BackgroundThe acute respiratory distress syndrome (ARDS) is characterized by disruption of the alveolar-capillary barrier resulting in accumulation of proteinaceous edema and increased inflammatory cells in the alveolar space. We previously found that endothelial progenitor cell (EPC) exosomes prevent endothelial dysfunction and lung injury in sepsis in part due to their encapsulation of miRNA-126. However, the effects of EPC exosomes in acute lung injury (ALI) remain unknown.MethodsTo determine if EPC exosomes would have beneficial effects in ALI, intratracheal administration of lipopolysaccharide (LPS) was used to induce ALI in mice. Lung permeability, inflammation, and the role of miRNA-126 in the alveolar-epithelial barrier function were examined.ResultsThe intratracheal administration of EPC exosomes reduced lung injury following LPS-induced ALI at 24 and 48 h. Compared to placebo, intratracheal administration of EPC exosomes significantly reduced the cell number, protein concentration, and cytokines/chemokines in the bronchoalveolar lavage fluid (BALF), indicating a reduction in permeability and inflammation. Further, EPC exosomes reduced myeloperoxidase (MPO) activity, lung injury score, and pulmonary edema, demonstrating protection against lung injury. Murine fibroblast (NIH3T3) exosomes, which do not contain abundant miRNA-126, did not provide these beneficial effects. In human small airway epithelial cells (SAECs), we found that overexpression of miRNA-126-3p can target phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2), while overexpression of miRNA-126-5p inhibits the inflammatory alarmin HMGB1 and permeability factor VEGFα. Interestingly, both miR-126-3p and 5p increase the expression of tight junction proteins suggesting a potential mechanism by which miRNA-126 may mitigate LPS-induced lung injury.ConclusionsOur data demonstrated that human EPC exosomes are beneficial in LPS-induced ALI mice, in part through the delivery of miRNA-126 into the injured alveolus.Electronic supplementary materialThe online version of this article (10.1186/s13054-019-2339-3) contains supplementary material, which is available to authorized users.

Microvascular dysfunction leads to multi-organ failure and mortality in sepsis. Our previous studies demonstrated that administration of exogenous endothelial progenitor cells (EPCs) confers protection in sepsis as evidenced by reduced vascular leakage, improved organ function, and increased survival. We hypothesize that EPCs protect the microvasculature through the exosomes-mediated transfer of microRNAs (miRNAs). Mice were rendered septic by cecal ligation and puncture (CLP), and EPC exosomes were administered intravenously at 4 hr after CLP. EPC exosomes treatment improved survival, suppressing lung and renal vascular leakage, and reducing liver and kidney dysfunction in septic mice. EPC exosomes attenuated sepsis-induced increases in plasma levels of cytokines and chemokine. Moreover, we determined miRNA contents of EPC exosomes with next-generation sequencing and found abundant miR-126-3p and 5p. We demonstrated that exosomal miR-126-5p and 3p suppressed LPS-induced high mobility group box 1 (HMGB1) and vascular cell adhesion molecule 1 (VCAM1) levels, respectively, in human microvascular endothelial cells (HMVECs). Inhibition of microRNA-126-5p and 3p through transfection with microRNA-126-5p and 3p inhibitors abrogated the beneficial effect of EPC exosomes. The inhibition of exosomal microRNA-126 failed to block LPS-induced increase in HMGB1 and VCAM1 protein levels in HMVECs and negated the protective effect of exosomes on sepsis survival. Thus, EPC exosomes prevent microvascular dysfunction and improve sepsis outcomes potentially through the delivery of miR-126.

Gastrointestinal healing is a topic rarely reviewed in the literature, yet it is of paramount importance to the surgeon. Failure of anastomotic healing may lead to life-threatening complications, additional surgical procedures, increased length of stay, increased cost, long-term disability, and reduced quality of life for the patient. The goal of this article is to review the biological response to wounded tissue, to outline discrete differences between skin and gastrointestinal healing, to discuss local and systemic factors important to gastrointestinal healing, and to compare methods of measuring collagen content and strength of the newly formed anastomosis. Part II of this review will focus on techniques and therapies available to optimize anastomotic healing.

Obesity is recognized as a worldwide health crisis. Obesity and its associated health complications such as diabetes, dyslipidemia, hypertension, and cardiovascular diseases impose a big social and economic burden. In an effort to identify safe, efficient, and long-term effective methods to treat obesity, various natural products with potential for inhibiting adipogenesis were revealed. This review aimed to discuss the molecular mechanisms underlying adipogenesis and the inhibitory effects of various phytochemicals, including those from natural sources, on the early stage of adipogenesis. We discuss key steps (proliferation and cell cycle) and their regulators (cell-cycle regulator, transcription factors, and intracellular signaling pathways) at the early stage of adipocyte differentiation as the mechanisms responsible for obesity.

Office-based unsedated small-caliber endoscopy is technically feasible, well tolerated, and accurate in screening for Barrett's esophagus, despite yielding a smaller biopsy specimen. This approach bears the potential to eliminate the infrastructure and cost required for intravenous sedation in this application.