Stem cell proliferation is tightly regulated in developing and adult tissues through the coordinated action of cell-intrinsic and extracellular signals.Although many extracellular cues were identified,the cell-intrins...Stem cell proliferation is tightly regulated in developing and adult tissues through the coordinated action of cell-intrinsic and extracellular signals.Although many extracellular cues were identified,the cell-intrinsic mechanisms underlying the decision of a stem cell to proliferate,enter a dormant quiescent state or differentiate into a specific cell type remains incompletely understood.展开更多
Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammat...Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.展开更多
Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central ne...Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.展开更多
An analytical model of a floating heaving box integrated with a vertical flexible porous membrane placed right next to the box applications to wave energy extraction and breakwater systems is developed under the reduc...An analytical model of a floating heaving box integrated with a vertical flexible porous membrane placed right next to the box applications to wave energy extraction and breakwater systems is developed under the reduced wave equation.The theoretical solutions for the heave radiating potential to the assigned physical model in the corresponding zones are attained by using the separation of variables approach along with the Fourier expansion.Applying the matching eigenfunction expansion technique and orthogonal conditions,the unknown coefficients that are involved in the radiated potentials are determined.The attained radiation potential allows the computation of hydrodynamic coefficients of the heaving buoy,Power Take-Off damping,and wave quantities.The accuracy of the analytical solution for the hydrodynamic coefficients is demonstrated for different oblique angles with varying numbers of terms in the series solution.The current analytical analysis findings are confirmed by existing published numerical boundary element method simulations.Several numerical results of the hydrodynamic coefficients,power capture,power take-off optimal damping,and transmission coefficients for numerous structural and physical aspects are conducted.It has been noted that the ideal power take-off damping increases as the angle of incidence rises,and the analysis suggests that the ability to capture waves is more effective in shallower waters compared to deeper ones.展开更多
The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurode...The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function.展开更多
Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kines...Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.展开更多
This study examines the methods to plan the development of offshore oilfields over the years,which are used to support the decision-making on the development of offshore oilfields.About 100 papers are analysed and cat...This study examines the methods to plan the development of offshore oilfields over the years,which are used to support the decision-making on the development of offshore oilfields.About 100 papers are analysed and categorised into different groups of main early-stage decisions.The present study stands in contrast to the contributions of the operations research and system engineering review articles,on the one hand,and the petroleum engineering review articles,on the other.This is because it does not focus on one methodological approach,nor does it limit the literature analysis by offshore oilfield characteristics.Consequently,the present analysis may offer valuable insights,for instance,by identifying environmental planning decisions as a recent yet highly significant concern that is currently being imposed on decision-making process.Thus,it is evident that the incorporation of safety criteria within the technical-economic decision-making process for the design of production systems would be a crucial requirement at development phase.展开更多
The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cereb...The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.展开更多
The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves gl...The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves global alterations,making understanding plastic responses triggered by local damage difficult.One key feature of the dentate gyrus is that it contains a well-defined neurogenic niche,the subgranular zone,and beyond neurogenesis,newly born granule cells may maintain a“young”phenotype throughout life,adding to the plastic nature of the structure.Here,we present a novel experimental model of local brain damage in organotypic entorhino-hippocampal cultures that results in the activation of adjacent newly born granule cells.A small piece of filter paper was placed on the surface of the granule cell layer of the dentate gyrus,which evoked a foreign body reaction of astrocytes,along with the activation of local young neurons expressing doublecortin.Forty-eight hours after foreign body placement,the number of doublecortin-immunoreactive cells increased in the subgranular zone in the direct vicinity of the foreign body,whereas overall increased doublecortin immunoreactivity was observed in the granule cell layer and molecular layer of the dentate gyrus.Foreign body placement in the pyramidal layer of the CA1 region evoked a comparable local astroglial reaction but did not lead to an increase in doublecortin-immunoreactive in either the CA1 region or the adjacent dentate gyrus.Seven days after foreign body placement in the dentate gyrus,the increase in doublecortin-immunoreactivity was no longer observed,indicating the transient activation of young cells.However,7 days after foreign body placement,the number of doublecortin-immunoreactive granule cells coimmunoreactive for calbindin was lower than that under the control conditions.As calbindin is a marker for mature granule cells,this result suggests that activated young cells remain at a more immature stage following foreign body placement.Live imaging of retrovirally green fluorescent protein-labeled newly born granule cells revealed the orientation and growth of their dendrites toward the foreign body placement.This novel experimental model of foreign body placement in organotypic entorhino-hippocampal cultures could serve as a valuable tool for studying both glial reactivity and neuronal plasticity,specifically of newly born neurons under controlled in vitro conditions.展开更多
Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mo...Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mortality.Although organis m-wide deterioration is observed during aging,organs with high metabolic demand,such as the brain,are more vulnerable.展开更多
Different forms of programmed cell death have been described to participate in the degeneration of dopaminergic neurons in Parkinson’s disease(PD).Given the critical role that disturbance of mitochondrial homeostasis...Different forms of programmed cell death have been described to participate in the degeneration of dopaminergic neurons in Parkinson’s disease(PD).Given the critical role that disturbance of mitochondrial homeostasis plays in the pathogenesis of PD,apoptosis can be reasonably considered as one of the cell death pathways involved in neuronal loss(Schon and Przedborski,2011).Multiple lines of evidence support that proposal such as the observations in postmortem human brain samples of PD patients including mitochondrial complex I deficiency,reactive oxygen species generation,and oxidative damage to lipids,proteins,and DNA,among others.展开更多
Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a w...Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;AguilarHernández et al., 2023).展开更多
Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic ...Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.展开更多
This article examines the complex relationship between disease perception,negative emotions,and their impact on postoperative recovery in patients with perianal diseases.These conditions not only cause physical discom...This article examines the complex relationship between disease perception,negative emotions,and their impact on postoperative recovery in patients with perianal diseases.These conditions not only cause physical discomfort,but also carry a significant emotional burden,often exacerbated by social stigma.Psycho-logical factors,including stress,anxiety,and depression,activate neuroendocrine pathways,such as the hypothalamic–pituitary–adrenal axis,disrupting the gut microbiota and leading to dysbiosis.This disruption can delay wound healing,prolong hospital stay,and intensify pain.Drawing on the findings of Hou et al,our article highlights the critical role of illness perception and negative emotions in shaping recovery outcomes.It advocates for a holistic approach that integrates psychological support and gut microbiota modulation,to enhance healing and improve overall patient outcomes.展开更多
Arboviral diseases are viral infections transmitted to humans through the bites of arthropods,such as mosquitoes,often causing a variety of pathologies associated with high levels of morbidity and mortality.Over the p...Arboviral diseases are viral infections transmitted to humans through the bites of arthropods,such as mosquitoes,often causing a variety of pathologies associated with high levels of morbidity and mortality.Over the past decades,these infections have proven to be a significant challenge to health systems worldwide,particularly following the considerable geographic expansion of the dengue virus(DENV)and its most recent outbreak in Latin America as well as the difficult-tocontrol outbreaks of yellow fever virus(YFV),chikungunya virus(CHIKV),and Zika virus(ZIKV),leaving behind a substantial portion of the population with complications related to these infections.Currently,the world is experiencing a period of intense globalization,which,combined with global warming,directly contributes to wider dissemination of arbovirus vectors across the globe.Consequently,all continents remain on high alert for potential new outbreaks.Thus,this review aims to provide a comprehensive understanding of the pathogenesis of the four main arboviruses today(DENV,ZIKV,YFV,and CHIKV)discussing their viral characteristics,immune responses,and mechanisms of viral evasion,as well as important clinical aspects for patient management.This includes associated symptoms,laboratory tests,treatments,existing or developing vaccines and the main associated complications,thus integrating a broad historical,scientific and clinical approach.展开更多
目的采用文献计量学对艾滋病扩大检测的相关文献进行分析,了解该领域的研究现状与趋势。方法基于Web of Science核心合集数据库,检索了发表于2015-2024年的文章进行文献计量学分析,运用VOSviewer和CiteSpace软件以及Bibiometrix平台进...目的采用文献计量学对艾滋病扩大检测的相关文献进行分析,了解该领域的研究现状与趋势。方法基于Web of Science核心合集数据库,检索了发表于2015-2024年的文章进行文献计量学分析,运用VOSviewer和CiteSpace软件以及Bibiometrix平台进行可视化,对艾滋病扩大检测关键词进行共现及突现等系统性分析。结果该领域共检索到508篇英文文献,2015-2024年发表的文章总体趋势平稳,总被引频次为6212,篇均被引频次为12.2。关键词共现图谱显示,近十年艾滋病扩大检测研究热点,集中在乌干达、非洲、南非等9个地区,关注跨性别女性、男男性行为者、注射吸毒者等高危行为人群以及青年、青少年等重点人群,并与艾滋病治疗和护理关联。关键词突现图谱显示,艾滋病自我检测、二次传递、急诊科、暴露前预防是近年艾滋病扩大检测研究的关注点。结论艾滋病扩大检测研究成为学术界关注领域。需重点关注疫情较重地区以及高危行为人群和重点人群,深挖自我检测、二次传递、急诊科、暴露前预防等潜力,提升HIV扩大检测的效率。展开更多
Recent studies have shown a noticeable increase in global Helicobacter pylori(H.pylori)resistance,with clarithromycin resistance surpassing 15%in various areas.However,inadequate epidemiological monitoring,especially ...Recent studies have shown a noticeable increase in global Helicobacter pylori(H.pylori)resistance,with clarithromycin resistance surpassing 15%in various areas.However,inadequate epidemiological monitoring,especially in developing countries,and the absence of uniform testing methods lead to discrepancies between regions and a possible underestimation of resistance levels.The complexity of treating H.pylori is driven by its highly dynamic genome,which is prone to frequent mutations contributing to phenotypical resistance.The usual course of action in empirical treatment involves using a combination of various drugs simultaneously,leading to significant resistance selection pressure and potential side effects.The emergence of H.pylori strains resistant to multiple drugs is closely tied to failures in first-line treatment,highlighting the need to prevent further resistance by using optimal initial empirical therapy or regimens guided by antibiotic susceptibility testing,requiring a collection of mixed samples and multiple isolates for accurate assessment.The emergence of new treatments like potassium-competitive acid blockers offers a hopeful approach to decrease antimicrobial usage while still ensuring effectiveness in comparison to traditional therapies with proton pump inhibitors.Additionally,the use of probiotics is under investigation to identify specific strains and formulations that may mitigate therapy-associated adverse effects.展开更多
BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in the...BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.展开更多
基金supported by the Argentine Agency for the Promotion of Science and Technology ANPCyT(PICT2019-1472 to GP,PICT2019-4597 to FL,PICT2020-1524 to GP,and PICT2021-00627 to FL)supported by an Independent Career Position from CONICETsupported by a postdoctoral fellowship from ANPCyT。
文摘Stem cell proliferation is tightly regulated in developing and adult tissues through the coordinated action of cell-intrinsic and extracellular signals.Although many extracellular cues were identified,the cell-intrinsic mechanisms underlying the decision of a stem cell to proliferate,enter a dormant quiescent state or differentiate into a specific cell type remains incompletely understood.
基金supported by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil(CAPES)[Finance Code 001](to MGS)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico(CNPq)fellowship[research grants 309840/2022-8]。
文摘Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.
基金supported by funds from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico do Brasil(CNPq)(312286/2023-6,307201/2023-6,and Instituto Nacional Saude Cerebral INSC,No.406020/2022-1)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior(CAPES)Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro-FAPERJ(E-26/010.002260/2019,E-26/010.001652/2019,E-26/010.101036/2018,E-26/202.774/2018,E-26/210.240/2020,E-26/211.138/2021,26/210.823/2021,E-26/211.325/2021,E-26/210.779/2021,E-26/201.086/2022,E-26/210.312/2022,E-26/203.262/2023,E-26/200.195/2023)(to LEBS)。
文摘Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.
基金Open access funding provided by FCT|FCCN(b-on)the Strategic Research Plan of the Centre for Marine Technology and Ocean Engineering(CENTEC),which is financed by the Portuguese Foundation for Science and Technology(Fundação para a Ciência e Tecnologia-FCT)under contract UIDB/UIDP/00134/2020.
文摘An analytical model of a floating heaving box integrated with a vertical flexible porous membrane placed right next to the box applications to wave energy extraction and breakwater systems is developed under the reduced wave equation.The theoretical solutions for the heave radiating potential to the assigned physical model in the corresponding zones are attained by using the separation of variables approach along with the Fourier expansion.Applying the matching eigenfunction expansion technique and orthogonal conditions,the unknown coefficients that are involved in the radiated potentials are determined.The attained radiation potential allows the computation of hydrodynamic coefficients of the heaving buoy,Power Take-Off damping,and wave quantities.The accuracy of the analytical solution for the hydrodynamic coefficients is demonstrated for different oblique angles with varying numbers of terms in the series solution.The current analytical analysis findings are confirmed by existing published numerical boundary element method simulations.Several numerical results of the hydrodynamic coefficients,power capture,power take-off optimal damping,and transmission coefficients for numerous structural and physical aspects are conducted.It has been noted that the ideal power take-off damping increases as the angle of incidence rises,and the analysis suggests that the ability to capture waves is more effective in shallower waters compared to deeper ones.
文摘The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function.
基金supported by the Portuguese Foundation for Science and Technology(FCT),Centro 2020 and Portugol2020 and the EU FEDER program,via the project GoBack to SIV(PTDC/CVT-CVT/32261/2017,CENTRO-01-0145-FEDER-032261)the doctoral grants of PDC(SFRH/BD/139974/2018)and BMS(2020.06525.BD and DOI 10.54499/2020.06525.BD)+5 种基金the post-doctoral grant to JPF(SFRH/BPD/113359/2015-program-contract described in paragraphs 4,5,6 of art.23 of Law no.100157/2016,of August 29,as amended by Law no.57/2017 of July 2019),the project PTDC/MED-NEU/1677/2021 to JBRthe Institute of Biomedicine iBiMED(UIDB/04501/2020 and DOI 10.54499/UIDB/04501/2020,UIDP/04501/2020 and DOI 10.54499/UIDP/04501/2020)its LiM Bioimaging Facility-a PPBI node(POCI-01-0145-FEDER-022122)supported by the Research Commission of the Medical Faculty of the Heinrich-Heine-University(HHU)Düsseldorf,of the Biologisch-Medizinisches Forschungszentrum(BMFZ)of HHUfinanced by the Spanish"Plan Nacional de Investigacion Cientifica,Desarrollo e Innovacion Tecnologica,Ministerio de Economia y Competitividad(Instituto de Salud CarlosⅢ)",co-financed by the European Union(FEDER program),(grant FIS P/20/00318 and FIS P23/00337 to VC)grant CPP2021-009070 to VC by the"Proyectos de colaboracion publico-privada,Plan de Investigacion Cientifica,Tecnica y de inovacion 2021-2023,Ministerio de Ciencia e Innovacion,Union Europea,Agencia Estatal de Investigacion,Espana"。
文摘Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.
基金the Strategic Research Plan of the Centre for Marine Technology and Ocean Engineering(CENTEC),which is financed by the Portuguese Foundation for Science and Technology(Fundação para a Ciência e a Tecnologia FCT)under contract UIDB/UIDP/00134/2020.
文摘This study examines the methods to plan the development of offshore oilfields over the years,which are used to support the decision-making on the development of offshore oilfields.About 100 papers are analysed and categorised into different groups of main early-stage decisions.The present study stands in contrast to the contributions of the operations research and system engineering review articles,on the one hand,and the petroleum engineering review articles,on the other.This is because it does not focus on one methodological approach,nor does it limit the literature analysis by offshore oilfield characteristics.Consequently,the present analysis may offer valuable insights,for instance,by identifying environmental planning decisions as a recent yet highly significant concern that is currently being imposed on decision-making process.Thus,it is evident that the incorporation of safety criteria within the technical-economic decision-making process for the design of production systems would be a crucial requirement at development phase.
基金supported by the Grant PID2021-126715OB-IOO financed by MCIN/AEI/10.13039/501100011033 and"ERDFA way of making Europe"by the Grant PI22CⅢ/00055 funded by Instituto de Salud CarlosⅢ(ISCⅢ)+6 种基金the UFIECPY 398/19(PEJ2018-004965) grant to RGS funded by AEI(Spain)the UFIECPY-396/19(PEJ2018-004961)grant financed by MCIN (Spain)FI23CⅢ/00003 grant funded by ISCⅢ-PFIS Spain) to PMMthe UFIECPY 328/22 (PEJ-2021-TL/BMD-21001) grant to LM financed by CAM (Spain)the grant by CAPES (Coordination for the Improvement of Higher Education Personnel)through the PDSE program (Programa de Doutorado Sanduiche no Exterior)to VSCG financed by MEC (Brazil)
文摘The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.
基金funded by the Alexander von Humboldt Stiftungsupported by DFG (SCH W534/6-1 to SWS)
文摘The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves global alterations,making understanding plastic responses triggered by local damage difficult.One key feature of the dentate gyrus is that it contains a well-defined neurogenic niche,the subgranular zone,and beyond neurogenesis,newly born granule cells may maintain a“young”phenotype throughout life,adding to the plastic nature of the structure.Here,we present a novel experimental model of local brain damage in organotypic entorhino-hippocampal cultures that results in the activation of adjacent newly born granule cells.A small piece of filter paper was placed on the surface of the granule cell layer of the dentate gyrus,which evoked a foreign body reaction of astrocytes,along with the activation of local young neurons expressing doublecortin.Forty-eight hours after foreign body placement,the number of doublecortin-immunoreactive cells increased in the subgranular zone in the direct vicinity of the foreign body,whereas overall increased doublecortin immunoreactivity was observed in the granule cell layer and molecular layer of the dentate gyrus.Foreign body placement in the pyramidal layer of the CA1 region evoked a comparable local astroglial reaction but did not lead to an increase in doublecortin-immunoreactive in either the CA1 region or the adjacent dentate gyrus.Seven days after foreign body placement in the dentate gyrus,the increase in doublecortin-immunoreactivity was no longer observed,indicating the transient activation of young cells.However,7 days after foreign body placement,the number of doublecortin-immunoreactive granule cells coimmunoreactive for calbindin was lower than that under the control conditions.As calbindin is a marker for mature granule cells,this result suggests that activated young cells remain at a more immature stage following foreign body placement.Live imaging of retrovirally green fluorescent protein-labeled newly born granule cells revealed the orientation and growth of their dendrites toward the foreign body placement.This novel experimental model of foreign body placement in organotypic entorhino-hippocampal cultures could serve as a valuable tool for studying both glial reactivity and neuronal plasticity,specifically of newly born neurons under controlled in vitro conditions.
文摘Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mortality.Although organis m-wide deterioration is observed during aging,organs with high metabolic demand,such as the brain,are more vulnerable.
基金supported by the Spanish Ministerio de Ciencia e Innovación/Agencia Española de Investigación(PID2021-124096OB-I00)(to JLV)JGR was granted by Demensfonden,The Royal Physiografic Society of Lund,Neurofonden,The Greta och Johan Kocks stiftelser,and Bertil och Ebon Norlins stiftelse.
文摘Different forms of programmed cell death have been described to participate in the degeneration of dopaminergic neurons in Parkinson’s disease(PD).Given the critical role that disturbance of mitochondrial homeostasis plays in the pathogenesis of PD,apoptosis can be reasonably considered as one of the cell death pathways involved in neuronal loss(Schon and Przedborski,2011).Multiple lines of evidence support that proposal such as the observations in postmortem human brain samples of PD patients including mitochondrial complex I deficiency,reactive oxygen species generation,and oxidative damage to lipids,proteins,and DNA,among others.
基金funded by CONAHCYT grant(252808)to GFCONAHCYT’s“Estancias Posdoctorales por México”program(662350)to HTB。
文摘Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;AguilarHernández et al., 2023).
基金supported by Fondo Nacional de Desarrollo Científico y Tecnológico(FONDECYT)#1200836,#1210644,and#1240888,and Agencia Nacional de Investigación y Desarrollo(ANID)-FONDAP#15130011(to LL)FONDECYT#3230227(to MFG).
文摘Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.
文摘This article examines the complex relationship between disease perception,negative emotions,and their impact on postoperative recovery in patients with perianal diseases.These conditions not only cause physical discomfort,but also carry a significant emotional burden,often exacerbated by social stigma.Psycho-logical factors,including stress,anxiety,and depression,activate neuroendocrine pathways,such as the hypothalamic–pituitary–adrenal axis,disrupting the gut microbiota and leading to dysbiosis.This disruption can delay wound healing,prolong hospital stay,and intensify pain.Drawing on the findings of Hou et al,our article highlights the critical role of illness perception and negative emotions in shaping recovery outcomes.It advocates for a holistic approach that integrates psychological support and gut microbiota modulation,to enhance healing and improve overall patient outcomes.
基金Supported by the Permanecer Program(part of the actions of the Office of Affirmative Actions)Education and Diversity of the Dean of Student Assistance at the Federal University of Bahia(UFBA)and CNPq Research Productivity Fellow.
文摘Arboviral diseases are viral infections transmitted to humans through the bites of arthropods,such as mosquitoes,often causing a variety of pathologies associated with high levels of morbidity and mortality.Over the past decades,these infections have proven to be a significant challenge to health systems worldwide,particularly following the considerable geographic expansion of the dengue virus(DENV)and its most recent outbreak in Latin America as well as the difficult-tocontrol outbreaks of yellow fever virus(YFV),chikungunya virus(CHIKV),and Zika virus(ZIKV),leaving behind a substantial portion of the population with complications related to these infections.Currently,the world is experiencing a period of intense globalization,which,combined with global warming,directly contributes to wider dissemination of arbovirus vectors across the globe.Consequently,all continents remain on high alert for potential new outbreaks.Thus,this review aims to provide a comprehensive understanding of the pathogenesis of the four main arboviruses today(DENV,ZIKV,YFV,and CHIKV)discussing their viral characteristics,immune responses,and mechanisms of viral evasion,as well as important clinical aspects for patient management.This includes associated symptoms,laboratory tests,treatments,existing or developing vaccines and the main associated complications,thus integrating a broad historical,scientific and clinical approach.
文摘目的采用文献计量学对艾滋病扩大检测的相关文献进行分析,了解该领域的研究现状与趋势。方法基于Web of Science核心合集数据库,检索了发表于2015-2024年的文章进行文献计量学分析,运用VOSviewer和CiteSpace软件以及Bibiometrix平台进行可视化,对艾滋病扩大检测关键词进行共现及突现等系统性分析。结果该领域共检索到508篇英文文献,2015-2024年发表的文章总体趋势平稳,总被引频次为6212,篇均被引频次为12.2。关键词共现图谱显示,近十年艾滋病扩大检测研究热点,集中在乌干达、非洲、南非等9个地区,关注跨性别女性、男男性行为者、注射吸毒者等高危行为人群以及青年、青少年等重点人群,并与艾滋病治疗和护理关联。关键词突现图谱显示,艾滋病自我检测、二次传递、急诊科、暴露前预防是近年艾滋病扩大检测研究的关注点。结论艾滋病扩大检测研究成为学术界关注领域。需重点关注疫情较重地区以及高危行为人群和重点人群,深挖自我检测、二次传递、急诊科、暴露前预防等潜力,提升HIV扩大检测的效率。
基金Supported by the Industrial Technological Initiation Scholarship of National Council for Scientific and Technological Development,CNPq,Brazil,No.0932204294929829 and No.7414780530977345the Scientific Initiation Scholarship Programme(PIBIC)of National Council for Scientific and Technological Development,CNPq,Brazil,No.5763023359532159,No.6472982965854452,and No.7340128440641417+2 种基金the Scientific Initiation Scholarship Programme(PIBIC)of Bahia State Research Support Foundation,FAPESB,Brazil,No.19.573.301.5418the PERMANECER Programme of Pro-Rectory of Student Assistance at Federal University of Bahia,No.R8EZ-4V4W-6LQX-5LC8the CNPq Research Productivity Fellow,No.4357511882624145.
文摘Recent studies have shown a noticeable increase in global Helicobacter pylori(H.pylori)resistance,with clarithromycin resistance surpassing 15%in various areas.However,inadequate epidemiological monitoring,especially in developing countries,and the absence of uniform testing methods lead to discrepancies between regions and a possible underestimation of resistance levels.The complexity of treating H.pylori is driven by its highly dynamic genome,which is prone to frequent mutations contributing to phenotypical resistance.The usual course of action in empirical treatment involves using a combination of various drugs simultaneously,leading to significant resistance selection pressure and potential side effects.The emergence of H.pylori strains resistant to multiple drugs is closely tied to failures in first-line treatment,highlighting the need to prevent further resistance by using optimal initial empirical therapy or regimens guided by antibiotic susceptibility testing,requiring a collection of mixed samples and multiple isolates for accurate assessment.The emergence of new treatments like potassium-competitive acid blockers offers a hopeful approach to decrease antimicrobial usage while still ensuring effectiveness in comparison to traditional therapies with proton pump inhibitors.Additionally,the use of probiotics is under investigation to identify specific strains and formulations that may mitigate therapy-associated adverse effects.
文摘BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.
