Approaches for the isolation and long-term expansion of pericytes from human and animal tissues.

Pericytes surround capillaries in every organ of the human body. They are also present around the vasa vasorum, the small blood vessels that supply the walls of larger arteries and veins. The clinical interest in pericytes is rapidly growing, with the recognition of their crucial roles in controlling vascular function and possible therapeutic applications in regenerative medicine. Nonetheless, discrepancies in methods used to define, isolate, and expand pericytes are common and may affect reproducibility. Separating pure pericyte preparations from the continuum of perivascular mesenchymal cells is challenging. Moreover, variations in functional behavior and antigenic phenotype in response to environmental stimuli make it difficult to formulate an unequivocal definition of bona fide pericytes. Very few attempts were made to develop pericytes as a clinical-grade product. Therefore, this review is devoted to appraising current methodologies’ pros and cons and proposing standardization and harmonization improvements. We highlight the importance of developing upgraded protocols to create therapeutic pericyte products according to the regulatory guidelines for clinical manufacturing. Finally, we describe how integrating RNA-seq techniques with single-cell spatial analysis, and functional assays may help realize the full potential of pericytes in health, disease, and tissue repair

MEK inhibitors:a promising targeted therapy for cardiovascular disease

Cardiovascular disease (CVD) represents the leading cause of mortality and disability all over the world. Identifying new targeted therapeutic approaches has become a priority of biomedical research to improve patient outcomes and quality of life. The RAS-RAF-MEK (mitogen-activated protein kinase kinase)-ERK (extracellular signal-regulated kinase) pathway is gaining growing interest as a potential signaling cascade implicated in the pathogenesis of CVD. This pathway is pivotal in regulating cellular processes like proliferation, growth, migration, differentiation, and survival, which are vital in maintaining cardiovascular homeostasis. In addition, ERK signaling is involved in controlling angiogenesis, vascular tone, myocardial contractility, and oxidative stress. Dysregulation of this signaling cascade has been linked to cell dysfunction and vascular and cardiac pathological remodeling, which contribute to the onset and progression of CVD. Recent and ongoing research has provided insights into potential therapeutic interventions targeting the RAS-RAF-MEK-ERK pathway to improve cardiovascular pathologies. Preclinical studies have demonstrated the efficacy of targeted therapy with MEK inhibitors (MEKI) in attenuating ERK activation and mitigating CVD progression in animal models. In this article, we first describe how ERK signaling contributes to preserving cardiovascular health. We then summarize current knowledge of the roles played by ERK in the development and progression of cardiac and vascular disorders, including atherosclerosis, myocardial infarction, cardiac hypertrophy, heart failure, and aortic aneurysm. We finally report novel therapeutic strategies for these CVDs encompassing MEKI and discuss advantages, challenges, and future developments for MEKI therapeutics

KAP-COVIDGLOBAL: a multinational survey of the levels and determinants of public knowledge, attitudes and practices towards COVID-19

Objective The adherence to public health recommendations to control COVID-19 spread is influenced by public knowledge, attitudes and practices (KAP). We performed this cross-sectional study to assess the levels and determinants of public KAP towards COVID-19 in a large, multinational sample.Design Cross-sectional study (survey).Setting The questionnaire was distributed to potential respondents via online platforms.Participants 71 890 individuals from 22 countries.Methods We formulated a four-section questionnaire in English, followed by validation and translation into seven languages. The questionnaire was distributed (May to June 2020) and each participant received a score for each KAP section.Results Overall, the participants had fair knowledge (mean score: 19.24±3.59) and attitudes (3.72±2.31) and good practices (12.12±1.83) regarding COVID-19. About 92% reported moderate to high compliance with national lockdown. However, significant gaps were observed: only 68.2% knew that infected individuals may be asymptomatic; 45.4% believed that antibiotics are an effective treatment; and 55.4% stated that a vaccine has been developed (at the time of data collection). 71.9% believed or were uncertain that COVID-19 is a global conspiracy; 36.8% and 51% were afraid of contacting doctors and Chinese people, respectively. Further, 66.4% reported the pandemic had moderate to high negative effects on their mental health. Female gender, higher education and urban residents had significantly (p≤0.001) higher knowledge and practice scores. Further, we observed significant correlations between all KAP scores.Conclusions Although the public have fair/good knowledge and practices regarding COVID-19, significant gaps should be addressed. Future awareness efforts should target less advantaged groups and future studies should develop new strategies to tackle COVID-19 negative mental health effects

Relationships between social spending and childhood obesity in OECD countries: an ecological study

Objectives The burden of childhood obesity is clustered among children in low-socioeconomic groups. Social spending on children—public welfare expenditure on families and education—may curb childhood obesity by reducing socioeconomic disadvantages. The objective of this study was to examine the relationship between social spending on children and childhood obesity across the Organisation for Economic Cooperation and Development (OECD) countries.Design Ecological study.Setting Data on social spending on children were obtained from the OECD Social Expenditure Database and the OECD educational finance indicators dataset during 2000–2015. Data on childhood obesity were obtained from the NCD Risk Factor Collaboration database.Participants Aggregated statistics on obesity among children aged 5–19 years, estimated for OECD 35 countries based on the measured height and weight on 31.5 million children.Outcome measures Country-level prevalence of obesity among children aged 5–19 years.Results In cross-sectional analyses in 2015, social spending on children was inversely associated with the prevalence of childhood obesity after adjusting for potential confounders (the gross domestic product per capita, unemployment rate, poverty rate, percentage of children aged <20 years and prevalence of childhood obesity in 2000). In addition, when we focused on changes from 2000 to 2015, an average annual increase of US$100 in social spending per child was associated with a decrease in childhood obesity by 0.6 percentage points for girls (p=0.007) and 0.7 percentage points for boys (p=0.04) between 2000 and 2015, after adjusting for the potential confounders. The dimensions of social spending that contributed to these associations between the changes in social spending on children and childhood obesity were early childhood education and care (ECEC) and school education for girls and ECEC for boys.Conclusion Countries that increase social spending on children tend to experience smaller increases in childhood obesity