Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway:a potential therapeutic approach for neurodegenerative diseases

The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain axis.The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine systems.Conversely,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host interactions.This reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological diseases.The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological diseases.This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological diseases.Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders.This can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage forms.These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

Small heat shock protein B8:from cell functions to its involvement in diseases and potential therapeutic applications

Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and migration.HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy.In line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and aggregation.In cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under investigation.Moreover,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar hemorrhage.Of note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other diseases.This is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial homeostasis.This review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its modulation.Drug-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.

Report on Cardiovascular Health and Diseases in China 2023:An Updated Summary

Since 1990,China has made considerable progress in resolving the problem of“treatment difficulty”of cardiovascular diseases(CVD).The prevalent unhealthy lifestyle among Chinese residents has exposed a massive proportion of the population to CVD risk factors,and this situation is further worsened due to the accelerated aging population in China.CVD remains one of the greatest threats to the health of Chinese residents.In terms of the proportions of disease mortality among urban and rural residents in China,CVD has persistently ranked first.In 2021,CVD accounted for 48.98%and 47.35%of deaths in rural and urban areas,respectively.Two out of every five deaths can be attributed to CVD.To implement a national policy“focusing on the primary health institute and emphasizing prevention”and truly achieve a shift of CVD prevention and treatment from hospitals to communities,the National Center for Cardiovascular Diseases has organized experts from relevant fields across China to compile the“Report on Cardiovascular Health and Diseases in China”annually since 2005.The 2024 report is established based on representative,published,and high-quality big-data research results from cross-sectional and cohort population epidemiological surveys,randomized controlled clinical trials,large sample registry studies,and typical community prevention and treatment cases,along with data from some projects undertaken by the National Center for Cardiovascular Diseases.These firsthand data not only enrich the content of the current report but also provide a more timely and comprehensive reflection of the status of CVD prevention and treatment in China.

Age-specific differences in the association between prediabetes and cardiovascular diseases in China:A national cross-sectional study

BACKGROUND Cardiovascular disease(CVD)is a leading cause of morbidity and mortality worldwide,the global burden of which is rising.It is still unclear the extent to which prediabetes contributes to the risk of CVD in various age brackets among adults.To develop a focused screening plan and treatment for Chinese adults with prediabetes,it is crucial to identify variations in the connection between prediabetes and the risk of CVD based on age.AIM To examine the clinical features of prediabetes and identify risk factors for CVD in different age groups in China.METHODS The cross-sectional study involved a total of 46239 participants from June 2007 through May 2008.A thorough evaluation was conducted.Individuals with prediabetes were categorized into two groups based on age.Chinese atherosclerotic CVD risk prediction model was employed to evaluate the risk of developing CVD over 10 years.Random forest was established in both age groups.SHapley Additive exPlanation method prioritized the importance of features from the perspective of assessment contribution.RESULTS In total,6948 people were diagnosed with prediabetes in this study.In prediabetes,prevalences of CVD were 5(0.29%)in the younger group and 148(2.85%)in the older group.Overall,11.11%of the younger group and 29.59% of the older group were intermediate/high-risk of CVD for prediabetes without CVD based on the Prediction for ASCVD Risk in China equation in ten years.In the younger age group,the 10-year risk of CVD was found to be more closely linked to family history of CVD rather than lifestyle,whereas in the older age group,resident status was more closely linked.CONCLUSION The susceptibility to CVD is age-specific in newly diagnosed prediabetes.It is necessary to develop targeted approaches for the prevention and management of CVD in adults across various age brackets.

Effects of loneliness and isolation on cardiovascular diseases:a two sample Mendelian Randomization Study

BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally linked.We conducted a Mendelian Randomization(MR)study to explore causal relationships between loneliness and isolation and multiple CVDs.METHODS Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study(GWAS)of 455,364 individuals of European ancestry in the IEU GWAS database.Summary data for 15 CVDs were also obtained from the IEU GWAS database.We used three MR methods including inverse variance weighting,MR-Egger,and weighted median estimation to assess the causal effect of exposure on outcomes.Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and pleiotropy.RESULTS MR analysis showed that loneliness and isolation were significantly associated with essential hypertension(OR=1.07,95%CI:1.03-1.12),atherosclerotic heart disease(OR=1.04;95%CI:1.02-1.06),myocardial infarction(OR=1.02;95%CI:1-1.04)and angina(OR=1.04;95%CI=1.02-1.06).No heterogeneity and pleiotropy effects were found in this study.CONCLUSIONS Causal relationship of loneliness and isolation with CVDs were found in this study.

The Importance of Setting Treatment Goals for Cardiovascular Diseases

Background: Guidelines are issued by most major organizations that focus on a specific disease entity. Guidelines should be a significant help to the practicing physician who may not be up-to-date with the recent medical literature. Unfortunately, when conflicting guidelines for a specific disease are published, confusion results. Purpose: This article provides a suggested guideline outcome measure that would benefit the physician and patient. Methods: A review of 19 different guidelines for cardiovascular disease treatment is one example of the lack of specific outcomes that currently exist. The basic problem with most guidelines is that they do not state the expected end result (i.e., the benefit to the patient) if that guideline is followed. When guidelines use cardiovascular disease risk factors to dictate therapy, the end benefit is never stated so that the patient can make an appropriate choice of which (if any) guideline to follow. Results: A good example is guidelines published by the American Heart Association for reducing cardiovascular disease. These guidelines are risk factor based and only indicate that cardiovascular disease would be reduced if followed. No specific percentage in the reduction of the incidence of disease is given. In contrast, when elimination of the disease is the stated goal of the guideline, the end result is clear. To date, this goal has been stated by only one organization devoted to eliminating cardiovascular disease. Conclusion: Guidelines need to be written to provide the physician and the patient with a specific end point that is expected when the guideline is followed. Patient acceptance and compliance will be much improved if the patient knows the risk/benefit of following the guideline’s recommendations.

Prevalence of Cardiovascular Risk Factors and Heart Diseases within the Urban and Rural Communities of the Town of Bougouni and Its Surroundings (Southern Mali): A Comparative Study

In Mali, few studies have been conducted on the prevalence of cardiovascular risk factors and diseases according to place of residence. The aim of this study was to assess the prevalence of risk factors and cardiovascular diseases according to residents in town of Bougouni and its rural area (southern Mali). Methods: This was a retrospective descriptive study from February 2019 to March 2024. All patients who visited the “CENTRE MEDICAL DE BOUGOUNI” clinic with known or suspected heart disease during the study period were included. Data were collected from medical records. Incomplete or unusable records were excluded. Data were processed using SPS version 22 software. Results: we included 452 patients with an average age of 50 ± 19 years. High blood pression has been found in 42.70% of cases, with higher prevalence in urban areas (47.01%) than in rural areas (41.50%). Diabetes and smoking were found respectively 5.31% and 8.19% in our population. The prevalence of diabetes was higher in urban areas (5.97%) than rural area (5.35%). smoking prevalence was higher in rural areas (8.49%) than urban areas (6.72%). Alcoholism was found in 2.21% of cases with a little difference between rural area (2.24%) and urban area (2.20%). 31.63% of our patients had no cardiovascular factor. Dyspnea was the reason of consultation in 5.75% of cases and atypical precordialgia in 13.72%. Headaches and dizziness in 8.63% of cases and 21.90% of patients presented other non-specific symptoms. Diagnosis of idiopathic dilated cardiomyopathy was found in 23.45% of cases with higher prevalence in rural areas (28.30%) than urban areas (13.43%). Ischaemic heart disease accounted for 9.29% of cases with a higher prevalence in rural areas (10.38%) than in urban areas (6.71%). PPCMs accounted for 5.98% of cases, with a slight increase in urban areas (6.66%) compared with rural areas (5.68%). Rheumatic valvulopathy accounted for 2.21% of cases;2.84% in rural areas and 0.74% in urban areas. Other valvular diseases accounted for 3.76% of cases;4.73% in rural areas and 1.48% in urban areas. Right heart diseases accounted for 3.98% of cases and stroke for 1.77%. Conclusion: The prevalence of cardiovascular risk factors and heart diseases is high in the rural and urban population of the town of Bougouni and its surroundings (Mali). Excepted smoking, the prevalence of other CV risk factors is higher in urban areas, whereas the prevalence of idiopathic dilated cardiomyopathy and ischemic heart disease is higher in rural areas. These data could serve as a basis for developing tailored preventive strategies, depending on the place of residence.

Protective effects of oleic acid and polyphenols in extra virgin olive oil on cardiovascular diseases

The Mediterranean diet has long been recognized as one of the most effective ways to prevent and improve cardiovascular disease.Extra virgin olive oil(EVOO)is the typical sources of fat in the Mediterranean diet which have been shown to have noteworthy nutritional value and positive impact on human health.It is worth noting that EVOO owes its superior nutritional value to its bioactive composition.The main component of EVOO is monounsaturated fatty acids(MUFAs)in the form of oleic acid.Oleic acid accounts for up to 70%-80%of EVOO.Secondly,EVOO contains approximately more than 30 phenolic compounds,of which HT is essential for the protection against cardiovascular diseases.In this review,we focused on the potential mechanisms of oleic acid and polyphenols combat cardiovascular diseases risk in terms of oxidative stress,inflammation,blood pressure,endothelial function and cholesterol.This review might provide a reference for the studies on cardiovascular protective effects of EVOO.

Wnt/β-catenin Signaling Cascades in Cardiovascular Diseases

Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is increasing yearly.Hypertension is a major risk factor for cardiovascular disease.Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes.Wnt signaling pathways include the canonical Wnt pathway(or Wnt/β-catenin pathway),the non canonical planar cell-polarity pathway,and the non-canonical calcium-dependent pathways.Abnormal Wnt signaling promotes cell proliferation and differentiation,cardiac malformations,various malignancies,so drugs targeting Wnt signaling play a great therapeutic potential.Wnt/β-catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation,migration,apoptosis,blood-brain barrier permeability,inflammation,oxidative stress,and immune response.Based on the latest research progress,this review summarizes the role of Wnt/β-catenin signaling in cardiovascular diseases,in order to provide new ideas for the prevention and treatment of cardiovascular diseases.

Cardiovascular diseases in European ethnic minorities: Beyond the traditional cardiovascular risk factors

This editorial is intended to be a reflection on cardiovascular disease(CVD)burden in European ethnic minorities.In some European countries,ethnic minority realities,due to their recent appearance,are still to be studied in depth.The experience of several European countries,where the migration processes started earlier,even more than a century ago,can help by being an example.Many studies have shown that major differences in CVD burden exist not only between countries,but also within the same country when considering different social strata and ethnic groups.The CV risk factors underlying heart disease have been well established.Important epidemiological studies have helped us understand that the underlying causes of heart disease as well as the behaviors that can help prevent them are the same.We are now well aware that CVD should be treated by considering a holistic approach.This is why the social determinants(SDs)of health that may worsen the disease burden or that,vice versa,may improve the treatment,and even more significantly,the prognosis of a patient’s illness should be taken into consideration.For ethnic minority patients,this holistic,hermeneutic approach is of importance.Several SDs of health that influence CVDs have been identified but their relevance for the health of ethnic minorities has not yet been clearly defined.In some European countries,most ethnic minorities are largely also religious minorities.Only a few studies have evaluated the role of religion,which is an important SD that affects the probability of having CV risk factors and diseases.Adolescents,particularly those belonging to the second generation,seem to be the weak link.If we believe that these young people are really citizens of their country of birth,then a way of recognizing their belonging to the community starts from a will to better understand their condition,in order to assist them while they grow physically and mentally.Thinking about safeguarding the health of this population should be more than a health task,rather a goal of social justice.

Interleukin-mediated therapies in liver diseases and comorbidity effects

Cytokines like interleukins(ILs)play important roles in inflammation and innate immune.Yang and Zhang carried out an interesting study related to ILs and hepatic diseases.They described the role of ILs in the pathogenesis and resolution of hepatic disorders.The authors summarized alcohol-related liver disease and virus-induced hepatitis,as far as clinical studies a fortiori carried out on ILmediated treatments pertaining to these dysfunctions.This editorial contributes to the review by Yang and Zhang titled,"Interleukins in liver disease treatment",and focuses on therapies mediated by ILs in comorbid liver diseases.The documentary search was conducted on recent pertinent literature,primarily using the Google Scholar and PubMed databases.

Overview of emerging therapies for demyelinating diseases

This paper provides an overview of autoimmune disorders of the central nervous system,specifically those caused by demyelination.We explore new research regarding potential therapeutic interventions,particularly those aimed at inducing remyelination.Remyelination is a detailed process,involving many cell types–oligodendrocyte precursor cells(OPCs),astrocytes,and microglia–and both the innate and adaptive immune systems.Our discussion of this process includes the differentiation potential of neural stem cells,the function of adult OPCs,and the impact of molecular mediators on myelin repair.Emerging therapies are also explored,with mechanisms of action including the induction of OPC differentiation,the transplantation of mesenchymal stem cells,and the use of molecular mediators.Further,we discuss current medical advancements in relation to many myelin-related disorders,including multiple sclerosis,optic neuritis,neuromyelitis optica spectrum disorder,myelin oligodendrocyte glycoprotein antibodyassociated disease,transverse myelitis,and acute disseminated encephalomyelitis.Beyond these emerging systemic therapies,we also introduce the dimethyl fumarate/silk fibroin nerve conduit and its potential role in the treatment of peripheral nerve injuries.Despite these aforementioned scientific advancements,this paper maintains the need for ongoing research to deepen our understanding of demyelinating diseases and advance therapeutic strategies that enhance affected patients’quality of life.

A Medicinal and Edible Plant Crocus sativus L.and Its Therapeutic Effects on Cardiovascular and Cerebrovascular Diseases

This paper introduces the biological characteristics,medicinal value,chemical component,and pharmacological effects of Crocus sativus L.,and explores its therapeutic effects on cardiovascular and cerebrovascular diseases such as angina pectoris and coronary heart disease.

Clonal hematopoiesis:a shared risk factor for cardiovascular diseases and tumors

Clonal hematopoiesis(CH)is a clonally expanded population of hematopoietic stem cells carrying somatic mutations that differentiate through multilineage hematopoiesis to form terminally differentiated mature hematopoietic cells carrying markers of the clonal mutation.Genes integral to critical cellular processes such as epigenetic regulation,DNA damage response,and inflammation frequently carry these mutations.Clonal hematopoiesis becomes increasingly prevalent with age and is associated with an increased risk of hematological tumors and some nonhematological conditions.Recent insights have revealed that the mutations driving CH are not only implicated in hematologic neoplasms but also possess the potential to influence cardiovascular pathogenesis.Here,we reviewed up-to-date findings about the roles of CH in cardiovascular diseases and tumors and explored the clinical significance of CH,as well as look forward to future related studies,so as to provide valuable references for future research and clinical practice.

Excess cardiovascular mortality in men with non-alcoholic fatty liver disease:A cause for concern!

Non-alcoholic fatty liver disease(NAFLD)has emerged as the commonest cause of chronic liver disease worldwide in recent years.With time,our understanding of NAFLD has evolved from an isolated liver condition to a systemic disease with significant manifestations beyond the liver.Amongst them,cardiovascular diseases(CVDs)are the most important and clinically relevant.Recent research supports a strong independent link between NALFD and CVD beyond the shared risk factors and pathophysiology.Female sex hormones are well known to not only protect against CVD in pre-menopausal females,but also contribute to improved adipose tissue function and preventing its systemic deposition.Recent research highlights the increased risk of major adverse cardiovascular-cerebral events(MACCE)amongst male with NAFLD compared to females.Further,racial variation was observed in MACCE outcomes in NAFLD,with excess mortality in the Native Americans and Asian Pacific Islanders compared to the other races.

Sex and racial disparities in non-alcoholic fatty liver disease-related cardiovascular events: National inpatient sample analysis (2019)

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)increases cardiovascular disease(CVD)risk irrespective of other risk factors.However,large-scale cardiovascular sex and race differences are poorly understood.AIM To investigate the relationship between NAFLD and major cardiovascular and cerebrovascular events(MACCE)in subgroups using a nationally representative United States inpatient sample.METHODS We examined National Inpatient Sample(2019)to identify adult hospitalizations with NAFLD by age,sex,and race using ICD-10-CM codes.Clinical and demographic characteristics,comorbidities,and MACCE-related mortality,acute myocardial infarction(AMI),cardiac arrest,and stroke were compared in NAFLD cohorts by sex and race.Multivariable regression analyses were adjusted for sociodemographic characteristics,hospitalization features,and comorbidities.RESULTS We examined 409130 hospitalizations[median 55(IQR 43-66)years]with NFALD.NAFLD was more common in females(1.2%),Hispanics(2%),and Native Americans(1.9%)than whites.Females often reported non-elective admissions,Medicare enrolment,the median age of 55(IQR 42-67),and poor income.Females had higher obesity and uncomplicated diabetes but lower hypertension,hyperlipidemia,and complicated diabetes than males.Hispanics had a median age of 48(IQR 37-60),were Medicaid enrollees,and had non-elective admissions.Hispanics had greater diabetes and obesity rates than whites but lower hypertension and hyperlipidemia.MACCE,all-cause mortality,AMI,cardiac arrest,and stroke were all greater in elderly individuals(P<0.001).MACCE,AMI,and cardiac arrest were more common in men(P<0.001).Native Americans(aOR 1.64)and Asian Pacific Islanders(aOR 1.18)had higher all-cause death risks than whites.CONCLUSION Increasing age and male sex link NAFLD with adverse MACCE outcomes;Native Americans and Asian Pacific Islanders face higher mortality,highlighting a need for tailored interventions and care.

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

Cell reprogramming therapy for Parkinson’s disease

Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.

Pathological and therapeutic effects of extracellular vesicles in neurological and neurodegenerative diseases

Extracellular vesicles are released by all cell types and contain proteins,microRNAs,mRNAs,and other bioactive molecules.Extracellular vesicles play an important role in intercellular communication and in the modulation of the immune system and neuroinflammation.The cargo of extra cellular vesicles(e.g.,proteins and microRNAs)is altered in pathological situations.Extracellular vesicles contribute to the pathogenesis of many pathologies associated with sustained inflammation and neuroinflammation,including cance r,diabetes,hype rammonemia and hepatic encephalopathy,and other neurological and neurodegenerative diseases.Extracellular vesicles may cross the blood-brain barrier and transfer pathological signals from the periphery to the brain.This contributes to inducing neuroinflammation and cognitive and motor impairment in hyperammonemia and hepatic encephalopathy and in neurodegenerative diseases.The mechanisms involved are beginning to be unde rstood.For example,increased tumor necrosis factor a in extracellular vesicles from plasma of hype rammonemic rats induces neuroinflammation and motor impairment when injected into normal rats.Identifying the mechanisms by which extracellular vesicles contribute to the pathogenesis of these diseases will help to develop new treatments and diagnostic tools for their easy and early detection.In contrast,extra cellular vesicles from mesenchymal stem cells have therapeutic utility in many of the above pathologies,by reducing inflammation and neuroinflammation and improving cognitive and motor function.These extra cellular vesicles recapitulate the beneficial effects of mesenchymal stem cells and have advantages as therapeutic tools:they are less immunoge nic,may not diffe rentiate to malignant cells,cross the blood-brain barrier,and may reach more easily target organs.Extracellular vesicles from mesenchymal stem cells have beneficial effects in models of ischemic brain injury,Alzheimer's and Parkinson's diseases,hyperammonemia,and hepatic encephalopathy.Extracellular vesicles from mesenchymal stem cells modulate the immune system,promoting the shift from a pro-inflammato ry to an anti-inflammatory state.For example,extracellular vesicles from mesenchymal stem cells modulate the Th17/Treg balance,promoting the anti-inflammatory Treg.Extracellular vesicles from mesenchymal stem cells may also act directly in the brain to modulate microglia activation,promoting a shift from a pro-inflammatory to an anti-inflammatory state.This reduces neuroinflammation and improves cognitive and motor function.Two main components of extracellular vesicles from mesenchymal stem cells which contribute to these beneficial effects are transforming growth factor-βand miR-124.Identifying the mechanisms by which extracellular vesicles from mesenchymal stem cells induce the beneficial effects and the main molecules(e.g.,proteins and mRNAs)involved may help to improve their therapeutic utility.The aims of this review are to summarize the knowledge of the pathological effects of extracellular vesicles in different pathologies,the therapeutic potential of extra cellular vesicles from mesenchymal stem cells to recover cognitive and motor function and the molecular mechanisms for these beneficial effects on neurological function.

The association of diet quality and physical activity with cardiovascular disease and mortality in 85,545 older Australians:A longitudinal study

Background:A quality diet and an active lifestyle are both important cornerstones of cardiovascular disease(CVD)prevention.However,despite their interlinked effects on metabolic health,the 2 behaviors are rarely considered jointly,particularly within the context of CVD prevention.We examined the independent,interactive,and joint associations of diet and physical activity with CVD hospitalization,CVD mortality,and all-cause mortality.Methods:CVD-free Australian participants aged 4574 years(n=85,545)reported physical activity,diet,sociodemographic,and lifestyle characteristics at baseline(20062009)and follow-up(20122015),and data were linked to hospitalization and death registries(03/31/2019 for CVD hospitalization and all-cause mortality and 12/08/2017 for CVD mortality).Diet quality was categorized as low,medium,and high based on meeting dietary recommendations.Physical activity was operationalized as(a)total moderate-to-vigorous physical activity(MVPA)as per guidelines,and(b)the composition of MVPA as the ratio of vigorous-intensity physical activity(VPA)to total MVPA.We used a left-truncated cause-specific Cox proportional hazards model using time-varying covariates.Results:During a median of 10.7 years of follow-up,6576 participants were admitted to the hospital for CVD and 6581 died from all causes(876 from CVD during 9.3 years).A high-quality diet was associated with a 17%lower risk of all-cause mortality than a low-quality diet,and the highest MVPA category(compared with the lowest)was associated with a 44%and 48%lower risk of CVD and all-cause mortality,respectively.Multiplicative interactions between diet and physical activity were non-significant.For all outcomes,the lowest risk combinations involved a high-quality diet and the highest MVPA categories.Accounting for total MVPA,some VPA was associated with further risk reduction of CVD hospitalization and all-cause mortality.Conclusion:For CVD prevention and longevity,one should adhere to both a healthy diet and an active lifestyle and incorporate some VPA when possible.