Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,sub...Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial dynamics.Given the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive dysfunction.This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).展开更多
Brain homeostasis refe rs to the normal working state of the brain in a certain period,which is impo rtant for overall health and normal life activities.Currently,there is a lack of effective treatment methods for the...Brain homeostasis refe rs to the normal working state of the brain in a certain period,which is impo rtant for overall health and normal life activities.Currently,there is a lack of effective treatment methods for the adverse consequences caused by brain homeostasis imbalance.Snapin is a protein that assists in the formation of neuronal synapses and plays a crucial role in the normal growth and development of synapses.Recently,many researchers have reported the association between snapin and neurologic and psychiatric disorders,demonstrating that snapin can improve brain homeostasis.Clinical manifestations of brain disease often involve imbalances in brain homeostasis and may lead to neurological and behavioral sequelae.This article aims to explo re the role of snapin in restoring brain homeostasis after injury or diseases,highlighting its significance in maintaining brain homeostasis and treating brain diseases.Additionally,it comprehensively discusses the implications of snapin in other extracerebral diseases such as diabetes and viral infections,with the objective of determining the clinical potential of snapin in maintaining brain homeostasis.展开更多
The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arth...The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains unclear.To address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic branching.Collectively,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.展开更多
Alzheimer’s disease(AD)is a major age-related form of dementia with a number of cases exponentially growing,causing enormous social and economic impact on individuals and society.Neuropathological hallmarks of AD,evi...Alzheimer’s disease(AD)is a major age-related form of dementia with a number of cases exponentially growing,causing enormous social and economic impact on individuals and society.Neuropathological hallmarks of AD,evident in postmortem AD brains,include a massive loss of the grey matter in the neocortex,extracellular deposition of amyloid-β(Aβ)in the form of senile plaques and cerebrovascular amyloid angiopathy,and intra-neuronal accumulation of neurofibrillary tangles,formed by hyper-phosphorylated tau protein.展开更多
Parkinson’s disease(PD) is characterized by the slow and progressive demise of dopamine(DA)-synthesizing neurons in the substantia nigra pars compacta(SNc),a nucleus located in the human ventral midbrain.Neuron death...Parkinson’s disease(PD) is characterized by the slow and progressive demise of dopamine(DA)-synthesizing neurons in the substantia nigra pars compacta(SNc),a nucleus located in the human ventral midbrain.Neuron death also affects other regions in the brain at later stages of PD.The concomitant lack of DA in the human forebrain(striatum) leads to the typical motor symptoms of this still uncurable neurodegenerative disorder.展开更多
Apolipoprotein E receptor 2(ApoER2)is a receptor for the protein ApoE,the most common genetic risk factor for late-onset Alzheimer's disease(AD).It is also a key modulator of syna ptic homeostasis,in part through ...Apolipoprotein E receptor 2(ApoER2)is a receptor for the protein ApoE,the most common genetic risk factor for late-onset Alzheimer's disease(AD).It is also a key modulator of syna ptic homeostasis,in part through its effect on the expression of neuronal genes including those implicated in AD and other neuropsychiatric disorders.In this perspective,we highlight several genes affected by ApoER2 and its alternatively spliced forms and how aberrant expression can be rescued by the reintroduction of the ApoER2 intracellular domain in the mouse hippocampus.展开更多
Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue,a process known as skeletal interoception,which is crucial for maintaining bone homeostasis.The hypothalamus...Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue,a process known as skeletal interoception,which is crucial for maintaining bone homeostasis.The hypothalamus,located in the central nervous system(CNS),plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system,neuropeptide release,and neuroendocrine mechanisms.These mechanisms control the differentiation of mesenchymal stem cells into osteoblasts(OBs),the activation of osteoclasts(OCs),and the functional activities of bone cells.Sensory nerves extensively innervate skeletal tissues,facilitating the transmission of interoceptive signals to the CNS.This review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological conditions.The findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.展开更多
Activating transcription factor 6(ATF6),one of the three sensor proteins in the endoplasmic reticulum(ER),is an important regulator of ER stress-induced apoptosis.ATF6 resides in the ER and,upon activation,is transloc...Activating transcription factor 6(ATF6),one of the three sensor proteins in the endoplasmic reticulum(ER),is an important regulator of ER stress-induced apoptosis.ATF6 resides in the ER and,upon activation,is translocated to the Golgi apparatus,where it is cleaved by site-1 protease(S1P)to generate an amino-terminal cytoplasmic fragment.Although recent studies have made progress in elucidating the regulatory mechanisms of ATF6,its function during early porcine embryonic development under high-temperature(HT)stress remains unclear.In this study,zygotes were divided into four groups:control,HT,HT+ATF6 knockdown,and HT+PF(S1P inhibitor).Results showed that HT exposure induced ER stress,which increased ATF6 protein expression and led to a decrease in the blastocyst rate.Next,ATF6 expression was knocked down in HT embryos under microinjection of ATF6 double-stranded RNA(dsRNA).Results revealed that ATF6 knockdown(ATF6-KD)attenuated the increased expression of CHOP,an ER stress marker,and Ca2+release induced by HT.In addition,ATF6-KD alleviated homeostasis dysregulation among organelles caused by HT-induced ER stress,and further reduced Golgi apparatus and mitochondrial dysfunction in HT embryos.AIFM2 is an important downstream effector of ATF6.Results showed that ATF6-KD reduced the occurrence of AIFM2-mediated embryonic apoptosis at HT.Taken together,our findings suggest that ATF6 is a crucial mediator of apoptosis during early porcine embryonic development,resulting from HT-induced ER stress and disruption of organelle homeostasis.展开更多
Nitrogen(N) and phosphorus(P) are two essential mineral nutrients for plant growth,which are required in relative high amount in plants.Plants have evolved a series of strategies for coordinately acquiring and utilizi...Nitrogen(N) and phosphorus(P) are two essential mineral nutrients for plant growth,which are required in relative high amount in plants.Plants have evolved a series of strategies for coordinately acquiring and utilizing N and P.However,physiological and molecular mechanisms underlying of N and P interactions remain largely unclear in soybean(Glycine max).In this study,interactions of N and P were demonstrated in soybean as reflected by significant increases of phosphate(Pi) concentration in both leaves and roots by N deficiency under Pi sufficient conditions.A total of four nitrogen limitation adaptation(NLA),encoding RING-type E3 ubiquitin ligase were subsequently identified in soybean genome.Among them,transcription of Gm NLA1-1 and Gm NLA1-3 was decreased in soybean by N starvation under Pi sufficient conditions,not for Gm NLA1-2.Suppression of all three Gm NLA1 members was able to increase Pi concentration regardless of the P and N availability in the growth medium,but decrease fresh weight under normal conditions in soybean hairy roots.However,comparted to changes in control lines at two N levels,N deficiency only resulted in a relatively higher increase of Pi concentration in Gm NLA1-1 or Gm NLA1-3 suppression lines,strongly indicating that Gm NLA1-1 and Gm NLA1-3 might regulate P homeostasis in soybean response to N starvation.Taken together,our result suggest that redundant and diverse functions present in Gm NLA1 members for soybean coordinate responses to P and N availability,which mediate P homeostasis.展开更多
Background:In rodents,research has revealed a role of liver X receptors(LXR) in controlling lipid homeostasis and regulating the synthesis of polyunsaturated fatty acids(PUFA).Recent data suggest that LXRB is the pred...Background:In rodents,research has revealed a role of liver X receptors(LXR) in controlling lipid homeostasis and regulating the synthesis of polyunsaturated fatty acids(PUFA).Recent data suggest that LXRB is the predominant LXR subtype in ruminant mammary cells,but its role in lipid metabolism is unknown.It was hypothesized that LXRB plays a role in lipid homeostasis via altering the synthesis of PUFA in the ruminant mammary gland.We used overexpression and knockdown of LXRB in goat primary mammary epithelial cells(GMEC) to evaluate abundance of lipogenic enzymes,fatty acid profiles,content of lipid stores and activity of the stearoyl-Co A desaturase(SCD1) promoter.Results:Overexpression of LXRB markedly upregulated the protein abundance of LXRB while incubation with si RNA targeting LXRB markedly decreased abundance of LXRB protein.Overexpression of LXRB plus T0901317(T09,a ligand for LXR) dramatically upregulated SCD1 and elongation of very long chain fatty acid-like fatty acid elongases 5–7(ELOVL 5–7),which are related to PUFA synthesis.Compared with the control,cells overexpressing LXRB and stimulated with T09 had greater concentrations of C16:0,16:1,18:1n7,18:1n9 and C18:2 as well as desaturation and elongation indices of C16:0.Furthermore,LXRB-overexpressing cells incubated with T09 had greater levels of triacylglycerol and cholesterol.Knockdown of LXRB in cells incubated with T09 led to downregulation of genes encoding elongases and desaturases.Knockdown of LXRB attenuated the increase in triacylglycerol and cholesterol that was induced by T09.In cells treated with dimethylsulfoxide,knockdown of LXRB increased the concentration of C16:0 at the expense of C18:0,while a significant decrease in C18:2 was observed in cells incubated with both si LXRB and T09.The abundance of sterol regulatory element binding transcription factor 1 precursor(p SREBP1) and its mature fragment(n SREBP1) was upregulated by T09,but not LXRB overexpression.In the cells cultured with T09,knockdown of LXRB downregulated the abundance for p SREBP1 and n SREBP1.Luciferase reporter assays revealed that the activities of wild type SCD1 promoter or fragment with SREBP1 response element(SRE) mutation were decreased markedly when LXRB was knocked down.Activity of the SCD1 promoter that was induced by T09 was blocked when the SRE mutation was introduced.Conclusion:The current study provides evidence of a physiological link between the LXRB and SREBP1 in the ruminant mammary cell.An important role was revealed for the LXRB-SREBP1 network in the synthesis of PUFA via the regulation of genes encoding elongases and desaturases.Thus,targeting this network might elicit broad effects on lipid homeostasis in ruminant mammary gland.展开更多
Homeostasis is the adaptability of a species to a changing environment.However,the ecological stoichiometric homeostasis of Robinia pseudoacacia L.in diff erent climatic regions is poorly understood but could provide ...Homeostasis is the adaptability of a species to a changing environment.However,the ecological stoichiometric homeostasis of Robinia pseudoacacia L.in diff erent climatic regions is poorly understood but could provide insights into its adaptability in the loess hilly region.This study sampled 20 year-old R.pseudoacacia plantations at 10 sites along a north–south transect on the Loess Plateau.Variations in the ecological stoichiometric characteristics of leaf and soil carbon,nitrogen,and phosphorus were analysed and homeostatic characteristics of leaf ecological stoichiometric parameters in diff erent climates were identifi ed.Factors aff ecting leaf stoichiometry were assessed.The results show that R.pseudoacacia leaves were rich in nitrogen and defi cient in phosphorous during tree growth and development.Nitrogen and phosphorous levels in the soils of the loess region were lower than the average in soils in the rest of China.All ecological stoichiometric parameters of R.pseudoacacia leaves in two diff erent climates were considered“strictly homeostasis”.Precipitation,available phosphorus,and soil C:P were the main factors aff ecting the variation of C:N:P stoichiometry of R.pseudoacacia leaves.R.pseudoacacia in the loess hilly region has strong ecologically homeostatic characteristics and suggests that it is well-adapted to the area.展开更多
Theasinensin A(TSA),a dimer of epigallocatechin gallate,has been preliminarily demonstrated to have hypoglycemia and anti-inflammatory effects.However,little information is available on its potential mechanisms of ant...Theasinensin A(TSA),a dimer of epigallocatechin gallate,has been preliminarily demonstrated to have hypoglycemia and anti-inflammatory effects.However,little information is available on its potential mechanisms of anti-diabetes.Therefore,the present study aimed to investigate the influence of TSA on glucose and lipid metabolism and gut microbiota in high-fat-diet/streptozotocin-induced diabetic mice.As result,TSA improved polydipsia,polyphagia and impaired glucose tolerance of diabetic mice,declined the fasting blood glucose and hepatic triglyceride level,and enhanced the expression at mRNA level of insulin receptor substrate,phosphoinositide 3-kinase,protein kinase B and glucagon-like peptide 1 receptor(GLP-1R)in the diabetic liver.Moreover,TSA could restore the disorder of gut microbiota of diabetic mice.High-dose(100 mg/kg)TSA showed better benefi cial effects from the blood biochemical parameters,hepatic function and gut microbiota.In general,high-dose TSA significantly modulated gut microbiota by increasing the relative abundance of Akkermansia and decreasing the relative abundances of Acetatifactor,Anaerotruncus,Pseudofl avonifactor,Oscillibacter and Clostridium clusters.The results indicated that TSA could exert an anti-diabetes effect in diabetic mice through restoring glucose homeostasis,declining hepatic steatosis,activating insulin and GLP-1 signaling pathways,and ameliorating gut microbiota dysbiosis.展开更多
Plant cell elongation depends on well-defined gene regulations,adequate nutrients,and timely cell wall modifications.Anther size is positively correlated with the number and viability of pollen grains,while little is ...Plant cell elongation depends on well-defined gene regulations,adequate nutrients,and timely cell wall modifications.Anther size is positively correlated with the number and viability of pollen grains,while little is known about molecular mechanisms underlying anther cell elongation.Here,we found that properly activated cell elongation regulators at transcriptional levels in loss-of-function ZmMs33 mutant(ms33-6038)anthers failed to promote maize anther elongation.ZmMs33 deficiency disrupted metabolic homeostasis mainly by inhibiting both photosynthesis in anther endothecium and lipid accumulation in anther tapetum.Importantly,ms33-6038 anthers displayed ectopic,premature and excessive secondary cell wall thickening in anther middle layer,which constrained cell elongation structurally and blocked nutrient flows across different anther wall layers.The metabolic disorder was only found in ms33-6038 mutant rather than several representative male-sterility lines at transcriptional and post-translational levels.Collectively,the disordered metabolisms and blocked nutrient flows defeated the activated cell elongation regulators,and finally inhibited anther elongation and growth with a unique‘‘idling effect”in ms33-6038 mutant.展开更多
Hepatosteatosis is characterized by abnormal accumulation of triglycerides(TG),leading to prolonged and chronic inflammatory infiltration.To date,there is still a lack of effective and economical therapies for hepatos...Hepatosteatosis is characterized by abnormal accumulation of triglycerides(TG),leading to prolonged and chronic inflammatory infiltration.To date,there is still a lack of effective and economical therapies for hepatosteatosis.Oridonin(ORI)is a major bioactive component extracted from the traditional Chinese medicinal herb Rabdosia rubescens.In this paper,we showed that ORI exerted significant protective effects against hepatic steatosis,inflammation and fibrosis,which was dependent on LXRa signaling.It is reported that LXRa regulated lipid homeostasis between triglyceride(TG)and phosphatidylethanolamine(PE)by promoting ATGL and EPT1 expression.Therefore,we implemented the lipidomic strategy and luciferase reporter assay to verify that ORI contributed to the homeostasis of lipids via the regulation of the ATGL gene associated with TG hydrolysis and the EPT1 gene related to PE synthesis in a LXRadependent manner,and the results showed the TG reduction and PE elevation.In detail,hepatic TG overload and lipotoxicity were reversed after ORI treatment by modulating the ATGL and EPT1 genes,respectively.Taken together,the data provide mechanistic insights to explain the bioactivity of ORI in attenuating TG accumulation and cytotoxicity and introduce exciting opportunities for developing novel natural activators of the LXRa-ATGL/EPT1 axis for pharmacologically treating hepatosteatosis and metabolic disorders.展开更多
Many tissues and organ systems have intrinsic regeneration capabilities that are largely driven and maintained by tissue-resident stem cell populations. In recent years, growing evidence has demonstrated that cellular...Many tissues and organ systems have intrinsic regeneration capabilities that are largely driven and maintained by tissue-resident stem cell populations. In recent years, growing evidence has demonstrated that cellular metabolic homeostasis plays a central role in mediating stem cell fate, tissue regeneration, and homeostasis. Thus, a thorough understanding of the mechanisms that regulate metabolic homeostasis in stem cells may contribute to our knowledge on how tissue homeostasis is maintained and provide novel insights for disease management. In this review, we summarize the known relationship between the regulation of metabolic homeostasis and molecular pathways in stem cells. We also discuss potential targets of metabolic homeostasis in disease therapy and describe the current limitations and future directions in the development of these novel therapeutic targets.展开更多
The mammalian intestinal epithelium constitutes the largest barrier against the external environment and makes flexible responses to various types of stimuli.Epithelial cells are fast-renewed to counteract constant da...The mammalian intestinal epithelium constitutes the largest barrier against the external environment and makes flexible responses to various types of stimuli.Epithelial cells are fast-renewed to counteract constant damage and disrupted barrier function to maintain their integrity.The homeostatic repair and regeneration of the intestinal epithelium are governed by the Lgr5+intestinal stem cells(ISCs)located at the base of crypts,which fuel rapid renewal and give rise to the different epithelial cell types.Protracted biological and physicochemical stress may challenge epithelial integrity and the function of ISCs.The field of ISCs is thus of interest for complete mucosal healing,given its relevance to diseases of intestinal injury and inflammation such as inflammatory bowel diseases.Here,we review the current understanding of the signals and mechanisms that control homeostasis and regeneration of the intestinal epithelium.We focus on recent insights into the intrinsic and extrinsic elements involved in the process of intestinal homeostasis,injury,and repair,which fine-tune the balance between self-renewal and cell fate specification in ISCs.Deciphering the regulatory machinery that modulates stem cell fate would aid in the development of novel therapeutics that facilitate mucosal healing and restore epithelial barrier function.展开更多
Brain energy homeostasis is a vital physiological function in maintaining a balanced internal metabolic environment.The impairment of energy homeostasis is recognized as a key pathophysiological basis for brain metabo...Brain energy homeostasis is a vital physiological function in maintaining a balanced internal metabolic environment.The impairment of energy homeostasis is recognized as a key pathophysiological basis for brain metabolic disorders and related neurodegenerative diseases.Dendrobium species(‘Shihu’in Chinese)such as D.officinale,D.huoshanense,D.nobile,D.chrysanthum,D.loddigesii,D.moniliforme,D.gratiosissimum,D.candidum and D.caulis are widely used as traditional Chinese medicines/nutraceuticals to control and treat neurodegenerative disorders.These dietary herbs and their derived compounds possess a variety of biological properties,such as suppression of oxidative stress and neuroinflammation,regulation of energy homeostasis mainly through improving brain mitochondria function,insulin signaling and lipid metabolism.Furthermore,they reduce neurotoxicity,alleviate brain injury and neuropathy,and prevent neurodegenerative conditions including stroke,Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease in humans and/or rodents.Moreover,the nutraceuticals from Dendrobium species promote gut health and aid digestion,which appear to be associated with beneficial effects on brain energy homeostasis.Based on the above-mentioned health benefits associated with Dendrobium species,this work reviews their nutraceutical role in neurodegenerative disorders and further suggests the need to elucidate mechanisms of the underlying molecular actions.展开更多
Immune-mediated liver injury is widely seen during hepatitis B virus(HBV) infection. Unsuccessful immune clearance of HBV results in chronic hepatitis and increases the risk of liver cirrhosis and hepatocellular carci...Immune-mediated liver injury is widely seen during hepatitis B virus(HBV) infection. Unsuccessful immune clearance of HBV results in chronic hepatitis and increases the risk of liver cirrhosis and hepatocellular carcinoma. HBV-related liver fibrosis(HBVLF),occurring as a result of HBV-induced chronic hepatitis,is a reversible,intermediate stage of chronic hepatitis B(CHB) and liver cirrhosis. Therefore,defining the pathogenesis of HBVLF is of practical significance for achieving better clinical outcomes. Recently,the homeostasis of CD4+ T cells was considered to be pivotal in the process of HBVLF. To better uncover the underlying mechanisms,in this review,we systematically retrospect the impacts of different CD4+T-cell subsets on CHB and HBVLF. We emphasize CD4+ T-cell homeostasis and the important balance between regulatory T(Treg) and T helper 17(Th17) cells. We discuss some cytokines associated with Treg and Th17 cells such as interleukin(IL)-17,IL-22,IL-21,IL-23,IL-10,IL-35 and IL-33,as well as surface molecules such as programmed cell death protein 1,cytotoxic T lymphocyte-associated antigen 4,T cell immunoglobulin domain and mucin domain-containing molecule 3 and cannabinoid receptor 2 that have potential therapeutic implications for the homeostasis of CD4+ T cells in CHB and HBVLF.展开更多
Objective To reveal the effects and related mechanisms of chlorogenic acid(CGA)on intestinal glucose homeostasis.Methods Forty male Sprague-Dawley rats were randomly and equally divided into four groups:normal chow(NC...Objective To reveal the effects and related mechanisms of chlorogenic acid(CGA)on intestinal glucose homeostasis.Methods Forty male Sprague-Dawley rats were randomly and equally divided into four groups:normal chow(NC),high-fat diet(HFD),HFD with low-dose CGA(20 mg/kg,HFD-LC),and HFD with high-dose CGA(90 mg/kg,HFD-HC).The oral glucose tolerance test was performed,and fast serum insulin(FSI)was detected using an enzyme-linked immunosorbent assay.The m RNA expression levels of glucose transporters(Sglt-1 and Glut-2)and proglucagon(Plg)in different intestinal segments(the duodenum,jejunum,ileum,and colon)were analyzed using quantitative real-time polymerase chain reaction.SGLT-1 protein and the morphology of epithelial cells in the duodenum and jejunum was localized by using immunofluorescence.Results At both doses,CGA ameliorated the HFD-induced body weight gain,maintained FSI,and increased postprandial 30-min glucagon-like peptide 1 secretion.High-dose CGA inhibited the HFD-induced elevation in Sglt-1 expression.Both CGA doses normalized the HFD-induced downregulation of Glut-2 and elevated the expression of Plg in all four intestinal segments.Conclusion An HFD can cause a glucose metabolism disorder in the rat intestine and affect body glucose homeostasis.CGA can modify intestinal glucose metabolism by regulating the expression of intestinal glucose transporters and Plg,thereby controlling the levels of blood glucose and insulin to maintain glucose homeostasis.展开更多
Autophagy is an evolutionarily conserved intracellular process,in which domestic cellular components are selectively digested for the recycling of nutrients and energy.This process is indispensable for cell homeostasi...Autophagy is an evolutionarily conserved intracellular process,in which domestic cellular components are selectively digested for the recycling of nutrients and energy.This process is indispensable for cell homeostasis maintenance and stress responses.Both genetic and functional studies have demonstrated that multiple proteins involved in autophagic activities are critical to the survival,differentiation,and functioning of bone cells,including osteoblasts,osteocytes,and osteoclasts.Dysregulation at the level of autophagic activity consequently disturbs the balance between bone formation and bone resorption and mediates the onset and progression of multiple bone diseases,including osteoporosis.This review aims to introduce the topic of autophagy,summarize the understanding of its relevance in bone physiology,and discuss its role in the onset of osteoporosis and therapeutic potential.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82271222(to ZL),81971012(to ZL),82071189(to XG),and 82201335(to YL)Key Clinical Projects of Peking University Third Hospital,No.BYSYZD2019027(to ZL)。
文摘Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial dynamics.Given the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive dysfunction.This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).
基金supported by the National Natural Science Foundation of China,Nos.82071382(to MZ),81601306(to HS)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(to MZ)+5 种基金Jiangsu 333 High Level Talent Training Project(2022)(to HS)the Jiangsu Maternal and Child Health Research Key Project(F202013)(to HS)Jiangsu Talent Youth Medical Program,No.QNRC2016245(to HS)Shanghai Key Lab of Forensic Medicine,No.KF2102(to MZ)Suzhou Science and Technology Development Project,No.SYS2020089(to MZ)the Fifth Batch of Gusu District Health Talent Training Project,No.GSWS2019060(to HS)。
文摘Brain homeostasis refe rs to the normal working state of the brain in a certain period,which is impo rtant for overall health and normal life activities.Currently,there is a lack of effective treatment methods for the adverse consequences caused by brain homeostasis imbalance.Snapin is a protein that assists in the formation of neuronal synapses and plays a crucial role in the normal growth and development of synapses.Recently,many researchers have reported the association between snapin and neurologic and psychiatric disorders,demonstrating that snapin can improve brain homeostasis.Clinical manifestations of brain disease often involve imbalances in brain homeostasis and may lead to neurological and behavioral sequelae.This article aims to explo re the role of snapin in restoring brain homeostasis after injury or diseases,highlighting its significance in maintaining brain homeostasis and treating brain diseases.Additionally,it comprehensively discusses the implications of snapin in other extracerebral diseases such as diabetes and viral infections,with the objective of determining the clinical potential of snapin in maintaining brain homeostasis.
基金supported by the National Natural Science Foundation of China,No.82272484(to XC).
文摘The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains unclear.To address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic branching.Collectively,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.
基金the following financial support grant FAR-2019 to DL from The Universita del Piemonte Orientale。
文摘Alzheimer’s disease(AD)is a major age-related form of dementia with a number of cases exponentially growing,causing enormous social and economic impact on individuals and society.Neuropathological hallmarks of AD,evident in postmortem AD brains,include a massive loss of the grey matter in the neocortex,extracellular deposition of amyloid-β(Aβ)in the form of senile plaques and cerebrovascular amyloid angiopathy,and intra-neuronal accumulation of neurofibrillary tangles,formed by hyper-phosphorylated tau protein.
文摘Parkinson’s disease(PD) is characterized by the slow and progressive demise of dopamine(DA)-synthesizing neurons in the substantia nigra pars compacta(SNc),a nucleus located in the human ventral midbrain.Neuron death also affects other regions in the brain at later stages of PD.The concomitant lack of DA in the human forebrain(striatum) leads to the typical motor symptoms of this still uncurable neurodegenerative disorder.
基金supported by NIH grants NS093382,NS108115,AG053391,HL063762 (to JH)supported by Blue Field Project to Cure FTD,BrightFocus Foundation (A20135245 and A2016396S)。
文摘Apolipoprotein E receptor 2(ApoER2)is a receptor for the protein ApoE,the most common genetic risk factor for late-onset Alzheimer's disease(AD).It is also a key modulator of syna ptic homeostasis,in part through its effect on the expression of neuronal genes including those implicated in AD and other neuropsychiatric disorders.In this perspective,we highlight several genes affected by ApoER2 and its alternatively spliced forms and how aberrant expression can be rescued by the reintroduction of the ApoER2 intracellular domain in the mouse hippocampus.
基金supported by the National Natural Science Foundation of China (No.82172408,81902234,81772314,and 81922045)the Original Exploration project (22ZR1480300)+4 种基金Outstanding Academic Leaders (Youth)project (21XD1422900)of Shanghai Science and Technology Innovation Action PlanPrinciple Investigator Innovation Team of Both Shanghai Sixth People’s Hospital and Shanghai Institute of Nutrition and Health,Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program (No.20191829)The Second Three-Year Action Plan for Promoting Clinical Skills and Clinical Innovation in Municipal Hospitals of Shanghai Shenkang (No.SHDC2020CR4032)Shanghai Excellent Academic Leader ProgramShanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration (No.20DZ2254100)。
文摘Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue,a process known as skeletal interoception,which is crucial for maintaining bone homeostasis.The hypothalamus,located in the central nervous system(CNS),plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system,neuropeptide release,and neuroendocrine mechanisms.These mechanisms control the differentiation of mesenchymal stem cells into osteoblasts(OBs),the activation of osteoclasts(OCs),and the functional activities of bone cells.Sensory nerves extensively innervate skeletal tissues,facilitating the transmission of interoceptive signals to the CNS.This review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological conditions.The findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.
基金supported by the National Research Foundation (NRF)of Korea Grant funded by the Korean Government (MSIT) (2020R1A4A1017552,2022R1A2C300769),Republic of Korea。
文摘Activating transcription factor 6(ATF6),one of the three sensor proteins in the endoplasmic reticulum(ER),is an important regulator of ER stress-induced apoptosis.ATF6 resides in the ER and,upon activation,is translocated to the Golgi apparatus,where it is cleaved by site-1 protease(S1P)to generate an amino-terminal cytoplasmic fragment.Although recent studies have made progress in elucidating the regulatory mechanisms of ATF6,its function during early porcine embryonic development under high-temperature(HT)stress remains unclear.In this study,zygotes were divided into four groups:control,HT,HT+ATF6 knockdown,and HT+PF(S1P inhibitor).Results showed that HT exposure induced ER stress,which increased ATF6 protein expression and led to a decrease in the blastocyst rate.Next,ATF6 expression was knocked down in HT embryos under microinjection of ATF6 double-stranded RNA(dsRNA).Results revealed that ATF6 knockdown(ATF6-KD)attenuated the increased expression of CHOP,an ER stress marker,and Ca2+release induced by HT.In addition,ATF6-KD alleviated homeostasis dysregulation among organelles caused by HT-induced ER stress,and further reduced Golgi apparatus and mitochondrial dysfunction in HT embryos.AIFM2 is an important downstream effector of ATF6.Results showed that ATF6-KD reduced the occurrence of AIFM2-mediated embryonic apoptosis at HT.Taken together,our findings suggest that ATF6 is a crucial mediator of apoptosis during early porcine embryonic development,resulting from HT-induced ER stress and disruption of organelle homeostasis.
基金supported by the National Key Research and Development Program of China (2021YFF1000500)Major Program of Guangdong Basic and Applied Research (2019B030302006)+2 种基金the National Natural Science Foundation of China (32172659,32172658, 31872164)the STIC Grant (SGDX20210823103535007)the Natural Science Foundation of Guangdong Province of China(2021A1515010826, 2020A1515110261)。
文摘Nitrogen(N) and phosphorus(P) are two essential mineral nutrients for plant growth,which are required in relative high amount in plants.Plants have evolved a series of strategies for coordinately acquiring and utilizing N and P.However,physiological and molecular mechanisms underlying of N and P interactions remain largely unclear in soybean(Glycine max).In this study,interactions of N and P were demonstrated in soybean as reflected by significant increases of phosphate(Pi) concentration in both leaves and roots by N deficiency under Pi sufficient conditions.A total of four nitrogen limitation adaptation(NLA),encoding RING-type E3 ubiquitin ligase were subsequently identified in soybean genome.Among them,transcription of Gm NLA1-1 and Gm NLA1-3 was decreased in soybean by N starvation under Pi sufficient conditions,not for Gm NLA1-2.Suppression of all three Gm NLA1 members was able to increase Pi concentration regardless of the P and N availability in the growth medium,but decrease fresh weight under normal conditions in soybean hairy roots.However,comparted to changes in control lines at two N levels,N deficiency only resulted in a relatively higher increase of Pi concentration in Gm NLA1-1 or Gm NLA1-3 suppression lines,strongly indicating that Gm NLA1-1 and Gm NLA1-3 might regulate P homeostasis in soybean response to N starvation.Taken together,our result suggest that redundant and diverse functions present in Gm NLA1 members for soybean coordinate responses to P and N availability,which mediate P homeostasis.
基金supported by the National Natural Science Foundation of China(31702090)Key R&D program of Zhejiang Province(2022C04017)+1 种基金Zhejiang Provincial Major Science and Technology Projects on Agricultural New Varieties Selection and Breeding(2021C02068-6)Opening fund in Key Laboratory of Molecular Animal Nutrition(Zhejiang University,KLMAN202103).
文摘Background:In rodents,research has revealed a role of liver X receptors(LXR) in controlling lipid homeostasis and regulating the synthesis of polyunsaturated fatty acids(PUFA).Recent data suggest that LXRB is the predominant LXR subtype in ruminant mammary cells,but its role in lipid metabolism is unknown.It was hypothesized that LXRB plays a role in lipid homeostasis via altering the synthesis of PUFA in the ruminant mammary gland.We used overexpression and knockdown of LXRB in goat primary mammary epithelial cells(GMEC) to evaluate abundance of lipogenic enzymes,fatty acid profiles,content of lipid stores and activity of the stearoyl-Co A desaturase(SCD1) promoter.Results:Overexpression of LXRB markedly upregulated the protein abundance of LXRB while incubation with si RNA targeting LXRB markedly decreased abundance of LXRB protein.Overexpression of LXRB plus T0901317(T09,a ligand for LXR) dramatically upregulated SCD1 and elongation of very long chain fatty acid-like fatty acid elongases 5–7(ELOVL 5–7),which are related to PUFA synthesis.Compared with the control,cells overexpressing LXRB and stimulated with T09 had greater concentrations of C16:0,16:1,18:1n7,18:1n9 and C18:2 as well as desaturation and elongation indices of C16:0.Furthermore,LXRB-overexpressing cells incubated with T09 had greater levels of triacylglycerol and cholesterol.Knockdown of LXRB in cells incubated with T09 led to downregulation of genes encoding elongases and desaturases.Knockdown of LXRB attenuated the increase in triacylglycerol and cholesterol that was induced by T09.In cells treated with dimethylsulfoxide,knockdown of LXRB increased the concentration of C16:0 at the expense of C18:0,while a significant decrease in C18:2 was observed in cells incubated with both si LXRB and T09.The abundance of sterol regulatory element binding transcription factor 1 precursor(p SREBP1) and its mature fragment(n SREBP1) was upregulated by T09,but not LXRB overexpression.In the cells cultured with T09,knockdown of LXRB downregulated the abundance for p SREBP1 and n SREBP1.Luciferase reporter assays revealed that the activities of wild type SCD1 promoter or fragment with SREBP1 response element(SRE) mutation were decreased markedly when LXRB was knocked down.Activity of the SCD1 promoter that was induced by T09 was blocked when the SRE mutation was introduced.Conclusion:The current study provides evidence of a physiological link between the LXRB and SREBP1 in the ruminant mammary cell.An important role was revealed for the LXRB-SREBP1 network in the synthesis of PUFA via the regulation of genes encoding elongases and desaturases.Thus,targeting this network might elicit broad effects on lipid homeostasis in ruminant mammary gland.
基金supported by the Science and Technology Innovation Program of the Shaanxi Academy of Forestry(SXLK2022-02-03)the National Natural Science Foundation of China(42077452).
文摘Homeostasis is the adaptability of a species to a changing environment.However,the ecological stoichiometric homeostasis of Robinia pseudoacacia L.in diff erent climatic regions is poorly understood but could provide insights into its adaptability in the loess hilly region.This study sampled 20 year-old R.pseudoacacia plantations at 10 sites along a north–south transect on the Loess Plateau.Variations in the ecological stoichiometric characteristics of leaf and soil carbon,nitrogen,and phosphorus were analysed and homeostatic characteristics of leaf ecological stoichiometric parameters in diff erent climates were identifi ed.Factors aff ecting leaf stoichiometry were assessed.The results show that R.pseudoacacia leaves were rich in nitrogen and defi cient in phosphorous during tree growth and development.Nitrogen and phosphorous levels in the soils of the loess region were lower than the average in soils in the rest of China.All ecological stoichiometric parameters of R.pseudoacacia leaves in two diff erent climates were considered“strictly homeostasis”.Precipitation,available phosphorus,and soil C:P were the main factors aff ecting the variation of C:N:P stoichiometry of R.pseudoacacia leaves.R.pseudoacacia in the loess hilly region has strong ecologically homeostatic characteristics and suggests that it is well-adapted to the area.
基金supported by the Key Technology R&D Program of Jiangsu Province(BE2020341)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Theasinensin A(TSA),a dimer of epigallocatechin gallate,has been preliminarily demonstrated to have hypoglycemia and anti-inflammatory effects.However,little information is available on its potential mechanisms of anti-diabetes.Therefore,the present study aimed to investigate the influence of TSA on glucose and lipid metabolism and gut microbiota in high-fat-diet/streptozotocin-induced diabetic mice.As result,TSA improved polydipsia,polyphagia and impaired glucose tolerance of diabetic mice,declined the fasting blood glucose and hepatic triglyceride level,and enhanced the expression at mRNA level of insulin receptor substrate,phosphoinositide 3-kinase,protein kinase B and glucagon-like peptide 1 receptor(GLP-1R)in the diabetic liver.Moreover,TSA could restore the disorder of gut microbiota of diabetic mice.High-dose(100 mg/kg)TSA showed better benefi cial effects from the blood biochemical parameters,hepatic function and gut microbiota.In general,high-dose TSA significantly modulated gut microbiota by increasing the relative abundance of Akkermansia and decreasing the relative abundances of Acetatifactor,Anaerotruncus,Pseudofl avonifactor,Oscillibacter and Clostridium clusters.The results indicated that TSA could exert an anti-diabetes effect in diabetic mice through restoring glucose homeostasis,declining hepatic steatosis,activating insulin and GLP-1 signaling pathways,and ameliorating gut microbiota dysbiosis.
基金funded by the National Key Research and Development Program of China(2021YFF1000302)Fundamental Research Funds for the Central Universities of China(06500136)the Interdisciplinary Research Project for Young Teachers of USTB(Fundamental Research Funds for the Central Universities)(FRF-IDRY-20-038).
文摘Plant cell elongation depends on well-defined gene regulations,adequate nutrients,and timely cell wall modifications.Anther size is positively correlated with the number and viability of pollen grains,while little is known about molecular mechanisms underlying anther cell elongation.Here,we found that properly activated cell elongation regulators at transcriptional levels in loss-of-function ZmMs33 mutant(ms33-6038)anthers failed to promote maize anther elongation.ZmMs33 deficiency disrupted metabolic homeostasis mainly by inhibiting both photosynthesis in anther endothecium and lipid accumulation in anther tapetum.Importantly,ms33-6038 anthers displayed ectopic,premature and excessive secondary cell wall thickening in anther middle layer,which constrained cell elongation structurally and blocked nutrient flows across different anther wall layers.The metabolic disorder was only found in ms33-6038 mutant rather than several representative male-sterility lines at transcriptional and post-translational levels.Collectively,the disordered metabolisms and blocked nutrient flows defeated the activated cell elongation regulators,and finally inhibited anther elongation and growth with a unique‘‘idling effect”in ms33-6038 mutant.
基金supported by the National Natural Science Foundation of China(Grant No.:81973388)Marine Economy Development Project of Guangdong Province(Project No.:GDNRC[2021]52)the Key Research and Development Program of Guangdong Province(Program No.:2020B1111030005).
文摘Hepatosteatosis is characterized by abnormal accumulation of triglycerides(TG),leading to prolonged and chronic inflammatory infiltration.To date,there is still a lack of effective and economical therapies for hepatosteatosis.Oridonin(ORI)is a major bioactive component extracted from the traditional Chinese medicinal herb Rabdosia rubescens.In this paper,we showed that ORI exerted significant protective effects against hepatic steatosis,inflammation and fibrosis,which was dependent on LXRa signaling.It is reported that LXRa regulated lipid homeostasis between triglyceride(TG)and phosphatidylethanolamine(PE)by promoting ATGL and EPT1 expression.Therefore,we implemented the lipidomic strategy and luciferase reporter assay to verify that ORI contributed to the homeostasis of lipids via the regulation of the ATGL gene associated with TG hydrolysis and the EPT1 gene related to PE synthesis in a LXRadependent manner,and the results showed the TG reduction and PE elevation.In detail,hepatic TG overload and lipotoxicity were reversed after ORI treatment by modulating the ATGL and EPT1 genes,respectively.Taken together,the data provide mechanistic insights to explain the bioactivity of ORI in attenuating TG accumulation and cytotoxicity and introduce exciting opportunities for developing novel natural activators of the LXRa-ATGL/EPT1 axis for pharmacologically treating hepatosteatosis and metabolic disorders.
基金the National Natural Science Foundation of China(82030031,L2224038,92149301)Chinese Academy of Medical Sciences Research Unit(2019-12M-5-031)+4 种基金Beijing Municipal Science&Technology Commission(Z181100001718208)Beijing Municipal Education Commission(119207020201)Beijing Municipality Government Grants(Beijing Laboratory of Oral Health-PXM2021_014226_000041,Beijing Scholar Program-PXM2021_014226_000020)Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202201)Young Scientist Program of Beijing Stomatological Hospital,Capital Medical University(YSP202308).
文摘Many tissues and organ systems have intrinsic regeneration capabilities that are largely driven and maintained by tissue-resident stem cell populations. In recent years, growing evidence has demonstrated that cellular metabolic homeostasis plays a central role in mediating stem cell fate, tissue regeneration, and homeostasis. Thus, a thorough understanding of the mechanisms that regulate metabolic homeostasis in stem cells may contribute to our knowledge on how tissue homeostasis is maintained and provide novel insights for disease management. In this review, we summarize the known relationship between the regulation of metabolic homeostasis and molecular pathways in stem cells. We also discuss potential targets of metabolic homeostasis in disease therapy and describe the current limitations and future directions in the development of these novel therapeutic targets.
基金Supported by the National Natural Science Foundation of China,No.82202766the Natural Science Foundation of Hubei Province of China,No.2022CFB686+1 种基金the Science Foundation of Union Hospital,No.2021xhyn102the Scientific Research Training Program for Young Talents in Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,China。
文摘The mammalian intestinal epithelium constitutes the largest barrier against the external environment and makes flexible responses to various types of stimuli.Epithelial cells are fast-renewed to counteract constant damage and disrupted barrier function to maintain their integrity.The homeostatic repair and regeneration of the intestinal epithelium are governed by the Lgr5+intestinal stem cells(ISCs)located at the base of crypts,which fuel rapid renewal and give rise to the different epithelial cell types.Protracted biological and physicochemical stress may challenge epithelial integrity and the function of ISCs.The field of ISCs is thus of interest for complete mucosal healing,given its relevance to diseases of intestinal injury and inflammation such as inflammatory bowel diseases.Here,we review the current understanding of the signals and mechanisms that control homeostasis and regeneration of the intestinal epithelium.We focus on recent insights into the intrinsic and extrinsic elements involved in the process of intestinal homeostasis,injury,and repair,which fine-tune the balance between self-renewal and cell fate specification in ISCs.Deciphering the regulatory machinery that modulates stem cell fate would aid in the development of novel therapeutics that facilitate mucosal healing and restore epithelial barrier function.
基金funded by the National Key Research and Development Program of China(2018YFC1706105)the National Natural Science Foundation of China(81872961)+1 种基金Key Project at Central Government Level(2060302)Collaborative Innovation Project of Dendrobium Industrialization Development in Anhui Province.
文摘Brain energy homeostasis is a vital physiological function in maintaining a balanced internal metabolic environment.The impairment of energy homeostasis is recognized as a key pathophysiological basis for brain metabolic disorders and related neurodegenerative diseases.Dendrobium species(‘Shihu’in Chinese)such as D.officinale,D.huoshanense,D.nobile,D.chrysanthum,D.loddigesii,D.moniliforme,D.gratiosissimum,D.candidum and D.caulis are widely used as traditional Chinese medicines/nutraceuticals to control and treat neurodegenerative disorders.These dietary herbs and their derived compounds possess a variety of biological properties,such as suppression of oxidative stress and neuroinflammation,regulation of energy homeostasis mainly through improving brain mitochondria function,insulin signaling and lipid metabolism.Furthermore,they reduce neurotoxicity,alleviate brain injury and neuropathy,and prevent neurodegenerative conditions including stroke,Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease in humans and/or rodents.Moreover,the nutraceuticals from Dendrobium species promote gut health and aid digestion,which appear to be associated with beneficial effects on brain energy homeostasis.Based on the above-mentioned health benefits associated with Dendrobium species,this work reviews their nutraceutical role in neurodegenerative disorders and further suggests the need to elucidate mechanisms of the underlying molecular actions.
基金Supported by The National Natural Science Foundation of China,No.81070341 and No.81270517
文摘Immune-mediated liver injury is widely seen during hepatitis B virus(HBV) infection. Unsuccessful immune clearance of HBV results in chronic hepatitis and increases the risk of liver cirrhosis and hepatocellular carcinoma. HBV-related liver fibrosis(HBVLF),occurring as a result of HBV-induced chronic hepatitis,is a reversible,intermediate stage of chronic hepatitis B(CHB) and liver cirrhosis. Therefore,defining the pathogenesis of HBVLF is of practical significance for achieving better clinical outcomes. Recently,the homeostasis of CD4+ T cells was considered to be pivotal in the process of HBVLF. To better uncover the underlying mechanisms,in this review,we systematically retrospect the impacts of different CD4+T-cell subsets on CHB and HBVLF. We emphasize CD4+ T-cell homeostasis and the important balance between regulatory T(Treg) and T helper 17(Th17) cells. We discuss some cytokines associated with Treg and Th17 cells such as interleukin(IL)-17,IL-22,IL-21,IL-23,IL-10,IL-35 and IL-33,as well as surface molecules such as programmed cell death protein 1,cytotoxic T lymphocyte-associated antigen 4,T cell immunoglobulin domain and mucin domain-containing molecule 3 and cannabinoid receptor 2 that have potential therapeutic implications for the homeostasis of CD4+ T cells in CHB and HBVLF.
基金supported by the National Natural Science foundation of China(No.31071531)the Scientific Research Fund of the Hunan Provincial Education Department(No.14A071)the China National Tobacco Corp Hunan Branch(15-17Aa04)
文摘Objective To reveal the effects and related mechanisms of chlorogenic acid(CGA)on intestinal glucose homeostasis.Methods Forty male Sprague-Dawley rats were randomly and equally divided into four groups:normal chow(NC),high-fat diet(HFD),HFD with low-dose CGA(20 mg/kg,HFD-LC),and HFD with high-dose CGA(90 mg/kg,HFD-HC).The oral glucose tolerance test was performed,and fast serum insulin(FSI)was detected using an enzyme-linked immunosorbent assay.The m RNA expression levels of glucose transporters(Sglt-1 and Glut-2)and proglucagon(Plg)in different intestinal segments(the duodenum,jejunum,ileum,and colon)were analyzed using quantitative real-time polymerase chain reaction.SGLT-1 protein and the morphology of epithelial cells in the duodenum and jejunum was localized by using immunofluorescence.Results At both doses,CGA ameliorated the HFD-induced body weight gain,maintained FSI,and increased postprandial 30-min glucagon-like peptide 1 secretion.High-dose CGA inhibited the HFD-induced elevation in Sglt-1 expression.Both CGA doses normalized the HFD-induced downregulation of Glut-2 and elevated the expression of Plg in all four intestinal segments.Conclusion An HFD can cause a glucose metabolism disorder in the rat intestine and affect body glucose homeostasis.CGA can modify intestinal glucose metabolism by regulating the expression of intestinal glucose transporters and Plg,thereby controlling the levels of blood glucose and insulin to maintain glucose homeostasis.
基金supported by grants from National Natural Science Foundation of China (81722014, 81801019)the Sichuan Provincial Science and Technology Department (2018JY0139, 2019JDRC0099, 2019YJ0101)+2 种基金the China Postdoctoral Science Foundation (2018M640929)Sichuan University (2018SCU12020)West China Hospital of Stomatology Sichuan University (WCHS-201702)
文摘Autophagy is an evolutionarily conserved intracellular process,in which domestic cellular components are selectively digested for the recycling of nutrients and energy.This process is indispensable for cell homeostasis maintenance and stress responses.Both genetic and functional studies have demonstrated that multiple proteins involved in autophagic activities are critical to the survival,differentiation,and functioning of bone cells,including osteoblasts,osteocytes,and osteoclasts.Dysregulation at the level of autophagic activity consequently disturbs the balance between bone formation and bone resorption and mediates the onset and progression of multiple bone diseases,including osteoporosis.This review aims to introduce the topic of autophagy,summarize the understanding of its relevance in bone physiology,and discuss its role in the onset of osteoporosis and therapeutic potential.
