Myostatin (MSTN), a member of the transforming growth factor-β superfamily, can negatively regulate the growth and development of skeletal muscle by autocrine or paracrine signaling. Mutation of the myostatin gene under artificial or natural conditions can lead to a significant increase in muscle quality and produce a double-muscle phenotype. Here, we review the similarities and differences between myostatin and other members of the transforming growth factor-β superfamily and the mechanisms of myostatin self-regulation. In addition, we focus extensively on the regulation of myostatin functions involved in myogenic differentiation, myofiber type conversion, and skeletal muscle protein synthesis and degradation. Also, we summarize the induction of reactive oxygen species generation and oxidative stress by myostatin in skeletal muscle. This review of recent insights into the function of myostatin will provide reference information for future studies of myostatin-regulated skeletal muscle formation and may have relevance to agricultural fields of study.

Because the effect of CXL in stiffening the tissue and reducing the interfibrillar spacing consistently decreased with reducing the irradiance duration, the Bunsen-Roscoe law may not be readily applicable in the CXL of corneal tissue. [J Refract Surg. 2018;34(1):51-58.].

Induced pluripotent stem cell (iPSC) derived endothelial cells (ECs) is a novel therapeutic option for ischemic diseases. Although the detailed mechanism of this novel therapy remains unknown, emerging evidence has demonstrated that exosomes derived from hiPSC-ECs play a critical role in this approach. In this study, we first isolated and characterized the exosomes from iPSCs-ECs (hiPSC-EC-Exo) and determined the functional roles of hiPSC-EC-Exo in neovascularization and the underlying mechanism. Further, we evaluated the effect of exosomes derived from hiPS-ECs on promoting angiogenesis in a mouse model bearing ischemic limbs. Our results showed that miR-199b-5p, an miRNA highly associated with angiogenesis, is significantly upregulated during the differentiation of hiPSC-ECs. Mechanically, our studies found that hiPSC-ECs expressing miR-199b-5p significantly promote cell migration, proliferation and tube formation through Jagged-1-dependent upregulation of VEGFR2 in HUVECs. Similarly, coculture of hiPSC-ECs-Exo with HUVECs also resulted in a significant improvement in HUVEC migration, proliferation, and tube formation, suggesting that exosome-mediated cell-cell communication in a paracrine manner may serve as a fundamental mechanism for iPSC-EC-based treatment. Consequently, we found that the transfer of hiPSC-ECs enriched with miR-199b-5p significantly enhanced micro-vessel density and blood perfusion in ischemic limbs in vivo. Taken together, our studies were the first to demonstrate that transfer of hiPSC-ECs-Exo is a promising approach to treat ischemic injury via the mechanism of promoting neovascularization.

Recently, a rapidly amplifying family of mouse LINE-1 (L1) has been identified and named T(F). The evolutionary context surrounding the derivation of the T(F) family was examined through phylogenetic analysis of sequences in the 3' portion of the repeat. The Mus musculus domesticus T(F) family was found to be the terminal subfamily of the previously identified L1Md4 lineage. The L1Md4 lineage joins the other prototypical mouse LINE-1 lineage (the L1MdA2 lineage) approximately 1 MYA at about the time of the common ancestor of M. m. domesticus, Mus spicilegus, and Mus spretus. However, the T(F) family from M. m. domesticus was found to join to the previously reported M. spretus Ms475 and Ms7024 LINE-1 families at just 0.5 MYA, indicating horizontal transfer. The T(F) family from M. m. domesticus was then found to be even more recently related to LINE-1's from another species, M. spicilegus. A separate spretus A2 lineage was found through a directed search of a PCR library. This lineage, in contrast to the spretus T(F) lineage, does join domesticus at about 1 MYA, as would be expected in the absence of horizontal transfer. A third major family was also found that splits off from the L1Md4 lineage shortly after its departure from the L1MdA2 lineage. The new family, named the Z family, was found to contain the de novo LINE-1 inserts causing the beige and med mutations. Whether the split with the Z family was before or after the recombination that introduced the F-type promoters and defined the inception of T(F) as a lineage is unclear. In enumerating copies of the various LINE-1 families, we found that T(F) 3' ends were not much more numerous than the reported number of 5' ends, suggesting that T(F) may not be subjected to the 90% truncation pattern typical of LINE-1 as a whole.

This study was undertaken to determine the in vitro effect of lentivirus-mediated siPin1 on cell cycle and apoptosis of vascular smooth muscle cells (VSMCs). Further we sought to provide insight into the mechanisms behind these processes. Human umbilical artery smooth muscle cells (HUASMCs) were transfected with lentiviral siPin1. Real-time RT-PCR and Western blotting were used to examine Pin1 mRNA and protein expression. MTT and [(3)H]thymidine incorporation assays were employed to observe cell proliferation status. The apoptotic rate and cell cycle were analyzed by Hoechst33258 staining and flow cytometry. Finally we measured the expression of cyclin D1, beta-catenin, CDK4, cytochrome c, procaspase-3, cleaved caspase-3, procaspase-9, cleaved caspase-9, Bcl-2, Bax, STAT3, phosphorylated STAT3 and VEGF in lentiviral siPin1 infected VSMCs. Lentivirus-mediated siPin1 effectively diminished endogenous Pin1 expression in VSMCs resulting in cell cycle arrest and enhancement of apoptosis. This was accompanied by downregulation of cyclin D1, beta-catenin, CDK4, increase of Bax/Bcl-2 ratio, release of cytochrome c, and activation of caspase-3 and -9. We concluded that this effect was mediated, at least in part, via the beta-catenin/cyclin D1/CDK4 cascade, and that the mitochondrial pathway was responsible for VSMC apoptosis in the absence of Pin1. Our observations raised the possibility that Pin1 might be a potential therapeutic target to prevent stenosis.