Human bone marrow mesenchymal stem cell derived-extracellular vesicles (HBMSC-EV) are known for their regenerative and anti-inflammatory effects in animal models of myocardial ischemia. However, it is not known whether the efficacy of the EVs can be modulated by pre-conditioning of HBMSC by exposing them to either starvation or hypoxia prior to EV collection. HBMSC-EVs were isolated following normoxia starvation (NS), normoxia non-starvation (NNS), hypoxia starvation (HS), or hypoxia non-starvation (HNS) pre-conditioning. The HBMSC-EVs were characterized by nanoparticle tracking analysis, electron microscopy, Western blot, and proteomic analysis. Comparative proteomic profiling revealed that starvation pre-conditioning led to a smaller variety of proteins expressed, with the associated lesser effect of normoxia versus hypoxia pre-conditioning. In the absence of starvation, normoxia and hypoxia pre-conditioning led to disparate HBMSC-EV proteomic profiles. HNS HBMSC-EV was found to have the greatest variety of proteins overall, with 74 unique proteins, the greatest number of redox proteins, and pathway analysis suggestive of improved angiogenic properties. Future HBMSC-EV studies in the treatment of cardiovascular disease may achieve the most therapeutic benefits from hypoxia non-starved pre-conditioned HBMSC. This study was limited by the lack of functional and animal models of cardiovascular disease and transcriptomic studies.

Aging is a risk factor for many non-communicable diseases such as cardiovascular and neurodegenerative diseases. Extracellular vesicles and particles (EVP) carry microRNAs that may play a role in age-related diseases and may induce oxidative stress. We hypothesized that aging could impact EVP miRNA and impair redox homeostasis, contributing to chronic age-related diseases. Our aims were to investigate the microRNA profiles of circulating total EVPs from aged and young adult animals and to evaluate the pro- and antioxidant machinery in circulating total EVPs. Plasma from 3- and 21-month-old male Wistar rats were collected, and total EVPs were isolated. MicroRNA isolation and microarray expression analysis were performed on EVPs to determine the predicted regulation of targeted mRNAs. Thirty-one mature microRNAs in circulating EVPs were impacted by age and were predicted to target molecules in canonical pathways directly related to cardiovascular diseases and oxidative status. Circulating total EVPs from aged rats had significantly higher NADPH oxidase levels and myeloperoxidase activity, whereas catalase activity was significantly reduced in EVPs from aged animals. Our data shows that circulating total EVP cargo—specifically microRNAs and oxidative enzymes—are involved in redox imbalance in the aging process and can potentially drive cardiovascular aging and, consequently, cardiac disease.

Background/Objectives: The present work aimed to compare the effects of the standardized dry extract from the leaves of Monteverdia ilicifolia, popularly known as “espinheira-santa”, with omeprazole in the management of dyspepsia related to gastroesophageal reflux disease (GERD). Methods: A double-blind, randomized, non-inferiority and double-dummy clinical trial was conducted. In total, 86 patients with GERD symptoms were randomized into three groups: Omeprazol (20 mg), M. ilicifolia (400 mg), or M. ilicifolia (860 mg). Capsules were provided by SUSTENTEC^®, Pato Bragato, Brazil. It was requested that the participants take three capsules before breakfast and dinner for 4 weeks. Clinical outcomes were obtained at the beginning and end of the study, with GERD symptoms (QS-GERD), the impact of heartburn symptoms on quality of life (HBQOL), and medical records. Results: Overall, 75.6% of the participants showed adherence without any differences among the experimental groups. All groups had significant reductions in both QS-GERD and HBQOL scores. Omeprazole and 400 and 860 mg of M. ilicifolia decreased the QS-GERD total scores at the endpoint compared to the baseline (Chi-square = 129.808; p < 0.0001), as well as individual item scores, such as heartburn intensity (Chi-square = 93.568, p < 0.0001) and heartburn after meals (Chi-square = 126.426, p < 0.0001). There were no differences among the experimental groups after the intervention. Conclusions: Our results suggest that capsules with a standardized dry extract from the leaves of M. ilicifolia at a dosage of 400 or 860 mg are non-inferior to omeprazole, a proton pump inhibitor.