The South Central Axis in Beijing showcases China’s image and highlights its cultural confidence.THE Central Axis is the centerpiece of the Chinese capital’s urban spatial layout.The southern extended section of the...The South Central Axis in Beijing showcases China’s image and highlights its cultural confidence.THE Central Axis is the centerpiece of the Chinese capital’s urban spatial layout.The southern extended section of the Central Axis,or the South Central Axis,stretches from the Yongdingmen Gate Tower in the north to the South Fifth Ring Road in the south.While being a strategic transport link facilitating the coordinated development of the Beijing-Tianjin-Hebei region,it also showcases China’s vision for the future and highlights its cultural confidence.展开更多
Accumulating evidence indicates that the neuro-immune axis is central to gastric cancer pathogenesis.Dynamic,bidirectional signaling between neural circuits and immune cells promotes tumor progression,shapes an immuno...Accumulating evidence indicates that the neuro-immune axis is central to gastric cancer pathogenesis.Dynamic,bidirectional signaling between neural circuits and immune cells promotes tumor progression,shapes an immunosuppressive microenvironment,and contributes to therapeutic resistance.We synthesize current knowledge on how autonomic(sympathetic and parasympathetic)and sensory innervation regulate gastric cancer biology.These circuits act through neurotransmitters(catecholamines,acetylcholine)and neuropeptides(substance P[SP],calcitonin gene-related peptide[CGRP])to foster tumor growth and angiogenesis,facilitate perineural invasion,and enable immune evasion by recruiting suppressive myeloid and lymphoid populations and by inducing checkpoint molecule expression.We also examine how chronic stress and the microbiota-gut-brain axis intensify immunosuppression via glucocorticoid signaling and microbially derived metabolites.In parallel,we discuss why current immunotherapies achieve only modest response rates(approximately 10%-20%)in many settings,emphasizing neurally mediated mechanisms of resistance.We evaluate therapeutic strategies that target the neuro-immune axis-including pharmacological neuromodulation,selective neural ablation,and rational combination regimens-and outline how single-cell approaches and neural-tumor-microenvironment organoid models can accelerate mechanism-driven translation.This review aims to integrate current evidence from neuroscience and immuno-oncology to construct a conceptual framework for neuro-immune regulation in gastric cancer and to identify potential therapeutic strategies to overcome treatment resistance by targeting neural-tumor-immune crosstalk.展开更多
Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
Cholangiocarcinoma(CCA)is a highly malignant tumor of the biliary tract with a poor prognosis.Currently,specific methods for the early diagnosis and risk stratification if CCA are lacking.With the emergence of the“gu...Cholangiocarcinoma(CCA)is a highly malignant tumor of the biliary tract with a poor prognosis.Currently,specific methods for the early diagnosis and risk stratification if CCA are lacking.With the emergence of the“gut-biliary-liver axis”concept,the intestinal and biliary microbiota are being increasingly recognized to play key roles in the initiation and progression of CCA.This review systematically synthesizes recent clinical and basic research and outlines characteristic patterns of dysbiosis in the feces,bile,and tumor tissues of patients with CCA.It further discusses key mechanisms,including microbiota-bile acid-biliary epithelial signaling,pathogen-associated molecular patterns-mediated chronic inflammation,and immune-metabolic remodeling.It also examines the associations of these mechanisms with tumor progression and treatment responses.On this basis,the review evaluates the potential of intestinal and biliary microbiota and their metabolites as biomarkers for the diagnosis,prognosis,and prediction of the treatment response of CCA.We believe this review demonstrates a theoretical basis for microbiota-targeted precision prevention and therapeutic strategies for the disease.展开更多
Background:Immunosuppression compromises the host’s ability to combat pathogens,thereby increasing susceptibility to multisystem disorders.However,safe and effective curative treatments for this condition are current...Background:Immunosuppression compromises the host’s ability to combat pathogens,thereby increasing susceptibility to multisystem disorders.However,safe and effective curative treatments for this condition are currently lacking.Modulating the gut microbiota and their metabolites represents a promising therapeutic strategy.Notably,the Chinese herbal compound Yunzhi Guben Gao(YZG)has demonstrated multi-target immunomodulatory potential.Methods:A mouse model of dexamethasone-induced immunosuppression was employed to evaluate the effects of YZG.Immune organ indices(thymus,spleen),serum cytokine levels(IL-2,TNF-α),mucosal immunity markers(pulmonary/colonic SIgA),gut microbiota structure,and short-chain fatty acids(SCFAs)abundance were evaluated.Key microbial genera and metabolites were identified via Spearman correlation analysis.Pseudo-germ-free model mice established via quadruple antibiotic treatment combined with isovaleric acid intervention were employed to evaluate whether YZG efficacy depends on the intestinal microbiota and its metabolites,and whether its intrinsic mechanisms involve the promotion of isovaleric acid production.Results:YZG intervention ameliorated systemic and mucosal immune function in immunosuppressed mice.Mechanistically,YZG remodeled gut microbiota structure and significantly increased SCFAs levels.Notably,the abundance of the genus Ligilactobacillus exhibited the strongest positive correlation with isovaleric acid levels.Ligilactobacillus abundance was also positively correlated with immune-enhancing parameters and negatively correlated with the proinflammatory cytokine TNF-α,suggesting that Ligilactobacillus plays a pivotal role in the YZG regulatory network.Experiments using pseudo-germ-free mice and isovaleric acid intervention further demonstrated that the immunoprotective effects of YZG are closely related to intestinal microbiota remodeling and increased isovaleric acid production.Conclusion:YZG alleviates immunosuppression through multiple mechanisms,primarily involving the enrichment of the probiotic genus Ligilactobacillus and the consequent increase in isovaleric acid production.This process coordinately modulates mucosal immunity,cytokine networks,and immune organ function.The elucidation of this“microbiota-metabolite-immunity”axis provides both a pharmacological basis for the clinical application of YZG and novel immune-restorative strategies targeting gut microecological regulation.展开更多
Oncology Research Editorial Office Published:19 January 2026 The published article titled“ABCB5-ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells”has been retracted from Oncology Research,Vol.25,No.3...Oncology Research Editorial Office Published:19 January 2026 The published article titled“ABCB5-ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells”has been retracted from Oncology Research,Vol.25,No.3,2017,pp.305-316.DOI:10.3727/096504016X14734149559061 URL:https://www.techscience.com/or/v25n3/56810.展开更多
Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and ...Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and osteoclast activity.However,the majority of research to date has focused on the direct effects of peripheral nerves and their neurotransmitters on bone regeneration.Emerging studies have begun to reveal a more intricate role of nerves in regulating the immune microenvironment,which is crucial for bone regeneration.This review summarizes how nerves influence bone regeneration through modulation of the immune microenvironment.We first discuss the changes in peripheral nerves during the regenerative process.We then describe conduction and paracrine pathways through which nerves affect the osteogenic immune microenvironment,emphasizing nerves,neural factors,and their impacts.Our goal is to deepen the understanding of the nerve-immune axis in bone regeneration.A better grasp of how nerves influence the osteogenic immune microenvironment may lead to new strategies that integrate the nervous,immune,and skeletal systems to promote bone regeneration.展开更多
BACKGROUND Post-stroke depression(PSD)is associated with hypothalamic-pituitary-adrenal(HPA)axis dysfunction and neurotransmitter deficits.Selective serotonin reuptake inhibitors(SSRIs)are commonly used,but their effi...BACKGROUND Post-stroke depression(PSD)is associated with hypothalamic-pituitary-adrenal(HPA)axis dysfunction and neurotransmitter deficits.Selective serotonin reuptake inhibitors(SSRIs)are commonly used,but their efficacy is limited.This study investigated whether combining SSRIs with traditional Chinese medicine(TCM)Free San could enhance their therapeutic effects.AIM To evaluate the clinical efficacy and safety of combining SSRIs with Free San in treating PSD,and to assess its impact on HPA axis function.METHODS Ninety-two patients with PSD were enrolled and randomly divided into control groups(n=46)and study groups(n=46).The control group received the SSRI paroxetine alone,whereas the study group received paroxetine combined with Free San for 4 weeks.Hamilton Depression Scale and TCM syndrome scores were assessed before and after treatment.Serum serotonin,norepinephrine,cortisol,cor-ticotropin-releasing hormone,and adrenocorticotropic hormone were measured.The treatment responses and adverse reactions were recorded.RESULTS After treatment,the Hamilton Depression Scale and TCM syndrome scores were significantly lower in the study group than in the control group(P<0.05).Serum serotonin and norepinephrine levels were significantly higher in the study group than in the control group,whereas cortisol,corticotropin-releasing hormone,and adrenocorticotropic hormone levels were significantly lower(P<0.05).The total efficacy rates were 84.78%and 65.22%in the study and control groups,respectively(P<0.05).No significant differences in adverse reactions were observed between the two groups(P>0.05).CONCLUSION Combining SSRIs with Free San can enhance therapeutic efficacy,improve depressive symptoms,and regulate HPA axis function in patients with PSD with good safety and clinical application value.展开更多
Background Excessive abdominal fat in broilers not only reduces feed efficiency and increases processing costs but also raises environmental concerns.This pathological overaccumulation results from complex metabolic d...Background Excessive abdominal fat in broilers not only reduces feed efficiency and increases processing costs but also raises environmental concerns.This pathological overaccumulation results from complex metabolic dysregulation across multiple organs.While current research largely centers on adipogenesis within adipose tissue,a comprehensive understanding of the cross-organ regulatory factors influencing this process remains elusive.Results Here,we employed a high-fat diet(HFD)model and multi-omics approaches to investigate cross-organ regulatory mechanisms underlying abdominal fat deposition in broilers.Our results demonstrated that HFD not only promoted fat accumulation but also altered meat quality traits.Through 16S rRNA amplicon sequencing,we identified significant gut microbiota dysbiosis in HFD-fed chickens,manifested by an increased abundance of Lactobacillus and a decreased abundance of Enterococcus.However,jejunal microbiota transplantation from HFD donors did not induce abdominal fat deposition in recipient chickens.Metabolomic profiling revealed that HFD elevated the level of succinic acid,a metabolite positively correlated with Lactobacillus abundance and potentially generated by Lactobacillus.This increase in succinic acid(SA)further triggered metabolic inflammation response in both jejunal tissue and serum.In vivo validation established succinic acid as a key inflammatory mediator facilitating HFD-induced cross-organ communication between the jejunum and abdominal adipose tissue,enhancing intestinal lipid uptake and subsequent abdominal fat deposition.Bulk and single-nucleus RNA sequencing(snRNA-seq)revealed that HFD induced macrophage population expansion and intensified adipocyte-macrophage crosstalk.Adipocyte-macrophage co-culture systems further elucidated that macrophages are an indispensable factor in succinic acid-induced fat deposition.Conclusion This study delineates a succinic acid-driven"gut-fat axis"governing abdominal fat deposition in broilers,integrating gut microbiota dysbiosis and macrophage-mediated inflammatory adipogenesis.By identifying succinic acid as a cross-organ signaling molecule that enhances lipid absorption and activates macrophage-dependent adipogenesis,we establish systemic metabolic-immune crosstalk as a pivotal regulatory mechanism.These findings redefine fat deposition as a process extending beyond adipose-centric models,advancing multi-omics-guided strategies for sustainable poultry production.展开更多
An increasing amount of evidence shows that type I interferon response,which is induced by cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)and stimulator of interferon genes(STING)is closely assoc...An increasing amount of evidence shows that type I interferon response,which is induced by cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)and stimulator of interferon genes(STING)is closely associated with health and neuroinflammatory diseases.Abnormal activation or loss of control of the cGAS-STING axis affects the development of neuroinflammation.Thus,we examined its role in major neurological diseases,including traumatic brain injury,Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,multiple sclerosis,herpes simplex encephalitis,and ataxia-telangiectasia.Additionally,targeted intervention of the cGAS-STING axis to control neuroinflammation and treat related diseases has become the focus of current clinical research.This article describes the development of cGAS inhibitors and small molecules that target the cGAS-STING axis and explores the potential applications of STING inhibitors and agonists in clinical research.In summary,the cGAS-STING axis may impact neurological diseases more than a single protein or gene.Future studies should focus on elucidating the functional dynamics and regulatory networks of this axis and delineating its crosstalk with other signaling cascades.These investigations will provide mechanistic insights for developing targeted therapeutic strategies for associated disorders and potentially facilitate drug repurposing across diverse disease contexts.展开更多
BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,...BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,has been shown to significantly improve clinical symptoms in patients with CAG,as demonstrated by a multicenter cohort study(overall effective rate:82.5%,P<0.01).However,the unclear molecular mechanisms and therapeutic targets of AWD limit its international acceptance.AIM To investigate the therapeutic mechanisms of AWD against CAG from an integrated perspective.METHODS In this study,N-methyl-N’-nitro-N-nitrosoguanidine was used to establish a CAG rat model.Serum-derived constituents transferred from AWD were first identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry.The concentrations of inflammatory cytokines in serum samples were determined by enzyme-linked immunosorbent assay.Moreover,gastric mucosal tissues were analyzed by quantitative realtime polymerase chain reaction to measure messenger RNA(mRNA)levels of the NLRP3 inflammasome.Western blotting was used to detect the protein expression of NLRP3,caspase-1,and interleukin(IL)-1β.To elucidate the regulatory mechanisms underlying AWD treatment,structural alterations of the gut microbiota(GM)and associated metabolites were analyzed using integrated high-throughput sequencing(16S rRNA)and liquid chromatography-mass spectrometry based untargeted metabolomics.This comprehensive approach systematically clarified AWD’s multi-target therapeutic mechanisms against CAG.RESULTS AWD notably reduced serum levels of pro-inflammatory cytokines,such as IL-1β,IL-18,tumor necrosis factor-α,and lipopolysaccharide,demonstrating significant statistical differences(all P<0.01).Additionally,AWD substantially inhibited NLRP3 mRNA expression in gastric mucosal tissue(P<0.01)and concurrently decreased the protein abundance of NLRP3,IL-1β,and caspase-1(all P<0.01),thereby suppressing inflammasome signaling activation.GM analysis indicated that AWD intervention significantly increased the relative abundance of beneficial bacteria.Associated microbial metabolites likely inhibited the NLRP3 inflammasome pathway by modulating immune cell function.Non-targeted metabolomics further indicated that AWD exerted anti-inflammatory effects by regulating critical metabolic pathways,including the Kaposi’s sarcoma-associated herpesvirus infection pathway,autophagy processes,and glycosylphosphatidylinositol-anchor biosynthesis.CONCLUSION AWD alleviates the pathological progression of CAG through multi-target synergistic mechanisms.On one hand,AWD directly suppresses gastric mucosal inflammation by inhibiting NLRP3 inflammasome activation.On the other hand,AWD remodels intestinal microbiota-metabolite homeostasis,enhances intestinal barrier function,and regulates mucosal immune responses.展开更多
Objective This study investigated the effect of reducing soluble epoxide hydrolase(sEH,encoded by the Ephx2 gene)on the mediation of EETs metabolism during ferroptosis in emphysema in vivo.Methods Male C57BL/6J wild-t...Objective This study investigated the effect of reducing soluble epoxide hydrolase(sEH,encoded by the Ephx2 gene)on the mediation of EETs metabolism during ferroptosis in emphysema in vivo.Methods Male C57BL/6J wild-type(WT)and Ephx2^(-/-)mice received whole-body exposure to either cigarette smoke(CS)or air for 16 weeks.The alveolar structure,pulmonary function,lung tissue morphology,cell death,and ferroptosis levels were assessed following exposure.Results CS exposure caused emphysema,reduced pulmonary function,and induced ferroptosis in mice compared with exposure to air.In contrast,following CS exposure,Ephx2^(-/-)mice exhibited significantly lower levels of emphysema,impaired lung function,lung cell death,intracellular iron,lipid reactive oxygen species,cyclooxygenase-2,4-hydroxynonenal,and malondialdehyde levels than those of WT mice.However,Ephx2^(-/-)mice exhibited higher levels of glutathione and ferritin heavy chain 1 than those of WT mice.SLC7A11 expression was significantly reduced,whereas glutathione peroxidase 4 expression was markedly increased in Ephx2^(-/-)mice compared with WT mice.Statistically significant differences(P<0.05)were observed.Conclusion These results suggest that Ephx2 deficiency inhibits ferroptosis to alleviate CS-induced emphysema,primarily by mitigating its inhibitory effect on the cystine/glutathione/glutathione peroxidase 4 axis.Therefore,Ephx2 represents an effective therapeutic target in CS-induced chronic obstructive pulmonary disease(COPD).展开更多
Glucocorticoids(GCs)such as prednisolone are widely used in conditions like nephrotic syndrome,asthma,and autoimmune diseases.However,prolonged or high-dose use may suppress the hypothalamic-pituitary-adrenal(HPA)axis...Glucocorticoids(GCs)such as prednisolone are widely used in conditions like nephrotic syndrome,asthma,and autoimmune diseases.However,prolonged or high-dose use may suppress the hypothalamic-pituitary-adrenal(HPA)axis,leading to secondary adrenal insufficiency(AI).This condition occurs when the adrenal glands fail to produce adequate cortisol,which is essential for regulating metabolism,immune response,and stress adaptation.Corticotropin-releasing hormone(CRH)from the hypothalamus stimulates the pituitary to release adrenocorticotropic hormone(ACTH),which then triggers cortisol production in the adrenal glands.Prolonged GC use disrupts this system by inhibiting CRH and ACTH secretion,leading to adrenal atrophy and reduced cortisol production.HPA axis suppression is primarily diagnosed through dynamic tests.Early morning cortisol levels above>18 ng/mL typically indicate normal function,while levels<3 ng/mL suggest AI.Intermediate values require additional testing,such as the insulin tolerance test,ACTH stimulation test,and metyrapone test.Prednisolone in nephrotic syndrome suppresses the HPA axis,heightening AI risk,influenced by dose,duration,and timing of administration.Careful GC management is essential to balance disease control with risks of HPA axis suppression.Early recognition and timely intervention can prevent adrenal crises and improve outcomes in pediatric patients.展开更多
We commend Worland et al for their work associating rifaximin-αuse with imp-roved muscle mass in individuals with liver cirrhosis.This observation adds momentum to the evolving gut-liver-muscle axis hypothesis.Howeve...We commend Worland et al for their work associating rifaximin-αuse with imp-roved muscle mass in individuals with liver cirrhosis.This observation adds momentum to the evolving gut-liver-muscle axis hypothesis.However,the retro-spective design and lack of functional outcomes invite caution in interpretation.Mechanistically,rifaximin may exert benefit beyond ammonia reduction through modulation of systemic inflammation,tumor necrosis factor alpha suppression,and restoration of myocyte integrity.Additionally,concerns about long-term anti-microbial resistance must be acknowledged.Overall,this study represents a valuable first step,but its implications require validation in future,prospective,mechanistically informed clinical trials.展开更多
Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are...Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are consequently lacking.The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host.The intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other factors.Such dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many diseases.In recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the brain.Indeed,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Similarly,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular disorders.Moreover,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies.As such,the intestinal flora may play an important role in age-related macular degeneration.Given the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic strategies.Currently,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration.Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.展开更多
With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterati...With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.展开更多
Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for pati...Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”展开更多
文摘The South Central Axis in Beijing showcases China’s image and highlights its cultural confidence.THE Central Axis is the centerpiece of the Chinese capital’s urban spatial layout.The southern extended section of the Central Axis,or the South Central Axis,stretches from the Yongdingmen Gate Tower in the north to the South Fifth Ring Road in the south.While being a strategic transport link facilitating the coordinated development of the Beijing-Tianjin-Hebei region,it also showcases China’s vision for the future and highlights its cultural confidence.
文摘Accumulating evidence indicates that the neuro-immune axis is central to gastric cancer pathogenesis.Dynamic,bidirectional signaling between neural circuits and immune cells promotes tumor progression,shapes an immunosuppressive microenvironment,and contributes to therapeutic resistance.We synthesize current knowledge on how autonomic(sympathetic and parasympathetic)and sensory innervation regulate gastric cancer biology.These circuits act through neurotransmitters(catecholamines,acetylcholine)and neuropeptides(substance P[SP],calcitonin gene-related peptide[CGRP])to foster tumor growth and angiogenesis,facilitate perineural invasion,and enable immune evasion by recruiting suppressive myeloid and lymphoid populations and by inducing checkpoint molecule expression.We also examine how chronic stress and the microbiota-gut-brain axis intensify immunosuppression via glucocorticoid signaling and microbially derived metabolites.In parallel,we discuss why current immunotherapies achieve only modest response rates(approximately 10%-20%)in many settings,emphasizing neurally mediated mechanisms of resistance.We evaluate therapeutic strategies that target the neuro-immune axis-including pharmacological neuromodulation,selective neural ablation,and rational combination regimens-and outline how single-cell approaches and neural-tumor-microenvironment organoid models can accelerate mechanism-driven translation.This review aims to integrate current evidence from neuroscience and immuno-oncology to construct a conceptual framework for neuro-immune regulation in gastric cancer and to identify potential therapeutic strategies to overcome treatment resistance by targeting neural-tumor-immune crosstalk.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
文摘Cholangiocarcinoma(CCA)is a highly malignant tumor of the biliary tract with a poor prognosis.Currently,specific methods for the early diagnosis and risk stratification if CCA are lacking.With the emergence of the“gut-biliary-liver axis”concept,the intestinal and biliary microbiota are being increasingly recognized to play key roles in the initiation and progression of CCA.This review systematically synthesizes recent clinical and basic research and outlines characteristic patterns of dysbiosis in the feces,bile,and tumor tissues of patients with CCA.It further discusses key mechanisms,including microbiota-bile acid-biliary epithelial signaling,pathogen-associated molecular patterns-mediated chronic inflammation,and immune-metabolic remodeling.It also examines the associations of these mechanisms with tumor progression and treatment responses.On this basis,the review evaluates the potential of intestinal and biliary microbiota and their metabolites as biomarkers for the diagnosis,prognosis,and prediction of the treatment response of CCA.We believe this review demonstrates a theoretical basis for microbiota-targeted precision prevention and therapeutic strategies for the disease.
基金supported by the Research Fund Project of the Education Department of Yunnan Province(No.2023Y0464)Research Project for Scientific Research Funds of Provincial Research Institutions in Heilongjiang Province(No.CZBZ2025ZR003).
文摘Background:Immunosuppression compromises the host’s ability to combat pathogens,thereby increasing susceptibility to multisystem disorders.However,safe and effective curative treatments for this condition are currently lacking.Modulating the gut microbiota and their metabolites represents a promising therapeutic strategy.Notably,the Chinese herbal compound Yunzhi Guben Gao(YZG)has demonstrated multi-target immunomodulatory potential.Methods:A mouse model of dexamethasone-induced immunosuppression was employed to evaluate the effects of YZG.Immune organ indices(thymus,spleen),serum cytokine levels(IL-2,TNF-α),mucosal immunity markers(pulmonary/colonic SIgA),gut microbiota structure,and short-chain fatty acids(SCFAs)abundance were evaluated.Key microbial genera and metabolites were identified via Spearman correlation analysis.Pseudo-germ-free model mice established via quadruple antibiotic treatment combined with isovaleric acid intervention were employed to evaluate whether YZG efficacy depends on the intestinal microbiota and its metabolites,and whether its intrinsic mechanisms involve the promotion of isovaleric acid production.Results:YZG intervention ameliorated systemic and mucosal immune function in immunosuppressed mice.Mechanistically,YZG remodeled gut microbiota structure and significantly increased SCFAs levels.Notably,the abundance of the genus Ligilactobacillus exhibited the strongest positive correlation with isovaleric acid levels.Ligilactobacillus abundance was also positively correlated with immune-enhancing parameters and negatively correlated with the proinflammatory cytokine TNF-α,suggesting that Ligilactobacillus plays a pivotal role in the YZG regulatory network.Experiments using pseudo-germ-free mice and isovaleric acid intervention further demonstrated that the immunoprotective effects of YZG are closely related to intestinal microbiota remodeling and increased isovaleric acid production.Conclusion:YZG alleviates immunosuppression through multiple mechanisms,primarily involving the enrichment of the probiotic genus Ligilactobacillus and the consequent increase in isovaleric acid production.This process coordinately modulates mucosal immunity,cytokine networks,and immune organ function.The elucidation of this“microbiota-metabolite-immunity”axis provides both a pharmacological basis for the clinical application of YZG and novel immune-restorative strategies targeting gut microecological regulation.
文摘Oncology Research Editorial Office Published:19 January 2026 The published article titled“ABCB5-ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells”has been retracted from Oncology Research,Vol.25,No.3,2017,pp.305-316.DOI:10.3727/096504016X14734149559061 URL:https://www.techscience.com/or/v25n3/56810.
基金supported by grants from the National Natural Science Foundation of China(No.82372382,82002333,32371412,and 32071349)the Central Guidance on Local Science and Technology Development Fund of Zhejiang Province(No.2024ZY01033)+1 种基金the Zhejiang Provincial Natural Science Foundation of China(No.LY24C100001)the Key Research and Development Program of Zhejiang(No.2022C01076).
文摘Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and osteoclast activity.However,the majority of research to date has focused on the direct effects of peripheral nerves and their neurotransmitters on bone regeneration.Emerging studies have begun to reveal a more intricate role of nerves in regulating the immune microenvironment,which is crucial for bone regeneration.This review summarizes how nerves influence bone regeneration through modulation of the immune microenvironment.We first discuss the changes in peripheral nerves during the regenerative process.We then describe conduction and paracrine pathways through which nerves affect the osteogenic immune microenvironment,emphasizing nerves,neural factors,and their impacts.Our goal is to deepen the understanding of the nerve-immune axis in bone regeneration.A better grasp of how nerves influence the osteogenic immune microenvironment may lead to new strategies that integrate the nervous,immune,and skeletal systems to promote bone regeneration.
基金Supported by Open Project of Jiangsu Province Key Laboratory of Integrated Traditional Chinese and Western Medicine for the Prevention and Treatment of Geriatric Diseases,No.202232.
文摘BACKGROUND Post-stroke depression(PSD)is associated with hypothalamic-pituitary-adrenal(HPA)axis dysfunction and neurotransmitter deficits.Selective serotonin reuptake inhibitors(SSRIs)are commonly used,but their efficacy is limited.This study investigated whether combining SSRIs with traditional Chinese medicine(TCM)Free San could enhance their therapeutic effects.AIM To evaluate the clinical efficacy and safety of combining SSRIs with Free San in treating PSD,and to assess its impact on HPA axis function.METHODS Ninety-two patients with PSD were enrolled and randomly divided into control groups(n=46)and study groups(n=46).The control group received the SSRI paroxetine alone,whereas the study group received paroxetine combined with Free San for 4 weeks.Hamilton Depression Scale and TCM syndrome scores were assessed before and after treatment.Serum serotonin,norepinephrine,cortisol,cor-ticotropin-releasing hormone,and adrenocorticotropic hormone were measured.The treatment responses and adverse reactions were recorded.RESULTS After treatment,the Hamilton Depression Scale and TCM syndrome scores were significantly lower in the study group than in the control group(P<0.05).Serum serotonin and norepinephrine levels were significantly higher in the study group than in the control group,whereas cortisol,corticotropin-releasing hormone,and adrenocorticotropic hormone levels were significantly lower(P<0.05).The total efficacy rates were 84.78%and 65.22%in the study and control groups,respectively(P<0.05).No significant differences in adverse reactions were observed between the two groups(P>0.05).CONCLUSION Combining SSRIs with Free San can enhance therapeutic efficacy,improve depressive symptoms,and regulate HPA axis function in patients with PSD with good safety and clinical application value.
基金supported by the National Key Research and Development Program of China(2022YFF1000201)National Scientific Foundation of China(32272861)the China Agriculture Research System of MOF and MARA(CARS-41)。
文摘Background Excessive abdominal fat in broilers not only reduces feed efficiency and increases processing costs but also raises environmental concerns.This pathological overaccumulation results from complex metabolic dysregulation across multiple organs.While current research largely centers on adipogenesis within adipose tissue,a comprehensive understanding of the cross-organ regulatory factors influencing this process remains elusive.Results Here,we employed a high-fat diet(HFD)model and multi-omics approaches to investigate cross-organ regulatory mechanisms underlying abdominal fat deposition in broilers.Our results demonstrated that HFD not only promoted fat accumulation but also altered meat quality traits.Through 16S rRNA amplicon sequencing,we identified significant gut microbiota dysbiosis in HFD-fed chickens,manifested by an increased abundance of Lactobacillus and a decreased abundance of Enterococcus.However,jejunal microbiota transplantation from HFD donors did not induce abdominal fat deposition in recipient chickens.Metabolomic profiling revealed that HFD elevated the level of succinic acid,a metabolite positively correlated with Lactobacillus abundance and potentially generated by Lactobacillus.This increase in succinic acid(SA)further triggered metabolic inflammation response in both jejunal tissue and serum.In vivo validation established succinic acid as a key inflammatory mediator facilitating HFD-induced cross-organ communication between the jejunum and abdominal adipose tissue,enhancing intestinal lipid uptake and subsequent abdominal fat deposition.Bulk and single-nucleus RNA sequencing(snRNA-seq)revealed that HFD induced macrophage population expansion and intensified adipocyte-macrophage crosstalk.Adipocyte-macrophage co-culture systems further elucidated that macrophages are an indispensable factor in succinic acid-induced fat deposition.Conclusion This study delineates a succinic acid-driven"gut-fat axis"governing abdominal fat deposition in broilers,integrating gut microbiota dysbiosis and macrophage-mediated inflammatory adipogenesis.By identifying succinic acid as a cross-organ signaling molecule that enhances lipid absorption and activates macrophage-dependent adipogenesis,we establish systemic metabolic-immune crosstalk as a pivotal regulatory mechanism.These findings redefine fat deposition as a process extending beyond adipose-centric models,advancing multi-omics-guided strategies for sustainable poultry production.
基金supported by the National Natural Science Foundation of China,No.82301382the Natural Science Foundation of Hebei Province,No.H2022316001+1 种基金Government Funded Clinical Medicine Excellent Talents Project,No.ZF2023126the Postdoctoral Research Support Program for Clinical Medicine of Hebei Medical University,No.PD2023004(all to QZ).
文摘An increasing amount of evidence shows that type I interferon response,which is induced by cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)and stimulator of interferon genes(STING)is closely associated with health and neuroinflammatory diseases.Abnormal activation or loss of control of the cGAS-STING axis affects the development of neuroinflammation.Thus,we examined its role in major neurological diseases,including traumatic brain injury,Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,multiple sclerosis,herpes simplex encephalitis,and ataxia-telangiectasia.Additionally,targeted intervention of the cGAS-STING axis to control neuroinflammation and treat related diseases has become the focus of current clinical research.This article describes the development of cGAS inhibitors and small molecules that target the cGAS-STING axis and explores the potential applications of STING inhibitors and agonists in clinical research.In summary,the cGAS-STING axis may impact neurological diseases more than a single protein or gene.Future studies should focus on elucidating the functional dynamics and regulatory networks of this axis and delineating its crosstalk with other signaling cascades.These investigations will provide mechanistic insights for developing targeted therapeutic strategies for associated disorders and potentially facilitate drug repurposing across diverse disease contexts.
基金Supported by the National Natural Science Foundation of China,No.81860843Guangxi Administration of Traditional Chinese Medicine Project,No.GZSY23-36 and No.GXZYA20240150。
文摘BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,has been shown to significantly improve clinical symptoms in patients with CAG,as demonstrated by a multicenter cohort study(overall effective rate:82.5%,P<0.01).However,the unclear molecular mechanisms and therapeutic targets of AWD limit its international acceptance.AIM To investigate the therapeutic mechanisms of AWD against CAG from an integrated perspective.METHODS In this study,N-methyl-N’-nitro-N-nitrosoguanidine was used to establish a CAG rat model.Serum-derived constituents transferred from AWD were first identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry.The concentrations of inflammatory cytokines in serum samples were determined by enzyme-linked immunosorbent assay.Moreover,gastric mucosal tissues were analyzed by quantitative realtime polymerase chain reaction to measure messenger RNA(mRNA)levels of the NLRP3 inflammasome.Western blotting was used to detect the protein expression of NLRP3,caspase-1,and interleukin(IL)-1β.To elucidate the regulatory mechanisms underlying AWD treatment,structural alterations of the gut microbiota(GM)and associated metabolites were analyzed using integrated high-throughput sequencing(16S rRNA)and liquid chromatography-mass spectrometry based untargeted metabolomics.This comprehensive approach systematically clarified AWD’s multi-target therapeutic mechanisms against CAG.RESULTS AWD notably reduced serum levels of pro-inflammatory cytokines,such as IL-1β,IL-18,tumor necrosis factor-α,and lipopolysaccharide,demonstrating significant statistical differences(all P<0.01).Additionally,AWD substantially inhibited NLRP3 mRNA expression in gastric mucosal tissue(P<0.01)and concurrently decreased the protein abundance of NLRP3,IL-1β,and caspase-1(all P<0.01),thereby suppressing inflammasome signaling activation.GM analysis indicated that AWD intervention significantly increased the relative abundance of beneficial bacteria.Associated microbial metabolites likely inhibited the NLRP3 inflammasome pathway by modulating immune cell function.Non-targeted metabolomics further indicated that AWD exerted anti-inflammatory effects by regulating critical metabolic pathways,including the Kaposi’s sarcoma-associated herpesvirus infection pathway,autophagy processes,and glycosylphosphatidylinositol-anchor biosynthesis.CONCLUSION AWD alleviates the pathological progression of CAG through multi-target synergistic mechanisms.On one hand,AWD directly suppresses gastric mucosal inflammation by inhibiting NLRP3 inflammasome activation.On the other hand,AWD remodels intestinal microbiota-metabolite homeostasis,enhances intestinal barrier function,and regulates mucosal immune responses.
基金funded by the National Natural Science Foundation of China(82000042,81870029)Beijing Municipal Natural Science Foundation(7204247)+3 种基金Capital’s Funds for Health Improvement and Research(grant number:2024-2-1101)Start-up Project of Beijing Friendship Hospital,Capital Medical University(Beijing,China)(yyqdktzx2020-3)Key Clinical Specialty Construction Program of Beijing(2020-2022)Research Fund of Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital(24QNPY034).
文摘Objective This study investigated the effect of reducing soluble epoxide hydrolase(sEH,encoded by the Ephx2 gene)on the mediation of EETs metabolism during ferroptosis in emphysema in vivo.Methods Male C57BL/6J wild-type(WT)and Ephx2^(-/-)mice received whole-body exposure to either cigarette smoke(CS)or air for 16 weeks.The alveolar structure,pulmonary function,lung tissue morphology,cell death,and ferroptosis levels were assessed following exposure.Results CS exposure caused emphysema,reduced pulmonary function,and induced ferroptosis in mice compared with exposure to air.In contrast,following CS exposure,Ephx2^(-/-)mice exhibited significantly lower levels of emphysema,impaired lung function,lung cell death,intracellular iron,lipid reactive oxygen species,cyclooxygenase-2,4-hydroxynonenal,and malondialdehyde levels than those of WT mice.However,Ephx2^(-/-)mice exhibited higher levels of glutathione and ferritin heavy chain 1 than those of WT mice.SLC7A11 expression was significantly reduced,whereas glutathione peroxidase 4 expression was markedly increased in Ephx2^(-/-)mice compared with WT mice.Statistically significant differences(P<0.05)were observed.Conclusion These results suggest that Ephx2 deficiency inhibits ferroptosis to alleviate CS-induced emphysema,primarily by mitigating its inhibitory effect on the cystine/glutathione/glutathione peroxidase 4 axis.Therefore,Ephx2 represents an effective therapeutic target in CS-induced chronic obstructive pulmonary disease(COPD).
文摘Glucocorticoids(GCs)such as prednisolone are widely used in conditions like nephrotic syndrome,asthma,and autoimmune diseases.However,prolonged or high-dose use may suppress the hypothalamic-pituitary-adrenal(HPA)axis,leading to secondary adrenal insufficiency(AI).This condition occurs when the adrenal glands fail to produce adequate cortisol,which is essential for regulating metabolism,immune response,and stress adaptation.Corticotropin-releasing hormone(CRH)from the hypothalamus stimulates the pituitary to release adrenocorticotropic hormone(ACTH),which then triggers cortisol production in the adrenal glands.Prolonged GC use disrupts this system by inhibiting CRH and ACTH secretion,leading to adrenal atrophy and reduced cortisol production.HPA axis suppression is primarily diagnosed through dynamic tests.Early morning cortisol levels above>18 ng/mL typically indicate normal function,while levels<3 ng/mL suggest AI.Intermediate values require additional testing,such as the insulin tolerance test,ACTH stimulation test,and metyrapone test.Prednisolone in nephrotic syndrome suppresses the HPA axis,heightening AI risk,influenced by dose,duration,and timing of administration.Careful GC management is essential to balance disease control with risks of HPA axis suppression.Early recognition and timely intervention can prevent adrenal crises and improve outcomes in pediatric patients.
文摘We commend Worland et al for their work associating rifaximin-αuse with imp-roved muscle mass in individuals with liver cirrhosis.This observation adds momentum to the evolving gut-liver-muscle axis hypothesis.However,the retro-spective design and lack of functional outcomes invite caution in interpretation.Mechanistically,rifaximin may exert benefit beyond ammonia reduction through modulation of systemic inflammation,tumor necrosis factor alpha suppression,and restoration of myocyte integrity.Additionally,concerns about long-term anti-microbial resistance must be acknowledged.Overall,this study represents a valuable first step,but its implications require validation in future,prospective,mechanistically informed clinical trials.
基金supported by the National Natural Science Foundation of China,No.82171080Nanjing Medical Science and Technology Development Project,No.YKK23264Postgraduate Research&Practice Innovation Program of Jiangsu Province,Nos.JX10414151,JX10414152(all to KL)。
文摘Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are consequently lacking.The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host.The intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other factors.Such dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many diseases.In recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the brain.Indeed,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Similarly,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular disorders.Moreover,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies.As such,the intestinal flora may play an important role in age-related macular degeneration.Given the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic strategies.Currently,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration.Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Foundation,No.22HHXBSS00047(to PL)Graduate Science and Technology Innovation Project of Tianjin,No.2022BKY173(to LZ)Tianjin Municipal Science and Technology Bureau Foundation,No.20201194(to PL).
文摘With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.
基金supported by the National Natural Science Foundation of China,No.82174112(to PZ)Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine,No.22HHZYSS00015(to PZ)State-Sponsored Postdoctoral Researcher Program,No.GZC20231925(to LN)。
文摘Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”
