Involvement of extracellular vesicle microRNA clusters in developing healthy and Rett syndrome brain organoids.

Rett syndrome (RTT) is a neurodevelopmental disorder caused by de novo mutations in the MECP2 gene. Although miRNAs in extracellular vesicles (EVs) have been suggested to play an essential role in several neurological conditions, no prior study has utilized brain organoids to profile EV-derived miRNAs during normal and RTT-affected neuronal development. Here we report the spatiotemporal expression pattern of EV-derived miRNAs in region-specific forebrain organoids generated from female hiPSCs with a MeCP2:R255X mutation and the corresponding isogenic control.

Hesperetin but not ellagic acid increases myosin heavy chain expression and cell fusion in C2C12 myoblasts in the presence of oxidative stress.

Introduction: Skeletal muscle regeneration is impaired in elderly. An oxidative stress-induced decrease in differentiation capacity of muscle satellite cells is a key factor in this process. The aim of this study is to investigate whether orange polyphenol hesperetin and pomegranate polyphenol ellagic acid enhance myoblast differentiation in the presence and absence of oxidative stress, and to explore underlying mechanisms.

Cancer EV stimulate endothelial glycolysis to fuel protein synthesis via mTOR and AMPKα activation.

Hypoxia is a common feature of solid tumours and activates adaptation mechanisms in cancer cells that induce therapy resistance and has profound effects on cellular metabolism. As such, hypoxia is an important contributor to cancer progression and is associated with a poor prognosis. Metabolic alterations in cells within the tumour microenvironment support tumour growth via, amongst others, the suppression of immune reactions and the induction of angiogenesis.

Fracture haematoma proteomics.

Aims: The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies.

Methods: A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry.

GABARAPL1 is essential in extracellular vesicle cargo loading and metastasis development.

Background And Purpose: Hypoxia is a common feature of tumours, associated with poor prognosis due to increased resistance to radio- and chemotherapy and enhanced metastasis development. Previously we demonstrated that GABARAPL1 is required for the secretion of extracellular vesicles (EV) with pro-angiogenic properties during hypoxia. Here, we explored the role of GABARAPL1 EV in the metastatic cascade.

2'-fucosyllactose alone or combined with resistant starch increases circulating short-chain fatty acids in lean men and men with prediabetes and obesity.

Background: Infusion of short-chain fatty acids (SCFA) to the distal colon beneficially affects human substrate and energy metabolism. Here, we hypothesized that the combination of 2'-fucosyllactose (2'-FL) with resistant starch (RS) increases distal colonic SCFA production and improves metabolic parameters.

Methods: In this randomized, crossover study, 10 lean (BMI 20-24.

Protein arginine deiminase 4 inactivates tissue factor pathway inhibitor-alpha by enzymatic modification of functional arginine residues.

Background: Tissue factor pathway inhibitor (TFPI) is an important regulator of coagulation and a link between inflammation and thrombosis. During thrombotic events, TFPI is proteolytically inactivated by neutrophil elastase while bound to neutrophil extracellular traps (NETs). Protein arginine deiminase 4 (PAD4) catalyzes the conversion of arginine to citrulline and is crucial for NET formation.

Butyrate and hexanoate-enriched triglycerides increase postprandrial systemic butyrate and hexanoate in men with overweight/obesity: A double-blind placebo-controlled randomized crossover trial.

Background: Short chain fatty acids (SCFA) are increasingly recognized for their potential ability to alleviate obesity-associated chronic low-grade inflammation and disturbed energy homeostasis. Evidence suggests that an increase in circulating SCFA might be necessary to induce beneficial alterations in energy metabolism.

Objective: To compare the bioaccessibility of two different SCFA-enriched triglycerides: Akovita SCT (butyrate and hexanoate esterified with long chain fatty acids) and tributyrin/caproin (solely butyrate and hexanoate) and investigate whether the SCFA from orally administrated Akovita SCT reach the circulation and affect postprandial metabolism in men with overweight/obesity.

Plasma Levels of Triglycerides and IL-6 Are Associated With Weight Regain and Fat Mass Expansion.

Context: Long-term weight loss (WL) maintenance is the biggest challenge for overweight and obesity because of the almost unavoidable phenomenon of partial or even total weight regain (WR) after WL.

Objective: In the present study we investigated the relations of (the changes of) adipocyte size and other risk biomarkers with WR during the follow-up of the Yoyo dietary intervention.

Methods: In this randomized controlled study, 48 overweight/obese participants underwent a very-low-calorie diet to lose weight, followed by a weight-stable period of 4 weeks and a follow-up period of 9 months.

The Effects of Mild Intermittent Hypoxia Exposure on the Abdominal Subcutaneous Adipose Tissue Proteome in Overweight and Obese Men: A First-in-Human Randomized, Single-Blind, and Cross-Over Study.

Adipose tissue (AT) oxygen tension (pO) has been implicated in AT dysfunction and metabolic perturbations in both rodents and humans. Compelling evidence suggests that hypoxia exposure alters metabolism, at least partly through effects on AT. However, it remains to be elucidated whether mild intermittent hypoxia (MIH) exposure impacts the AT proteome.

Heterogeneity of Lipid and Protein Cartilage Profiles Associated with Human Osteoarthritis with or without Type 2 Diabetes Mellitus.

Osteoarthritis (OA) is a multifactorial pathology and comprises a wide range of distinct phenotypes. In this context, the characterization of the different molecular profiles associated with each phenotype can improve the classification of OA. In particular, OA can coexist with type 2 diabetes mellitus (T2DM).

An in vitro model for hypertrophic adipocytes: Time-dependent adipocyte proteome and secretome changes under high glucose and high insulin conditions.

Obesity is the consequence of a positive energy balance and characterized by enlargement of the adipose tissue, which in part is due to hyperplasia and hypertrophy of the adipocytes. Not much is known about the transition of normal mature adipocytes to the hypertrophic state, which in vivo is very hard to study. Here, we have maintained mature human SGBS cells as a surrogate for adipocytes, changes of morphological and molecular metabolism of the adipocytes were monitored over the first 4 days and the last 4 days.

Association of and gene variation with energy restriction induced adaptations in resting energy expenditure and physical activity.

Background: Energy restriction induces adaptations in resting energy expenditure (REE) and physical activity; inter-individual variability could be ascribed to genetic predisposition.The aim was to examine if changes in REE and physical activity as a result of weight loss were affected by candidate single nucleotide polymorphisms (SNPs).

Methods: 148 subjects (39 men, 109 women), mean ± SD age: 41 ± 9 year; body mass index (BMI): 31.

Endurance-Type Exercise Increases Bulk and Individual Mitochondrial Protein Synthesis Rates in Rats.

Physical activity increases muscle protein synthesis rates. However, the impact of exercise on the coordinated up- and/or downregulation of individual protein synthesis rates in skeletal muscle tissue remains unclear. The authors assessed the impact of exercise on mixed muscle, myofibrillar, and mitochondrial protein synthesis rates as well as individual protein synthesis rates in vivo in rats.

Molecular adaptation in adipose tissue in response to overfeeding with a high-fat diet under sedentary conditions in South Asian and Caucasian men.

For the same BMI, South Asians have a higher body fat percentage than Caucasians. There might be differences in the fatty acid (FA) handling in adipose tissue when both ethnicities are exposed to high-fat overfeeding. The objective of the present study was to investigate the molecular adaptation in relation to FA metabolism in response to overfeeding with a high-fat diet (OHFD) in South Asian and Caucasian men.

Glucose Restriction Plus Refeeding in Vitro Induce Changes of the Human Adipocyte Secretome with an Impact on Complement Factors and Cathepsins.

Adipose tissue is a major endocrine organ capable of secreting adipokines with a role in whole-body metabolism. Changes in the secretome profile during the development of obesity is suspected to contribute to the risk of health complications such as those associated with weight regain after weight loss. However, the number of studies on weight regain is limited and secretome changes during weight regain have hardly been investigated.

Adipocyte abundances of CES1, CRYAB, ENO1 and GANAB are modified in-vitro by glucose restriction and are associated with cellular remodelling during weight regain.

Long-term weight loss maintenance is a problem of overweight and obesity. Changes of gene expression during weight loss (WL) by calorie restriction (CR) are linked to the risk of weight regain (WR). However, detailed information on genes/proteins involved in the mechanism is still lacking.

Association of FTO and ADRB2 gene variation with energy restriction induced adaptations in resting energy expenditure and physical activity.

Background: Energy restriction induces adaptations in resting energy expenditure (REE) and physical activity; inter-individual variability could be ascribed to genetic predisposition. The aim was to examine if changes in REE and physical activity as a result of weight loss were affected by candidate single nucleotide polymorphisms (SNPs).

Methods: 148 subjects (39 men, 109 women), mean ± SD age: 41 ± 9 year; body mass index (BMI): 31.

Mass Spectrometric Identification of Cardiac Troponin T in Urine of Patients Suffering from Acute Myocardial Infarction.

Background: Because of its high cardiospecificity, cardiac troponin T (cTnT) is one of the first-choice biomarkers to diagnose acute myocardial infarction (AMI). cTnT is extensively fragmented in serum of patients suffering from AMI. However, it is currently unknown whether all cTnT is completely degraded in the body or whether some cTnT fragments can leave the body via urine.

Brain tissue plasticity: protein synthesis rates of the human brain.

All tissues undergo continuous reconditioning via the complex orchestration of changes in tissue protein synthesis and breakdown rates. Skeletal muscle tissue has been well studied in this regard, and has been shown to turnover at a rate of 1-2% per day in vivo in humans. Few data are available on protein synthesis rates of other tissues.

Paternal Exposure to Environmental Chemical Stress Affects Male Offspring's Hepatic Mitochondria.

Preconceptional paternal exposures may affect offspring's health, which cannot be explained by mutations in germ cells, but by persistent changes in the regulation of gene expression. Therefore, we investigated whether pre-conceptional paternal exposure to benzo[a]pyrene (B[a]P) could alter the offspring's phenotype. Male C57BL/6 mice were exposed to B[a]P by gavage for 6 weeks, 3× per week, and were crossed with unexposed BALB-c females 6 weeks after the final exposure.

Ultrafiltration combined with size exclusion chromatography efficiently isolates extracellular vesicles from cell culture media for compositional and functional studies.

Appropriate isolation methods are essential for unravelling the relative contribution of extracellular vesicles (EVs) and the EV-free secretome to homeostasis and disease. We hypothesized that ultrafiltration followed by size exclusion chromatography (UF-SEC) provides well-matched concentrates of EVs and free secreted molecules for proteomic and functional studies. Conditioned media of BEAS-2B bronchial epithelial cells were concentrated on 10 kDa centrifuge filters, followed by separation of EVs and free protein using sepharose CL-4B SEC.

Genetic Predictors of ≥5% Weight Loss by Multidisciplinary Advice to Severely Obese Subjects.

Background: Weight loss success is determined by genetic factors, which may differ according to treatment strategy.

Methods: From a multidisciplinary obesity treatment program involving dietary advice, psychological counseling, and increased physical activity, 587 subjects (68% female; 46.1 ± 12.