to injury,but they can also pro-mote liver growth and resolution of chronic liver injury and fibrosis.In chronic liver injury models in mice,macrophage colony stimulating factor(CSF)1 stimu-lates pro-regenerative macrophages.AIM To determine whether stimulation of macrophages with macrophage CSF could promote liver repair after I/R injury.METHODS We investigated the impact of perisurgical treatment with a long-circulating CSF1-Fc conjugate on liver injury and hepatocyte proliferation after 70%ischemia for 60 minutes at 6 hours,48 hours and 7 days post reperfusion in rats.Circulating and liver tissue monocyte and macrophage subsets in the ischaemic and oxyge-nated lobes were assessed using quantitative PCR and flow cytometry.RESULTS CSF1-Fc treatment did not affect the extent of hepatocellular injury post-reperfu-sion,as indicated by serum transaminases.Liver I/R injury,especially necrotic area,was reduced in CSF1-Fc-treated rats 48 h post-surgery.This was associated with increased accumulation of macrophages in both the oxygenated and ischemic lobes(ILs),and peri-necrotic zone localization in the IL.CSF1-Fc treatment also promoted liver growth,associated with increased parenchymal and non-parenchymal cell proliferation.CSF1-Fc increased the abundance of CD43+non-classical monocytes,consistent with the role of CSF1 signaling in monocyte maturation,and increased CD163 expression on mature macrophages.CONCLUSION This study suggests CSF1 stimulation drives monocytes/macrophages towards a pro-regenerative response and perisurgical CSF1 treatment might augment liver regeneration in patients undergoing liver resection.展开更多
Trained immunity is a phenomenon in which brief exposure to an infectious agent or a vaccine can induce long-lasting changes in the host’s immune system,enhancing protection against subsequent infections.The concept ...Trained immunity is a phenomenon in which brief exposure to an infectious agent or a vaccine can induce long-lasting changes in the host’s immune system,enhancing protection against subsequent infections.The concept of trained immunity has a significant impact on the field of immunology and has the potential to revolutionize how we approach vaccination and infectious disease control.Investigations into trained immunity are rapidly advanc-ing and have led to the development of new vaccines and immunotherapeutic strategies that harness the power of this phenomenon.While more investigations are needed to fully understand the mechanisms of trained immunity and its potential limitations,the prospects for its future application in clinical practice are promising.Here,we describe trained immunity as a biological process and explore the innate cues,epigenetic changes,and metabolic reprogram-ming activities that affect how trained immunity is induced.展开更多
Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary d...Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary disease(COPD).Disruptions in microbial balance during RV infections can impair immune homeostasis and worsen disease outcomes.Recent studies emphasize RV-induced regulation of antiviral defenses,cytokine production,and immune tolerance.This review explores the interplay between RV,the immune system,and microbiota,highlighting the importance of these interactions in guiding effective therapies for respiratory in-fections.It advances existing literature by considering microbiota-mediated therapies as a novel approach to managing RV exacerbations in respiratory diseases like asthma and COPD.展开更多
Sepsis is characterized by immune dysregulation that are responsible for an increase in secondary in-fections and mortality.Acupuncture is a potential alternative treatment for sepsis.In this comprehensive literature ...Sepsis is characterized by immune dysregulation that are responsible for an increase in secondary in-fections and mortality.Acupuncture is a potential alternative treatment for sepsis.In this comprehensive literature review,we found that acupuncture is beneficial in treating immune disorders associated with sepsis.Acupuncture can improve immune disorders associated with sepsis and regulate the functions of innate and adaptive immune cells.Specifically,acupuncture can reduce the number of neutrophils in sep-sis,promote the polarization of macrophages towards M2-like macrophages,and alleviate inflammation by reducing the activation of microglia and astrocytes.Furthermore,acupuncture can increase the per-centage of T cells and modulate the balance between T cell subsets.The immunomodulatory mechanism of acupuncture in sepsis may be attributed to the balance of the autonomic nervous system,including activation of the sympathetic-adrenal axis,vagal-cholinergic pathway,and vagal-adrenal axis.In addition,acupuncture can inhibit inflammation by preserving the integrity of the intestinal barrier and regulating the composition of the intestinal microbiota.Clinical studies have also demonstrated that acupuncture can enhance the number of peripheral natural killer(NK)cells and T cell subsets,as well as the expres-sion of human leukocyte antigen DR(HLA-DR).Moreover,acupuncture can decrease the ratio of white blood cells to neutrophils and reduce the levels of inflammatory factors.Therefore,acupuncture has the potential to improve immune function in sepsis.Further investigation of its mechanism is expected to provide a scientific and reliable foundation for the application of acupuncture in sepsis treatment.展开更多
Ring finger protein 122(RNF122),an E3 ubiquitin ligase,orchestrates antiviral immune responses in mammals by targeting retinoic acid-inducible gene 1 and melanoma differentiation-associated gene 5 for ubiquitination.H...Ring finger protein 122(RNF122),an E3 ubiquitin ligase,orchestrates antiviral immune responses in mammals by targeting retinoic acid-inducible gene 1 and melanoma differentiation-associated gene 5 for ubiquitination.However,its functional relevance in teleosts has yet to be clearly defined,particularly regarding the identification of substrate-specific regulatory sites.This study characterized RNF122 from mandarin fish(Siniperca chuatsi),termed scRNF122,and investigated its regulatory impact on stimulator of interferon genes(STING)-mediated antiviral signaling.Results showed that scRNF122 expression was up-regulated in response to mandarin fish ranavirus(MRV)infection,and its overexpression suppressed scSTING-mediated interferon(IFN)production and enhanced MRV replication.Co-immunoprecipitation confirmed a direct interaction between scRNF122 and scSTING.Functional assays demonstrated that scRNF122 facilitated scSTING degradation through the ubiquitin-proteasome pathway,a process impeded by MG132 treatment.Ubiquitination analyses of various scSTING mutants revealed that scRNF122 catalyzed scSTING ubiquitination at K95,K117,and K155 residues.Moreover,scRNF122 significantly impaired scSTING-dependent antiviral responses by engaging negative regulatory elements within the signaling cascade.Overall,scRNF122 was identified as a negative modulator of STING-mediated IFN signaling in mandarin fish,diminishing STING-dependent antiviral activity and promoting its degradation via the ubiquitin-proteasome pathway at lysine residues K95,K117,and K155.These findings provide mechanistic insight into the post-translational control of STING in teleosts and establish a foundation for future investigations into antiviral immune regulation.展开更多
Objective To estimate the antiviral activities of ulvan derived from Ulva pertusa,and initiate a preliminary exploration into its mechanism for the potential utilization of ulvans in the future.Methods Employing metho...Objective To estimate the antiviral activities of ulvan derived from Ulva pertusa,and initiate a preliminary exploration into its mechanism for the potential utilization of ulvans in the future.Methods Employing methodologies rooted in molecular biology and virology,such as viral infection and FACS,the effect of ulvan on virus infection and the innate immune responses in cells were evaluated.Results Ulvan significantly restricted vesicular stomatitis virus(VSV)infection.Preliminary exploration on its mechanism indicated that ulvan activated the innate immune,and induced type I interferons(IFN-Ⅰ)expression to restrict viral infection.展开更多
In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing i...In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing is complex and involves a coordinated series of biological events,including inflammation,cell proliferation,and tissue remodeling.The innate immune system is important in the early stages of wound repair,with inflammation being a crucial initial phase in tissue rege-neration.However,the inflammatory response should be regulated,as excessive or dysregulated inflammation can impair healing.Platelet concentrates,specifi-cally PRF,have originated as promising tools to optimize the tissue repair process.PRF is a second-generation platelet concentrate,and the release of growth factors(GFs)plays a determining role in several aspects of wound healing,including promoting cell proliferation,stimulating angiogenesis,and modulating inflam-mation.PRF forms a fibrin matrix that entraps platelets and GFs.This structure allows for their sustained release over time,which is believed to provide a more favorable microenvironment for tissue repair.Recent research by Sá-Oliveira et al has provided valuable evidence supporting the efficacy of PRF in promoting wound healing.Their study,conducted on an animal model,demonstrated that PRF-based dressings were more effective in accelerating wound closure in the early stages of the healing process,enhancing tissue repair,and modulating the inflammatory response.We explore how PRF's unique properties contribute to a more controlled and effective healing process.By examining these findings,we aim to highlight PRF's potential as a promising therapeutic strategy for improved wound management.展开更多
Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polariz...Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polarization,to train the innate immune system by epigenic modification have been reported in laboratory animal research.Methods:In the current in vitro research,murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus,a coronavirus existed in mouse.At 3-,6-,12-,24-,and 48-h post infection(hpi.),the attached cells were washed with PBS and harvested in Trizol reagent.Then The harvest is subjected to transcriptome sequencing.Results:The transcriptome analysis showed the immediate(3 hpi.)up regulation of DEGs related to inflammation,like Il1b and Il6.DEGs related to M2 differential po-larization,like Irf4 showed up regulation at 24 hpi.,the late term after viral infection.In addition,DEGs related to metabolism and histone modification,like Ezh2 were de-tected,which might correlate with the trained immunity of macrophages.Conclusions:The current in vitro viral infection study showed the key innated im-munity character of macrophages,which suggested the replacement value of viral infection cells model,to reduce the animal usage in preclinical research.展开更多
Avian malaria,caused by parasites of the genus Plasmodium,is prevalent among wild bird populations worldwide and can have significant impact on avian health and populations.With the rise in global temperatures due to ...Avian malaria,caused by parasites of the genus Plasmodium,is prevalent among wild bird populations worldwide and can have significant impact on avian health and populations.With the rise in global temperatures due to climate change,concerns have arisen about the spread of southern malaria species,that potentially can affect previously unexposed bird populations.We studied juvenile siskins infected with two distinct malaria parasites:Plasmodium relictum(SGS1 lineage)and P.ashfordi(GRW2 lineage).While the former is common in the Northern Palearctic,the latter is primarily found in Central and Southern Africa.We assessed the impact of these infections on siskins'physiological well-being using resting metabolic rate(RMR)and interleukin-6(IL-6)levels.Changes in RMR reflect the energetic cost of disease,while IL-6 serves as a one of the inflammatory cytokines in the innate immune system's response to infection.Our experimental findings reveal distinct outcomes during the acute phase of SGS1 and GRW2 infections.Infection with SGS1 was marked by reduced RMR and IL-6 levels in siskins.A similar IL-6 pattern was observed in the GRW2 group initially,though it was not sustained.Additionally,GRW2-infected siskins showed distinct RMR dynamics compared to SGS1-infected birds.Our study did not conclusively demonstrate that tropical malaria has more severe effects on siskins.However,similarities with previous studies with SGS1 infected birds and variations in disease progression between the two experimental groups underscore the complexity of host-parasite interactions in avian malaria infections.展开更多
基金supported by grants from the National Natural Science Foundation of China(32172498 and W2433052)the National Key R&D Program of China(2021YFD1000500)the Natural Science Foundation of Guangdong,China(2023A1515010305)。
文摘The red imported fire ant,Solenopsis invicta Buren,is a highly invasive eusocial insect pest that threatens native biodiversity,agriculture,and human health.The innate immune system and intricate social immune responses of S.invicta pose challenges to the development of effective control strategies.Micro RNAs(mi RNAs)play critical roles in the post-transcriptional regulation of gene expression,which influences various biological processes,including immunity and host-pathogen interactions.While the mi RNA-mediated response of insects to pathogens has been extensively studied in solitary insects,little is known about the innate immune responses of individual members within a colony.To address this gap,we constructed small RNA libraries from Metarhizium anisopliae-infected S.invicta workers and investigated the temporal dynamics of mi RNA-mediated immune responses to the entomopathogen.Several differentially expressed mi RNAs were identified,and they were found to regulate genes involved in the Toll,IMD,and melanization immune pathways.Quantitative real-time PCR(q RT-PCR)was employed to analyze the spatiotemporal dynamics of key mi RNAs/target genes,specifically mi R-71/Mod SP1-Relish and mi R-7/Lysozyme2-Serine protease7.A dual luciferase assay(in vitro)was performed to validate the interactions between mi RNAs and their target genes.Overexpression of mi R-71 and mi R-7(via mi RNA mimics)efficiently suppressed their target genes,impaired the antifungal immune response of S.invicta and increased the susceptibility to M.anisopliae infection compared to controls.Furthermore,RNA interference-based gene silencing elucidated the roles of these immune genes in regulating fungal susceptibility,thus providing vital clues for developing virulent and effective mycoinsecticides using modern genetic engineering tools.
基金supported by the Scientific Research Project of Anhui ProvincialHealth Commission(Grant No.AHWJ2021b063)National Natural Scientific Foundation of China(Grant No.82160048)+1 种基金Natural Science Foundation Project of Anhui Province(Grant No.2308085MH265)Major Scientific Research Project of Anhui Provincial Department of Education(Grant No.2024AH040205).
文摘Objectives:Postmenopausal osteoporosis is the most common form of osteoporosis in clinical practice,affecting millions of postmenopausal women worldwide.Postmenopausal osteoporosis demands safe and effective therapies.This study aimed to evaluate the potential of hederagenin(Hed)for treating osteoporosis and to elucidate its underlying mechanisms of action.Methods:The anti-osteoporotic potential of Hed was assessed by investigating its effects on ovariectomy(OVX)-induced bone loss in mice and on receptor activator of NF-kappaB ligand(RANKL)-induced osteoclast differentiation in RAW264.7 cells.Network pharmacology analysis and molecular docking were employed to identify key targets,which were subsequently validated experimentally.Results:In vitro,Hed suppressed osteoclastogenesis by inhibiting the formation of osteoclasts and F-actin rings and by down-regulating osteoclastspecific genes(Atp6v0d2 and Acp5).In vivo,Hed significantly amelioratedOVX-induced bone loss,restoring trabecular bone volume fraction(BV/TV)and trabecular number(Tb.N),while reducing trabecular separation(Tb.Sp).Network pharmacology analysis identified 142 overlapping targets linking Hed to osteoporosis,including tumor necrosis factor alpha(TNF-α),interleukin-6(IL-6),and IL-1β,with enrichment in innate immune signaling and osteoclast differentiation.Molecular docking analysis indicated strong binding affinities between Hed and targets such as TNF-α,IL-6,and IL-1β.Experimentally,Hed was found to decrease RANKL,elevate osteoprotegerin(OPG),and suppress intestinalmRNA levels of pro-inflammatory cytokines such as IL-1β,IL-6,IL-17A,and TNF-α.Conclusion:Hed exerts significant anti-osteoporotic effects inOVX-induced osteoporosis through a dualmechanism involving the suppression of both osteoclastogenesis and innate immune signaling pathways.These findings highlighted Hed’s novel role in modulating immune-bone crosstalk,offering a promising strategy for treating osteolytic diseases without estrogenic side effects.
基金supported by grants from STI2030-Major Projects,No.2021ZD0204000(to YS)Key Strategic Science and Technology Cooperation Project of the Ministry of Science and Technology of China,No.SQ2023YFE0201430(to YS)+1 种基金the National Natural Science Foundation of China,Nos.31820103005(to YS),32200620(to LW)the Natural Science Foundation of Zhejiang Province of China,No.LZ24C090003(to YS)。
文摘The cerebellum is receiving increasing attention for its cognitive,emotional,and social functions,as well as its unique metabolic profiles.Cerebellar microglia exhibit specialized and highly immunogenic phenotypes under both physiological and pathological conditions.These immune cells communicate with intrinsic and systemic factors and contribute to the structural and functional compartmentalization of the cerebellum.In this review,we discuss the roles of microglia in the cerebellar microenvironment,neuroinflammation,cerebellar adaptation,and neuronal activity,the associated molecular and cellular mechanisms,and potential therapeutic strategies targeting cerebellar microglia in the context of neuroinflammation.Future directions and unresolved questions in this field are further highlighted,particularly regarding therapeutic interventions targeting cerebellar microglia,functional mechanisms and activities of microglia in the cerebellar circuitry,neuronal connectivity,and neurofunctional outcomes of their activity.Cerebellar morphology and neuronal performance are influenced by both intrinsic and systemic factors that are actively monitored by microglia in both healthy and diseased states.Under pathological conditions,local subsets of microglia exhibit diverse responses to the altered microenvironment that contribute to the structural and functional compartmentalization of the cerebellum.Microglia in the cerebellum undergo early maturation during the embryonic stage and display specialized,highly immunogenic phenotypes.In summary,cerebellar microglia have the capacity to serve as regulatory tools that influence outcomes across a wide range of neurological and systemic conditions,including neurodevelopmental,neurodegenerative,metabolic,and stress-related disorders.
文摘Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reticulum that contributes toward its unique adaptability.It is now recognized that mitochondrial perturbations can activate various innate immune pathways,such as the nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome complex by propagating inflammatory signaling in response to damage-associated molecular patterns(DAMPs).The NLRP3 inflammasome is a multimeric protein complex and is a prominent regulator of innate immunity and cell death by mediating the activation of caspase-1,pro-inflammatory cytokines interleukin-1βand interleukin-18 and pro-pyroptotic protein gasdermin-D.While several studies have begun to demonstrate the relationship between various mitochondrial DAMPs(mtDAMPs)and NLRP3 inflammasome activation,the influence of various metabolic states on the production of these DAMPs and subsequent inflammatory profile remains poorly understood.This narrative review aimed to address this by highlighting the effects of skeletal muscle use and disuse on mitochondrial quality mechanisms including mitochondrial biogenesis,fusion,fission and mitophagy.Secondly,this review summarized the impact of alterations in mitochondrial quality control mechanisms following muscle denervation,aging,and exercise training in relation to NLRP3 inflammasome activation.By consolidating the current body of literature,this work aimed to further the understanding of innate immune signaling within skeletal muscle,which can highlight areas for future research and therapeutic strategies to regulate NLRP3 inflammasome activation during divergent metabolic conditions.
基金financially supported by the Key R&D Special Project of Henan Province,China (241111110300)the National Natural Science Foundation of China (32402849)+2 种基金the Department of Henan Science and Technology,China (252102110035)the Doctoral Research Initiation Fund of Henan University of Animal Husbandry and Economy,China (2022HNUAHEDF033)Key Research Projects of Higher Education Institutions in Henan Province,China (25A150025)。
文摘Innate immunity is the primary defense against viral infections,with Toll-like receptors(TLRs) playing a crucial role in this process.This study aims to highlight the effectiveness of a pyrrolo[3,2-d]pyrimidine derivative(named TLR713),a potential TLR7 agonist,in inhibiting pseudorabies virus(PRV) replication both in vitro and in vivo.Tests on PK-15 cells demonstrated that TLR713 had no significant impact on cell viability,cell cycle progression,or apoptosis at concentrations of 0–3 μmol L^(–1).TLR713 could promote the phosphorylation of IκBα,p38,and JNK through TLR7,and increase the expression of inflammatory cytokines.In vitro,when cells were treated with TLR713,PRV proliferation was inhibited via TLR7 pathway.Analysis of the viral life cycle indicated that TLR713 could inhibit the replication of PRV,but not affect viral attachment,entry,assembly,or release.In vivo,TLR713 showed no side effects on mice at a concentration of 25 mg kg^(–1).It improved the survival rate of PRV-infected mice,reduced tissue viral load,and alleviated the inflammatory response.In summary,this study highlights the potential of TLR713 as a novel TLR7 agonist capable of inhibiting PRV replication and may offer new opportunities for developing antiviral therapies.
基金supported by the National Natural Science Foundation of China,Nos.82304990(to NY),81973748(to JC),82174278(to JC)the National Key R&D Program of China,No.2023YFE0209500(to JC)+4 种基金China Postdoctoral Science Foundation,No.2023M732380(to NY)Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine,No.202102010014(to JC)Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University,No.201911(to JC)National Innovation and Entrepreneurship Training Program for Undergraduates in China,No.202310559128(to NY and QM)Innovation and Entrepreneurship Training Program for Undergraduates at Jinan University,Nos.CX24380,CX24381(both to NY and QM)。
文摘Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily involving abnormal development and damage of the dopaminergic system,pose significant public health challenges.Microglia,as the primary immune cells in the brain,are crucial in regulating neuronal circuit development and survival.From the embryonic stage to adulthood,microglia exhibit stage-specific gene expression profiles,transcriptome characteristics,and functional phenotypes,enhancing the susceptibility to early life stress.However,the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood.This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia,leading to dopaminergic system disorders,along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions.Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support(e.g.,insulin-like growth factor-1)and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning.Furthermore,blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission.Furthermore,inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress–induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic–pituitary–adrenal axis,the gut–brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.
基金supported by grants PICT 2019-08512017-2203,UBACYT and PIP CONICET(to AJR).
文摘Traumatic brain injury is a global health crisis,causing significant death and disability worldwide.Neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this response.Following traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain regions.Homeostatic astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are overexpressed.This altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive recovery.In addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional recovery.Current therapeutic strategies for traumatic brain injury are focused on preventing acute complications.Statins,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of astrocytes.In this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.
基金Supported by Shenzhen Medical Research Fund,No.D2301010Shenzhen Science and Technology Program,No.RCYX20231211090346060。
文摘Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.
基金supported by the National Key R&D Program of China(2023YFA1800100and 2024YFF1206600)the National Natural Science Foundation of China(32100664)the Basic and Applied Basic Research Foundation of Guangdong Province(2024B1515040019 and 2022A1515012042).
文摘Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary effects rather than reversing its pathogenic mechanisms(Jeong et al.,2019).The pathogenesis of IBD involves intestinal barrier dysfunction,tissue damage,and dysregulated innate and adaptive immune responses(de Souza et al.,2017).Elevated neutrophil activity has been reported in IBD(Danne et al.,2024),yet the precise roles and mechanisms of neutrophils in disease progression remain to be elucidated.
基金supported by research grants from the Ningbo Science and Technology Plan Project,No.2022Z143hezuo(to BL)the National Natural Science Foundation of China,No.82201520(to XD)。
文摘Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.
基金supported by the National Natural Science Foundation of China-Distinguished Young Scholars Fund(Grant No.82425043)Research Grant Council Collaborative Research Fund[RGC CRF](Grant Nos.C7008-22G and C5016-23G)+5 种基金Health and Medical Research Fund[HMRF](Grant Nos.08192516 and 11221526)Research Grant Council Research Fellow Scheme[RGC RFS]2024(Grant No.RFS2425-7S01)Research Grant Council Research Impact Fund[RGC RIF](Grant No.R5008-22)Research Grant Council Theme Based Research Scheme[RGC TBRS](Grant No.T12-716/22-R)Shenzhen Science and Technology Program(Grant No.ZDSYS20210623091811035)supported by the Centre for Oncology and Immunology under the Health@InnoHK initiative funded by the Innovation and Technology Commission,the Government of Hong Kong SAR,China.
文摘The cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)pathway has significantly deepened our knowledge about innate immune sensing.The cGAS-STING pathway was originally identified as having a role in detecting cytosolic deoxyribonucleic acid(DNA)for stimulating antiviral responses.Recently,the cGAS-STING pathway has increasingly been acknowledged to be important in tumor immunology with deterministic roles in cancer progression and therapeutic responses.This review will discuss the molecular mechanisms underlying cGAS-STING signaling,the paradoxical roles in cancer progression and suppression,and the relevance and translational potential of targeting this pathway,especially in the context of hepatocellular carcinoma(HCC).Emerging research directions and therapeutic strategies that leverage cGAS-STING activation to enhance anti-tumor immunity will also be highlighted.
基金Supported by the German Research Foundation(Deutsche Forschungsgemeinschaft)and the Australian National Health and Medical Research Council and the Mater Foundation.
文摘BACKGROUND In the context of hepatobiliary and liver transplant surgery,ischemia-reperfusion(I/R)injury can occur due to temporary interruption of blood flow to the organ followed by a potentially damaging inflammatory response to reperfusion.Ma-crophages can drive inflammation in response to injury,but they can also pro-mote liver growth and resolution of chronic liver injury and fibrosis.In chronic liver injury models in mice,macrophage colony stimulating factor(CSF)1 stimu-lates pro-regenerative macrophages.AIM To determine whether stimulation of macrophages with macrophage CSF could promote liver repair after I/R injury.METHODS We investigated the impact of perisurgical treatment with a long-circulating CSF1-Fc conjugate on liver injury and hepatocyte proliferation after 70%ischemia for 60 minutes at 6 hours,48 hours and 7 days post reperfusion in rats.Circulating and liver tissue monocyte and macrophage subsets in the ischaemic and oxyge-nated lobes were assessed using quantitative PCR and flow cytometry.RESULTS CSF1-Fc treatment did not affect the extent of hepatocellular injury post-reperfu-sion,as indicated by serum transaminases.Liver I/R injury,especially necrotic area,was reduced in CSF1-Fc-treated rats 48 h post-surgery.This was associated with increased accumulation of macrophages in both the oxygenated and ischemic lobes(ILs),and peri-necrotic zone localization in the IL.CSF1-Fc treatment also promoted liver growth,associated with increased parenchymal and non-parenchymal cell proliferation.CSF1-Fc increased the abundance of CD43+non-classical monocytes,consistent with the role of CSF1 signaling in monocyte maturation,and increased CD163 expression on mature macrophages.CONCLUSION This study suggests CSF1 stimulation drives monocytes/macrophages towards a pro-regenerative response and perisurgical CSF1 treatment might augment liver regeneration in patients undergoing liver resection.
文摘Trained immunity is a phenomenon in which brief exposure to an infectious agent or a vaccine can induce long-lasting changes in the host’s immune system,enhancing protection against subsequent infections.The concept of trained immunity has a significant impact on the field of immunology and has the potential to revolutionize how we approach vaccination and infectious disease control.Investigations into trained immunity are rapidly advanc-ing and have led to the development of new vaccines and immunotherapeutic strategies that harness the power of this phenomenon.While more investigations are needed to fully understand the mechanisms of trained immunity and its potential limitations,the prospects for its future application in clinical practice are promising.Here,we describe trained immunity as a biological process and explore the innate cues,epigenetic changes,and metabolic reprogram-ming activities that affect how trained immunity is induced.
文摘Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary disease(COPD).Disruptions in microbial balance during RV infections can impair immune homeostasis and worsen disease outcomes.Recent studies emphasize RV-induced regulation of antiviral defenses,cytokine production,and immune tolerance.This review explores the interplay between RV,the immune system,and microbiota,highlighting the importance of these interactions in guiding effective therapies for respiratory in-fections.It advances existing literature by considering microbiota-mediated therapies as a novel approach to managing RV exacerbations in respiratory diseases like asthma and COPD.
基金Supported by the National Natural Science Foundation of China:No.82374563,82004467,82305370China Postdoctoral Science Foundation:No.2022M721536+1 种基金Tianjin Graduate Research Innovation Project:2022BKY177TUTCM Graduate Research Innovation Project:YJSKC-20221016。
文摘Sepsis is characterized by immune dysregulation that are responsible for an increase in secondary in-fections and mortality.Acupuncture is a potential alternative treatment for sepsis.In this comprehensive literature review,we found that acupuncture is beneficial in treating immune disorders associated with sepsis.Acupuncture can improve immune disorders associated with sepsis and regulate the functions of innate and adaptive immune cells.Specifically,acupuncture can reduce the number of neutrophils in sep-sis,promote the polarization of macrophages towards M2-like macrophages,and alleviate inflammation by reducing the activation of microglia and astrocytes.Furthermore,acupuncture can increase the per-centage of T cells and modulate the balance between T cell subsets.The immunomodulatory mechanism of acupuncture in sepsis may be attributed to the balance of the autonomic nervous system,including activation of the sympathetic-adrenal axis,vagal-cholinergic pathway,and vagal-adrenal axis.In addition,acupuncture can inhibit inflammation by preserving the integrity of the intestinal barrier and regulating the composition of the intestinal microbiota.Clinical studies have also demonstrated that acupuncture can enhance the number of peripheral natural killer(NK)cells and T cell subsets,as well as the expres-sion of human leukocyte antigen DR(HLA-DR).Moreover,acupuncture can decrease the ratio of white blood cells to neutrophils and reduce the levels of inflammatory factors.Therefore,acupuncture has the potential to improve immune function in sepsis.Further investigation of its mechanism is expected to provide a scientific and reliable foundation for the application of acupuncture in sepsis treatment.
基金supported by the National Key Research and Development Program of China(2022YFE0203900,2024YFD2401101)China Agriculture Research System(CARS-46)+1 种基金National Natural Science Foundation of China(32473201)Guangdong S&T Program(2022B1111030001,2024B1212040007)。
文摘Ring finger protein 122(RNF122),an E3 ubiquitin ligase,orchestrates antiviral immune responses in mammals by targeting retinoic acid-inducible gene 1 and melanoma differentiation-associated gene 5 for ubiquitination.However,its functional relevance in teleosts has yet to be clearly defined,particularly regarding the identification of substrate-specific regulatory sites.This study characterized RNF122 from mandarin fish(Siniperca chuatsi),termed scRNF122,and investigated its regulatory impact on stimulator of interferon genes(STING)-mediated antiviral signaling.Results showed that scRNF122 expression was up-regulated in response to mandarin fish ranavirus(MRV)infection,and its overexpression suppressed scSTING-mediated interferon(IFN)production and enhanced MRV replication.Co-immunoprecipitation confirmed a direct interaction between scRNF122 and scSTING.Functional assays demonstrated that scRNF122 facilitated scSTING degradation through the ubiquitin-proteasome pathway,a process impeded by MG132 treatment.Ubiquitination analyses of various scSTING mutants revealed that scRNF122 catalyzed scSTING ubiquitination at K95,K117,and K155 residues.Moreover,scRNF122 significantly impaired scSTING-dependent antiviral responses by engaging negative regulatory elements within the signaling cascade.Overall,scRNF122 was identified as a negative modulator of STING-mediated IFN signaling in mandarin fish,diminishing STING-dependent antiviral activity and promoting its degradation via the ubiquitin-proteasome pathway at lysine residues K95,K117,and K155.These findings provide mechanistic insight into the post-translational control of STING in teleosts and establish a foundation for future investigations into antiviral immune regulation.
文摘Objective To estimate the antiviral activities of ulvan derived from Ulva pertusa,and initiate a preliminary exploration into its mechanism for the potential utilization of ulvans in the future.Methods Employing methodologies rooted in molecular biology and virology,such as viral infection and FACS,the effect of ulvan on virus infection and the innate immune responses in cells were evaluated.Results Ulvan significantly restricted vesicular stomatitis virus(VSV)infection.Preliminary exploration on its mechanism indicated that ulvan activated the innate immune,and induced type I interferons(IFN-Ⅰ)expression to restrict viral infection.
基金Supported by The Oman Ministry of Higher Education,Research,and Innovation,No.BFP/RGP/HSS/24/015.
文摘In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing is complex and involves a coordinated series of biological events,including inflammation,cell proliferation,and tissue remodeling.The innate immune system is important in the early stages of wound repair,with inflammation being a crucial initial phase in tissue rege-neration.However,the inflammatory response should be regulated,as excessive or dysregulated inflammation can impair healing.Platelet concentrates,specifi-cally PRF,have originated as promising tools to optimize the tissue repair process.PRF is a second-generation platelet concentrate,and the release of growth factors(GFs)plays a determining role in several aspects of wound healing,including promoting cell proliferation,stimulating angiogenesis,and modulating inflam-mation.PRF forms a fibrin matrix that entraps platelets and GFs.This structure allows for their sustained release over time,which is believed to provide a more favorable microenvironment for tissue repair.Recent research by Sá-Oliveira et al has provided valuable evidence supporting the efficacy of PRF in promoting wound healing.Their study,conducted on an animal model,demonstrated that PRF-based dressings were more effective in accelerating wound closure in the early stages of the healing process,enhancing tissue repair,and modulating the inflammatory response.We explore how PRF's unique properties contribute to a more controlled and effective healing process.By examining these findings,we aim to highlight PRF's potential as a promising therapeutic strategy for improved wound management.
基金CAMs innovation Fund for Medical Sciences,Grant/Award Number:2022-12M-CoV19-005National Key Projects,Grant/Award Number:2023YFF0724900 and 2021YFF0702802。
文摘Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polarization,to train the innate immune system by epigenic modification have been reported in laboratory animal research.Methods:In the current in vitro research,murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus,a coronavirus existed in mouse.At 3-,6-,12-,24-,and 48-h post infection(hpi.),the attached cells were washed with PBS and harvested in Trizol reagent.Then The harvest is subjected to transcriptome sequencing.Results:The transcriptome analysis showed the immediate(3 hpi.)up regulation of DEGs related to inflammation,like Il1b and Il6.DEGs related to M2 differential po-larization,like Irf4 showed up regulation at 24 hpi.,the late term after viral infection.In addition,DEGs related to metabolism and histone modification,like Ezh2 were de-tected,which might correlate with the trained immunity of macrophages.Conclusions:The current in vitro viral infection study showed the key innated im-munity character of macrophages,which suggested the replacement value of viral infection cells model,to reduce the animal usage in preclinical research.
基金supported by the Russian Science Foundation grant(grant Ng 20-14-00049).
文摘Avian malaria,caused by parasites of the genus Plasmodium,is prevalent among wild bird populations worldwide and can have significant impact on avian health and populations.With the rise in global temperatures due to climate change,concerns have arisen about the spread of southern malaria species,that potentially can affect previously unexposed bird populations.We studied juvenile siskins infected with two distinct malaria parasites:Plasmodium relictum(SGS1 lineage)and P.ashfordi(GRW2 lineage).While the former is common in the Northern Palearctic,the latter is primarily found in Central and Southern Africa.We assessed the impact of these infections on siskins'physiological well-being using resting metabolic rate(RMR)and interleukin-6(IL-6)levels.Changes in RMR reflect the energetic cost of disease,while IL-6 serves as a one of the inflammatory cytokines in the innate immune system's response to infection.Our experimental findings reveal distinct outcomes during the acute phase of SGS1 and GRW2 infections.Infection with SGS1 was marked by reduced RMR and IL-6 levels in siskins.A similar IL-6 pattern was observed in the GRW2 group initially,though it was not sustained.Additionally,GRW2-infected siskins showed distinct RMR dynamics compared to SGS1-infected birds.Our study did not conclusively demonstrate that tropical malaria has more severe effects on siskins.However,similarities with previous studies with SGS1 infected birds and variations in disease progression between the two experimental groups underscore the complexity of host-parasite interactions in avian malaria infections.
