Metabolic labeling of cardiomyocyte-derived small extracellular-vesicle (sEV) miRNAs identifies miR-208a in cardiac regulation of lung gene expression.

Toxoplasma gondii uracil phosphoribosyltransferase (UPRT) converts 4-thiouracil (4TUc) into 4-thiouridine (4TUd), which is incorporated into nascent RNAs and can be biotinylated, then labelled with streptavidin conjugates or isolated via streptavidin-affinity methods. Here, we generated mice that expressed T. gondii UPRT only in cardiomyocytes ( UPRT mice) and tested our hypothesis that CM-derived miRNAs ( miRs) are transferred into remote organs after myocardial infarction (MI) by small extracellular vesicles (sEV) that are released from the heart into the peripheral blood ( sEV).

Hepatic Sam68 Regulates Systemic Glucose Homeostasis and Insulin Sensitivity.

Hepatic glucose production (HGP) is an important component of glucose homeostasis, and deregulated HGP, particularly through gluconeogenesis, contributes to hyperglycemia and pathology of type-2 diabetes (T2D). It has been shown that the gluconeogenic gene expression is governed primarily by the transcription factor cAMP-response element (CRE)-binding protein (CREB) and its coactivator, CREB-regulated transcriptional coactivator 2 (CRTC2). Recently, we have discovered that Sam68, an adaptor protein and Src kinase substrate, potently promotes hepatic gluconeogenesis by promoting CRTC2 stability; however, the detailed mechanisms remain unclear.

Reporter Systems for Assessments of Extracellular Vesicle Transfer.

Extracellular vesicles (EVs) are lipid bilayer particles naturally released from most if not all cell types to mediate inter-cellular exchange of bioactive molecules. Mounting evidence suggest their important role in diverse pathophysiological processes in the development, growth, homeostasis, and disease. Thus, sensitive and reliable assessments of functional EV cargo transfer from donor to acceptor cells are extremely important.

Extracellular vesicles in cardiovascular disease: Biological functions and therapeutic implications.

Extracellular vesicles (EVs), including exosomes and microvesicles, are lipid bilayer particles naturally released from the cell. While exosomes are formed as intraluminal vesicles (ILVs) of the multivesicular endosomes (MVEs) and released to extracellular space upon MVE-plasma membrane fusion, microvesicles are generated through direct outward budding of the plasma membrane. Exosomes and microvesicles have same membrane orientation, different yet overlapping sizes; their cargo contents are selectively packed and dependent on the source cell type and functional state.

Human Umbilical Cord Mesenchymal Stem Cell Derived Exosomes Delivered Using Silk Fibroin and Sericin Composite Hydrogel Promote Wound Healing.

Recent studies have shown that the hydrogels formed by composite biomaterials are better choice than hydrogels formed by single biomaterial for tissue repair. We explored the feasibility of the composite hydrogel formed by silk fibroin (SF) and silk sericin (SS) in tissue repair for the excellent mechanical properties of SF, and cell adhesion and biocompatible properties of SS. In our study, the SF SS hydrogel was formed by SF and SS protein with separate extraction method (LiBr dissolution for SF and hot alkaline water dissolution for SS), while SF-SS hydrogel was formed by SF and SS protein using simultaneous extraction method (LiBr dissolution for SF and SS protein).

Ablation of Sam68 in adult mice increases thermogenesis and energy expenditure.

Genetic deletion of Src associated in mitosis of 68kDa (Sam68), a pleiotropic adaptor protein prevents high-fat diet-induced weight gain and insulin resistance. To clarify the role of Sam68 in energy metabolism in the adult stage, we generated an inducible Sam68 knockout mice. Knockout of Sam68 was induced at the age of 7-10 weeks, and then we examined the metabolic profiles of the mice.

Visualization and Identification of Bioorthogonally Labeled Exosome Proteins Following Systemic Administration in Mice.

Exosomes transport biologically active cargo (e.g., proteins and microRNA) between cells, including many of the paracrine factors that mediate the beneficial effects associated with stem-cell therapy.

Self-Assembling Peptide-Based Hydrogels in Angiogenesis.

Ischemic diseases, especially in the heart and the brain, have become a serious threat to human health. Growth factor and cell therapy are emerging as promising therapeutic strategies; however, their retention and sustainable functions in the injured tissue are limited. Self-assembling peptide (SAP)-based hydrogels, mimicking the extracellular matrix, are therefore introduced to encapsulate and controllably release cells, cell-derived exosomes or growth factors, thus promoting angiogenesis and tissue recovery after ischemia.

Human umbilical cord mesenchymal stem cell derived exosomes encapsulated in functional peptide hydrogels promote cardiac repair.

Stem cell-derived exosomes have been recognized as a potential therapy for cardiovascular disease. However, the low retention rate of exosomes after transplantation in vivo remains a major challenge in clinical applications. The aim of this study is to investigate whether human umbilical cord mesenchymal stem cell derived exosomes (UMSC-Exo) encapsulated in functional peptide hydrogels could increase the retention and stability of exosomes and improve heart function in a rat myocardial infarction model.

Delivery of miR-675 by stem cell-derived exosomes encapsulated in silk fibroin hydrogel prevents aging-induced vascular dysfunction in mouse hindlimb.

Vascular disease is a major complication of aging, but the molecular mechanisms underlying the aging-induced vascular dysfunction remain unclear, and there is no effective treatment to prevent aging induced diseases. The objectives of the present study are to identify the signaling pathway mediating aging-induced vascular dysfunction and to develop an exosome based therapy to inhibit aging process. We used 11-month-old C57BL6 mice as pre-aging animal model and HO treated H9C2 cells as an in vitro aging model to examine the therapeutic effect of miR-675.

Exosomes Mediate the Beneficial Effects of Exercise.

It is known that moderate exercise can prevent the development of cardiovascular diseases, but the exact molecular mechanisms mediating cardioprotective effect of exercise remain unknown. Emerging evidence suggests that exercise has great impact on the biogenesis of exosomes, which have been found in both interstitial fluid and circulation, and play important roles in cellular communication. Exosomes carry functional molecules such as mRNAs, microRNA, and specific proteins, which can be used in the early diagnosis and targeted therapy of a variety of diseases.

Vitellogenin receptor selectively endocytoses female-specific and highly-expressed hemolymph proteins in the silkworm, Bombyx mori.

VgR, a member of the LDLR family, functions to transport vitellogenin into the ovaries to protome ovarian growth and embryonic development. In insects, the only widely accepted ligand of VgR is Vg. Recently, BmVgR has been shown to interact with BmSP1 in vitro.

Vertebrate estrogen regulates the development of female characteristics in silkworm, Bombyx mori.

The vertebrate estrogens include 17-β-estradiol (E2), which has an analog in silkworm ovaries. In this study, the Bombyx mori vitellogenin gene (BmVg) was used as a biomarker to analyze the function of the E2 in silkworm. In most oviparous animals, Vg has female-specific expression.

The Broad Complex isoform 2 (BrC-Z2) transcriptional factor plays a critical role in vitellogenin transcription in the silkworm Bombyx mori.

Background: Vitellogenin (Vg) is synthesized in the fat body of the female silkworm Bombyx mori and transported to the oocyte as a source of nutrition for embryo development. It is well known that ecdysone regulates physiological, developmental and behavioral events in silkworm. However, it is still not clear how the ecdysone regulates B.