The pathophysiology of ischemic stroke is complex and multifactorial,involving various forms of cell death such as apoptosis,autophagy,and necrosis.A recent study suggests that oxidative and inflammatory stress can in...The pathophysiology of ischemic stroke is complex and multifactorial,involving various forms of cell death such as apoptosis,autophagy,and necrosis.A recent study suggests that oxidative and inflammatory stress can induce ferroptosis,a specialized form of cell death characterized by the accumulation of lipid peroxides dependent on intracellular iron overload(Li and Jia,2023).展开更多
Although poly(lactic acid)(PLA)is a good environmentally-friendly bio-degradable polymer which is used to substitute traditional petrochemical-based polymer packaging films,the barrier properties of PLA films are stil...Although poly(lactic acid)(PLA)is a good environmentally-friendly bio-degradable polymer which is used to substitute traditional petrochemical-based polymer packaging films,the barrier properties of PLA films are still insufficient for high-barrier packaging applications.In this study,oxygen scavenger hydroxyl-terminated polybutadiene(HTPB)and cobalt salt catalyst were incorporated into the PLA/poly(butylene adipate-co-terephthalate)(PLA/PBAT),followed by melting extrusion and three-layer co-extrusion blown film process to prepare the composite films.The oxygen permeability coefficient of the composite film combined with 6 wt%oxygen scavenger and 0.4 wt%catalyst was decreased significantly from 377.00 cc·mil·m^(-2)·day^(-1)·0.1 MPa^(-1) to 0.98 cc·mil·m^(-2)·day^(-1)·0.1 MPa^(-1),showing a remarkable enhancement of 384.69 times compared with the PLA/PBAT composite film.Meanwhile,the degradation behavior of the composite film was also accelerated,exhibiting a mass loss of nearly 60%of the original mass after seven days of degradation in an alkaline environment,whereas PLA/PBAT composite film only showed a mass loss of 32%.This work has successfully prepared PLA/PBAT composite films with simultaneously improved oxygen barrier property and degradation behavior,which has great potential for high-demanding green chemistry packaging industries,including food,agricultural,and military packaging.展开更多
The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting...The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.展开更多
Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)...Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.展开更多
This article discusses the recent study written by Koizumi et al.Alcohol-associated liver disease(ALD)is a major cause of liver-related morbidity and mortality,which is driven by complex mechanisms,including lipid acc...This article discusses the recent study written by Koizumi et al.Alcohol-associated liver disease(ALD)is a major cause of liver-related morbidity and mortality,which is driven by complex mechanisms,including lipid accumulation,apoptosis,and inflammatory responses exacerbated by gut barrier dysfunction.The study explored the therapeutic potential of elafibranor,a dual peroxisome proliferatoractivated receptor alpha/delta agonist.In clinical trials,elafibranor has shown promise for the treatment of other liver conditions;however,its effects on ALD remain unclear.The authors’findings indicate that elafibranor significantly reduced liver fibrosis and enhanced gut barrier integrity in patients with ALD.These positive effects of elafibranor are mediated through multiple pathways.Elafibranor promotes lipid metabolism,reduces oxidative stress,and inhibits inflammatory responses by restoring gut barrier function.Specifically,it improves hepatocyte function by enhancing autophagic and antioxidant capacity,and it mitigates inflammation by suppressing the lipopolysaccharide/toll-like receptor 4/nuclear factor kappa B signaling pathway.These findings indicate that elafibranor has promising clinical applications.In addition,the study highlights elafibranor’s potential as a therapeutic agent for liver diseases,particularly ALD.This article underscores the importance of understanding the mechanistic pathways underlying ALD and suggests directions for future research aimed at elucidating the benefits and limitations of elafibranor.展开更多
The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the bloo...The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progress on cross-blood-brain barrier drug delivery are summarized.This review may contribute to the development of new approaches for the treatment of neurological diseases.展开更多
Dear Editor,Reproductive healthcare and autonomy are integral to overall health,well-being,and human fundamental rights[1].However,for individuals with disabilities,access to reproductive healthcare and their autonomy...Dear Editor,Reproductive healthcare and autonomy are integral to overall health,well-being,and human fundamental rights[1].However,for individuals with disabilities,access to reproductive healthcare and their autonomy is significantly jeopardized due to a combination of parameters[1].Disabled people have to deal with a wide range of social barriers while they decide to access healthcare facilities for reproductive health[2,3].展开更多
Probiotic extracellular vesicles(pEVs)are biologically active nanoparticle structures that can regulate the intestinal tract through direct or indirect mechanisms.They enhance the intestinal barrier function in livest...Probiotic extracellular vesicles(pEVs)are biologically active nanoparticle structures that can regulate the intestinal tract through direct or indirect mechanisms.They enhance the intestinal barrier function in livestock and poultry and help alleviate intestinal diseases.The specific effects of pEVs depend on their internal functional components,including nucleic acids,proteins,lipids,and other substances.This paper presents a narrative review of the impact of pEVs on the intestinal barrier across various segments of the intestinal tract,exploring their mechanisms of action while highlighting the limitations of current research.Investigating the mechanisms through which probiotics oper-ate via pEVs could deepen our understanding and provide a theoretical foundation for their application in livestock production.展开更多
After 20 years of rapid development,China's photovoltaic industry has become a leading industry in the international market.In recent years,photovoltaic power,a renewable and clean energy,has attracted global atte...After 20 years of rapid development,China's photovoltaic industry has become a leading industry in the international market.In recent years,photovoltaic power,a renewable and clean energy,has attracted global attention.This paper sorts out the technical barriers to trade related to the photovoltaic industry in Europe and the United States,analyzes the short-term and long-term impact on China,and finally puts forward countermeasures.展开更多
Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A complet...Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers.Under high temperature(HT),a 1(Control,HT-CON)+2(Zn source)×2(added Zn level)factorial arrangement of treatments was used.The 2 added Zn sources were Zn-Prot M and Zn sulfate(ZnS),and the 2 added Zn levels were 30 and 60 mg/kg.Under normal temperature(NT),a CON group(NT-CON)and pair-fed group(NT-PF)were included.Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1,occludin,junctional adhesion molecule-A(JAMA),zonula occludens-1(ZO-1)and zinc finger protein A20(A20)in the jejunum,and HS also remarkably increased serum fluorescein isothiocyanate dextran(FITC-D),endotoxin and interleukin(IL)-1βcontents,serum diamine oxidase(DAO)and matrix metalloproteinase(MMP)-2 activities,nuclear factor kappa-B(NF-κB)p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum.However,dietary supplementation with Zn,especially organic Zn as Zn-Prot M at 60 mg/kg,significantly decreased serum FITC-D,endotoxin and IL-1βcontents,serum DAO and MMP-2 activities,NF-κB p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers,and notably promoted mRNA and protein expression levels of claudin-1,ZO-1 and A20.Conclusions Our results suggest that dietary Zn,especially 60 mg Zn/kg as Zn-Prot M,can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.展开更多
Rigid barrier deflectors can effectively prevent overspilling landslides,and can satisfy disaster prevention requirements.However,the mechanisms of interaction between natural granular flow and rigid barrier deflector...Rigid barrier deflectors can effectively prevent overspilling landslides,and can satisfy disaster prevention requirements.However,the mechanisms of interaction between natural granular flow and rigid barrier deflectors require further investigation.To date,few studies have investigated the impact of deflectors on controlling viscous debris flows for geological disaster prevention.To investigate the effect of rigid barrier deflectors on impact mechanisms,a numerical model using the smoothed particle hydrodynamics(SPH)method with the Herschel–Bulkley model is proposed to simulate the interaction between natural viscous flow and single/dual barriers with and without deflectors.This model was validated using laboratory flume test data from the literature.Then,the model was used to investigate the influence of the deflector angle and multi-barrier arrangements.The optimal configuration of multi-barriers was analyzed with consideration to the barrier height and distance between the barriers,because these metrics have a significant impact on the viscous flow pile-up,run-up,and overflow mechanisms.The investigation considered the energy dissipation process,retention efficiency,and dead-zone formation.Compared with bare barriers with similar geometric characteristics and spatial distribution,rigid barriers with deflectors exhibit superior effectiveness in preventing the overflow and overspilling of viscous debris flow.Recommendations for the rational design of deflectors and the optimal arrangement of multi-barriers are provided to mitigate geological disasters.展开更多
Rigid barrier is a straightforward and effective countermeasure widely used for mitigating debris flow.However,in current designs,it remains unclear how to optimize the rigid barrier to enhance its mechanical properti...Rigid barrier is a straightforward and effective countermeasure widely used for mitigating debris flow.However,in current designs,it remains unclear how to optimize the rigid barrier to enhance its mechanical properties.Therefore,this study investigates the influence of the shape of the upstream face of the rigid barrier,referred to as the'barrier shape',on the impact dynamics of debris flow entraining a boulder onto rigid barrier.This study employs a coupled numerical approach involving smoothed particle hydrodynamics(SPH),the discrete element method(DEM),and the finite element method(FEM).The simulation results demonstrate that the barrier shape can affect the mechanical properties of the rigid barrier by altering the interaction mode between the debris flow and the barrier.Compared to vertical and slanted barriers,a curved barrier exhibits superior mechanical properties when subjected to debris flow impact.Furthermore,reducing the slope of the upstream face appropriately proves to be an effective method for enhancing the impact resistance of slanted barriers.The relevant findings from this study can serve as valuable references for the structural optimization of rigid barriers.展开更多
Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrati...Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrations,it can lead to pathological changes in the body.The impact of DON on human/animal health and animal productivity has thus attracted a great deal of attention around the world.DON causes severe damage to the intestine,including compromised intestinal barrier,mucosal damage,weakened immune function,and alterations in gut microbiota composition.These effects exacerbate intestinal infections and inflammation in livestock and poultry,posing adverse effects on overall health.Furthermore,research into biological methods for DON detoxification is a crucial avenue for future studies.This includes the utilization of adsorption,enzymatic degradation,and other biological approaches to mitigate DON's impact,offering new strategies for prevention and treatment of DON-induced diseases.Future research will focus on identifying highly efficient detoxifying microorganisms or enzymes to reduce DON levels in food and feed,thereby mitigating its risks to both animals and human health.展开更多
Research Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition in children that significantly impacts physical health and quality of life. Adherence to treatment regimens is crucial for effective...Research Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition in children that significantly impacts physical health and quality of life. Adherence to treatment regimens is crucial for effective disease management but is often hindered by various psychosocial and socioeconomic barriers. Parental mental health issues, family dynamics, financial constraints, and limited access to specialized care contribute to inconsistent treatment adherence, exacerbating the condition. Purpose/Aim: The aim of this study is to explore the multifaceted barriers to treatment adherence in children with AD and evaluate the effectiveness of current interventions targeting these challenges. The study seeks to identify strategies that can improve adherence and health outcomes by addressing psychosocial and socioeconomic factors. Method: The method involves a comprehensive review of existing literature on the impact of psychosocial and socioeconomic factors on treatment adherence in children with AD. The study also examines various interventions designed to address these barriers, including community support programs, family-centered interventions, financial aid, integrated care models, and telehealth solutions. Results: Results indicate that psychosocial barriers, such as parental anxiety and depression, significantly hinder effective disease management. Family dynamics, including poor communication and single-parent households, complicate adherence efforts. Socioeconomic factors, such as financial constraints and limited healthcare access, further impede adherence. Interventions that address these barriers show promise in improving treatment adherence and health outcomes. Community support programs and family-centered interventions enhance parental mental health and family communication. Financial aid programs and integrated care models help mitigate economic and logistical challenges. Telehealth solutions improve access to specialized care, particularly in underserved areas. Conclusion: The study concludes that a holistic approach integrating medical treatment with psychosocial and socioeconomic support is essential for managing pediatric AD effectively. Policy recommendations include increased funding for community support programs, expanded telehealth services, and the integration of social services with medical care. Addressing these barriers comprehensively can enhance treatment adherence and improve the quality of life for children with AD. Further research should focus on long-term outcomes and diverse populations to refine these interventions and ensure they meet the needs of all affected children.展开更多
BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome prolifer...BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.展开更多
Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain barrier.However,the potential links between them following ischemic strok...Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain barrier.However,the potential links between them following ischemic stroke remain largely unknown.The present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin pathway.Meanwhile,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia rats.Moreove r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and migration.Overexpression ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,respectively.In addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/reoxygenation.Thus,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.展开更多
Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is no...Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.展开更多
Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the bloo...Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the blood-brain barrier.Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction.In this study,we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells,and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells.We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells.However,post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction.We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier.We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier.In a clinical study,we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation.We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation.These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.展开更多
The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous system.Blood-brain barrier breakdown is a common pathology in various neur...The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous system.Blood-brain barrier breakdown is a common pathology in various neurological diseases,such as Alzheimer’s disease,stroke,multiple sclerosis,and Parkinson’s disease.Traditionally,it has been considered a consequence of neuroinflammation or neurodegeneration,but recent advanced imaging techniques and detailed studies in animal models show that blood-brain barrier breakdown occurs early in the disease process and may precede neuronal loss.Thus,the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective therapeutics.To elucidate the molecular mechanism underlying blood-brain barrier breakdown and translate them into therapeutic strategies for neurological diseases,there is a growing demand for experimental models of human origin that allow for functional assessments.Recently,several human induced pluripotent stem cell-derived blood-brain barrier models have been established and various in vitro blood-brain barrier models using microdevices have been proposed.Especially in the Alzheimer’s disease field,the human evidence for blood-brain barrier dysfunction has been demonstrated and human induced pluripotent stem cell-derived blood-brain barrier models have suggested the putative molecular mechanisms of pathological blood-brain barrier.In this review,we summarize recent evidence of blood-brain barrier dysfunction in Alzheimer’s disease from pathological analyses,imaging studies,animal models,and stem cell sources.Additionally,we discuss the potential future directions for blood-brain barrier research.展开更多
The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervo...The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.展开更多
文摘The pathophysiology of ischemic stroke is complex and multifactorial,involving various forms of cell death such as apoptosis,autophagy,and necrosis.A recent study suggests that oxidative and inflammatory stress can induce ferroptosis,a specialized form of cell death characterized by the accumulation of lipid peroxides dependent on intracellular iron overload(Li and Jia,2023).
基金financial support of this work by the National Natural Science Foundation of China(Nos.22378332,52003219)the Open Fund of Zhejiang Key Laboratory of Flexible Electronics(No.2022FE008)+1 种基金the Natural Science Foundation of Ningbo(NO.2022J058)Ministry of Industry and Information Technology high quality development project(TC220A04A-206).
文摘Although poly(lactic acid)(PLA)is a good environmentally-friendly bio-degradable polymer which is used to substitute traditional petrochemical-based polymer packaging films,the barrier properties of PLA films are still insufficient for high-barrier packaging applications.In this study,oxygen scavenger hydroxyl-terminated polybutadiene(HTPB)and cobalt salt catalyst were incorporated into the PLA/poly(butylene adipate-co-terephthalate)(PLA/PBAT),followed by melting extrusion and three-layer co-extrusion blown film process to prepare the composite films.The oxygen permeability coefficient of the composite film combined with 6 wt%oxygen scavenger and 0.4 wt%catalyst was decreased significantly from 377.00 cc·mil·m^(-2)·day^(-1)·0.1 MPa^(-1) to 0.98 cc·mil·m^(-2)·day^(-1)·0.1 MPa^(-1),showing a remarkable enhancement of 384.69 times compared with the PLA/PBAT composite film.Meanwhile,the degradation behavior of the composite film was also accelerated,exhibiting a mass loss of nearly 60%of the original mass after seven days of degradation in an alkaline environment,whereas PLA/PBAT composite film only showed a mass loss of 32%.This work has successfully prepared PLA/PBAT composite films with simultaneously improved oxygen barrier property and degradation behavior,which has great potential for high-demanding green chemistry packaging industries,including food,agricultural,and military packaging.
基金supported by the grants from the Spanish Ministry of Economy and Competitiveness(SAF2017-85602-R)the Spanish Ministry of Science and Innovation(PID2020-119638RB-I00 to EGR)FPU-program(FPU17/02616 to JCG)。
文摘The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.
基金supported by the National Natural Science Foundation of China,No.8227050826(to PL)Tianjin Science and Technology Bureau Foundation,No.20201194(to PL)Tianjin Graduate Research and Innovation Project,No.2022BKY174(to CW).
文摘Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.
文摘This article discusses the recent study written by Koizumi et al.Alcohol-associated liver disease(ALD)is a major cause of liver-related morbidity and mortality,which is driven by complex mechanisms,including lipid accumulation,apoptosis,and inflammatory responses exacerbated by gut barrier dysfunction.The study explored the therapeutic potential of elafibranor,a dual peroxisome proliferatoractivated receptor alpha/delta agonist.In clinical trials,elafibranor has shown promise for the treatment of other liver conditions;however,its effects on ALD remain unclear.The authors’findings indicate that elafibranor significantly reduced liver fibrosis and enhanced gut barrier integrity in patients with ALD.These positive effects of elafibranor are mediated through multiple pathways.Elafibranor promotes lipid metabolism,reduces oxidative stress,and inhibits inflammatory responses by restoring gut barrier function.Specifically,it improves hepatocyte function by enhancing autophagic and antioxidant capacity,and it mitigates inflammation by suppressing the lipopolysaccharide/toll-like receptor 4/nuclear factor kappa B signaling pathway.These findings indicate that elafibranor has promising clinical applications.In addition,the study highlights elafibranor’s potential as a therapeutic agent for liver diseases,particularly ALD.This article underscores the importance of understanding the mechanistic pathways underlying ALD and suggests directions for future research aimed at elucidating the benefits and limitations of elafibranor.
基金supported by the National Natural Science Foundation of China,No.82104412(to TD)Shaanxi Provincial Key R&D Program,No.2023-YBSF-165(to TD)+1 种基金the Natural Science Foundation of Shaanxi Department of Science and Technology,No.2018JM7022(to FM)Shaanxi Provincial Key Industry Chain Project,No.2021ZDLSF04-11(to PW)。
文摘The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progress on cross-blood-brain barrier drug delivery are summarized.This review may contribute to the development of new approaches for the treatment of neurological diseases.
文摘Dear Editor,Reproductive healthcare and autonomy are integral to overall health,well-being,and human fundamental rights[1].However,for individuals with disabilities,access to reproductive healthcare and their autonomy is significantly jeopardized due to a combination of parameters[1].Disabled people have to deal with a wide range of social barriers while they decide to access healthcare facilities for reproductive health[2,3].
基金National Nature Science Foundation of China(32272898).
文摘Probiotic extracellular vesicles(pEVs)are biologically active nanoparticle structures that can regulate the intestinal tract through direct or indirect mechanisms.They enhance the intestinal barrier function in livestock and poultry and help alleviate intestinal diseases.The specific effects of pEVs depend on their internal functional components,including nucleic acids,proteins,lipids,and other substances.This paper presents a narrative review of the impact of pEVs on the intestinal barrier across various segments of the intestinal tract,exploring their mechanisms of action while highlighting the limitations of current research.Investigating the mechanisms through which probiotics oper-ate via pEVs could deepen our understanding and provide a theoretical foundation for their application in livestock production.
文摘After 20 years of rapid development,China's photovoltaic industry has become a leading industry in the international market.In recent years,photovoltaic power,a renewable and clean energy,has attracted global attention.This paper sorts out the technical barriers to trade related to the photovoltaic industry in Europe and the United States,analyzes the short-term and long-term impact on China,and finally puts forward countermeasures.
基金Key International Cooperation Program of the National Natural Science Foundation of China(32120103011)Jiangsu Shuang Chuang Tuan Dui program(JSSCTD202147)+1 种基金Jiangsu Shuang Chuang Ren Cai program(JSSCRC2021541)Initiation Funds of Yangzhou University for Distinguished Scientists.
文摘Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers.Under high temperature(HT),a 1(Control,HT-CON)+2(Zn source)×2(added Zn level)factorial arrangement of treatments was used.The 2 added Zn sources were Zn-Prot M and Zn sulfate(ZnS),and the 2 added Zn levels were 30 and 60 mg/kg.Under normal temperature(NT),a CON group(NT-CON)and pair-fed group(NT-PF)were included.Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1,occludin,junctional adhesion molecule-A(JAMA),zonula occludens-1(ZO-1)and zinc finger protein A20(A20)in the jejunum,and HS also remarkably increased serum fluorescein isothiocyanate dextran(FITC-D),endotoxin and interleukin(IL)-1βcontents,serum diamine oxidase(DAO)and matrix metalloproteinase(MMP)-2 activities,nuclear factor kappa-B(NF-κB)p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum.However,dietary supplementation with Zn,especially organic Zn as Zn-Prot M at 60 mg/kg,significantly decreased serum FITC-D,endotoxin and IL-1βcontents,serum DAO and MMP-2 activities,NF-κB p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers,and notably promoted mRNA and protein expression levels of claudin-1,ZO-1 and A20.Conclusions Our results suggest that dietary Zn,especially 60 mg Zn/kg as Zn-Prot M,can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.
基金supported by the National Natural Science Foundation of China(Grant Nos.42120104008 and 42207198).
文摘Rigid barrier deflectors can effectively prevent overspilling landslides,and can satisfy disaster prevention requirements.However,the mechanisms of interaction between natural granular flow and rigid barrier deflectors require further investigation.To date,few studies have investigated the impact of deflectors on controlling viscous debris flows for geological disaster prevention.To investigate the effect of rigid barrier deflectors on impact mechanisms,a numerical model using the smoothed particle hydrodynamics(SPH)method with the Herschel–Bulkley model is proposed to simulate the interaction between natural viscous flow and single/dual barriers with and without deflectors.This model was validated using laboratory flume test data from the literature.Then,the model was used to investigate the influence of the deflector angle and multi-barrier arrangements.The optimal configuration of multi-barriers was analyzed with consideration to the barrier height and distance between the barriers,because these metrics have a significant impact on the viscous flow pile-up,run-up,and overflow mechanisms.The investigation considered the energy dissipation process,retention efficiency,and dead-zone formation.Compared with bare barriers with similar geometric characteristics and spatial distribution,rigid barriers with deflectors exhibit superior effectiveness in preventing the overflow and overspilling of viscous debris flow.Recommendations for the rational design of deflectors and the optimal arrangement of multi-barriers are provided to mitigate geological disasters.
基金supported by the National Key Research and Development Program of China(No.2022YFC3005704)the National Natural Science Foundation of China(No.42277143)+3 种基金the Natural Science Foundation of Sichuan Province(2024NSFSC0100)the Fundamental Research Funds for the Central Universities(No.2682023ZTPY022)Projects of Science and Technology Research and Development Program of China Railway Group Limited(2021-Special Class-03)the Natural Science Foundation of Sichuan Province(2024NSFSC0834).
文摘Rigid barrier is a straightforward and effective countermeasure widely used for mitigating debris flow.However,in current designs,it remains unclear how to optimize the rigid barrier to enhance its mechanical properties.Therefore,this study investigates the influence of the shape of the upstream face of the rigid barrier,referred to as the'barrier shape',on the impact dynamics of debris flow entraining a boulder onto rigid barrier.This study employs a coupled numerical approach involving smoothed particle hydrodynamics(SPH),the discrete element method(DEM),and the finite element method(FEM).The simulation results demonstrate that the barrier shape can affect the mechanical properties of the rigid barrier by altering the interaction mode between the debris flow and the barrier.Compared to vertical and slanted barriers,a curved barrier exhibits superior mechanical properties when subjected to debris flow impact.Furthermore,reducing the slope of the upstream face appropriately proves to be an effective method for enhancing the impact resistance of slanted barriers.The relevant findings from this study can serve as valuable references for the structural optimization of rigid barriers.
基金funded by the National Natural Science Foundation of China(32273074,31972746,31872538 and 31772809)the Basic Scientific Research Project of Liaoning Provincial Department of Education,China(LJKZ0632)。
文摘Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrations,it can lead to pathological changes in the body.The impact of DON on human/animal health and animal productivity has thus attracted a great deal of attention around the world.DON causes severe damage to the intestine,including compromised intestinal barrier,mucosal damage,weakened immune function,and alterations in gut microbiota composition.These effects exacerbate intestinal infections and inflammation in livestock and poultry,posing adverse effects on overall health.Furthermore,research into biological methods for DON detoxification is a crucial avenue for future studies.This includes the utilization of adsorption,enzymatic degradation,and other biological approaches to mitigate DON's impact,offering new strategies for prevention and treatment of DON-induced diseases.Future research will focus on identifying highly efficient detoxifying microorganisms or enzymes to reduce DON levels in food and feed,thereby mitigating its risks to both animals and human health.
文摘Research Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition in children that significantly impacts physical health and quality of life. Adherence to treatment regimens is crucial for effective disease management but is often hindered by various psychosocial and socioeconomic barriers. Parental mental health issues, family dynamics, financial constraints, and limited access to specialized care contribute to inconsistent treatment adherence, exacerbating the condition. Purpose/Aim: The aim of this study is to explore the multifaceted barriers to treatment adherence in children with AD and evaluate the effectiveness of current interventions targeting these challenges. The study seeks to identify strategies that can improve adherence and health outcomes by addressing psychosocial and socioeconomic factors. Method: The method involves a comprehensive review of existing literature on the impact of psychosocial and socioeconomic factors on treatment adherence in children with AD. The study also examines various interventions designed to address these barriers, including community support programs, family-centered interventions, financial aid, integrated care models, and telehealth solutions. Results: Results indicate that psychosocial barriers, such as parental anxiety and depression, significantly hinder effective disease management. Family dynamics, including poor communication and single-parent households, complicate adherence efforts. Socioeconomic factors, such as financial constraints and limited healthcare access, further impede adherence. Interventions that address these barriers show promise in improving treatment adherence and health outcomes. Community support programs and family-centered interventions enhance parental mental health and family communication. Financial aid programs and integrated care models help mitigate economic and logistical challenges. Telehealth solutions improve access to specialized care, particularly in underserved areas. Conclusion: The study concludes that a holistic approach integrating medical treatment with psychosocial and socioeconomic support is essential for managing pediatric AD effectively. Policy recommendations include increased funding for community support programs, expanded telehealth services, and the integration of social services with medical care. Addressing these barriers comprehensively can enhance treatment adherence and improve the quality of life for children with AD. Further research should focus on long-term outcomes and diverse populations to refine these interventions and ensure they meet the needs of all affected children.
文摘BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.
基金supported by the National Natural Science Foundation of China,No.81771250(to XC)the Natural Science Foundation of Fujian Province,Nos.2020J011059(to XC),2020R1011004(to YW),2021J01374(to XZ)+1 种基金Medical Innovation Project of Fujian Province,No.2021 CXB002(to XC)Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare(to XC)。
文摘Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain barrier.However,the potential links between them following ischemic stroke remain largely unknown.The present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin pathway.Meanwhile,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia rats.Moreove r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and migration.Overexpression ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,respectively.In addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/reoxygenation.Thus,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.
基金supported by China Scholarship Council(202208210093,to RJ)。
文摘Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.
基金supported by the Ningbo Public Welfare Science and Technology Program,No.2022S023(to JY)Ningbo Natural Science Foundation,No.2022J211(to JS)+2 种基金Ningbo Medical and Health Brand Discipline,No.PPXK2018-04(to XG)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the blood-brain barrier.Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction.In this study,we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells,and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells.We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells.However,post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction.We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier.We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier.In a clinical study,we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation.We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation.These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.
基金supported by the Uehara Memorial Foundation,JSPS under the Joint Research Program implemented in association with SNSF(JRPs),Grant No.JPJSJRP20221507 and KAKENHI Grant No.22K15711,JST FOREST Program(Grant No.JPMJFR2269,Japan)2022 iPS Academia Japan Grant,Life Science Foundation of Japan,Kato Memorial Bioscience Foundation,THE YUKIHIKO MIYATA MEMORIAL TRUST FOR ALS RESEARCH,the ICHIRO KANEHARA FOUNDATION,Takeda Science Foundation,and the YAMAGUCHI UNIVERSITY FUNDATION(all to HN).
文摘The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous system.Blood-brain barrier breakdown is a common pathology in various neurological diseases,such as Alzheimer’s disease,stroke,multiple sclerosis,and Parkinson’s disease.Traditionally,it has been considered a consequence of neuroinflammation or neurodegeneration,but recent advanced imaging techniques and detailed studies in animal models show that blood-brain barrier breakdown occurs early in the disease process and may precede neuronal loss.Thus,the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective therapeutics.To elucidate the molecular mechanism underlying blood-brain barrier breakdown and translate them into therapeutic strategies for neurological diseases,there is a growing demand for experimental models of human origin that allow for functional assessments.Recently,several human induced pluripotent stem cell-derived blood-brain barrier models have been established and various in vitro blood-brain barrier models using microdevices have been proposed.Especially in the Alzheimer’s disease field,the human evidence for blood-brain barrier dysfunction has been demonstrated and human induced pluripotent stem cell-derived blood-brain barrier models have suggested the putative molecular mechanisms of pathological blood-brain barrier.In this review,we summarize recent evidence of blood-brain barrier dysfunction in Alzheimer’s disease from pathological analyses,imaging studies,animal models,and stem cell sources.Additionally,we discuss the potential future directions for blood-brain barrier research.
基金funding from European Regional Development Fund(project No 13.1.1-LMT-K-718-05-0005)under grant agreement with the Research Council of Lithuania(LMTLT)。
文摘The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.
