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
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
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
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
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
Nanocrystals have emerged as cutting-edge functional materials benefiting from the increased surface and enhanced coupling of electronic states.High-resolution imaging in transmission electron microscope can provide i...Nanocrystals have emerged as cutting-edge functional materials benefiting from the increased surface and enhanced coupling of electronic states.High-resolution imaging in transmission electron microscope can provide invaluable structural information of crystalline materials,albeit it remains greatly challenging to nanocrystals due to the arduousness of accurate zone axis adjustment.Herein,a homemade software package,called SmartAxis,is developed for rapid yet accurate zone axis alignment of nanocrystals.Incident electron beam tilt is employed as an eccentric goniometer to measure the angular deviation of a crystal to a zone axis,and then serves as a linkage to calculate theαandβtilts of goniometer based on an accurate quantitative relationship.In this way,high-resolution imaging of one identical small Au nanocrystal,as well as electron beam-sensitive MIL-101 metal-organic framework crystals,along multiple zone axes,was performed successfully by using this accurate,time-and electron dose-saving zone axis alignment software package.展开更多
Dear Editor,Lung cancer is a major global health concern,with 2.2 million patients diagnosed in 2020.Non-small cell lung cancer(NSCLC)accounts for 80%of these cases,primarily comprising two subtypes:lung adenocarcinom...Dear Editor,Lung cancer is a major global health concern,with 2.2 million patients diagnosed in 2020.Non-small cell lung cancer(NSCLC)accounts for 80%of these cases,primarily comprising two subtypes:lung adenocarcinoma(LUAD)and squamous cell carcinoma(LUSC)[1].Researchers use immunohisto-chemistry,next-generation sequencing,and single-cell RNA sequencing to study genetic alterations,tumor heterogeneity,and tumor microenvironments,aiming to identify potential therapeutic options for specific NSCLC subtypes[2].展开更多
A recent study by Wang et al,published in the World Journal of Psychiatry,provided preventative and therapeutic strategies for the comorbidity of obesity and depression.The gut-brain axis,which acts as a two-way commu...A recent study by Wang et al,published in the World Journal of Psychiatry,provided preventative and therapeutic strategies for the comorbidity of obesity and depression.The gut-brain axis,which acts as a two-way communication system between the gastrointestinal tract and the central nervous system,plays a pivotal role in the pathogenesis of these conditions.Evidence suggests that metabolic byproducts,such as short-chain fatty acids,lipopolysaccharide and bile acids,which are generated by the gut microbiota,along with neurotransmitters and inflammatory mediators within the gut-brain axis,modulate the host's metabolic processes,neuronal regulation,and immune responses through diverse mechanisms.The interaction between obesity and depression via the gut-brain axis involves disruptions in the gut microbiota balance,inflammatory immune responses,and alterations in the neuroendocrine system.Modulating the gut-brain axis,for example,through a ketogenic diet,the use of probiotics,and the supplementation of antioxidants,offers new remedial approaches for obesity and depression.Future research that explores the mechanisms of the gut-brain axis is needed to provide more evidence for clinical treatment.展开更多
The gut-liver axis represents a complex,bidirectional communication network between the gastrointestinal tract and the liver,playing a central role in maintaining metabolic homeostasis.In diabetes,disruption of this a...The gut-liver axis represents a complex,bidirectional communication network between the gastrointestinal tract and the liver,playing a central role in maintaining metabolic homeostasis.In diabetes,disruption of this axis,mediated by gut microbiota dysbiosis,impaired intestinal barrier function,and pro-inflammatory signaling,contributes significantly to insulin resistance,hepatic steatosis,and systemic metabolic dysfunction.This review explores the underlying mechanisms by which microbial alterations,increased gut permeability,and inflammatory pathways influence hepatic insulin resistance and glucose metabolism.In addition to established mechanisms,emerging pathways involving neuroendocrine circuits,microbial metabolites,and immune mediators are discussed,offering deeper insight into gut-liver interactions in metabolic disease.The review also outlines therapeutic strategies targeting the gut-liver axis,including microbiota modulation,barrier function enhancement,and anti-inflammatory interventions,emphasizing their potential in advancing diabetes management.A conceptual framework is proposed to integrate these components into a precision medicine approach for metabolic regulation.Key challenges in clinical translation,including patient heterogeneity and the absence of reliable biomarkers to guide treatment decisions are also discussed to inform future research.By linking mechanistic understanding with therapeutic innovation,the review highlights the gut-liver axis as a promising target for personalized diabetes care.展开更多
Chronotype is determined by circadian rhythms,influenced by polygenic variations and environmental factors. Typically, chronotypes are categorized into morning-, intermediate-, and evening-types^([1]). Most cognitive ...Chronotype is determined by circadian rhythms,influenced by polygenic variations and environmental factors. Typically, chronotypes are categorized into morning-, intermediate-, and evening-types^([1]). Most cognitive functions follow daily and circadian rhythms, with the “synchronization effect” reflecting performance variations between optimal and non-optimal times based on an individual's chronotype.展开更多
OBJECTIVE:To explore the correlation between acupuncture treatment for allergic rhinitis(AR) and hypothalamic-pituitary-adrenal(HPA) axis regulation by investigating changes in serum immune factors,HPA axis-associated...OBJECTIVE:To explore the correlation between acupuncture treatment for allergic rhinitis(AR) and hypothalamic-pituitary-adrenal(HPA) axis regulation by investigating changes in serum immune factors,HPA axis-associated hormone levels,activation levels of paraventricular nucleus(PVN) neurons,and the severity of nasal mucosal lesions,in rats with AR before and after acupuncture treatment.METHODS:After establishing the AR rat model,ovalbumin was administered via nasal drip to all groups except the blank control.Each group received continuous treatment for 14 d:the acupuncture,acupuncture + RU-486(mifepristone),and RU-486 groups received acupuncture only,RU486 intraperitoneal injection and acupuncture,and RU-486 intraperitoneal injection only,respectively.Following the intervention period,behavioral scoring was performed on all AR rats,and peripheral blood,nasal mucosa samples,and brains tissue(containing PVN region) were obtained following euthanization.Interleukin(IL-4,IL-5,IL-13),interferon gamma(IFN-γ),corticosterone(CORT),and corticotrophin-releasing hormone(CRH) levels were evaluated in peripheral blood samples.Adrenocorticotropic hormone(ACTH) levels were determined using an enzyme-linked immunoassay assay,and hematoxylin and eosin staining was performed on the nasal mucosa samples.The expression levels of c-Fos in PVN neurons following acupuncture treatment were evaluated by immunofluorescent staining.RESULTS:Following the intervention period,the behavioral scores for the blank control group were lower than those of other groups(P < 0.05),while the acupuncture group scores were lower than those in the model control,acupuncture + RU486,and RU486 groups(P < 0.05).The blank control group had lower serum IL-4,IL-5,and IL-13 levels than those in the other groups(P < 0.05).The acupuncture group had lower serum IL-4,IL-5,and IL-13 levels than those in the model control,acupuncture + RU486,and RU486 groups(P < 0.05).The blank control group had the highest serum IFN-γ levels among all groups,followed by the acupuncture group.The serum CORT,CRH,and ACTH levels in the blank control group were lower than those in the remaining groups(P < 0.05).These biomarker levels were also lower in the acupuncture group than those in the model control,acupuncture + RU486,and RU486 groups(P < 0.05).Compared with model,rats in the acupuncture group exhibited an increased c-Fos expression in PVN neurons.CONCLUSION:Acupuncture can alleviate AR symptoms and regulate serum inflammatory factor levels and HPA axis-related hormones in AR rats.Moreover,these effects are inhibited by glucocorticoid antagonists,suggesting that acupuncture may regulate AR symptoms through HPA axis regulation.展开更多
Sepsis,a life-threatening condition,can lead to acute skin failure characterized by extensive skin damage.This is often due to decreased blood flow,inflammation,and increased susceptibility to infection.Acute skin fai...Sepsis,a life-threatening condition,can lead to acute skin failure characterized by extensive skin damage.This is often due to decreased blood flow,inflammation,and increased susceptibility to infection.Acute skin failure in people with sepsis is often associated with sleep disturbances,anxiety,and poor mood.Inflammatory markers and lactate levels correlate with these psychiatric symptoms,suggesting a link between skin and brain function.The skin and the central nervous system(CNS)have bidirectional communication.The CNS is also in close contact with the digestive tract.The gut,skin,and brain influence each other’s functions thr-ough nervous,hormonal,and immune pathways,forming a gut-skin-brain axis.Understanding the interaction among the gut,skin,and CNS is critical to the diag-nosis and treatment of various skin and neurological disorders.By recognizing individual variations in gut microbiota,immune responses,and neural pathways,treatments can be tailored to specific patient needs,enhancing efficacy and minimizing side effects.The gut plays a large role in mental health.Under-standing the gut skin brain axis,will lead to improved mental health outcomes.展开更多
Neurodegenerative diseases(NDs),mainly including Alzheimer’s disease,Parkinson’s disease,and multiple sclerosis,represent a major public health challenge with the steady increase of aging population worldwide.Emergi...Neurodegenerative diseases(NDs),mainly including Alzheimer’s disease,Parkinson’s disease,and multiple sclerosis,represent a major public health challenge with the steady increase of aging population worldwide.Emerging evidence has revealed the key role of the microbiota-gut-brain axis in the pathogenesis of NDs.Diet is one of the most important environmental factors shaping the structure and function of gut microbiota.Manipulating the gut microbiota through specific diet patterns may represent a promising approach for NDs prevention.In this review,we highlight gut microbiota variations in NDs,outline several crucial signaling pathways of the gut-brain communication,and discuss the interplay of nutrients-microbes and biological effect of diet-derived microbial metabolites on neural physiology.In particular,we summarized the current knowledge about the application of dietary patterns in NDs to prevent disease progression via the modulation of the gut microbiota.Our study provides novel insights on the diet-microbiota-gut-brain axis in neurodegenerative disorders and highlights the potential of developing microbiome-targeted personalized dietary intervention for NDs management.展开更多
Background Pork quality and flavor are critical determinants of consumer preference,yet the role of gut microbiota in shaping meat characteristics remains underexplored.In this study,we investigated how a probiotic co...Background Pork quality and flavor are critical determinants of consumer preference,yet the role of gut microbiota in shaping meat characteristics remains underexplored.In this study,we investigated how a probiotic consortium(FAM:Lactobacillus acidophilus and Bacillus subtilis)modulates the gut-muscle axis to enhance pork flavor.Results In finishing pigs,FAM supplementation significantly increased flavor-associated nucleotides and umamienhancing amino acids in longissimus dorsi muscle.Metagenomic analysis revealed FAM-driven enrichment of glycandegrading Prevotella and short-chain fatty acid-producing Phascolarctobacterium,accompanied by reduced antibiotic resistance genes and virulence factors.Spearman correlation linked Prevotella copri abundance with elevated muscle amino acids,suggesting microbial-encoded CAZymes as key mediators.Conclusions This study provides the first evidence that probiotic-induced gut microbiota remodeling enhances pork flavor through metabolic cross-talk along the gut-muscle axis.The findings suggest a novel strategy for improving pork quality via dietary interventions targeting gut microbiota.展开更多
Background Systemic inflammatory responses and oxidative stress occur in laying hens during the aging process,particularly during the post-peaking laying period,which generally result in multi-organ damages,leading to...Background Systemic inflammatory responses and oxidative stress occur in laying hens during the aging process,particularly during the post-peaking laying period,which generally result in multi-organ damages,leading to significant declines in egg performance and quality.Chlorogenic acid(CGA)-enriched extract from Eucommia ulmoides leaves has anti-inflammatory and antioxidant activities.However,the mechanisms underlying whether and how CGA alleviates systemic inflammatory responses and oxidative stress to improve egg performance and quality in postpeaking laying hens remain unclear.In this study,the potential regulatory mechanisms of CGA in alleviating inflammatory responses and oxidative stress along the gut-liver axis were investigated.A total of 36055-week-old Hy-line white-laying hens were randomly selected and divided into four groups.The hens in the four groups were fed a basal diet(CON)or basal diets supplemented with 200,400,and 800 mg/kg of CGA(CGA200,CGA400,and CGA800,respectively)for 10 weeks.Results The results demonstrated that CGA significantly alleviated intestinal and hepatic damages resulting from systemic inflammatory responses and oxidative stress,thereby improving the laying performance and egg quality of post-peaking laying hens.CGA reduced systemic inflammation by improving intestinal barrier function and modulating inflammation-associated microbiota(Blautia and Megamonas),thus inhibiting endotoxin translocation.CGA can also reduce oxidative stress by upregulating the NRF-2 pathway-related genes and increasing antioxidant enzyme activities in the liver.The results of transcriptome sequencing revealed that CGA promoted lipid metabolism by regulating hepatic adipocytokine pathway-related genes/protein and reduced the inflammatory responses and apoptosis in liver by regulating PI3K/AKT pathway-related genes/proteins,which was also verified by qPCR and western blotting.Conclusion CGA alleviated multi-organ damages and dysfunction by suppressing the systemic inflammatory responses and oxidative stress in post-peaking laying hens,thereby improving egg performance and quality.The optimal dose of CGA is 400 mg/kg in this experiment.These results provide a sound theoretical basis for the application of CGA as an exogenous animal feed additive for laying hens.展开更多
Aflatoxin B_1(AFB_1)is a common contaminant in cereals of global concern,and long-term low-dose exposure can adversely affect human health.Here,we showed that populations with dietary patterns characterized by high-fa...Aflatoxin B_1(AFB_1)is a common contaminant in cereals of global concern,and long-term low-dose exposure can adversely affect human health.Here,we showed that populations with dietary patterns characterized by high-fat diet(HFD)might have an increased risk of exposure to high levels of AFB_1.Our data indicated that chronic exposure of AFB_1 induced“gut-liver axis”injury in mice under HFD and normal diet(ND)patterns.AFB_1 further aggravated hepatic and intestinal injury,and intestinal microbiota disruption in HFD mice.Bifidobacterium breve BAA-2849 intervention analysis showed that liver injury and lipid disorders caused by AFB_1 exposure were alleviated by regulating the proportions of different gut microbes.We demonstrated through a mice model that the populations with a dietary pattern of HFD might be more susceptible to AFB_1 exposure and adverse effects on the gut-liver axis,and the toxicity of AFB_1 exposure can be alleviated by regulating the gut microbiota.展开更多
The incidence rate and harmfulness of depression are increasing yearly,and the research on the antidepressant effect of regulating the intestinal microecology balance has attracted widespread attention.The purpose of ...The incidence rate and harmfulness of depression are increasing yearly,and the research on the antidepressant effect of regulating the intestinal microecology balance has attracted widespread attention.The purpose of this research was to study the preventive effects and the regulatory mechanism of edible Lilium-egg yolk compound powder(BHT)on gut-brain crosstalk in depressive rats induced by chronic unpredictable mild stress(CUMS)through the“microbiota-gut-brain”axis.Results showed that infusion of BHT for 21 days ameliorated the morphology of the hippocampus and colon,increased the rate of sucrose preference,reduced the immobility time of forced swimming,increased the expression level of anti-inflammatory cytokine interleukin(IL)-10 in serum,up-regulated the expression level of plasma neurotransmitter 5-hydroxytryptamine(5-HT),downregulated the expression of inflammatory factors tumor necrosis factor-α(TNF-α),IL-6,and IL-1βand neurotransmitter glutamic acid(Glu)in serum,and decreased the expression levels of lipopolysaccharide(LPS),diamine oxidase(DAO)and lactate dehydrogenase(LD)in plasma.The underlying mechanism may be to reduce the activation of microglia(lower levels of CD11 antigen-like family member B(CD11b),ionized calcium binding adaptor molecule 1(Iba1)protein and gene expression),regulate hippocampal glucocorticoid receptor/brain-derived neurotrophic factor/neuropeptide Y(GR/BDNF/NPY)signaling pathway(higher levels of GR,BDNF,NPY protein and gene expression),enhance intestinal mucosal barrier function(higher levels of ZO-1,occludin protein and gene expression),regulate the composition and structure of intestinal flora(analysis results of linear discriminant analysis effect size(LEf Se)combined with random forest showed that Prevotella and Paraprevotella might be biomarkers of BHT intervention in depression),and it is related to the improvement of glutathione metabolism,and other metabolic pathways.Pearson correlation analysis found that 5-HT is strongly positively correlated with Prevotella,and Glu has a strong negative correlation with Prevotella.In conclusion,BHT can exert its antidepressant effect on CUMS-induced rats through microbiota-gut-brain interaction,can be used as an alternative to food recuperation for human depression.展开更多
Esculetin,a natural dihydroxy coumarin derived from the Chinese herbal medicine Cortex Fraxini,has demonstrated significant pharmacological activities,including anticancer properties.Ferroptosis,an iron-dependent form...Esculetin,a natural dihydroxy coumarin derived from the Chinese herbal medicine Cortex Fraxini,has demonstrated significant pharmacological activities,including anticancer properties.Ferroptosis,an iron-dependent form of regulated cell death,has garnered considerable attention due to its lethal effect on tumor cells.However,the exact role of ferroptosis in esculetin-mediated anti-hepatocellular carcinoma(HCC)effects remains poorly understood.This study investigated the impact of esculetin on HCC cells both in vitro and in vivo.The findings indicate that esculetin effectively inhibited the growth of HCC cells.Importantly,esculetin promoted the accumulation of intracellular Fe^(2+),leading to an increase in ROS production through the Fenton reaction.This event subsequently induced lipid peroxidation(LPO)and triggered ferroptosis within the HCC cells.The occurrence of ferroptosis was confirmed by the elevation of malondialdehyde(MDA)levels,the depletion of glutathione peroxidase(GSH-Px)activity,and the disruption of mitochondrial morphology.Notably,the inhibitor of ferroptosis,ferrostatin-1(Fer-1),attenuated the anti-tumor effect of esculetin in HCC cells.Furthermore,the findings revealed that esculetin inhibited the Nrf2-xCT/GPx4 axis signaling in HCC cells.Overexpression of Nrf2 upregulated the expression of downstream SLC7A11 and GPX4,consequently alleviating esculetin-induced ferroptosis.In conclusion,this study suggests that esculetin exerts an anti-HCC effect by inhibiting the activity of the Nrf2-xCT/GPx4 axis,thereby triggering ferroptosis in HCC cells.These findings may contribute to the potential clinical use of esculetin as a candidate for HCC treatment.展开更多
Ubiquitous energy-dense diets exacerbate the prevalence of metabolic syndrome across generations and increase cardiometabolic risks in offspring[1,2].This pervasive public health challenge has catalyzed intensive rese...Ubiquitous energy-dense diets exacerbate the prevalence of metabolic syndrome across generations and increase cardiometabolic risks in offspring[1,2].This pervasive public health challenge has catalyzed intensive research into the intricate regulation of energy substrate metabolism.展开更多
Parkinson's disease has long been considered a disorder that primarily affects the brain,as it is defined by the dopaminergic neurodegeneration in the substantia nigra and the brain accumulation of Lewy bodies con...Parkinson's disease has long been considered a disorder that primarily affects the brain,as it is defined by the dopaminergic neurodegeneration in the substantia nigra and the brain accumulation of Lewy bodies containingα-synuclein protein.In recent decades,however,accumulating research has revealed that Parkinson's disease also involves the gut and uncovered an intimate and important bidirectional link between the brain and the gut,called the“gut–brain axis.”Numerous clinical studies demonstrate that gut dysfunction frequently precedes motor symptoms in Parkinson's disease patients,with findings including impaired intestinal permeability,heightened inflammation,and distinct gut microbiome profiles and metabolites.Furthermore,α-synuclein deposition has been consistently observed in the gut of Parkinson's disease patients,suggesting a potential role in disease initiation.Importantly,individuals with vagotomy have a reduced Parkinson's disease risk.From these observations,researchers have hypothesized thatα-synuclein accumulation may initiate in the gut and subsequently propagate to the central dopaminergic neurons through the gut–brain axis,leading to Parkinson's disease.This review comprehensively examines the gut's involvement in Parkinson's disease,focusing on the concept of a gut-origin for the disease.We also examine the interplay between altered gut-related factors and the accumulation of pathologicalα-synuclein in the gut of Parkinson's disease patients.Given the accessibility of the gut to both dietary and pharmacological interventions,targeting gut-localizedα-synuclein represents a promising avenue for developing effective Parkinson's disease therapies.展开更多
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.
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 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.”
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 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.
基金supported by the National Key R&D Program of China(No.2021YFA1501002)Thousand Talents Program for Distinguished Young Scholars.X.Li thanks the National Natural Science Foundation of China(No.22309021).
文摘Nanocrystals have emerged as cutting-edge functional materials benefiting from the increased surface and enhanced coupling of electronic states.High-resolution imaging in transmission electron microscope can provide invaluable structural information of crystalline materials,albeit it remains greatly challenging to nanocrystals due to the arduousness of accurate zone axis adjustment.Herein,a homemade software package,called SmartAxis,is developed for rapid yet accurate zone axis alignment of nanocrystals.Incident electron beam tilt is employed as an eccentric goniometer to measure the angular deviation of a crystal to a zone axis,and then serves as a linkage to calculate theαandβtilts of goniometer based on an accurate quantitative relationship.In this way,high-resolution imaging of one identical small Au nanocrystal,as well as electron beam-sensitive MIL-101 metal-organic framework crystals,along multiple zone axes,was performed successfully by using this accurate,time-and electron dose-saving zone axis alignment software package.
基金support through Manipal University Jaipur for the Enhanced Seed Grant under the Endowment Fund(Grant No.E3/2023-24/QE-04-05).
文摘Dear Editor,Lung cancer is a major global health concern,with 2.2 million patients diagnosed in 2020.Non-small cell lung cancer(NSCLC)accounts for 80%of these cases,primarily comprising two subtypes:lung adenocarcinoma(LUAD)and squamous cell carcinoma(LUSC)[1].Researchers use immunohisto-chemistry,next-generation sequencing,and single-cell RNA sequencing to study genetic alterations,tumor heterogeneity,and tumor microenvironments,aiming to identify potential therapeutic options for specific NSCLC subtypes[2].
文摘A recent study by Wang et al,published in the World Journal of Psychiatry,provided preventative and therapeutic strategies for the comorbidity of obesity and depression.The gut-brain axis,which acts as a two-way communication system between the gastrointestinal tract and the central nervous system,plays a pivotal role in the pathogenesis of these conditions.Evidence suggests that metabolic byproducts,such as short-chain fatty acids,lipopolysaccharide and bile acids,which are generated by the gut microbiota,along with neurotransmitters and inflammatory mediators within the gut-brain axis,modulate the host's metabolic processes,neuronal regulation,and immune responses through diverse mechanisms.The interaction between obesity and depression via the gut-brain axis involves disruptions in the gut microbiota balance,inflammatory immune responses,and alterations in the neuroendocrine system.Modulating the gut-brain axis,for example,through a ketogenic diet,the use of probiotics,and the supplementation of antioxidants,offers new remedial approaches for obesity and depression.Future research that explores the mechanisms of the gut-brain axis is needed to provide more evidence for clinical treatment.
文摘The gut-liver axis represents a complex,bidirectional communication network between the gastrointestinal tract and the liver,playing a central role in maintaining metabolic homeostasis.In diabetes,disruption of this axis,mediated by gut microbiota dysbiosis,impaired intestinal barrier function,and pro-inflammatory signaling,contributes significantly to insulin resistance,hepatic steatosis,and systemic metabolic dysfunction.This review explores the underlying mechanisms by which microbial alterations,increased gut permeability,and inflammatory pathways influence hepatic insulin resistance and glucose metabolism.In addition to established mechanisms,emerging pathways involving neuroendocrine circuits,microbial metabolites,and immune mediators are discussed,offering deeper insight into gut-liver interactions in metabolic disease.The review also outlines therapeutic strategies targeting the gut-liver axis,including microbiota modulation,barrier function enhancement,and anti-inflammatory interventions,emphasizing their potential in advancing diabetes management.A conceptual framework is proposed to integrate these components into a precision medicine approach for metabolic regulation.Key challenges in clinical translation,including patient heterogeneity and the absence of reliable biomarkers to guide treatment decisions are also discussed to inform future research.By linking mechanistic understanding with therapeutic innovation,the review highlights the gut-liver axis as a promising target for personalized diabetes care.
基金supported by Zhongda Hospital Affiliated to Southeast University,Jiangsu Province High-Level Hospital Construction Funds(Grant No.GSP-LCYJFH07)。
文摘Chronotype is determined by circadian rhythms,influenced by polygenic variations and environmental factors. Typically, chronotypes are categorized into morning-, intermediate-, and evening-types^([1]). Most cognitive functions follow daily and circadian rhythms, with the “synchronization effect” reflecting performance variations between optimal and non-optimal times based on an individual's chronotype.
基金the National Natural Science Foundation of China:to Explore the Mechanism of Acupuncture Treatment on Rats with Allergic Rhinitis from the Hypothalamic-Pituitary-Adrenal (HPA) Axis and Serum Immune Factor Levels (No.82004455)。
文摘OBJECTIVE:To explore the correlation between acupuncture treatment for allergic rhinitis(AR) and hypothalamic-pituitary-adrenal(HPA) axis regulation by investigating changes in serum immune factors,HPA axis-associated hormone levels,activation levels of paraventricular nucleus(PVN) neurons,and the severity of nasal mucosal lesions,in rats with AR before and after acupuncture treatment.METHODS:After establishing the AR rat model,ovalbumin was administered via nasal drip to all groups except the blank control.Each group received continuous treatment for 14 d:the acupuncture,acupuncture + RU-486(mifepristone),and RU-486 groups received acupuncture only,RU486 intraperitoneal injection and acupuncture,and RU-486 intraperitoneal injection only,respectively.Following the intervention period,behavioral scoring was performed on all AR rats,and peripheral blood,nasal mucosa samples,and brains tissue(containing PVN region) were obtained following euthanization.Interleukin(IL-4,IL-5,IL-13),interferon gamma(IFN-γ),corticosterone(CORT),and corticotrophin-releasing hormone(CRH) levels were evaluated in peripheral blood samples.Adrenocorticotropic hormone(ACTH) levels were determined using an enzyme-linked immunoassay assay,and hematoxylin and eosin staining was performed on the nasal mucosa samples.The expression levels of c-Fos in PVN neurons following acupuncture treatment were evaluated by immunofluorescent staining.RESULTS:Following the intervention period,the behavioral scores for the blank control group were lower than those of other groups(P < 0.05),while the acupuncture group scores were lower than those in the model control,acupuncture + RU486,and RU486 groups(P < 0.05).The blank control group had lower serum IL-4,IL-5,and IL-13 levels than those in the other groups(P < 0.05).The acupuncture group had lower serum IL-4,IL-5,and IL-13 levels than those in the model control,acupuncture + RU486,and RU486 groups(P < 0.05).The blank control group had the highest serum IFN-γ levels among all groups,followed by the acupuncture group.The serum CORT,CRH,and ACTH levels in the blank control group were lower than those in the remaining groups(P < 0.05).These biomarker levels were also lower in the acupuncture group than those in the model control,acupuncture + RU486,and RU486 groups(P < 0.05).Compared with model,rats in the acupuncture group exhibited an increased c-Fos expression in PVN neurons.CONCLUSION:Acupuncture can alleviate AR symptoms and regulate serum inflammatory factor levels and HPA axis-related hormones in AR rats.Moreover,these effects are inhibited by glucocorticoid antagonists,suggesting that acupuncture may regulate AR symptoms through HPA axis regulation.
文摘Sepsis,a life-threatening condition,can lead to acute skin failure characterized by extensive skin damage.This is often due to decreased blood flow,inflammation,and increased susceptibility to infection.Acute skin failure in people with sepsis is often associated with sleep disturbances,anxiety,and poor mood.Inflammatory markers and lactate levels correlate with these psychiatric symptoms,suggesting a link between skin and brain function.The skin and the central nervous system(CNS)have bidirectional communication.The CNS is also in close contact with the digestive tract.The gut,skin,and brain influence each other’s functions thr-ough nervous,hormonal,and immune pathways,forming a gut-skin-brain axis.Understanding the interaction among the gut,skin,and CNS is critical to the diag-nosis and treatment of various skin and neurological disorders.By recognizing individual variations in gut microbiota,immune responses,and neural pathways,treatments can be tailored to specific patient needs,enhancing efficacy and minimizing side effects.The gut plays a large role in mental health.Under-standing the gut skin brain axis,will lead to improved mental health outcomes.
基金supported by National Natural Science Foundation of China(32230081)National Natural Science Foundation of China(32001677)China Postdoctoral Science Foundation(2020M680256).
文摘Neurodegenerative diseases(NDs),mainly including Alzheimer’s disease,Parkinson’s disease,and multiple sclerosis,represent a major public health challenge with the steady increase of aging population worldwide.Emerging evidence has revealed the key role of the microbiota-gut-brain axis in the pathogenesis of NDs.Diet is one of the most important environmental factors shaping the structure and function of gut microbiota.Manipulating the gut microbiota through specific diet patterns may represent a promising approach for NDs prevention.In this review,we highlight gut microbiota variations in NDs,outline several crucial signaling pathways of the gut-brain communication,and discuss the interplay of nutrients-microbes and biological effect of diet-derived microbial metabolites on neural physiology.In particular,we summarized the current knowledge about the application of dietary patterns in NDs to prevent disease progression via the modulation of the gut microbiota.Our study provides novel insights on the diet-microbiota-gut-brain axis in neurodegenerative disorders and highlights the potential of developing microbiome-targeted personalized dietary intervention for NDs management.
基金funded by the Key Science and Technology Plan Project of Haikou 546(2023–2024).
文摘Background Pork quality and flavor are critical determinants of consumer preference,yet the role of gut microbiota in shaping meat characteristics remains underexplored.In this study,we investigated how a probiotic consortium(FAM:Lactobacillus acidophilus and Bacillus subtilis)modulates the gut-muscle axis to enhance pork flavor.Results In finishing pigs,FAM supplementation significantly increased flavor-associated nucleotides and umamienhancing amino acids in longissimus dorsi muscle.Metagenomic analysis revealed FAM-driven enrichment of glycandegrading Prevotella and short-chain fatty acid-producing Phascolarctobacterium,accompanied by reduced antibiotic resistance genes and virulence factors.Spearman correlation linked Prevotella copri abundance with elevated muscle amino acids,suggesting microbial-encoded CAZymes as key mediators.Conclusions This study provides the first evidence that probiotic-induced gut microbiota remodeling enhances pork flavor through metabolic cross-talk along the gut-muscle axis.The findings suggest a novel strategy for improving pork quality via dietary interventions targeting gut microbiota.
基金financially supported by the Collaborative Extension Program for Advancements in Agricultural Technologies of Zhejiang Province(Grant no:2023ZDXT15)the Key Research&Development Program of Zhejiang Province(Grant no:2024C02004)Bureau of Science and Technology of Xinchang County Foundation.
文摘Background Systemic inflammatory responses and oxidative stress occur in laying hens during the aging process,particularly during the post-peaking laying period,which generally result in multi-organ damages,leading to significant declines in egg performance and quality.Chlorogenic acid(CGA)-enriched extract from Eucommia ulmoides leaves has anti-inflammatory and antioxidant activities.However,the mechanisms underlying whether and how CGA alleviates systemic inflammatory responses and oxidative stress to improve egg performance and quality in postpeaking laying hens remain unclear.In this study,the potential regulatory mechanisms of CGA in alleviating inflammatory responses and oxidative stress along the gut-liver axis were investigated.A total of 36055-week-old Hy-line white-laying hens were randomly selected and divided into four groups.The hens in the four groups were fed a basal diet(CON)or basal diets supplemented with 200,400,and 800 mg/kg of CGA(CGA200,CGA400,and CGA800,respectively)for 10 weeks.Results The results demonstrated that CGA significantly alleviated intestinal and hepatic damages resulting from systemic inflammatory responses and oxidative stress,thereby improving the laying performance and egg quality of post-peaking laying hens.CGA reduced systemic inflammation by improving intestinal barrier function and modulating inflammation-associated microbiota(Blautia and Megamonas),thus inhibiting endotoxin translocation.CGA can also reduce oxidative stress by upregulating the NRF-2 pathway-related genes and increasing antioxidant enzyme activities in the liver.The results of transcriptome sequencing revealed that CGA promoted lipid metabolism by regulating hepatic adipocytokine pathway-related genes/protein and reduced the inflammatory responses and apoptosis in liver by regulating PI3K/AKT pathway-related genes/proteins,which was also verified by qPCR and western blotting.Conclusion CGA alleviated multi-organ damages and dysfunction by suppressing the systemic inflammatory responses and oxidative stress in post-peaking laying hens,thereby improving egg performance and quality.The optimal dose of CGA is 400 mg/kg in this experiment.These results provide a sound theoretical basis for the application of CGA as an exogenous animal feed additive for laying hens.
基金supported by grants from the National Natural Science Foundation of China(32125031)the Fundamental Research Funds for the Central Universities(JUSRP222001)Collaborative Innovation Center for Food Safety and Quality Control,China。
文摘Aflatoxin B_1(AFB_1)is a common contaminant in cereals of global concern,and long-term low-dose exposure can adversely affect human health.Here,we showed that populations with dietary patterns characterized by high-fat diet(HFD)might have an increased risk of exposure to high levels of AFB_1.Our data indicated that chronic exposure of AFB_1 induced“gut-liver axis”injury in mice under HFD and normal diet(ND)patterns.AFB_1 further aggravated hepatic and intestinal injury,and intestinal microbiota disruption in HFD mice.Bifidobacterium breve BAA-2849 intervention analysis showed that liver injury and lipid disorders caused by AFB_1 exposure were alleviated by regulating the proportions of different gut microbes.We demonstrated through a mice model that the populations with a dietary pattern of HFD might be more susceptible to AFB_1 exposure and adverse effects on the gut-liver axis,and the toxicity of AFB_1 exposure can be alleviated by regulating the gut microbiota.
基金financial support of the Natural Science Foundation of Hunan Province(2023JJ60481)the Natural Science Foundation of Changsha Municipality(kq2208181)+3 种基金the Hunan Provincial Department of Education’s Outstanding Youth Science Research Project(22B0360)the Hunan Provincial Department of Education’s Science Research Project(22C0191)the National Ministry of Agriculture’s Edible Lily Longshan Comprehensive Experimental Station Project(CARS-21)the Hunan University of Chinese Medicine Graduate Innovation Project(2023CX157)。
文摘The incidence rate and harmfulness of depression are increasing yearly,and the research on the antidepressant effect of regulating the intestinal microecology balance has attracted widespread attention.The purpose of this research was to study the preventive effects and the regulatory mechanism of edible Lilium-egg yolk compound powder(BHT)on gut-brain crosstalk in depressive rats induced by chronic unpredictable mild stress(CUMS)through the“microbiota-gut-brain”axis.Results showed that infusion of BHT for 21 days ameliorated the morphology of the hippocampus and colon,increased the rate of sucrose preference,reduced the immobility time of forced swimming,increased the expression level of anti-inflammatory cytokine interleukin(IL)-10 in serum,up-regulated the expression level of plasma neurotransmitter 5-hydroxytryptamine(5-HT),downregulated the expression of inflammatory factors tumor necrosis factor-α(TNF-α),IL-6,and IL-1βand neurotransmitter glutamic acid(Glu)in serum,and decreased the expression levels of lipopolysaccharide(LPS),diamine oxidase(DAO)and lactate dehydrogenase(LD)in plasma.The underlying mechanism may be to reduce the activation of microglia(lower levels of CD11 antigen-like family member B(CD11b),ionized calcium binding adaptor molecule 1(Iba1)protein and gene expression),regulate hippocampal glucocorticoid receptor/brain-derived neurotrophic factor/neuropeptide Y(GR/BDNF/NPY)signaling pathway(higher levels of GR,BDNF,NPY protein and gene expression),enhance intestinal mucosal barrier function(higher levels of ZO-1,occludin protein and gene expression),regulate the composition and structure of intestinal flora(analysis results of linear discriminant analysis effect size(LEf Se)combined with random forest showed that Prevotella and Paraprevotella might be biomarkers of BHT intervention in depression),and it is related to the improvement of glutathione metabolism,and other metabolic pathways.Pearson correlation analysis found that 5-HT is strongly positively correlated with Prevotella,and Glu has a strong negative correlation with Prevotella.In conclusion,BHT can exert its antidepressant effect on CUMS-induced rats through microbiota-gut-brain interaction,can be used as an alternative to food recuperation for human depression.
基金supported by the Natural Science Foundations of Fujian Province(Nos.2021J05063 and 2023J01541)a startup grant for High-level Talents of Fujian Medical University(No.XRCZX2021014)。
文摘Esculetin,a natural dihydroxy coumarin derived from the Chinese herbal medicine Cortex Fraxini,has demonstrated significant pharmacological activities,including anticancer properties.Ferroptosis,an iron-dependent form of regulated cell death,has garnered considerable attention due to its lethal effect on tumor cells.However,the exact role of ferroptosis in esculetin-mediated anti-hepatocellular carcinoma(HCC)effects remains poorly understood.This study investigated the impact of esculetin on HCC cells both in vitro and in vivo.The findings indicate that esculetin effectively inhibited the growth of HCC cells.Importantly,esculetin promoted the accumulation of intracellular Fe^(2+),leading to an increase in ROS production through the Fenton reaction.This event subsequently induced lipid peroxidation(LPO)and triggered ferroptosis within the HCC cells.The occurrence of ferroptosis was confirmed by the elevation of malondialdehyde(MDA)levels,the depletion of glutathione peroxidase(GSH-Px)activity,and the disruption of mitochondrial morphology.Notably,the inhibitor of ferroptosis,ferrostatin-1(Fer-1),attenuated the anti-tumor effect of esculetin in HCC cells.Furthermore,the findings revealed that esculetin inhibited the Nrf2-xCT/GPx4 axis signaling in HCC cells.Overexpression of Nrf2 upregulated the expression of downstream SLC7A11 and GPX4,consequently alleviating esculetin-induced ferroptosis.In conclusion,this study suggests that esculetin exerts an anti-HCC effect by inhibiting the activity of the Nrf2-xCT/GPx4 axis,thereby triggering ferroptosis in HCC cells.These findings may contribute to the potential clinical use of esculetin as a candidate for HCC treatment.
基金supported by grants from the National Natural Science Foundation of China(32400841)the China Postdoctoral Science Foundation(2023M743143).
文摘Ubiquitous energy-dense diets exacerbate the prevalence of metabolic syndrome across generations and increase cardiometabolic risks in offspring[1,2].This pervasive public health challenge has catalyzed intensive research into the intricate regulation of energy substrate metabolism.
基金supported by the National Research Foundation(NRF)of Korea(2022R1C1C1005741 and RS-2023-00217595)。
文摘Parkinson's disease has long been considered a disorder that primarily affects the brain,as it is defined by the dopaminergic neurodegeneration in the substantia nigra and the brain accumulation of Lewy bodies containingα-synuclein protein.In recent decades,however,accumulating research has revealed that Parkinson's disease also involves the gut and uncovered an intimate and important bidirectional link between the brain and the gut,called the“gut–brain axis.”Numerous clinical studies demonstrate that gut dysfunction frequently precedes motor symptoms in Parkinson's disease patients,with findings including impaired intestinal permeability,heightened inflammation,and distinct gut microbiome profiles and metabolites.Furthermore,α-synuclein deposition has been consistently observed in the gut of Parkinson's disease patients,suggesting a potential role in disease initiation.Importantly,individuals with vagotomy have a reduced Parkinson's disease risk.From these observations,researchers have hypothesized thatα-synuclein accumulation may initiate in the gut and subsequently propagate to the central dopaminergic neurons through the gut–brain axis,leading to Parkinson's disease.This review comprehensively examines the gut's involvement in Parkinson's disease,focusing on the concept of a gut-origin for the disease.We also examine the interplay between altered gut-related factors and the accumulation of pathologicalα-synuclein in the gut of Parkinson's disease patients.Given the accessibility of the gut to both dietary and pharmacological interventions,targeting gut-localizedα-synuclein represents a promising avenue for developing effective Parkinson's disease therapies.
