Extracellular vesicles (EVs) function as potent mediators of intercellular communication for many in vivo processes, contributing to both health and disease related conditions. Given their biological origins and diverse functionality from correspondingly unique “cargo” compositions, both endogenous and modified EVs are garnering attention as promising therapeutic modalities and vehicles for targeted therapeutic delivery applications. Their diversity in composition, however, has revealed a significant need for more comprehensive analytical-based characterization methods, and manufacturing processes that are consistent and scalable. In this review, we explore the dynamic landscape of EV research and development efforts, ranging from novel isolation approaches, to their analytical assessment through novel characterization techniques, and to their production by industrial-scale manufacturing process considerations. Expanding the horizon of these topics to EVs for in-human applications, we underscore the need for stringent development and adherence to Good Manufacturing Practice (GMP) guidelines. Wherein, the intricate interplay of raw materials, production in bioreactors, and isolation practices, along with analytical assessments compliant with the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines, in conjunction with reference standard materials, collectively pave the way for standardized and consistent GMP production processes.

INTRODUCTIONDeveloping effective exercise programmes for the paediatric population is a strategy for decreasing obesity and is expected to help in eventually limiting obesity-associated long-term health and societal impact. In this study, the effects of a 12-week twice weekly additional exercise training, which comprised a combination of circuit-based resistance training and aerobic exercises, in additional to typical physical education sessions, on aerobic fitness, body composition and serum C-reactive protein (CRP) and lipids were analysed in 13- to 14-year-old obese boys contrasted with a control group.

MATERIALS AND METHODSBoth the exercise group (EG, n = 12) and control group (CG, n = 12) participated in the typical 2 sessions of 40-minute physical education (PE) per week in schools, but only EG participated in additional 2 sessions per week of 45 to 60 minutes per session of exercise training, which comprised a combination of circuit-based resistance training and aerobic exercises maintained at 65% to 85% maximum heart rate (HRmax = 220 - age). Body composition was measured using dual energy X-ray absorptiometry (DEXA). Fasting serum CRP and blood lipids were analysed pre- and postexercise programme. Aerobic fitness was measured by an objective laboratory submaximal exercise test, PWC170 (Predicted Work Capacity at HR 170 bpm).

RESULTSExercise training significantly improved lean muscle mass, body mass index, fitness, resting HR, systolic blood pressure and triglycerides in EG. Serum CRP concentrations were elevated at baseline in both groups, but training did not result in a change in CRP levels. In the CG, body weight increased significantly at the end of the 12-week period.

CONCLUSIONThis study supports the value of an additional exercise training programme, beyond the typical twice weekly physical education classes, to produce physiological benefits in the management of obesity in adolescents, including prevention of weight gain.

Adolescent ; C-Reactive Protein ; analysis ; metabolism ; Exercise Therapy ; Humans ; Lipids ; analysis ; blood ; Male ; Obesity ; physiopathology ; therapy ; Physical Fitness ; physiology

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
Adenocarcinoma of Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Carcinoma, Squamous Cell/genetics* ; Genetic Heterogeneity ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Lung Neoplasms/genetics* ; Polymorphism, Single Nucleotide