Female mosquitoes of several species require blood from warmblooded animals,including humans for the purpose of reproduction.In this process,several microbes residing in the salivary gland and midgut of mosquitoes als...Female mosquitoes of several species require blood from warmblooded animals,including humans for the purpose of reproduction.In this process,several microbes residing in the salivary gland and midgut of mosquitoes also get transferred from one human individual to the other–a traditional model by which many vector-borne diseases(VBDs)get transmitted in the population through mosquitoes belonging to Anopheles,Aedes,Culex and other genera.展开更多
Vector-borne diseases are highly sensitive to environment and to environmental changes. Rift Valley Fever (RFV) is a mosquito-borne zootic virus associated with severe diseases in human beings and economic consequence...Vector-borne diseases are highly sensitive to environment and to environmental changes. Rift Valley Fever (RFV) is a mosquito-borne zootic virus associated with severe diseases in human beings and economic consequences to livestock sector. Animal and human movements have a fundamental impact on RVF transmission. In recent years, there has been a growing interest in the use of mathematics and agent based models to represent and analyze the dynamic of RFV transmission. However, no previous study has taken into consideration animal herds’ mobility and precipitation factors to understand the disease spread. This limitation underlines the necessity to use computational model approach based on multi-agent system in the study of vector-borne diseases transmission and diffusion. In this paper, a multi-agent system combining conceptual model expressiveness is used to study animal herds’ mobility and the precipitation parameter impact on the Rift Valley Fever outbreak in Ferlo Barkedji in Northern Senegal. Simulation scenarios with various parameters, including rain quality, hosts, vectors, camp dispersal around ponds, etc., are unrolled. The different results we have obtained show that the evolution of the number of infected hosts and infected vectors depend on the degree of animal herds’ mobility and on precipitations. Our model provides a framework that permits predicting the spread of the disease associated with the mobility of animal herds.展开更多
Vector-borne diseases(VBDs),primarily transmitted through the bites of vectors such as mosquitoes,ticks,and sandflies,have been recognized as a critical global public health priority.This systematic review summarizes ...Vector-borne diseases(VBDs),primarily transmitted through the bites of vectors such as mosquitoes,ticks,and sandflies,have been recognized as a critical global public health priority.This systematic review summarizes the pivotal role of geospatial technologies,including geographic information systems(GIS),remote sensing(RS),and advanced spatial statistical methodologies,in enhancing disease surveillance systems.We conducted a comprehensive literature screening across the PubMed and OVID Medline databases,identifying 652 relevant studies published between 2015 and 2024.These studies were analyzed to evaluate the application of geospatial approaches to several critical VBDs such as malaria,dengue fever,yellow fever,and other VBDs.The integration of GIS and RS enables high-resolution mapping of vector habitats and disease hotspots by analyzing environmental factors.Advanced spatial statistical models effectively quantify the influence of environmental and socioeconomic variables,predict transmission risk,and detect significant spatial clusters.Phylogeographic analyses elucidate pathogen origins and transmission pathways,while animal migration tracking reveals the role of long-distance vector and host dispersal in disease spread.These approaches have facilitated the development of actionable risk maps that support targeted interventions,optimize resource allocation,and underpin early warning systems for diseases such as malaria,dengue fever,yellow fever,and Zika virus disease.In summary,geospatial epidemiology plays a critical role in VBD control by providing evidence-based insights into transmission dynamics.Future efforts should prioritize interdisciplinary collaboration and the development of integrated,real-time surveillance platforms that combine multisource data and predictive modeling.展开更多
Background: Social determinants of health (SDOH) significantly influence diseases with environmental components, like vector-borne parasitic diseases. This study aims to examine how these factors influence vector-born...Background: Social determinants of health (SDOH) significantly influence diseases with environmental components, like vector-borne parasitic diseases. This study aims to examine how these factors influence vector-borne parasitic diseases (VBPDs) transmission in Chad and provide recommendations for policy improvements. Methods: The study adopts the WHO Conceptual Framework of SDOH to compare two regions in Southern Chad: Kouh-Est, which has an ongoing vector control program, and Grand-Sido, which lacks such a program. The study includes both nomadic and sedentary populations to provide a comprehensive understanding of the SDOH influencing VBPDs. Households were randomly selected. Data on sociodemographic characteristics, literacy, knowledge of VBPDs and protective measures, and access to education and health facilities were collected. Results: A total of 202 households from 17 villages, including 820 participants, were surveyed. Agriculture, livestock, and fishing were the main occupations, involving 84.1% of participants. Literacy was low, with 36.7% non-educated, 47.7% completing primary school, 14.5% secondary school, and only 0.3% reaching tertiary education. Most villages lacked schools beyond the primary level, and nomadic populations were significantly less educated than sedentary ones (p Conclusion: Educational deficiencies, lack of protective measures against vectors, inadequate healthcare resources, and lifestyle conditions aggravated by poor road infrastructure, limited transportation, and economic constraints contribute to worsened VBPDs outcomes in these rural populations. Addressing these systemic issues in the surveyed communities is essential for improving health equity and VBPDs outcomes in these regions specifically and in similar populations settings more broadly.展开更多
Introduction:Vector-borne diseases(VBDs)represent a significant category of infectious diseases.Analyzing the epidemiological characteristics of VBDs in China,including their temporal and spatial distributions,provide...Introduction:Vector-borne diseases(VBDs)represent a significant category of infectious diseases.Analyzing the epidemiological characteristics of VBDs in China,including their temporal and spatial distributions,provides essential evidence for developing effective prevention and control strategies.Methods:Data for 14 types of VBDs from 2005 to 2024 were obtained from the China National Infectious Disease Surveillance System.These diseases were categorized as mosquito-borne,tick-borne,rodent-borne,and other VBDs.Using the Mann-Kendall trend test,we analyzed demographic characteristics,spatial distribution,temporal trends,and seasonal patterns of notified cases over the 20-year period.Results:From 2005 to 2024,a total of 1,129,736 VBD cases were reported in China.Scrub typhus(28.17%),malaria(20.8%),hemorrhagic fever with renal syndrome(HFRS,18.4%),dengue(12.61%),and schistosomiasis(8.42%)collectively accounted for 88.4%of all cases.Over a 20-year period,mosquitoborne and rodent-borne diseases indicated significant declining trends(P<0.05),while tick-borne and other VBDs demonstrated significant increasing trends(P<0.05).Dengue,scrub typhus,and severe fever with thrombocytopenia syndrome(SFTS)expanded geographically,with annual increases of 10.89,12.37,and 7.07 reporting cities,respectively.Although diseases such as plague,malaria,and schistosomiasis have been effectively controlled,the incidence of scrub typhus,dengue,HFRS,and SFTS has remained high in recent years.Conclusions:The burden of VBDs in China remains substantial,with an increasing trend observed over the past 5 years.The rising incidence and geographic expansion of scrub typhus,dengue,and SFTS warrant particular attention from public health authorities.展开更多
Background:Diseases transmitted to humans by vectors account for 17%of all infectious diseases and remain significant public health problems.Through the years,great strides have been taken towards combatting vectorbor...Background:Diseases transmitted to humans by vectors account for 17%of all infectious diseases and remain significant public health problems.Through the years,great strides have been taken towards combatting vectorborne diseases(VBDs),most notably through large scale and coordinated control programmes,which have contributed to the decline of the global mortality attributed to VBDs.However,with environmental changes,including climate change,the impact on VBDs is anticipated to be significant,in terms of VBD-related hazards,vulnerabilities and exposure.While there is growing awareness on the vulnerability of the African continent to VBDs in the context of climate change,there is still a paucity of research being undertaken in this area,and impeding the formulation of evidence-based health policy change.Main body:One way in which the gap in knowledge and evidence can be filled is for donor institutions to support research in this area.The collaboration between the WHO Special Programme for Research and Training in Tropical Diseases(TDR)and the International Centre for Research and Development(IDRC)builds on more than 10 years of partnership in research capacity-building in the field of tropical diseases.From this partnership was born yet another research initiative on VBDs and the impact of climate change in the Sahel and sub-Saharan Africa.This paper lists the projects supported under this research initiative and provides a brief on some of the policy and good practice recommendations emerging from the ongoing implementation of the research projects.Conclusion:Data generated from the research initiative are expected to be uptaken by stakeholders(including communities,policy makers,public health practitioners and other relevant partners)to contribute to a better understanding of the impacts of social,environmental and climate change on VBDs(i.e.the nature of the hazard,vulnerabilities,exposure),and improve the ability of African countries to adapt to and reduce the effects of these changes in ways that benefit their most vulnerable populations.展开更多
This paper highlights the critical importance of evidence on vector-borne diseases(VBD)prevention and control interventions in urban settings when assessing current and future needs,with a view to setting policy prior...This paper highlights the critical importance of evidence on vector-borne diseases(VBD)prevention and control interventions in urban settings when assessing current and future needs,with a view to setting policy priorities that promote inclusive and equitable urban health services.Research should produce knowledge about policies and interventions that are intended to control and prevent VBDs at the population level and to reduce inequities.Such interventions include policy,program,and resource distribution approaches that address the social determinants of health and exert influence at organizational and system levels.展开更多
Background:Climate-based disease forecasting has been proposed as a potential tool in climate change adaptation for the health sector.Here we explore the relevance of climate data,drivers and predictions for vector-bo...Background:Climate-based disease forecasting has been proposed as a potential tool in climate change adaptation for the health sector.Here we explore the relevance of climate data,drivers and predictions for vector-borne disease control efforts in Africa.Methods:Using data from a number of sources we explore rainfall and temperature across the African continent,from seasonality to variability at annual,multi-decadal and timescales consistent with climate change.We give particular attention to three regions defined as WHO-TDR study zones in Western,Eastern and Southern Africa.Our analyses include 1)time scale decomposition to establish the relative importance of year-to-year,decadal and long term trends in rainfall and temperature;2)the impact of the El Niño Southern Oscillation(ENSO)on rainfall and temperature at the Pan African scale;3)the impact of ENSO on the climate of Tanzania using high resolution climate products and 4)the potential predictability of the climate in different regions and seasons using Generalized Relative Operating Characteristics.We use these analyses to review the relevance of climate forecasts for applications in vector borne disease control across the continent.Results:Timescale decomposition revealed long term warming in all three regions of Africa-at the level of 0.1-0.3°C per decade.Decadal variations in rainfall were apparent in all regions and particularly pronounced in the Sahel and during the East African long rains(March-May).Year-to-year variability in both rainfall and temperature,in part associated with ENSO,were the dominant signal for climate variations on any timescale.Observed climate data and seasonal climate forecasts were identified as the most relevant sources of climate information for use in early warning systems for vector-borne diseases but the latter varied in skill by region and season.Conclusions:Adaptation to the vector-borne disease risks of climate variability and change is a priority for government and civil society in African countries.Understanding rainfall and temperature variations and trends at multiple timescales and their potential predictability is a necessary first step in the incorporation of relevant climate information into vector-borne disease control decision-making.展开更多
Background:The control of vector-borne diseases(VBD)is one of the greatest challenges on the global health agenda.Rapid and uncontrolled urbanization has heightened the interest in addressing these challenges through ...Background:The control of vector-borne diseases(VBD)is one of the greatest challenges on the global health agenda.Rapid and uncontrolled urbanization has heightened the interest in addressing these challenges through an integrated vector management(IVM)approach.The aim was to identify components related to impacts,economic evaluation,and sustainability that might contribute to this integrated approach to VBD prevention.Main body:We conducted a scoping review of available literature(2000-2016)using PubMed,Web of Science,Cochrane,CINAHL,Econlit,LILACS,Global Health Database,Scopus,and Embase,as well as Tropical Diseases Bulletin,WHOLIS,WHO Pesticide Evaluation Scheme,and Google Scholar.MeSH terms and free-text terms were used.A data extraction form was used,including TIDieR and ASTAIRE.MMAT and CHEERS were used to evaluate quality.Of the 42 documents reviewed,30 were focused on dengue,eight on malaria,and two on leishmaniasis.More than a half of the studies were conducted in the Americas.Half used a quantitative descriptive approach(n=21),followed by cluster randomized controlled trials(n=11).Regarding impacts,outcomes were:a)use of measures for vector control;b)vector control;c)health measures;and d)social measures.IVM reduced breeding sites,the entomology index,and parasite rates.Results were heterogeneous,with variable magnitudes,but in all cases were favourable to the intervention.Evidence of IVM impacts on health outcomes was very limited but showed reduced incidence.Social outcomes were improved abilities and capacities,empowerment,and community knowledge.Regarding economic evaluation,only four studies performed an economic analysis,and intervention benefits outweighed costs.Costeffectiveness was dependent on illness incidence.The results provided key elements to analyze sustainability in terms of three dimensions(social,economic,and environmental),emphasizing the implementation of a community-focused eco-bio-social approach.Conclusions:IVM has an impact on reducing vector breeding sites and the entomology index,but evidence of impacts on health outcomes is limited.Social outcomes are improved abilities and capacities,empowerment,and community knowledge.Economic evaluations are scarce,and cost-effectiveness is dependent on illness incidence.Community capacity building is the main component of sustainability,together with collaboration,institutionalization,and routinization of activities.Findings indicate a great heterogeneity in the interventions and highlight the need for characterizing interventions rigorously to facilitate transferability.展开更多
The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
We look at the link between climate change and vector-borne diseases in low-and middle-income countries in Africa.The large endemicity and escalating threat of diseases such as malaria and arboviral diseases,intensifi...We look at the link between climate change and vector-borne diseases in low-and middle-income countries in Africa.The large endemicity and escalating threat of diseases such as malaria and arboviral diseases,intensified by climate change,disproportionately affects vulnerable communities globally.We highlight the urgency of prioritizing research and development,advocating for robust scientific inquiry to promote adaptation strategies,and the vital role that the next generation of African research leaders will play in addressing these challenges.Despite significant challenges such as funding shortages within countries,various pan-African-oriented funding bodies such as the African Academy of Sciences,the Africa Research Excellence Fund,the Wellcome Trust,the U.S.National Institutes of Health,and the Bill and Melinda Gates Foundation as well as initiatives such as the African Research Initiative for Scientific Excellence and the Pan-African Mosquito Control Association,have empowered(or are empowering)these researchers by supporting capacity building activities,including continental and global networking,skill development,mentoring,and African-led research.This article underscores the urgency of increased national investment in research,proposing the establishment of research government agencies to drive evidence-based interventions.Collaboration between governments and scientific communities,sustained by pan-African funding bodies,is crucial.Through these efforts,African nations are likely to enhance the resilience and adaptive capacity of their systems and communities by navigating these challenges effectively,fostering scientific excellence and implementing transformative solutions against climate-sensitive vector-borne diseases.展开更多
Background:In 2015,following a call for proposals from the Special Programme for Research and Training in Tropical Diseases(TDR),six scoping reviews on the prevention and control of vector-borne diseases in urban area...Background:In 2015,following a call for proposals from the Special Programme for Research and Training in Tropical Diseases(TDR),six scoping reviews on the prevention and control of vector-borne diseases in urban areas were conducted.Those reviews provided a clear picture of the available knowledge and highlighted knowledge gaps,as well as needs and opportunities for future research.Based on the research findings of the scoping reviews,a concept mapping exercise was undertaken to produce a list of priority research needs to be addressed.Methods:Members of the six research teams responsible for the“VEctor boRne DiseAses Scoping reviews”(VERDAS)consortium’s scoping reviews met for 2 days with decision-makers from Colombia,Brazil,Peru,Pan-American Health Organization,and World Health Organization.A total of 11 researchers and seven decision-makers(from ministries of health,city and regional vector control departments,and vector control programs)completed the concept mapping,answering the question:“In view of the knowledge synthesis and your own expertise,what do we still need to know about vector-borne diseases and other infectious diseases of poverty in urban areas?”Participants rated each statement on two scales from 1 to 5,one relative to‘priority’and the other to‘policy relevance’,and grouped statements into clusters based on their own individual criteria and expertise.Results:The final map consisted of 12 clusters.Participants considered those entitled“Equity”,“Technology”,and“Surveillance”to have the highest priority.The cluster considered the most important concerns equity issues,confirming that these issues are rarely addressed in research on vector-borne diseases.On the other hand,the“Population mobility”and“Collaboration”clusters were considered to be the lowest priority but remained identified by participants as research priorities.The average policy relevance scores for each of the 12 clusters were roughly the same as the priority scores for all clusters.Some issues were not addressed during the brain-storming.This is the case for governance and for access and quality of care.Conclusions:Based on this work,and adopting a participatory approach,the concept mapping exercise conducted collaboratively with researchers from these teams and high-level decision-makers identified research themes for which studies should be carried out as a priority.展开更多
The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide associa...The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide association study(GWAS)summary statistics from European populations,we performed a genome-wide pleiotropic analysis to investigate the shared genetic basis and causal associations between skin and GIT diseases.We observed extensive genetic correlations and overlaps between skin and GIT diseases.A total of 298 pleiotropic loci were identified,75 of which were colocalized,and 61 exhibited pleiotropic effects across multiple trait pairs,including 2p16.1(PUS10),6p21.32(HLA-DRB1),10q21.2(ZNF365),and 19q13.11(SLC7A10).Additionally,five novel loci were identified based on the pleiotropic analysis;among them,the 15q22.2 locus harboring RORA was validated by the latest inflammatory bowel disease GWAS.Gene-based analysis identified 394 unique pleiotropic genes,which were enriched in GSA-associated tissues and the immune system,and protein-protein interaction analysis further revealed that the GPCR-cAMP,chromatin remodeling,JAK-STAT,and HLA-mediated immunity pathways were involved in GSA comorbidity.Notably,the JAK-STAT pathway showed strong potential for drug repurposing,with adalimumab targeting tumor necrosis factor and ustekinumab targeting interleukin-12 subunit beta already being used to treat both skin and GIT diseases.Finally,Mendelian randomization analysis identified five significant causal associations,and subsequent mediation analysis identified three potential microbiota-GIT-skin pathways.Taken together,our study demonstrated that the shared genetic factors between skin and GIT diseases were widely distributed across the genome.These findings will enhance our understanding of the genetic mechanisms underlying GSA comorbidity.展开更多
Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as ...Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as deep brain stimulation and transcranial magnetic stimulation,show limitations such as invasiveness,restricted cortical targeting,and irreversible tissue effects.In this context,low-intensity transcranial ultrasound has emerged as a promising noninvasive alternative that can penetrate deep into the brain and modulate neuroplasticity.This review comprehensively assesses the therapeutic mechanisms,efficacy,and translational potential of low-intensity transcranial ultrasound in treating neurodegenerative diseases,with emphasis on its role in promoting neuronal regeneration,modulating neuroinflammation,and enhancing functional recovery.We summarize the findings of previous studies and systematically illustrate the potential of low-intensity transcranial ultrasound in regulating cell death mechanisms,enhancing neural repair and regeneration,and alleviating symptoms associated with neurodegenerative diseases.Preclinical findings indicate that low-intensity transcranial ultrasound can enhance the release of neurotrophic factors(e.g.,brain-derived neurotrophic factor),promote autophagy to clear protein aggregates,modulate microglial activation,and temporarily open the blood-brain barrier to facilitate targeted drug delivery.Existing clinical trial data show that low-intensity transcranial ultrasound can reduce amyloid-βplaques,improve motor and cognitive deficits,and promote remyelination in various disease models.Early clinical trials suggest that low-intensity transcranial ultrasound may enhance cognitive scores in Alzheimer’s disease and alleviate motor symptoms in Parkinson’s disease,all while demonstrating a favorable safety profile.Past studies support the notion that by integrating safety,precision,and reversibility,low-intensity transcranial ultrasound can transform the treatment landscape for neurodegenerative disease.However,more advancements are necessary for future clinical application of low-intensity transcranial ultrasound,including optimizing parameters such as frequency,intensity,and duty cycle;considering individual anatomical differences;and confirming long-term efficacy.We believe establishing standardized protocols,conducting larger trials,and investigating the underlying mechanisms to clarify dose-response relationships and refine personalized application strategies are essential in this regard.Future research should focus on translating preclinical findings into clinical practice,addressing technical challenges,and exploring combination therapies with pharmacological or gene interventions.展开更多
Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide.Altogether,the burden of neurological d...Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide.Altogether,the burden of neurological disorders has increased considerably over the past 30 years because of population aging.Overall,neurological diseases significantly impair cognitive and motor functions and their incidence will increase as societies age and the world's population continues to grow.Autism spectrum disorder,motor neuron disease,encephalopathy,epilepsy,stroke,ataxia,Alzheimer's disease,amyotrophic lateral sclerosis,Huntington's disease,and Parkinson's disease represent a non-exhaustive list of neurological illnesses.These affections are due to perturbations in cellular homeostasis leading to the progressive injury and death of neurons in the nervous system.Among the common features of neurological handicaps,we find protein aggregation,oxidative stress,neuroinflammation,and mitochondrial impairment in the target tissues,e.g.,the brain,cerebellum,and spinal cord.The high energy requirements of neurons and their inability to produce sufficient adenosine triphosphate by glycolysis,are responsible for their dependence on functional mitochondria for their integrity.Reactive oxygen species,produced along with the respiration process within mitochondria,can lead to oxidative stress,which compromises neuronal survival.Besides having an essential role in energy production and oxidative stress,mitochondria are indispensable for an array of cellular processes,such as amino acid metabolism,iron-sulfur cluster biosynthesis,calcium homeostasis,intrinsic programmed cell death(apoptosis),and intraorganellar signaling.Despite the progress made in the last decades in the understanding of a growing number of genetic and molecular causes of central nervous diseases,therapies that are effective to diminish or halt neuronal dysfunction/death are rare.Given the genetic complexity responsible for neurological disorders,the development of neuroprotective strategies seeking to preserve mitochondrial homeostasis is a realistic challenge to lastingly diminish the harmful evolution of these pathologies and so to recover quality of life.A promising candidate is the neuroglobin,a globin superfamily member of 151 amino acids,which is found at high levels in the brain,the eye,and the cerebellum.The protein,which localizes to mitochondria,is involved in electron transfer,oxygen storage and defence against oxidative stress;hence,possessing neuroprotective properties.This review surveys up-to-date knowledge and emphasizes on existing investigations regarding neuroglobin physiological functions,which remain since its discovery in 2000 under intense debate and the possibility of using neuroglobin either by gene therapy or its direct delivery into the brain to treat neurological disorders.展开更多
Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown t...Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown that PPARαplays a key role in the onset and progression of neurodegenerative diseases.Consequently,peroxisome proliferator-activated receptor alpha agonists have garnered increasing attention as potential treatments for neurological disorders.This review aims to clarify the research progress regarding peroxisome proliferator-activated receptor alpha in nervous system diseases.Peroxisome proliferator-activated receptor alpha is present in all cell types within adult mouse and adult neural tissues.Although it is conventionally believed to be primarily localized in the nucleus,its function may be regulated by a dynamic balance between cytoplasmic and nuclear shuttling.Both endogenous and exogenous peroxisome proliferator-activated receptor alpha agonists bind to the peroxisome proliferator-activated response element to exert their biological effects.Peroxisome proliferator-activated receptor alpha plays a significant therapeutic role in neurodegenerative diseases.For instance,peroxisome proliferator-activated receptor alpha agonist gemfibrozil has been shown to reduce levels of soluble and insoluble amyloid-beta in the hippocampus of Alzheimer's disease mouse models through the autophagy-lysosomal pathway.Additionally,peroxisome proliferator-activated receptor alpha is essential for the normal development and functional maintenance of the substantia nigra,and it can mitigate motor dysfunction in Parkinson's disease mouse models.Furthermore,peroxisome proliferator-activated receptor alpha has been found to reduce neuroinflammation and oxidative stress in various neurological diseases.In summary,peroxisome proliferator-activated receptor alpha plays a crucial role in the onset and progression of multiple nervous system diseases,and peroxisome proliferator-activated receptor alpha agonists hold promise as new therapeutic agents for the treatment of neurodegenerative diseases,providing new options for patient care.展开更多
Neurodegenerative diseases,which mainly include Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,Wilson’s disease,and Huntington’s disease,are a group of disorders characterized by loss of neu...Neurodegenerative diseases,which mainly include Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,Wilson’s disease,and Huntington’s disease,are a group of disorders characterized by loss of neurons in the brain and spinal cord.However,the underlying pathogenetic mechanisms of these disorders remain unclear.The metal ion hypothesis is considered a possible cause of a variety of neurodegenerative diseases.This hypothesis posits that the homeostatic imbalance of metal ions leads to oxidative stress,neuroinflammation,excessive aggregation of pathological proteins,and other serious consequences in neurons.The powerful endogenous metal ion chelator metallothionein plays an important role in regulating metal ion homeostasis to alleviate neurodegenerative diseases.This article provides an overview of the pathogenesis of neurodegenerative diseases in relation to metal ions such as copper,iron,and zinc and the contribution of metallothionein to the regulation of metal ion homeostasis.The review focuses on the role of metal ions in the course of neurodegenerative diseases and the molecular mechanisms through which endogenous metallothionein ameliorates metal ion overload to alleviate neurodegenerative diseases.A thorough understanding of these molecular mechanisms can provide a theoretical foundation for the development of new therapeutic strategies,with the aim of more effectively treating these devastating diseases in the future.展开更多
Chemical exchange saturation transfer magnetic resonance imaging is an advanced imaging technique that enables the detection of compounds at low concentrations with high sensitivity and spatial resolution and has been...Chemical exchange saturation transfer magnetic resonance imaging is an advanced imaging technique that enables the detection of compounds at low concentrations with high sensitivity and spatial resolution and has been extensively studied for diagnosing malignancy and stroke.In recent years,the emerging exploration of chemical exchange saturation transfer magnetic resonance imaging for detecting pathological changes in neurodegenerative diseases has opened up new possibilities for early detection and repetitive scans without ionizing radiation.This review serves as an overview of chemical exchange saturation transfer magnetic resonance imaging with detailed information on contrast mechanisms and processing methods and summarizes recent developments in both clinical and preclinical studies of chemical exchange saturation transfer magnetic resonance imaging for Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,and Huntington’s disease.A comprehensive literature search was conducted using databases such as PubMed and Google Scholar,focusing on peer-reviewed articles from the past 15 years relevant to clinical and preclinical applications.The findings suggest that chemical exchange saturation transfer magnetic resonance imaging has the potential to detect molecular changes and altered metabolism,which may aid in early diagnosis and assessment of the severity of neurodegenerative diseases.Although promising results have been observed in selected clinical and preclinical trials,further validations are needed to evaluate their clinical value.When combined with other imaging modalities and advanced analytical methods,chemical exchange saturation transfer magnetic resonance imaging shows potential as an in vivo biomarker,enhancing the understanding of neuropathological mechanisms in neurodegenerative diseases.展开更多
Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute cour...Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.展开更多
Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several...Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several decades of research worldwide.In 2021 and again in 2023,two monoclonal antibodies,aducanumab and lecanemab,have been approved by the U.S.Food and Drug Administration,and a third,donanemab,is currently under review.However,these treatments have very limited efficacy on cognitive functions and are accompanied by major side effects:amyloid-related imaging abnormalities,microhemorrhages,and accelerated brain volume loss(Høilund-Carlsen et al.,2024).展开更多
文摘Female mosquitoes of several species require blood from warmblooded animals,including humans for the purpose of reproduction.In this process,several microbes residing in the salivary gland and midgut of mosquitoes also get transferred from one human individual to the other–a traditional model by which many vector-borne diseases(VBDs)get transmitted in the population through mosquitoes belonging to Anopheles,Aedes,Culex and other genera.
文摘Vector-borne diseases are highly sensitive to environment and to environmental changes. Rift Valley Fever (RFV) is a mosquito-borne zootic virus associated with severe diseases in human beings and economic consequences to livestock sector. Animal and human movements have a fundamental impact on RVF transmission. In recent years, there has been a growing interest in the use of mathematics and agent based models to represent and analyze the dynamic of RFV transmission. However, no previous study has taken into consideration animal herds’ mobility and precipitation factors to understand the disease spread. This limitation underlines the necessity to use computational model approach based on multi-agent system in the study of vector-borne diseases transmission and diffusion. In this paper, a multi-agent system combining conceptual model expressiveness is used to study animal herds’ mobility and the precipitation parameter impact on the Rift Valley Fever outbreak in Ferlo Barkedji in Northern Senegal. Simulation scenarios with various parameters, including rain quality, hosts, vectors, camp dispersal around ponds, etc., are unrolled. The different results we have obtained show that the evolution of the number of infected hosts and infected vectors depend on the degree of animal herds’ mobility and on precipitations. Our model provides a framework that permits predicting the spread of the disease associated with the mobility of animal herds.
基金supported by the National Natural Science Foundation of China(82330103,82370016).
文摘Vector-borne diseases(VBDs),primarily transmitted through the bites of vectors such as mosquitoes,ticks,and sandflies,have been recognized as a critical global public health priority.This systematic review summarizes the pivotal role of geospatial technologies,including geographic information systems(GIS),remote sensing(RS),and advanced spatial statistical methodologies,in enhancing disease surveillance systems.We conducted a comprehensive literature screening across the PubMed and OVID Medline databases,identifying 652 relevant studies published between 2015 and 2024.These studies were analyzed to evaluate the application of geospatial approaches to several critical VBDs such as malaria,dengue fever,yellow fever,and other VBDs.The integration of GIS and RS enables high-resolution mapping of vector habitats and disease hotspots by analyzing environmental factors.Advanced spatial statistical models effectively quantify the influence of environmental and socioeconomic variables,predict transmission risk,and detect significant spatial clusters.Phylogeographic analyses elucidate pathogen origins and transmission pathways,while animal migration tracking reveals the role of long-distance vector and host dispersal in disease spread.These approaches have facilitated the development of actionable risk maps that support targeted interventions,optimize resource allocation,and underpin early warning systems for diseases such as malaria,dengue fever,yellow fever,and Zika virus disease.In summary,geospatial epidemiology plays a critical role in VBD control by providing evidence-based insights into transmission dynamics.Future efforts should prioritize interdisciplinary collaboration and the development of integrated,real-time surveillance platforms that combine multisource data and predictive modeling.
文摘Background: Social determinants of health (SDOH) significantly influence diseases with environmental components, like vector-borne parasitic diseases. This study aims to examine how these factors influence vector-borne parasitic diseases (VBPDs) transmission in Chad and provide recommendations for policy improvements. Methods: The study adopts the WHO Conceptual Framework of SDOH to compare two regions in Southern Chad: Kouh-Est, which has an ongoing vector control program, and Grand-Sido, which lacks such a program. The study includes both nomadic and sedentary populations to provide a comprehensive understanding of the SDOH influencing VBPDs. Households were randomly selected. Data on sociodemographic characteristics, literacy, knowledge of VBPDs and protective measures, and access to education and health facilities were collected. Results: A total of 202 households from 17 villages, including 820 participants, were surveyed. Agriculture, livestock, and fishing were the main occupations, involving 84.1% of participants. Literacy was low, with 36.7% non-educated, 47.7% completing primary school, 14.5% secondary school, and only 0.3% reaching tertiary education. Most villages lacked schools beyond the primary level, and nomadic populations were significantly less educated than sedentary ones (p Conclusion: Educational deficiencies, lack of protective measures against vectors, inadequate healthcare resources, and lifestyle conditions aggravated by poor road infrastructure, limited transportation, and economic constraints contribute to worsened VBPDs outcomes in these rural populations. Addressing these systemic issues in the surveyed communities is essential for improving health equity and VBPDs outcomes in these regions specifically and in similar populations settings more broadly.
基金Supported by the consultancy project(2023-JB-12)from the Chinese Academy of Engineering(CAE)the Key Program of the National Natural Science Foundation of China(GRANT32090023).
文摘Introduction:Vector-borne diseases(VBDs)represent a significant category of infectious diseases.Analyzing the epidemiological characteristics of VBDs in China,including their temporal and spatial distributions,provides essential evidence for developing effective prevention and control strategies.Methods:Data for 14 types of VBDs from 2005 to 2024 were obtained from the China National Infectious Disease Surveillance System.These diseases were categorized as mosquito-borne,tick-borne,rodent-borne,and other VBDs.Using the Mann-Kendall trend test,we analyzed demographic characteristics,spatial distribution,temporal trends,and seasonal patterns of notified cases over the 20-year period.Results:From 2005 to 2024,a total of 1,129,736 VBD cases were reported in China.Scrub typhus(28.17%),malaria(20.8%),hemorrhagic fever with renal syndrome(HFRS,18.4%),dengue(12.61%),and schistosomiasis(8.42%)collectively accounted for 88.4%of all cases.Over a 20-year period,mosquitoborne and rodent-borne diseases indicated significant declining trends(P<0.05),while tick-borne and other VBDs demonstrated significant increasing trends(P<0.05).Dengue,scrub typhus,and severe fever with thrombocytopenia syndrome(SFTS)expanded geographically,with annual increases of 10.89,12.37,and 7.07 reporting cities,respectively.Although diseases such as plague,malaria,and schistosomiasis have been effectively controlled,the incidence of scrub typhus,dengue,HFRS,and SFTS has remained high in recent years.Conclusions:The burden of VBDs in China remains substantial,with an increasing trend observed over the past 5 years.The rising incidence and geographic expansion of scrub typhus,dengue,and SFTS warrant particular attention from public health authorities.
基金This research portfolio received funding support from the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases(TDR)Geneva,Switzerland and the International Development Research Center,Canada.
文摘Background:Diseases transmitted to humans by vectors account for 17%of all infectious diseases and remain significant public health problems.Through the years,great strides have been taken towards combatting vectorborne diseases(VBDs),most notably through large scale and coordinated control programmes,which have contributed to the decline of the global mortality attributed to VBDs.However,with environmental changes,including climate change,the impact on VBDs is anticipated to be significant,in terms of VBD-related hazards,vulnerabilities and exposure.While there is growing awareness on the vulnerability of the African continent to VBDs in the context of climate change,there is still a paucity of research being undertaken in this area,and impeding the formulation of evidence-based health policy change.Main body:One way in which the gap in knowledge and evidence can be filled is for donor institutions to support research in this area.The collaboration between the WHO Special Programme for Research and Training in Tropical Diseases(TDR)and the International Centre for Research and Development(IDRC)builds on more than 10 years of partnership in research capacity-building in the field of tropical diseases.From this partnership was born yet another research initiative on VBDs and the impact of climate change in the Sahel and sub-Saharan Africa.This paper lists the projects supported under this research initiative and provides a brief on some of the policy and good practice recommendations emerging from the ongoing implementation of the research projects.Conclusion:Data generated from the research initiative are expected to be uptaken by stakeholders(including communities,policy makers,public health practitioners and other relevant partners)to contribute to a better understanding of the impacts of social,environmental and climate change on VBDs(i.e.the nature of the hazard,vulnerabilities,exposure),and improve the ability of African countries to adapt to and reduce the effects of these changes in ways that benefit their most vulnerable populations.
基金Valery Ridde holds a CIHR-funded Research Chair in Applied Public Health(CPP-137901).
文摘This paper highlights the critical importance of evidence on vector-borne diseases(VBD)prevention and control interventions in urban settings when assessing current and future needs,with a view to setting policy priorities that promote inclusive and equitable urban health services.Research should produce knowledge about policies and interventions that are intended to control and prevent VBDs at the population level and to reduce inequities.Such interventions include policy,program,and resource distribution approaches that address the social determinants of health and exert influence at organizational and system levels.
基金Funding for the work came from WHO PO 21353027(PI MCT)in support of WHO-TDR IDRC-funded project:“Population health vulnerabilities to vectorborne diseases:increasing resilience under climate change conditions in Africa”WHO PO 201487225(PI MCT)as a technical contribution to the Global Framework for Climate Services.ÁM was supported via the Atmospheric and Oceanic Sciences(AOS)Program at Princeton University.
文摘Background:Climate-based disease forecasting has been proposed as a potential tool in climate change adaptation for the health sector.Here we explore the relevance of climate data,drivers and predictions for vector-borne disease control efforts in Africa.Methods:Using data from a number of sources we explore rainfall and temperature across the African continent,from seasonality to variability at annual,multi-decadal and timescales consistent with climate change.We give particular attention to three regions defined as WHO-TDR study zones in Western,Eastern and Southern Africa.Our analyses include 1)time scale decomposition to establish the relative importance of year-to-year,decadal and long term trends in rainfall and temperature;2)the impact of the El Niño Southern Oscillation(ENSO)on rainfall and temperature at the Pan African scale;3)the impact of ENSO on the climate of Tanzania using high resolution climate products and 4)the potential predictability of the climate in different regions and seasons using Generalized Relative Operating Characteristics.We use these analyses to review the relevance of climate forecasts for applications in vector borne disease control across the continent.Results:Timescale decomposition revealed long term warming in all three regions of Africa-at the level of 0.1-0.3°C per decade.Decadal variations in rainfall were apparent in all regions and particularly pronounced in the Sahel and during the East African long rains(March-May).Year-to-year variability in both rainfall and temperature,in part associated with ENSO,were the dominant signal for climate variations on any timescale.Observed climate data and seasonal climate forecasts were identified as the most relevant sources of climate information for use in early warning systems for vector-borne diseases but the latter varied in skill by region and season.Conclusions:Adaptation to the vector-borne disease risks of climate variability and change is a priority for government and civil society in African countries.Understanding rainfall and temperature variations and trends at multiple timescales and their potential predictability is a necessary first step in the incorporation of relevant climate information into vector-borne disease control decision-making.
文摘Background:The control of vector-borne diseases(VBD)is one of the greatest challenges on the global health agenda.Rapid and uncontrolled urbanization has heightened the interest in addressing these challenges through an integrated vector management(IVM)approach.The aim was to identify components related to impacts,economic evaluation,and sustainability that might contribute to this integrated approach to VBD prevention.Main body:We conducted a scoping review of available literature(2000-2016)using PubMed,Web of Science,Cochrane,CINAHL,Econlit,LILACS,Global Health Database,Scopus,and Embase,as well as Tropical Diseases Bulletin,WHOLIS,WHO Pesticide Evaluation Scheme,and Google Scholar.MeSH terms and free-text terms were used.A data extraction form was used,including TIDieR and ASTAIRE.MMAT and CHEERS were used to evaluate quality.Of the 42 documents reviewed,30 were focused on dengue,eight on malaria,and two on leishmaniasis.More than a half of the studies were conducted in the Americas.Half used a quantitative descriptive approach(n=21),followed by cluster randomized controlled trials(n=11).Regarding impacts,outcomes were:a)use of measures for vector control;b)vector control;c)health measures;and d)social measures.IVM reduced breeding sites,the entomology index,and parasite rates.Results were heterogeneous,with variable magnitudes,but in all cases were favourable to the intervention.Evidence of IVM impacts on health outcomes was very limited but showed reduced incidence.Social outcomes were improved abilities and capacities,empowerment,and community knowledge.Regarding economic evaluation,only four studies performed an economic analysis,and intervention benefits outweighed costs.Costeffectiveness was dependent on illness incidence.The results provided key elements to analyze sustainability in terms of three dimensions(social,economic,and environmental),emphasizing the implementation of a community-focused eco-bio-social approach.Conclusions:IVM has an impact on reducing vector breeding sites and the entomology index,but evidence of impacts on health outcomes is limited.Social outcomes are improved abilities and capacities,empowerment,and community knowledge.Economic evaluations are scarce,and cost-effectiveness is dependent on illness incidence.Community capacity building is the main component of sustainability,together with collaboration,institutionalization,and routinization of activities.Findings indicate a great heterogeneity in the interventions and highlight the need for characterizing interventions rigorously to facilitate transferability.
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
基金the financial assistance of the European Union(Grant no.ARISE-PP-FA-072),through the African Research Initiative for Scientific Excellence(ARISE),pilot programme.ARISE is implemented by the African Academy of Sciences with support from the European Commission and the African Union Commission.
文摘We look at the link between climate change and vector-borne diseases in low-and middle-income countries in Africa.The large endemicity and escalating threat of diseases such as malaria and arboviral diseases,intensified by climate change,disproportionately affects vulnerable communities globally.We highlight the urgency of prioritizing research and development,advocating for robust scientific inquiry to promote adaptation strategies,and the vital role that the next generation of African research leaders will play in addressing these challenges.Despite significant challenges such as funding shortages within countries,various pan-African-oriented funding bodies such as the African Academy of Sciences,the Africa Research Excellence Fund,the Wellcome Trust,the U.S.National Institutes of Health,and the Bill and Melinda Gates Foundation as well as initiatives such as the African Research Initiative for Scientific Excellence and the Pan-African Mosquito Control Association,have empowered(or are empowering)these researchers by supporting capacity building activities,including continental and global networking,skill development,mentoring,and African-led research.This article underscores the urgency of increased national investment in research,proposing the establishment of research government agencies to drive evidence-based interventions.Collaboration between governments and scientific communities,sustained by pan-African funding bodies,is crucial.Through these efforts,African nations are likely to enhance the resilience and adaptive capacity of their systems and communities by navigating these challenges effectively,fostering scientific excellence and implementing transformative solutions against climate-sensitive vector-borne diseases.
文摘Background:In 2015,following a call for proposals from the Special Programme for Research and Training in Tropical Diseases(TDR),six scoping reviews on the prevention and control of vector-borne diseases in urban areas were conducted.Those reviews provided a clear picture of the available knowledge and highlighted knowledge gaps,as well as needs and opportunities for future research.Based on the research findings of the scoping reviews,a concept mapping exercise was undertaken to produce a list of priority research needs to be addressed.Methods:Members of the six research teams responsible for the“VEctor boRne DiseAses Scoping reviews”(VERDAS)consortium’s scoping reviews met for 2 days with decision-makers from Colombia,Brazil,Peru,Pan-American Health Organization,and World Health Organization.A total of 11 researchers and seven decision-makers(from ministries of health,city and regional vector control departments,and vector control programs)completed the concept mapping,answering the question:“In view of the knowledge synthesis and your own expertise,what do we still need to know about vector-borne diseases and other infectious diseases of poverty in urban areas?”Participants rated each statement on two scales from 1 to 5,one relative to‘priority’and the other to‘policy relevance’,and grouped statements into clusters based on their own individual criteria and expertise.Results:The final map consisted of 12 clusters.Participants considered those entitled“Equity”,“Technology”,and“Surveillance”to have the highest priority.The cluster considered the most important concerns equity issues,confirming that these issues are rarely addressed in research on vector-borne diseases.On the other hand,the“Population mobility”and“Collaboration”clusters were considered to be the lowest priority but remained identified by participants as research priorities.The average policy relevance scores for each of the 12 clusters were roughly the same as the priority scores for all clusters.Some issues were not addressed during the brain-storming.This is the case for governance and for access and quality of care.Conclusions:Based on this work,and adopting a participatory approach,the concept mapping exercise conducted collaboratively with researchers from these teams and high-level decision-makers identified research themes for which studies should be carried out as a priority.
基金supported by grants from the National Natural Science Foundation of China(Grant No.32470658)the National Key Research and Development Program of China(Grant Nos.2022YFC2502400 and 2022YFC2502402).
文摘The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide association study(GWAS)summary statistics from European populations,we performed a genome-wide pleiotropic analysis to investigate the shared genetic basis and causal associations between skin and GIT diseases.We observed extensive genetic correlations and overlaps between skin and GIT diseases.A total of 298 pleiotropic loci were identified,75 of which were colocalized,and 61 exhibited pleiotropic effects across multiple trait pairs,including 2p16.1(PUS10),6p21.32(HLA-DRB1),10q21.2(ZNF365),and 19q13.11(SLC7A10).Additionally,five novel loci were identified based on the pleiotropic analysis;among them,the 15q22.2 locus harboring RORA was validated by the latest inflammatory bowel disease GWAS.Gene-based analysis identified 394 unique pleiotropic genes,which were enriched in GSA-associated tissues and the immune system,and protein-protein interaction analysis further revealed that the GPCR-cAMP,chromatin remodeling,JAK-STAT,and HLA-mediated immunity pathways were involved in GSA comorbidity.Notably,the JAK-STAT pathway showed strong potential for drug repurposing,with adalimumab targeting tumor necrosis factor and ustekinumab targeting interleukin-12 subunit beta already being used to treat both skin and GIT diseases.Finally,Mendelian randomization analysis identified five significant causal associations,and subsequent mediation analysis identified three potential microbiota-GIT-skin pathways.Taken together,our study demonstrated that the shared genetic factors between skin and GIT diseases were widely distributed across the genome.These findings will enhance our understanding of the genetic mechanisms underlying GSA comorbidity.
基金supported by STI2030-Major Project,No,2021ZD0204200(to LX).
文摘Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as deep brain stimulation and transcranial magnetic stimulation,show limitations such as invasiveness,restricted cortical targeting,and irreversible tissue effects.In this context,low-intensity transcranial ultrasound has emerged as a promising noninvasive alternative that can penetrate deep into the brain and modulate neuroplasticity.This review comprehensively assesses the therapeutic mechanisms,efficacy,and translational potential of low-intensity transcranial ultrasound in treating neurodegenerative diseases,with emphasis on its role in promoting neuronal regeneration,modulating neuroinflammation,and enhancing functional recovery.We summarize the findings of previous studies and systematically illustrate the potential of low-intensity transcranial ultrasound in regulating cell death mechanisms,enhancing neural repair and regeneration,and alleviating symptoms associated with neurodegenerative diseases.Preclinical findings indicate that low-intensity transcranial ultrasound can enhance the release of neurotrophic factors(e.g.,brain-derived neurotrophic factor),promote autophagy to clear protein aggregates,modulate microglial activation,and temporarily open the blood-brain barrier to facilitate targeted drug delivery.Existing clinical trial data show that low-intensity transcranial ultrasound can reduce amyloid-βplaques,improve motor and cognitive deficits,and promote remyelination in various disease models.Early clinical trials suggest that low-intensity transcranial ultrasound may enhance cognitive scores in Alzheimer’s disease and alleviate motor symptoms in Parkinson’s disease,all while demonstrating a favorable safety profile.Past studies support the notion that by integrating safety,precision,and reversibility,low-intensity transcranial ultrasound can transform the treatment landscape for neurodegenerative disease.However,more advancements are necessary for future clinical application of low-intensity transcranial ultrasound,including optimizing parameters such as frequency,intensity,and duty cycle;considering individual anatomical differences;and confirming long-term efficacy.We believe establishing standardized protocols,conducting larger trials,and investigating the underlying mechanisms to clarify dose-response relationships and refine personalized application strategies are essential in this regard.Future research should focus on translating preclinical findings into clinical practice,addressing technical challenges,and exploring combination therapies with pharmacological or gene interventions.
基金supported by AFM-Telethon grants N°21704 and 23264,Universite Paris Cite(Paris)the National Institute of Health and Medical Research(INSERM)+3 种基金the National Center for Scientific Research(CNRS)the French Association Connaître les Syndromes Cerebelleux(CSC)(to MCD)GV/2021/188 granted from Conselleria of Innovation,Universities,28 Science and Society digital of the Community of Valencia(Spain)(to ITC)Subprograma Atraccion de Talento-Contratos Postdoctorales de la Universitat de Valencia(to IMY).
文摘Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide.Altogether,the burden of neurological disorders has increased considerably over the past 30 years because of population aging.Overall,neurological diseases significantly impair cognitive and motor functions and their incidence will increase as societies age and the world's population continues to grow.Autism spectrum disorder,motor neuron disease,encephalopathy,epilepsy,stroke,ataxia,Alzheimer's disease,amyotrophic lateral sclerosis,Huntington's disease,and Parkinson's disease represent a non-exhaustive list of neurological illnesses.These affections are due to perturbations in cellular homeostasis leading to the progressive injury and death of neurons in the nervous system.Among the common features of neurological handicaps,we find protein aggregation,oxidative stress,neuroinflammation,and mitochondrial impairment in the target tissues,e.g.,the brain,cerebellum,and spinal cord.The high energy requirements of neurons and their inability to produce sufficient adenosine triphosphate by glycolysis,are responsible for their dependence on functional mitochondria for their integrity.Reactive oxygen species,produced along with the respiration process within mitochondria,can lead to oxidative stress,which compromises neuronal survival.Besides having an essential role in energy production and oxidative stress,mitochondria are indispensable for an array of cellular processes,such as amino acid metabolism,iron-sulfur cluster biosynthesis,calcium homeostasis,intrinsic programmed cell death(apoptosis),and intraorganellar signaling.Despite the progress made in the last decades in the understanding of a growing number of genetic and molecular causes of central nervous diseases,therapies that are effective to diminish or halt neuronal dysfunction/death are rare.Given the genetic complexity responsible for neurological disorders,the development of neuroprotective strategies seeking to preserve mitochondrial homeostasis is a realistic challenge to lastingly diminish the harmful evolution of these pathologies and so to recover quality of life.A promising candidate is the neuroglobin,a globin superfamily member of 151 amino acids,which is found at high levels in the brain,the eye,and the cerebellum.The protein,which localizes to mitochondria,is involved in electron transfer,oxygen storage and defence against oxidative stress;hence,possessing neuroprotective properties.This review surveys up-to-date knowledge and emphasizes on existing investigations regarding neuroglobin physiological functions,which remain since its discovery in 2000 under intense debate and the possibility of using neuroglobin either by gene therapy or its direct delivery into the brain to treat neurological disorders.
基金supported by grants from Tianjin Scientific Research Project in Key Areas of Traditional Chinese Medicine,Tianjin Municipal Health Commission,No.2024012(to JL)Tianjin Municipal Education Commission Project,No.2021KJ217(to CS)。
文摘Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown that PPARαplays a key role in the onset and progression of neurodegenerative diseases.Consequently,peroxisome proliferator-activated receptor alpha agonists have garnered increasing attention as potential treatments for neurological disorders.This review aims to clarify the research progress regarding peroxisome proliferator-activated receptor alpha in nervous system diseases.Peroxisome proliferator-activated receptor alpha is present in all cell types within adult mouse and adult neural tissues.Although it is conventionally believed to be primarily localized in the nucleus,its function may be regulated by a dynamic balance between cytoplasmic and nuclear shuttling.Both endogenous and exogenous peroxisome proliferator-activated receptor alpha agonists bind to the peroxisome proliferator-activated response element to exert their biological effects.Peroxisome proliferator-activated receptor alpha plays a significant therapeutic role in neurodegenerative diseases.For instance,peroxisome proliferator-activated receptor alpha agonist gemfibrozil has been shown to reduce levels of soluble and insoluble amyloid-beta in the hippocampus of Alzheimer's disease mouse models through the autophagy-lysosomal pathway.Additionally,peroxisome proliferator-activated receptor alpha is essential for the normal development and functional maintenance of the substantia nigra,and it can mitigate motor dysfunction in Parkinson's disease mouse models.Furthermore,peroxisome proliferator-activated receptor alpha has been found to reduce neuroinflammation and oxidative stress in various neurological diseases.In summary,peroxisome proliferator-activated receptor alpha plays a crucial role in the onset and progression of multiple nervous system diseases,and peroxisome proliferator-activated receptor alpha agonists hold promise as new therapeutic agents for the treatment of neurodegenerative diseases,providing new options for patient care.
基金supported by the National Natural Science Foundation of China,No.82460711Science and Technology Foundation of Guizhou Province,No.ZK[2021]-014(both to FZ).
文摘Neurodegenerative diseases,which mainly include Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,Wilson’s disease,and Huntington’s disease,are a group of disorders characterized by loss of neurons in the brain and spinal cord.However,the underlying pathogenetic mechanisms of these disorders remain unclear.The metal ion hypothesis is considered a possible cause of a variety of neurodegenerative diseases.This hypothesis posits that the homeostatic imbalance of metal ions leads to oxidative stress,neuroinflammation,excessive aggregation of pathological proteins,and other serious consequences in neurons.The powerful endogenous metal ion chelator metallothionein plays an important role in regulating metal ion homeostasis to alleviate neurodegenerative diseases.This article provides an overview of the pathogenesis of neurodegenerative diseases in relation to metal ions such as copper,iron,and zinc and the contribution of metallothionein to the regulation of metal ion homeostasis.The review focuses on the role of metal ions in the course of neurodegenerative diseases and the molecular mechanisms through which endogenous metallothionein ameliorates metal ion overload to alleviate neurodegenerative diseases.A thorough understanding of these molecular mechanisms can provide a theoretical foundation for the development of new therapeutic strategies,with the aim of more effectively treating these devastating diseases in the future.
基金supported by The University of Hong Kong,China(109000487,109001694,204610401,and 204610519)National Natural Science Foundation of China(82402225)(to JH).
文摘Chemical exchange saturation transfer magnetic resonance imaging is an advanced imaging technique that enables the detection of compounds at low concentrations with high sensitivity and spatial resolution and has been extensively studied for diagnosing malignancy and stroke.In recent years,the emerging exploration of chemical exchange saturation transfer magnetic resonance imaging for detecting pathological changes in neurodegenerative diseases has opened up new possibilities for early detection and repetitive scans without ionizing radiation.This review serves as an overview of chemical exchange saturation transfer magnetic resonance imaging with detailed information on contrast mechanisms and processing methods and summarizes recent developments in both clinical and preclinical studies of chemical exchange saturation transfer magnetic resonance imaging for Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,and Huntington’s disease.A comprehensive literature search was conducted using databases such as PubMed and Google Scholar,focusing on peer-reviewed articles from the past 15 years relevant to clinical and preclinical applications.The findings suggest that chemical exchange saturation transfer magnetic resonance imaging has the potential to detect molecular changes and altered metabolism,which may aid in early diagnosis and assessment of the severity of neurodegenerative diseases.Although promising results have been observed in selected clinical and preclinical trials,further validations are needed to evaluate their clinical value.When combined with other imaging modalities and advanced analytical methods,chemical exchange saturation transfer magnetic resonance imaging shows potential as an in vivo biomarker,enhancing the understanding of neuropathological mechanisms in neurodegenerative diseases.
基金supported by the National Key Research and Development Program of China,No.2022YFC2703101(to YC)the National Natural Science Fundation of China,No.82371422(to YC)+1 种基金the National Innovation and Entrepreneurship Training Program for College Students,No.202310611408(to XW)the 1·3·5 Project for Disciplines of Excellence Clinical Research Fund,West China Hospital,Sichuan University,No.2023HXFH032(to YC)。
文摘Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.
文摘Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several decades of research worldwide.In 2021 and again in 2023,two monoclonal antibodies,aducanumab and lecanemab,have been approved by the U.S.Food and Drug Administration,and a third,donanemab,is currently under review.However,these treatments have very limited efficacy on cognitive functions and are accompanied by major side effects:amyloid-related imaging abnormalities,microhemorrhages,and accelerated brain volume loss(Høilund-Carlsen et al.,2024).
