Chinese medicine,with its rich historical roots and holistic approach,has been a fundamental aspect of healthcare in East Asia and is now gaining global recognition.Founded on centuries of empirical knowledge and phil...Chinese medicine,with its rich historical roots and holistic approach,has been a fundamental aspect of healthcare in East Asia and is now gaining global recognition.Founded on centuries of empirical knowledge and philosophical insight,Chinese medicine draws heavily from classical texts to guide its practices in herbal medicine and acupuncture.Despite its cultural and historical significance,integrating Chinese medicine into global healthcare systems presents challenges,notably the need for evidence-based practices to enhance credibility,ensure patient safety,and foster broader acceptance within the medical community.This paper explores how Chinese medicine can adopt evidence-based practices by incorporating principles of Western medicine into its research methodologies.It reviews the origins and philosophical foundations of Chinese medicine,examining its reliance on classical texts and empirical methods.The paper also highlights the differences between the personalised approach of Chinese medicine,which tailors treatments to individual needs,and the standardised protocols typical of Western medicine.Additionally,it addresses methodological challenges in Chinese medicine research,such as inconsistent diagnostic criteria and insufficient design rigour.To bridge these gaps,innovative research methodologies that respect the unique variability of Chinese medicine are needed.By adopting evidence-based practices and rigorous scientific validation,Chinese medicine can enhance its legitimacy and facilitate its integration into the global healthcare landscape.展开更多
BACKGROUND Numerous studies have reported specific expression profiles of peripheral blood mononuclear cells(PBMCs)that are associated with infectious,autoimmune,and inflammatory disorders,including chronic liver dise...BACKGROUND Numerous studies have reported specific expression profiles of peripheral blood mononuclear cells(PBMCs)that are associated with infectious,autoimmune,and inflammatory disorders,including chronic liver diseases.AIM To identify potential differences in the transcriptome profiles of PBMCs between male patients with non-alcoholic fatty liver disease(NAFLD)and healthy male adolescents.METHODS PBMCs were isolated from 16 male adolescents with NAFLD and 14 healthy age-matched male peers.The collected cells were cultured in vitro for 18 hours without and with autologous fecal extracts(FEs).Differentially expressed genes(DEGs)were investigated using RNA sequencing.Levels of interleukin(IL)-6,tumor necrosis factor-α,IL-10,and IL-1βsecreted into the culture medium were determined using enzyme-linked immunosorbent assays.DEGs were functionally analyzed through annotation according to the Gene Ontology and Reactome databases.RESULTS In total,151(118 protein-coding)and 97(65 protein-coding)DEGs were identified when the RNA profiles of PBMCs stimulated without and with FEs,respectively,were compared between NAFLD patients and controls.Functional enrichment analysis of DEGs identified several pathways,which were predominantly involved in metabolism and inflammatory responses in non-stimulated and FE-stimulated PBMCs,respectively.FEs increased secretion of IL-6 and IL-1βby PBMCs isolated from controls and of all four cytokines by PBMCs isolated from NAFLD patients.IL-1βsecretion was significantly higher in FE-stimulated PBMCs isolated from NAFLD patients than in those isolated from controls.CONCLUSION Our data suggest that changes in PBMC gene expression may provide candidate biomarkers for NAFLD development,which require validation in larger cohorts.展开更多
Objectives:This scoping review aims to methodically identify and analyse the determinants which influence maternal mortality and healthcare utilization in women of childbearing years in Nigeria.The review specifically...Objectives:This scoping review aims to methodically identify and analyse the determinants which influence maternal mortality and healthcare utilization in women of childbearing years in Nigeria.The review specifically addresses the difficulties faced in assessing medical care,and the ongoing initiatives to lower the maternal mortality ratio.Methods:Primary studies(published after year 2000)focused on maternal mortality,health determinants,and the utilization of maternal healthcare services in Nigeria were retrieved following a systematic search across multiple databases,including Scopus,PubMed,Google Scholar,and Web of Science.These were screened using defined inclusion and exclusion criteria.Data from these studies were extracted and thematically analysed to identify common themes and trends.Results:A total of 21 publications were included in this review comprising 2 qualitative,17 quantitative,and2 mixed study designs.Major health determinants identified in these studies include hypertensive disorders of pregnancy,haemorrhage,and sepsis/septicaemia,contributing as much as 29%,24%,and 14.2%of maternal deaths respectively in over 10%of the reviewed studies.Similarly,social-economic determinants including poverty,maternal education,health system issues and culture significantly impacted the utilization of maternal healthcare services,inadvertently impacting maternal mortality.Despite various maternal health interventions such as the"Abiye"Safe Motherhood Initiative,the Integrated Maternal,Newborn,and Child Health Strategy and strengthening emergency obstetric care by governmental and non-governmental agencies,early childbearing,unemployment,large family sizes,and dependence on male spouses continued to result in suboptimal utilization of services and adverse maternal outcomes.Conclusion:This scoping review comprehensively integrated existing data from published studies to provide a detailed picture of maternal mortality,its health determinants,and factors influencing care utilization among women of childbearing age in Nigeria and approaches to reduce maternal mortality in the country and possibly in the West African sub-region.展开更多
In recent years,the gut microbiota has become an integral research topic in human health owing to its impact on digestion,immunity,metabolic processes,and mental health.The possibilities of microbiome treatment have i...In recent years,the gut microbiota has become an integral research topic in human health owing to its impact on digestion,immunity,metabolic processes,and mental health.The possibilities of microbiome treatment have increased interest in dietary approaches,with a special focus on the intake of fermented foods.This has revived some of the most profound and practical constructs derived from food therapy in Chinese medicine(CM),where food therapy,along with fermented options,actively preserves health and prevents disease.In CM,the spleen and stomach system refers to the postnatal foundation of the body,which controls the processes of chewing,nutrient assimilation,and energy production(qi).The balance between intestinal and overall health is the foundation of psychosomatic well-being and is of utmost importance.Fermented foods can boost the spleen,alleviate stagnant food syndrome,dispel excess fluids,enhance protective functions,and strengthen the immune system.This review aimed to integrate the conceptual and clinical paradigms of CM with those of Western medicine,focusing on the role of fermented foods in gut microbiota regulation.This article discusses prominent fermented foods in CM and their classical functions,alongside the currently available peer-reviewed literature(published within the last 7 years)on their impact on gut flora and other clinical outcomes.Mechanistic considerations regarding the production of probiotics and other active metabolites,such as short-chain fatty acids,and the modulation of the intestinal barrier are discussed.This review also examines multidisciplinary approaches to dietary customs worldwide and outlines the clinical applications of these findings in the context of chronic disease management and gastrointestinal health.展开更多
Chemical exposure during prenatal development has significant implications for both maternal and child health.Compared to blood,saliva is a non-invasive and less resource-intensive,alternative.Given the temporal varia...Chemical exposure during prenatal development has significant implications for both maternal and child health.Compared to blood,saliva is a non-invasive and less resource-intensive,alternative.Given the temporal variability of xenobiotic metabolites(XM),repeated sampling is essential.Therefore,saliva offers a valuable tool for the longitudinal assessment of prenatal exposomes.Despite its potential,no studies have explored saliva for XM measurement.This study pioneered using saliva to assess XM detectability and investigate the associations between prenatal XM and endogenous metabolomes in pregnant women.Saliva samples were analysed using mass spectrometry from 80 pregnant women at 24–34 weeks gestation.Metabolomes and exposomes were annotated using the Human Metabolome and U.S.Environmental Protection Agency databases.Metabolome-XM associations were clustered using Glay community clustering.Linear regression models,adjusted for age,estimated associations between catecholamines and XMs.XM levels were validated in a cohort of women(n=14)with and without preeclampsia.Our study identified 582 metabolomes and 125 XM in saliva,demonstrating its potential as a matrix for exposure measurement.After false discovery rate correction,18109 significant metabolome-XM associations were identified.Community clustering revealed 37 connected clusters,with the largest cluster(238 nodes)enriched in tyrosine and catecholamine metabolism.Food-contactchemicals and food-additives were significantly associated with higher catecholamine and their metabolite levels.Subgroup analyses revealed higher concentrations of these chemicals in women with preeclampsia compared to healthy controls.This study demonstrates that saliva contains valuable molecular data for measuring exposomes.Food-related chemicals were associated with higher catecholamine levels,which may be relevant to the prevalence of hypertensive crises in pregnancy.展开更多
Brown carbon(BrC)has attracted widespread attention because of its strong absorption of solar radiation in the ultraviolet-visible wavelength range,which causes adverse impacts on human health.Originally,BrC was a phy...Brown carbon(BrC)has attracted widespread attention because of its strong absorption of solar radiation in the ultraviolet-visible wavelength range,which causes adverse impacts on human health.Originally,BrC was a physically defined class of substances.However,current research has gradually shifted towards the identification of its chemical groups,because its light-absorbing capability,chemical properties and health effects mainly depend on the chemical composition of its chromophores.Therefore,this review mainly focuses on the chemical understanding of BrC based on chromophores,and the secondary formation mechanism of chromophores,photosensitized reactions,and human health effects of BrC were detailly summarized.Firstly,BrC chromophores are divided into five categories:nitrogen-heterocycles,nitrogen-chain,aromatic species,oligomers and sulfur-containing organic compounds.Different chromophore precursor species exhibit variations,and their formation mechanisms are also distinct.Secondly,BrC can trigger the production of secondary organic aerosol(SOA)precursors or cause SOA growth because BrC is an important component of light-absorbing particles formed during incomplete combustion of biomass and fossil fuels,potentially exerting adverse effects on human health.Finally,developing sufficiently separated methods for BrC and refining algorithms and machine learning can lead to a more effective understanding of the chemical composition of chromophores,thus enabling better evaluation of the atmospheric effects and health impacts of BrC.In all,this review provides new insights into the categories of BrC chromophores and new advance in secondary formation mechanisms,photosensitized reactions,and human health effects on the basis of chemical structures.展开更多
Background Relative energy deficiency in sport(REDs)results from exposure to problematic low energy availability.It is a serious condition affecting the health and athletic performance of up to 80%of elite female athl...Background Relative energy deficiency in sport(REDs)results from exposure to problematic low energy availability.It is a serious condition affecting the health and athletic performance of up to 80%of elite female athletes.REDs is established to have negative short-term effects on reproductive function,but the long-term impact of this condition is unknown.Therefore,we examined the impact of secondary amenorrhea with or without a concurrent diagnosis of REDs on perinatal health outcomes.Methods Postpartum individuals(≥18 years of age)completed an online questionnaire that covered demographics,reproductive history(including a diagnosis of REDs or secondary amenorrhea),and maternal/fetal health outcomes.Logistic regression was used to determine the relationship between previously diagnosed REDs or secondary amenorrhea with perinatal health outcomes.Results A total of 1025 previously pregnant participants completed the survey(33.1±3.4 years,mean±SD).Prior to pregnancy,6.1%had been previously diagnosed with REDs and 20.5%had a history with secondary amenorrhea.Individuals diagnosed with REDs had 3.5-times higher odds of having premature labor(odds ratio,(OR)=3.52,95%confidence interval(95%CI):1.26–9.81)and 2.6-times higher odds of preterm delivery(OR=2.62,95%CI:1.05–6.58)compared to those who had not experienced REDs or secondary amenorrhea.However,in individuals who did not have a history of REDs,secondary amenorrhea did not increase the odds of adverse pregnancy or delivery outcomes.Conclusion A history of REDs,but not secondary amenorrhea,may increase the odds of premature labor and preterm delivery.展开更多
Background Obsessive-compulsive disorder(OCD)is classified by the World Health Organization as 1 of the 10 most disabling conditions.However,nationally representative epidemiological data on OCD are not yet available ...Background Obsessive-compulsive disorder(OCD)is classified by the World Health Organization as 1 of the 10 most disabling conditions.However,nationally representative epidemiological data on OCD are not yet available in China.Aims To investigate the prevalence,comorbidity,role impairment and healthcare utilisation of OCD in China.Methods The present study used a multistage clustered area probability sample to obtain representative populationbased data of adults from 157 nationwide disease surveillance points across 31 provinces in China.Trained interviewers conducted face-to-face interviews with respondents to collect information based on the Composite International Diagnostic Interview 3.0.Data weighting was performed to account for differential selection probabilities and response rates,and to post-stratify the sample to ensure its representativeness of the population in China.Results A total of 28140 respondents(12537(44.55%)males and 15603(55.45%)females)completed the diagnostic interview.Two-thirds of the respondents with liftime OCD had comorbid mental disorders,with OCD typically emerging later than the comorbidities.The most common comorbidities were mood disorders(39.67%,odds ratio(OR):9.60,95%confidence interval(CI)7.35 to 12.53)and anxiety disorders(32.75%,OR:13.33,95%CI 10.14 to 17.52).Overall,588(weighted 58.19%)respondents with obsessions or compulsions experienced role impairment,which was most severe in those reporting unspecified symptoms.Only 46(6.74%)respondents with lifetime OCD and 28(6.48%)with 12-month OCD received any healthcare services for their conditions.Conclusions The weighted lifetime and 12-month prevalence of OCD were 2.43%and 1.63%,respectively.Most patients with OCD reported comorbid mental disorders and role impairment,but very few sought healthcare services.National programmes to expand service coverage and increase awareness of OCD are essential to meet healthcare needs in China.展开更多
Background and objectives:The ongoing mpox outbreaks have garnered significant attention due to their public health implications,particularly the potential mental health impacts.Despite the growing concern,there has b...Background and objectives:The ongoing mpox outbreaks have garnered significant attention due to their public health implications,particularly the potential mental health impacts.Despite the growing concern,there has been limited exploration of the intersection between mpox and mental health within the research literature.This study aims to conduct a comprehensive bibliometric analysis to examine global research trends,regional distribution,and thematic focus areas related to mpox's psychological and psychiatric implications.Methods:We conducted a bibliometric analysis using Scopus and the Web of Science database.The analysis was carried out using the R-bibliometrics package and involved identifying literature on mpox and mental health,focusing on global research trends,regional distribution,and thematic areas of study.The analysis included 416 documents obtained from 295 sources from January 1,2014 to August 27,2024.Results:Our analysis revealed a growing but unevenly distributed literature on mpox and mental health.Most studies concentrated on the relationship between mpox and conditions such as depression and anxiety,while other psychiatric outcomes remain underexplored.The geographic distribution of research was also uneven,with regions like Europe and the Americas receiving more focus than others.Conclusions:The study highlights the need for more targeted research on the mental health sequelae of mpox,particularly for vulnerable populations and regions that are currently underrepresented in the literature.Future research should include longitudinal studies to assess the long-term effects of mpox on mental health and the development of robust methodologies to establish causality.Integrating mental health considerations into public health responses to mpox outbreaks is crucial,with significant implications for research,policy,and clinical practice.展开更多
To the editor:Peer workers-people with personal experiences of using mental health services,trained to provide support to others currently using similar services--are increasingly integrated into the workforce of ment...To the editor:Peer workers-people with personal experiences of using mental health services,trained to provide support to others currently using similar services--are increasingly integrated into the workforce of mental health systems internationally.展开更多
Background Health promotion(HP)interventions delivered through sports clubs have demonstrated promising outcomes among men,but less is known about which aspects of the interventions work,for whom,and under what circum...Background Health promotion(HP)interventions delivered through sports clubs have demonstrated promising outcomes among men,but less is known about which aspects of the interventions work,for whom,and under what circumstances.This rapid realist review aimed to understand the contexts,mechanisms,and outcomes of HP interventions for men delivered through sports clubs.Methods A systematic literature search was conducted in February 2023 for studies published after 2013 in MEDLINE,Embase,and SPORTDiscus databases.Included studies:(a)were delivered by or in collaboration with sports clubs,(b)targeted men aged 18+years,and(c)reported 1 or more HP outcomes.A grey literature search was also performed.Studies were included in a realist synthesis based on richness and rigor.Hereafter,context-mechanism-outcome(CMO)configurations were developed.Results We identified and screened 3358 studies,finally including 59 studies describing 22 interventions.Most HP interventions were delivered in high income countries,included Caucasian men aged 35-65 years with overweight/obesity,and used professional sports clubs(mostly football)for recruitment and facilities.Quantitative HP outcomes were reported across 19 interventions.Of these 19 interventions,the majority reported on weight(n=18),physical activity(n=12),mental health(n=10),and diet(n=9).We identified 13 CMOs related to how HP interventions affected men's recruitment,engagement,and health behavior maintenance.Conclusion Our findings show that using sports clubs for HP interventions is effective for engaging men.Recruitment was facilitated by leveraging sports clubs’identity,addressing masculinity-related barriers,improving accessibility,and building trust.Engagement was enhanced through shared identity experiences,safe spaces,inclusive competition,and self-efficacy.However,there's limited evidence on behavior maintenance post-intervention,though involving community stakeholders seemed vital.In general,considerations should be made to avoid perpetuating traditional masculine norms,which may exclude some men and reinforce unhealthy behaviors.These findings can guide intervention development,emphasizing the need to harness men's perspectives in the process.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
Neutralizing antibodies are essential tools in antiviral therapy and epidemic preparedness,capable of directlyinhibiting viral entry and limiting disease progression.However,traditional antibody discovery strategies—...Neutralizing antibodies are essential tools in antiviral therapy and epidemic preparedness,capable of directlyinhibiting viral entry and limiting disease progression.However,traditional antibody discovery strategies—suchas animal immunization or B cell isolation from infected individuals—are often hindered by biosafety concerns,lengthy development timelines,and limited adaptability during outbreaks.In the present study,we aimed toestablish a robust and rapid in vitro platform for the efficient isolation of neutralizing antibodies targetingconserved viral epitopes.We developed an epitope-guided negative screening strategy that integrates phagedisplay technology with rational antigen mutagenesis to exclude antibodies against variable regions whileenriching for those that recognize functionally constrained epitopes.When applied to the receptor-binding domainof severe acute respiratory syndrome coronavirus 2,this method enabled the identification of six neutralizingantibodies(one IgG and five nanobodies)exhibiting broad-spectrum neutralizing activity across multiple viralvariants.Notably,antibodies recognizing distinct epitopes demonstrated significant synergistic neutralizationwhen used in combination(P<0.05).This screening approach facilitates the rapid discovery of potent andmutation-resistant antibodies and holds promise for application to other emerging pathogens.Our findingsunderscore the potential of epitope-guided,in vitro platforms in expediting therapeutic antibody developmentunder conditions of high biosafety requirements.展开更多
Breast cancer(BC)remains the most frequently diagnosed malignancy worldwide,with an estimated 2.3 million new cases and approximately 685,000 deaths reported in 2020.Forecasts suggest a substantial rise in global inci...Breast cancer(BC)remains the most frequently diagnosed malignancy worldwide,with an estimated 2.3 million new cases and approximately 685,000 deaths reported in 2020.Forecasts suggest a substantial rise in global incidence,with new annual cases projected to reach 3.2 million by 2050,representing a 39%increase.Additionally,BC is expected to account for approximately 7.7%of the anticipated$25.2 trillion global economic burden associated with cancer by 2050.These trends underscore an urgent need for affordable,widely accessible and effective therapeutic strategies,particularly in low-and middle-income countries.Statins,commonly prescribed for the treatment of hypercholesterolaemia via inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A(HMG-CoA)reductase,have garnered increasing interest for their potential anticancer properties.This review focuses on the mechanistic underpinnings and therapeutic implications of statin use,particularly simvastatin,in the context of BC.Statins exert their primary effect through inhibition of the mevalonate pathway,which is crucial for cholesterol and isoprenoid biosynthesis.Disruption of this pathway impairs the prenylation of key signalling proteins,including members of the Ras and Rho GTPase families,which are essential for cancer cell proliferation,survival and metastasis.Preclinical evidence has demonstrated that simvastatin can induce tumour cell apoptosis,arrest cell-cycle progression and inhibit oncogenic signalling pathways.These effects have been particularly pronounced in hormone receptor-negative and triple-negative breast cancer(TNBC)subtypes,which are often associated with poor prognosis and limited treatment options.Epidemiological and observational studies further support a potential association between statin use and reduced BC recurrence and mortality.Nevertheless,robust evidence from randomised controlled trials remains limited,and further investigation is required to establish causality and define optimal therapeutic regimens.Given their well-established safety profile,global accessibility and pleiotropic effects,statins,especially simvastatin,represent a promising class of repurposed drugs in the adjuvant treatment of BC.This review synthesises evidence from the past two decades,highlighting the need for continued clinical research to validate and optimise the use of statins as adjunctive agents in BC therapy.展开更多
AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patie...AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patients diagnosed with MS and a control group of 43 healthy hospital staff matched in terms of age and sex at Iran University,department of neurology and ophthalmology from March 2020 to March 2021.The ophthalmic parameters of each patient were recorded,and optical coherence tomography was used to evaluate the retinal thickness in the layers.RESULTS:This study enrolled a total of 85 participants,with a mean age of 40.44±11.52 years,including 61 females(72%).The control group consisted of 43 individuals with a mean age of 39.49±11.07 years,while the MS group comprised 42 participants with a mean age of 41.40±12.01 years.The mean disease duration in the MS group was 8.45±6.04 a.The thickness of the ganglion cell layer in the right eye was significantly lower in the MS group compared to the control group(P=0.034).In addition,except for the left nasal sector(P=0.106),the mean peripapillary neurofibrillation in all examined sectors were significantly lower in the MS group than in the control group(P<0.05).The average vessel density in both the deep and superficial capillary plexuses across all regions of both eyes was lower in the MS group than in the control group,with all comparisons for the superficial capillary plexus showing statistical significance(P<0.05 for all except the left nasal sector).CONCLUSION:The thickness of the retina of patients with MS is significantly reduced.Therefore,optical coherence tomography results can be used as a reliable tool to evaluate disease progression and prognosis in MS patients.展开更多
[Objectives]To investigate the efficacy and potential mechanism of the topical preparation Jineijin-Shanzha Patch(composed of Galli Gigerii Endothelium Corneum and Crataegi Fructus)in improving functional dyspepsia(FD...[Objectives]To investigate the efficacy and potential mechanism of the topical preparation Jineijin-Shanzha Patch(composed of Galli Gigerii Endothelium Corneum and Crataegi Fructus)in improving functional dyspepsia(FD)based on network pharmacology.[Methods]Firstly,we reviewed the existing research progress on each constituent drug of the Jineijin Shanzha Patch for FD improvement.Following this,identified overlapping genes were utilized to construct both a"Drug-Active Component-FD Target"network and a Protein-Protein Interaction(PPI)network specific to the patch.In addition,Gene Ontology(GO)analysis was carried out.[Results]We identified that the 13 herbs in the Jineijin Shanzha Patch are mainly used for food stagnation,qi stagnation,and spleen deficiency.Screening revealed 43 active patch components,1414 FD-related targets,and 284 shared targets between them.The PPI network analysis further identified the top 10 core targets from these shared targets.From the"Drug-Active Component-FD Target"network,we identified the core elements.These included the herbal components Vignae Semen(from Liushenqu),Crataegi Fructus,and Pseudostellariae Radix;the active components quercetin,genistein,and apigenin;and the key targets CASP3,BCL2,and CASP9.GO analysis of the 284 overlapping targets indicated that the Jineijin Shanzha Patch may exert its therapeutic effects via regulation of biological processes such as the response to lipopolysaccharide,response to bacterium-derived molecules,and regulation of the apoptotic signaling pathway.[Conclusions]The main active components of the Jineijin Shanzha Patch(quercetin,genistein,and apigenin)may improve FD by modulating signaling pathways such as the response to lipopolysaccharide,response to bacterium-derived molecules,and regulation of the apoptotic signaling pathway,thereby acting on key targets including CASP3,BCL2,and CASP9.展开更多
Arthropod melanization is a crucial defense mechanism mediated by a complex cascade of CLIP domain serine proteases(CLIPs).In this study,it was confirmed that microRNA-11903a(miR-11903a)targets Aedes-CLIPB9(AeCLIPB9)b...Arthropod melanization is a crucial defense mechanism mediated by a complex cascade of CLIP domain serine proteases(CLIPs).In this study,it was confirmed that microRNA-11903a(miR-11903a)targets Aedes-CLIPB9(AeCLIPB9)by bioinformatics prediction and dual-luciferase reporter assays.Following intrathoracic injection of miR-11903a agomir and antagomir,Real-time quantitative polymerase chain reaction confirmed that AeCLIPB9 is negatively regulated by miR-11903a.Spatiotemporal expression analysis revealed that miR-11903a is most abundant in 4th instar larvae,followed by pupae and adults,and highly expressed in the wings,head,and midgut of female adults.Following pathogen infection,AeCLIPB9 and miR-11903a exhibited opposite expression trends,indicating their potential roles in mosquito innate immunity.To further investigate the relationship between AeCLIPB9 and miR-11903a,double-strand CLIPB9 was synthesized and RNA interference was performed.Seven-d survival assays revealed that both AeCLIPB9 and miR-11903a were crucial immune factors in fighting pathogens.Finally,longevity assays demonstrated that miR-11903a influenced mosquito lifespan.展开更多
Background Frailty is common and significantly impacts prognosis in heart failure(HF). The Vulnerable Elders Survey-13(VES-13), widely used in oncogeriatrics and public health, remains unexplored as a frailty screenin...Background Frailty is common and significantly impacts prognosis in heart failure(HF). The Vulnerable Elders Survey-13(VES-13), widely used in oncogeriatrics and public health, remains unexplored as a frailty screening tool in HF outpatients. In this study, we prospectively evaluated VES-13 against a multimodal screening assessment in detecting frailty and predicting individual risk of adverse prognosis.Methods Frailty was assessed at the initial visit using both a multimodal approach, incorporating Barthel Index, Older American Resources and Services scale, Pfeiffer Test, abbreviated Geriatric Depression Scale, age > 85 years, lacking support systems,and VES-13. Patients scoring ≥ 3 on VES-13 or meeting at least one multimodal criterion were classified as frail. Endpoints included all-cause mortality, a composite of death or HF hospitalization, and recurrent HF hospitalizations.Results A total of 301 patients were evaluated. VES-13 identified 40.2% as frail and the multimodal assessment 33.2%. In Cox regression analyses, frailty identified by VES-13 showed greater prognostic significance than the multimodal assessment for allcause mortality(HR = 3.70 [2.15–6.33], P < 0.001 vs. 2.40 [1.46–4.0], P = 0.001) and the composite endpoint(HR = 3.13 [2.02–4.84], P< 0.001 vs. 1.96 [1.28–2.99], P = 0.002). Recurrent HF hospitalizations were four times more frequent in VES-13 frail patients while two times in those identified as frail by the multimodal assessment. Additionally, stratifying patients by VES-13 tertiles provided robust risk differentiation.Conclusions VES-13, a simple frailty tool, outperformed a comprehensive multimodal assessment and could be easily integrated into routine HF care, highlighting its clinical utility in identifying patients at risk for poor outcomes.展开更多
High-quality silage is the cornerstone to sustainable livestock development and animal food production.As the core fermentation bacteria of silage,Lactobacillus directly regulates silage fermentation by producing lact...High-quality silage is the cornerstone to sustainable livestock development and animal food production.As the core fermentation bacteria of silage,Lactobacillus directly regulates silage fermentation by producing lactic acid,enzymes,and other bioactive molecules.However,traditional screening methods for functional strains are labor-intensive and time-consuming.Recent advances in synthetic biology,particularly the development of CRISPR-Cas genome editing technology,offer a revolutionary approach to designing Lactobacillus strains with customized traits.This review systematically reviewed the importance of silage in sustainable agricultural development and the limitations of current silage preparation and promotion.It also discussed the application of strain engineering approaches in optimizing the phenotypic performance of Lactobacillus for better silage.Building on this,we reviewed the research progress of CRISPR-Cas9 gene editing in Lactobacillus and discussed how to leverage its high efficiency and precision to optimize the strain's traits for improved silage quality and functionality.CRISPR-Cas9 toolkits are expected to achieve directed evolution of strain performance,ultimately yielding next-generation silage microbial inoculants with multiple functions,adaptability to multiple substrates,and eco-friendly characteristics.The use of such innovative biotechnologies would facilitate resource-efficient utilization,promote animal performance and health for sustainable development in livestock production.展开更多
In recent years,the field of neuroimmunology has witnessed a profound paradigm shift.Research has expanded beyond the traditional focus on the central nervous system to unravel the dynamic interplay between peripheral...In recent years,the field of neuroimmunology has witnessed a profound paradigm shift.Research has expanded beyond the traditional focus on the central nervous system to unravel the dynamic interplay between peripheral immunity and neural networks.Cutting-edge methodologies have unmasked a tripartite communication axis enabling peripheral immune signals to mediate the CNS:(1)neural communication via vagal afferents,(2)humoral signaling through circumventricular organ cytokine diffusion,and(3)cellular interactions involving bone marrow-derived macrophages[1].展开更多
文摘Chinese medicine,with its rich historical roots and holistic approach,has been a fundamental aspect of healthcare in East Asia and is now gaining global recognition.Founded on centuries of empirical knowledge and philosophical insight,Chinese medicine draws heavily from classical texts to guide its practices in herbal medicine and acupuncture.Despite its cultural and historical significance,integrating Chinese medicine into global healthcare systems presents challenges,notably the need for evidence-based practices to enhance credibility,ensure patient safety,and foster broader acceptance within the medical community.This paper explores how Chinese medicine can adopt evidence-based practices by incorporating principles of Western medicine into its research methodologies.It reviews the origins and philosophical foundations of Chinese medicine,examining its reliance on classical texts and empirical methods.The paper also highlights the differences between the personalised approach of Chinese medicine,which tailors treatments to individual needs,and the standardised protocols typical of Western medicine.Additionally,it addresses methodological challenges in Chinese medicine research,such as inconsistent diagnostic criteria and insufficient design rigour.To bridge these gaps,innovative research methodologies that respect the unique variability of Chinese medicine are needed.By adopting evidence-based practices and rigorous scientific validation,Chinese medicine can enhance its legitimacy and facilitate its integration into the global healthcare landscape.
基金Supported by the National Science Centre,No.UMO-2018/31/B/NZ5/02735.
文摘BACKGROUND Numerous studies have reported specific expression profiles of peripheral blood mononuclear cells(PBMCs)that are associated with infectious,autoimmune,and inflammatory disorders,including chronic liver diseases.AIM To identify potential differences in the transcriptome profiles of PBMCs between male patients with non-alcoholic fatty liver disease(NAFLD)and healthy male adolescents.METHODS PBMCs were isolated from 16 male adolescents with NAFLD and 14 healthy age-matched male peers.The collected cells were cultured in vitro for 18 hours without and with autologous fecal extracts(FEs).Differentially expressed genes(DEGs)were investigated using RNA sequencing.Levels of interleukin(IL)-6,tumor necrosis factor-α,IL-10,and IL-1βsecreted into the culture medium were determined using enzyme-linked immunosorbent assays.DEGs were functionally analyzed through annotation according to the Gene Ontology and Reactome databases.RESULTS In total,151(118 protein-coding)and 97(65 protein-coding)DEGs were identified when the RNA profiles of PBMCs stimulated without and with FEs,respectively,were compared between NAFLD patients and controls.Functional enrichment analysis of DEGs identified several pathways,which were predominantly involved in metabolism and inflammatory responses in non-stimulated and FE-stimulated PBMCs,respectively.FEs increased secretion of IL-6 and IL-1βby PBMCs isolated from controls and of all four cytokines by PBMCs isolated from NAFLD patients.IL-1βsecretion was significantly higher in FE-stimulated PBMCs isolated from NAFLD patients than in those isolated from controls.CONCLUSION Our data suggest that changes in PBMC gene expression may provide candidate biomarkers for NAFLD development,which require validation in larger cohorts.
文摘Objectives:This scoping review aims to methodically identify and analyse the determinants which influence maternal mortality and healthcare utilization in women of childbearing years in Nigeria.The review specifically addresses the difficulties faced in assessing medical care,and the ongoing initiatives to lower the maternal mortality ratio.Methods:Primary studies(published after year 2000)focused on maternal mortality,health determinants,and the utilization of maternal healthcare services in Nigeria were retrieved following a systematic search across multiple databases,including Scopus,PubMed,Google Scholar,and Web of Science.These were screened using defined inclusion and exclusion criteria.Data from these studies were extracted and thematically analysed to identify common themes and trends.Results:A total of 21 publications were included in this review comprising 2 qualitative,17 quantitative,and2 mixed study designs.Major health determinants identified in these studies include hypertensive disorders of pregnancy,haemorrhage,and sepsis/septicaemia,contributing as much as 29%,24%,and 14.2%of maternal deaths respectively in over 10%of the reviewed studies.Similarly,social-economic determinants including poverty,maternal education,health system issues and culture significantly impacted the utilization of maternal healthcare services,inadvertently impacting maternal mortality.Despite various maternal health interventions such as the"Abiye"Safe Motherhood Initiative,the Integrated Maternal,Newborn,and Child Health Strategy and strengthening emergency obstetric care by governmental and non-governmental agencies,early childbearing,unemployment,large family sizes,and dependence on male spouses continued to result in suboptimal utilization of services and adverse maternal outcomes.Conclusion:This scoping review comprehensively integrated existing data from published studies to provide a detailed picture of maternal mortality,its health determinants,and factors influencing care utilization among women of childbearing age in Nigeria and approaches to reduce maternal mortality in the country and possibly in the West African sub-region.
文摘In recent years,the gut microbiota has become an integral research topic in human health owing to its impact on digestion,immunity,metabolic processes,and mental health.The possibilities of microbiome treatment have increased interest in dietary approaches,with a special focus on the intake of fermented foods.This has revived some of the most profound and practical constructs derived from food therapy in Chinese medicine(CM),where food therapy,along with fermented options,actively preserves health and prevents disease.In CM,the spleen and stomach system refers to the postnatal foundation of the body,which controls the processes of chewing,nutrient assimilation,and energy production(qi).The balance between intestinal and overall health is the foundation of psychosomatic well-being and is of utmost importance.Fermented foods can boost the spleen,alleviate stagnant food syndrome,dispel excess fluids,enhance protective functions,and strengthen the immune system.This review aimed to integrate the conceptual and clinical paradigms of CM with those of Western medicine,focusing on the role of fermented foods in gut microbiota regulation.This article discusses prominent fermented foods in CM and their classical functions,alongside the currently available peer-reviewed literature(published within the last 7 years)on their impact on gut flora and other clinical outcomes.Mechanistic considerations regarding the production of probiotics and other active metabolites,such as short-chain fatty acids,and the modulation of the intestinal barrier are discussed.This review also examines multidisciplinary approaches to dietary customs worldwide and outlines the clinical applications of these findings in the context of chronic disease management and gastrointestinal health.
基金supported by grants from Singhealth Duke-NUS Academic Medicine Research grant(AM/SU035/2020)NMRC Clinician-Scientist Individual Research Grant New Investigator Grant(CNIG20nov-0003).
文摘Chemical exposure during prenatal development has significant implications for both maternal and child health.Compared to blood,saliva is a non-invasive and less resource-intensive,alternative.Given the temporal variability of xenobiotic metabolites(XM),repeated sampling is essential.Therefore,saliva offers a valuable tool for the longitudinal assessment of prenatal exposomes.Despite its potential,no studies have explored saliva for XM measurement.This study pioneered using saliva to assess XM detectability and investigate the associations between prenatal XM and endogenous metabolomes in pregnant women.Saliva samples were analysed using mass spectrometry from 80 pregnant women at 24–34 weeks gestation.Metabolomes and exposomes were annotated using the Human Metabolome and U.S.Environmental Protection Agency databases.Metabolome-XM associations were clustered using Glay community clustering.Linear regression models,adjusted for age,estimated associations between catecholamines and XMs.XM levels were validated in a cohort of women(n=14)with and without preeclampsia.Our study identified 582 metabolomes and 125 XM in saliva,demonstrating its potential as a matrix for exposure measurement.After false discovery rate correction,18109 significant metabolome-XM associations were identified.Community clustering revealed 37 connected clusters,with the largest cluster(238 nodes)enriched in tyrosine and catecholamine metabolism.Food-contactchemicals and food-additives were significantly associated with higher catecholamine and their metabolite levels.Subgroup analyses revealed higher concentrations of these chemicals in women with preeclampsia compared to healthy controls.This study demonstrates that saliva contains valuable molecular data for measuring exposomes.Food-related chemicals were associated with higher catecholamine levels,which may be relevant to the prevalence of hypertensive crises in pregnancy.
基金supported by the National Natural Science Foundation of China(Nos.42020104001,42327806 and 42177354).
文摘Brown carbon(BrC)has attracted widespread attention because of its strong absorption of solar radiation in the ultraviolet-visible wavelength range,which causes adverse impacts on human health.Originally,BrC was a physically defined class of substances.However,current research has gradually shifted towards the identification of its chemical groups,because its light-absorbing capability,chemical properties and health effects mainly depend on the chemical composition of its chromophores.Therefore,this review mainly focuses on the chemical understanding of BrC based on chromophores,and the secondary formation mechanism of chromophores,photosensitized reactions,and human health effects of BrC were detailly summarized.Firstly,BrC chromophores are divided into five categories:nitrogen-heterocycles,nitrogen-chain,aromatic species,oligomers and sulfur-containing organic compounds.Different chromophore precursor species exhibit variations,and their formation mechanisms are also distinct.Secondly,BrC can trigger the production of secondary organic aerosol(SOA)precursors or cause SOA growth because BrC is an important component of light-absorbing particles formed during incomplete combustion of biomass and fossil fuels,potentially exerting adverse effects on human health.Finally,developing sufficiently separated methods for BrC and refining algorithms and machine learning can lead to a more effective understanding of the chemical composition of chromophores,thus enabling better evaluation of the atmospheric effects and health impacts of BrC.In all,this review provides new insights into the categories of BrC chromophores and new advance in secondary formation mechanisms,photosensitized reactions,and human health effects on the basis of chemical structures.
基金funded by a Christenson Professorship in Active Healthy Livingfunded by the Health Sciences TD Bank Undergraduate Research Awardsupport from the FIFA Female Athlete Project
文摘Background Relative energy deficiency in sport(REDs)results from exposure to problematic low energy availability.It is a serious condition affecting the health and athletic performance of up to 80%of elite female athletes.REDs is established to have negative short-term effects on reproductive function,but the long-term impact of this condition is unknown.Therefore,we examined the impact of secondary amenorrhea with or without a concurrent diagnosis of REDs on perinatal health outcomes.Methods Postpartum individuals(≥18 years of age)completed an online questionnaire that covered demographics,reproductive history(including a diagnosis of REDs or secondary amenorrhea),and maternal/fetal health outcomes.Logistic regression was used to determine the relationship between previously diagnosed REDs or secondary amenorrhea with perinatal health outcomes.Results A total of 1025 previously pregnant participants completed the survey(33.1±3.4 years,mean±SD).Prior to pregnancy,6.1%had been previously diagnosed with REDs and 20.5%had a history with secondary amenorrhea.Individuals diagnosed with REDs had 3.5-times higher odds of having premature labor(odds ratio,(OR)=3.52,95%confidence interval(95%CI):1.26–9.81)and 2.6-times higher odds of preterm delivery(OR=2.62,95%CI:1.05–6.58)compared to those who had not experienced REDs or secondary amenorrhea.However,in individuals who did not have a history of REDs,secondary amenorrhea did not increase the odds of adverse pregnancy or delivery outcomes.Conclusion A history of REDs,but not secondary amenorrhea,may increase the odds of premature labor and preterm delivery.
基金funded by the special research project for non-profit public service of the Chinese Ministry of Health(grant number:201202022 to YH)the national twelfth five-year plan for science and technology support of the Chinese Ministry of Science and Technology(grant numbers:2012BAI01B01 to YH)+1 种基金the National Key R&D Program of China(grant numbers:2017YFC0907800 to YH and 2017YFC0907801 to GX)the Major Projects of the Health Commission of Hunan Province(grant number:W20241001 to YZ)。
文摘Background Obsessive-compulsive disorder(OCD)is classified by the World Health Organization as 1 of the 10 most disabling conditions.However,nationally representative epidemiological data on OCD are not yet available in China.Aims To investigate the prevalence,comorbidity,role impairment and healthcare utilisation of OCD in China.Methods The present study used a multistage clustered area probability sample to obtain representative populationbased data of adults from 157 nationwide disease surveillance points across 31 provinces in China.Trained interviewers conducted face-to-face interviews with respondents to collect information based on the Composite International Diagnostic Interview 3.0.Data weighting was performed to account for differential selection probabilities and response rates,and to post-stratify the sample to ensure its representativeness of the population in China.Results A total of 28140 respondents(12537(44.55%)males and 15603(55.45%)females)completed the diagnostic interview.Two-thirds of the respondents with liftime OCD had comorbid mental disorders,with OCD typically emerging later than the comorbidities.The most common comorbidities were mood disorders(39.67%,odds ratio(OR):9.60,95%confidence interval(CI)7.35 to 12.53)and anxiety disorders(32.75%,OR:13.33,95%CI 10.14 to 17.52).Overall,588(weighted 58.19%)respondents with obsessions or compulsions experienced role impairment,which was most severe in those reporting unspecified symptoms.Only 46(6.74%)respondents with lifetime OCD and 28(6.48%)with 12-month OCD received any healthcare services for their conditions.Conclusions The weighted lifetime and 12-month prevalence of OCD were 2.43%and 1.63%,respectively.Most patients with OCD reported comorbid mental disorders and role impairment,but very few sought healthcare services.National programmes to expand service coverage and increase awareness of OCD are essential to meet healthcare needs in China.
文摘Background and objectives:The ongoing mpox outbreaks have garnered significant attention due to their public health implications,particularly the potential mental health impacts.Despite the growing concern,there has been limited exploration of the intersection between mpox and mental health within the research literature.This study aims to conduct a comprehensive bibliometric analysis to examine global research trends,regional distribution,and thematic focus areas related to mpox's psychological and psychiatric implications.Methods:We conducted a bibliometric analysis using Scopus and the Web of Science database.The analysis was carried out using the R-bibliometrics package and involved identifying literature on mpox and mental health,focusing on global research trends,regional distribution,and thematic areas of study.The analysis included 416 documents obtained from 295 sources from January 1,2014 to August 27,2024.Results:Our analysis revealed a growing but unevenly distributed literature on mpox and mental health.Most studies concentrated on the relationship between mpox and conditions such as depression and anxiety,while other psychiatric outcomes remain underexplored.The geographic distribution of research was also uneven,with regions like Europe and the Americas receiving more focus than others.Conclusions:The study highlights the need for more targeted research on the mental health sequelae of mpox,particularly for vulnerable populations and regions that are currently underrepresented in the literature.Future research should include longitudinal studies to assess the long-term effects of mpox on mental health and the development of robust methodologies to establish causality.Integrating mental health considerations into public health responses to mpox outbreaks is crucial,with significant implications for research,policy,and clinical practice.
基金funded by National Institute for Health Research(NIHR)(RP-PG-1212-20019)。
文摘To the editor:Peer workers-people with personal experiences of using mental health services,trained to provide support to others currently using similar services--are increasingly integrated into the workforce of mental health systems internationally.
基金supported by the 5 Steno Diabetes Centers in Denmark,which are partly funded by the Novo Nordisk Foundation.
文摘Background Health promotion(HP)interventions delivered through sports clubs have demonstrated promising outcomes among men,but less is known about which aspects of the interventions work,for whom,and under what circumstances.This rapid realist review aimed to understand the contexts,mechanisms,and outcomes of HP interventions for men delivered through sports clubs.Methods A systematic literature search was conducted in February 2023 for studies published after 2013 in MEDLINE,Embase,and SPORTDiscus databases.Included studies:(a)were delivered by or in collaboration with sports clubs,(b)targeted men aged 18+years,and(c)reported 1 or more HP outcomes.A grey literature search was also performed.Studies were included in a realist synthesis based on richness and rigor.Hereafter,context-mechanism-outcome(CMO)configurations were developed.Results We identified and screened 3358 studies,finally including 59 studies describing 22 interventions.Most HP interventions were delivered in high income countries,included Caucasian men aged 35-65 years with overweight/obesity,and used professional sports clubs(mostly football)for recruitment and facilities.Quantitative HP outcomes were reported across 19 interventions.Of these 19 interventions,the majority reported on weight(n=18),physical activity(n=12),mental health(n=10),and diet(n=9).We identified 13 CMOs related to how HP interventions affected men's recruitment,engagement,and health behavior maintenance.Conclusion Our findings show that using sports clubs for HP interventions is effective for engaging men.Recruitment was facilitated by leveraging sports clubs’identity,addressing masculinity-related barriers,improving accessibility,and building trust.Engagement was enhanced through shared identity experiences,safe spaces,inclusive competition,and self-efficacy.However,there's limited evidence on behavior maintenance post-intervention,though involving community stakeholders seemed vital.In general,considerations should be made to avoid perpetuating traditional masculine norms,which may exclude some men and reinforce unhealthy behaviors.These findings can guide intervention development,emphasizing the need to harness men's perspectives in the process.
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 the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(Grant No.22KJB310001 to W.G.)the Special Project of the Jiangsu Provincial Department of Science and Technology(Grant No.BE2023603 to W.G.)the Nanjing Medical University Science and Technology Development Foundation(Grant No.NMUB20210006 to W.G.).
文摘Neutralizing antibodies are essential tools in antiviral therapy and epidemic preparedness,capable of directlyinhibiting viral entry and limiting disease progression.However,traditional antibody discovery strategies—suchas animal immunization or B cell isolation from infected individuals—are often hindered by biosafety concerns,lengthy development timelines,and limited adaptability during outbreaks.In the present study,we aimed toestablish a robust and rapid in vitro platform for the efficient isolation of neutralizing antibodies targetingconserved viral epitopes.We developed an epitope-guided negative screening strategy that integrates phagedisplay technology with rational antigen mutagenesis to exclude antibodies against variable regions whileenriching for those that recognize functionally constrained epitopes.When applied to the receptor-binding domainof severe acute respiratory syndrome coronavirus 2,this method enabled the identification of six neutralizingantibodies(one IgG and five nanobodies)exhibiting broad-spectrum neutralizing activity across multiple viralvariants.Notably,antibodies recognizing distinct epitopes demonstrated significant synergistic neutralizationwhen used in combination(P<0.05).This screening approach facilitates the rapid discovery of potent andmutation-resistant antibodies and holds promise for application to other emerging pathogens.Our findingsunderscore the potential of epitope-guided,in vitro platforms in expediting therapeutic antibody developmentunder conditions of high biosafety requirements.
基金supported by Rural Health Research Institute,Charles Sturt University.
文摘Breast cancer(BC)remains the most frequently diagnosed malignancy worldwide,with an estimated 2.3 million new cases and approximately 685,000 deaths reported in 2020.Forecasts suggest a substantial rise in global incidence,with new annual cases projected to reach 3.2 million by 2050,representing a 39%increase.Additionally,BC is expected to account for approximately 7.7%of the anticipated$25.2 trillion global economic burden associated with cancer by 2050.These trends underscore an urgent need for affordable,widely accessible and effective therapeutic strategies,particularly in low-and middle-income countries.Statins,commonly prescribed for the treatment of hypercholesterolaemia via inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A(HMG-CoA)reductase,have garnered increasing interest for their potential anticancer properties.This review focuses on the mechanistic underpinnings and therapeutic implications of statin use,particularly simvastatin,in the context of BC.Statins exert their primary effect through inhibition of the mevalonate pathway,which is crucial for cholesterol and isoprenoid biosynthesis.Disruption of this pathway impairs the prenylation of key signalling proteins,including members of the Ras and Rho GTPase families,which are essential for cancer cell proliferation,survival and metastasis.Preclinical evidence has demonstrated that simvastatin can induce tumour cell apoptosis,arrest cell-cycle progression and inhibit oncogenic signalling pathways.These effects have been particularly pronounced in hormone receptor-negative and triple-negative breast cancer(TNBC)subtypes,which are often associated with poor prognosis and limited treatment options.Epidemiological and observational studies further support a potential association between statin use and reduced BC recurrence and mortality.Nevertheless,robust evidence from randomised controlled trials remains limited,and further investigation is required to establish causality and define optimal therapeutic regimens.Given their well-established safety profile,global accessibility and pleiotropic effects,statins,especially simvastatin,represent a promising class of repurposed drugs in the adjuvant treatment of BC.This review synthesises evidence from the past two decades,highlighting the need for continued clinical research to validate and optimise the use of statins as adjunctive agents in BC therapy.
文摘AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patients diagnosed with MS and a control group of 43 healthy hospital staff matched in terms of age and sex at Iran University,department of neurology and ophthalmology from March 2020 to March 2021.The ophthalmic parameters of each patient were recorded,and optical coherence tomography was used to evaluate the retinal thickness in the layers.RESULTS:This study enrolled a total of 85 participants,with a mean age of 40.44±11.52 years,including 61 females(72%).The control group consisted of 43 individuals with a mean age of 39.49±11.07 years,while the MS group comprised 42 participants with a mean age of 41.40±12.01 years.The mean disease duration in the MS group was 8.45±6.04 a.The thickness of the ganglion cell layer in the right eye was significantly lower in the MS group compared to the control group(P=0.034).In addition,except for the left nasal sector(P=0.106),the mean peripapillary neurofibrillation in all examined sectors were significantly lower in the MS group than in the control group(P<0.05).The average vessel density in both the deep and superficial capillary plexuses across all regions of both eyes was lower in the MS group than in the control group,with all comparisons for the superficial capillary plexus showing statistical significance(P<0.05 for all except the left nasal sector).CONCLUSION:The thickness of the retina of patients with MS is significantly reduced.Therefore,optical coherence tomography results can be used as a reliable tool to evaluate disease progression and prognosis in MS patients.
基金Supported by Putuo District Science and Technology R&D Platform Project,Shanghai(2024QX04).
文摘[Objectives]To investigate the efficacy and potential mechanism of the topical preparation Jineijin-Shanzha Patch(composed of Galli Gigerii Endothelium Corneum and Crataegi Fructus)in improving functional dyspepsia(FD)based on network pharmacology.[Methods]Firstly,we reviewed the existing research progress on each constituent drug of the Jineijin Shanzha Patch for FD improvement.Following this,identified overlapping genes were utilized to construct both a"Drug-Active Component-FD Target"network and a Protein-Protein Interaction(PPI)network specific to the patch.In addition,Gene Ontology(GO)analysis was carried out.[Results]We identified that the 13 herbs in the Jineijin Shanzha Patch are mainly used for food stagnation,qi stagnation,and spleen deficiency.Screening revealed 43 active patch components,1414 FD-related targets,and 284 shared targets between them.The PPI network analysis further identified the top 10 core targets from these shared targets.From the"Drug-Active Component-FD Target"network,we identified the core elements.These included the herbal components Vignae Semen(from Liushenqu),Crataegi Fructus,and Pseudostellariae Radix;the active components quercetin,genistein,and apigenin;and the key targets CASP3,BCL2,and CASP9.GO analysis of the 284 overlapping targets indicated that the Jineijin Shanzha Patch may exert its therapeutic effects via regulation of biological processes such as the response to lipopolysaccharide,response to bacterium-derived molecules,and regulation of the apoptotic signaling pathway.[Conclusions]The main active components of the Jineijin Shanzha Patch(quercetin,genistein,and apigenin)may improve FD by modulating signaling pathways such as the response to lipopolysaccharide,response to bacterium-derived molecules,and regulation of the apoptotic signaling pathway,thereby acting on key targets including CASP3,BCL2,and CASP9.
基金supported by the Major Science and Technology Plan of Hainan Province(ZDKJ2021035)the National Natural Science Foundation of China(U22A20363)the Innovative Research Projects for Postgraduates in Hainan Province(Qhyb2022-41).
文摘Arthropod melanization is a crucial defense mechanism mediated by a complex cascade of CLIP domain serine proteases(CLIPs).In this study,it was confirmed that microRNA-11903a(miR-11903a)targets Aedes-CLIPB9(AeCLIPB9)by bioinformatics prediction and dual-luciferase reporter assays.Following intrathoracic injection of miR-11903a agomir and antagomir,Real-time quantitative polymerase chain reaction confirmed that AeCLIPB9 is negatively regulated by miR-11903a.Spatiotemporal expression analysis revealed that miR-11903a is most abundant in 4th instar larvae,followed by pupae and adults,and highly expressed in the wings,head,and midgut of female adults.Following pathogen infection,AeCLIPB9 and miR-11903a exhibited opposite expression trends,indicating their potential roles in mosquito innate immunity.To further investigate the relationship between AeCLIPB9 and miR-11903a,double-strand CLIPB9 was synthesized and RNA interference was performed.Seven-d survival assays revealed that both AeCLIPB9 and miR-11903a were crucial immune factors in fighting pathogens.Finally,longevity assays demonstrated that miR-11903a influenced mosquito lifespan.
文摘Background Frailty is common and significantly impacts prognosis in heart failure(HF). The Vulnerable Elders Survey-13(VES-13), widely used in oncogeriatrics and public health, remains unexplored as a frailty screening tool in HF outpatients. In this study, we prospectively evaluated VES-13 against a multimodal screening assessment in detecting frailty and predicting individual risk of adverse prognosis.Methods Frailty was assessed at the initial visit using both a multimodal approach, incorporating Barthel Index, Older American Resources and Services scale, Pfeiffer Test, abbreviated Geriatric Depression Scale, age > 85 years, lacking support systems,and VES-13. Patients scoring ≥ 3 on VES-13 or meeting at least one multimodal criterion were classified as frail. Endpoints included all-cause mortality, a composite of death or HF hospitalization, and recurrent HF hospitalizations.Results A total of 301 patients were evaluated. VES-13 identified 40.2% as frail and the multimodal assessment 33.2%. In Cox regression analyses, frailty identified by VES-13 showed greater prognostic significance than the multimodal assessment for allcause mortality(HR = 3.70 [2.15–6.33], P < 0.001 vs. 2.40 [1.46–4.0], P = 0.001) and the composite endpoint(HR = 3.13 [2.02–4.84], P< 0.001 vs. 1.96 [1.28–2.99], P = 0.002). Recurrent HF hospitalizations were four times more frequent in VES-13 frail patients while two times in those identified as frail by the multimodal assessment. Additionally, stratifying patients by VES-13 tertiles provided robust risk differentiation.Conclusions VES-13, a simple frailty tool, outperformed a comprehensive multimodal assessment and could be easily integrated into routine HF care, highlighting its clinical utility in identifying patients at risk for poor outcomes.
基金supported by the National Nature Science Foundation of China(No.U20A2002)。
文摘High-quality silage is the cornerstone to sustainable livestock development and animal food production.As the core fermentation bacteria of silage,Lactobacillus directly regulates silage fermentation by producing lactic acid,enzymes,and other bioactive molecules.However,traditional screening methods for functional strains are labor-intensive and time-consuming.Recent advances in synthetic biology,particularly the development of CRISPR-Cas genome editing technology,offer a revolutionary approach to designing Lactobacillus strains with customized traits.This review systematically reviewed the importance of silage in sustainable agricultural development and the limitations of current silage preparation and promotion.It also discussed the application of strain engineering approaches in optimizing the phenotypic performance of Lactobacillus for better silage.Building on this,we reviewed the research progress of CRISPR-Cas9 gene editing in Lactobacillus and discussed how to leverage its high efficiency and precision to optimize the strain's traits for improved silage quality and functionality.CRISPR-Cas9 toolkits are expected to achieve directed evolution of strain performance,ultimately yielding next-generation silage microbial inoculants with multiple functions,adaptability to multiple substrates,and eco-friendly characteristics.The use of such innovative biotechnologies would facilitate resource-efficient utilization,promote animal performance and health for sustainable development in livestock production.
基金supported by the STI2030-Major Projects(2021ZD0200600)the National Natural Science Foundation of China(81971269).
文摘In recent years,the field of neuroimmunology has witnessed a profound paradigm shift.Research has expanded beyond the traditional focus on the central nervous system to unravel the dynamic interplay between peripheral immunity and neural networks.Cutting-edge methodologies have unmasked a tripartite communication axis enabling peripheral immune signals to mediate the CNS:(1)neural communication via vagal afferents,(2)humoral signaling through circumventricular organ cytokine diffusion,and(3)cellular interactions involving bone marrow-derived macrophages[1].
