No abstract

Differentiation of embryonic and adult myogenic progenitors undergoes a complex series of cell rearrangements and specification events which are controlled by distinct gene regulatory networks. Delineation of the molecular mechanisms that regulate skeletal muscle specification and formation should be important for understanding congenital myopathies and muscular degenerative diseases. Retinoic acid (RA) signaling plays an important role in development. However, the role of RA signaling in adult myogenic progenitors is poorly understood. Here, we investigate the role of RA signaling in regulating myogenic differentiation of myoblastic progenitor cells. Using the mouse myoblast progenitor C2C12 line as a model, we have found that the endogenous expression of most RAR and RXR isotypes is readily detected. While the nuclear receptor co-repressors are highly expressed, two of the three nuclear receptor coactivators and the enzymes involved in RA synthesis are expressed at low level or undetectable, suggesting that the RA signaling pathway may be repressed in myogenic progenitors. Using the α-myosin heavy chain promoter-driven reporter (MyHC-GLuc), we have demonstrated that either ATRA or 9CRA is able to effectively induce myogenic differentiation, which can be synergistically enhanced when both ATRA and 9CRA are used. Upon ATRA and 9CRA treatment of C2C12 cells the expression of late myogenic markers significantly increases. We have further shown that adenovirus-mediated exogenous expression of RARα and/or RXRα is able to effectively induce myogenic differentiation in a ligand-independent fashion. Morphologically, ATRA and 9CRA-treated C2C12 cells exhibit elongated cell body and become multi-nucleated myoblasts, and even form myoblast fusion. Ultrastructural analysis under transmission electron microscope reveals that RA-treated myogenic progenitor cells exhibit an

Mesenchymal stem cells (MSCs) are candidates for cell therapy of kidney diseases. However, the application of MSC derived from human umbilical cord (UC-MSC) in treating acute renal failure (ARF) has not been reported. UC-MSCs, 10(6), were transplantated via the left carotid artery into ARF rats which was established by clamping bilateral pedicles for 60 min and reperfusing. Serum creatinine and urea nitrogen decreased 4.8 times and 3.6 times as well as caspase-3 and IL-1beta decreased 5.8 times and 9 times compared to control groups, respectively. The percent of proliferative cell nuclear antigen (PCNA)-positive cells (53% +/- 7.5%) was higher than that in the control groups (17% +/- 4.5%). In addition, the transplanted UC-MSCs could reside in local injury sites, leading to the relief of hyperemia and inflammation, but no obvious transdifferentiation into renal-like cells. The results lay the foundation for further study on the potential application of UC-MSC in human disease.

A series of oxovanadium complexes with mixed ligands, a tridentate ONO-donor Schiff base ligand [viz., salicylidene anthranilic acid (SAA)], and a bidentate NN ligand [viz., 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), dipyrido[3,2-a:2',3'-c]phenazine (dppz), or 7-methyldipyrido[3,2-a:2',3'-c]phenazine (dppm)], have been synthesized and characterized by elemental analysis, electrospray ionization mass spectrometry, UV-vis spectroscopy, Fourier transform IR spectroscopy, EPR spectroscopy, and X-ray crystallography. Crystal structures of both complexes, [V(IV)O(SAA)(bpy)].0.25bpy and [V(IV)O(SAA)(phen)].0.33H(2)O, reveal that oxovanadium(IV) is coordinated with one nitrogen and two oxygen atoms from the Schiff base and two nitrogen atoms from the bidentate planar ligands, in a distorted octahedral geometry (VO(3)N(3)). The oxidation state of V(IV) with d(1) configuration was confirmed by EPR spectroscopy. The speciation of VO-SAA-bpy in aqueous solution was investigated by potentiomtreic pH titrations, and the results revealed that the main species are two ternary complexes at a pH range of 7.0-7.4, and one is the isolated crystalline complex. The complexes have been found to be potent inhibitors against human protein tyrosine phosphatase 1B (PTP1B) (IC(50) approximately 30-61 nM), T-cell protein tyrosine phosphatase (TCPTP), and Src homology phosphatase 1 (SHP-1) in vitro. Interestingly, the [V(IV)O(SAA)(bpy)] complex selectively inhibits PTP1B over the other two phosphatases (approximate ninefold selectivity against SHP-1 and about twofold selectivity against TCPTP). Kinetics assays suggest that the complexes inhibit PTP1B in a competitive and reversible manner. These suggest that the complexes may be promising candidates as novel antidiabetic agents.

An optically active, rigid rodlike helical polysilane with 6,9,12‐trioxatetradecyl and (S)‐2‐methylbutyl substituents (1) was newly obtained as a very high molecular weight polymer of several million. Due to the presence of trietheral substituent, 1 was readily soluble in a polar solvent such as ethanol and a mixture of ethanol and water, but was insoluble in pure water. Polysilane 1 in pure ethanol at room temperature exhibited an intense and narrow ultraviolet (UV) and circular dichroism (CD) absorptions at 323 nm, associated with an almost mirror imaged fluorescence (FL) at 328 nm, that are characteristic of rigid rodlike, single‐screw‐sense helical polysilanes reported previously. When solution temperature was changed from 60°C to −104°C, a global shape of 1 expanded associated with an increase of segment length, whereas a screw pitch tended to be wound tightly. On the other hand, as a solvent polarity became poor, a global shape of 1 shrunk associated with an decrease of segment length and formed a chiral motif with an M‐helicity between two helical segments with a kink. At a ratio of 50% of ethanol/water of 50:50 (v/v), 1 became insoluble and formed aggregates. Chirality 10:667–675, 1998. © 1998 Wiley‐Liss, Inc.

Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD + )-dependent protein deacetylases, which regulate important biological processes ranging from apoptosis, age-associated pathophysiologies, adipocyte and muscle differentiation, and energy expenditure to gluconeogenesis. Very recently, sirtuin 5 (SIRT5) has received considerable attention due to that it was found to have weak deacetylase activity but strong desuccinylase, demalonylase and deglutarylase activities, and it was also found to be associated with several human diseases such as cancer, Alzheimer's disease, and Parkinson's disease. In this review, we for the first time summarized the structure characteristics, known peptide and small-molecule inhibitors of SIRT5, extracted some clues from current available information and introduced some feasible, practical in silico methods, which might be useful in further efforts to develop new SIRT5 inhibitors.Sirtuin, SIRT5 inhibitor, crystal structure, small-molecule inhibitors, computer-aided drug design Citation:Yang, L., Ma, X., He, Y., Yuan, C., Chen, Q., Li, G., and Chen, X. (2017). Sirtuin 5: a review of structure, known inhibitors and clues for developing new inhibitors. Sci China Life Sci 60, 249-256.

Single-layer light emitting diodes (LEDs) were fabricated using poly[bis(p-butylphenyl)silane] as the emissive layer. An efficient and stable electroluminescence with a maximum at 407 nm was observed at room temperature under a forward electric field greater than 6×105 V/cm. The coincidence of electroluminescence with photoluminescence suggests the origin of the electroluminescence in an excited silicon chain segment. The high external quantum efficiency (0.1% photons/electron), narrow emission (full width at half maximum=15 nm), improved operating stability, and good solubility in organic solvents provide the possibility of using polysilanes for ultraviolet LEDs.

We report on an H(D)-atom Rydberg tagging experiment for H(D)N(3) photolysis providing detailed dynamical information on the wavelength dependence of the H(D) + N(3) channel. We observe subtle yet striking changes in the photochemical dynamics as the photolysis energy passes through approximately 5.6 eV. In addition to producing linear azide with an average of approximately 40% of available energy appearing as translation, a second H(D)-atom producing channel grows in above this energy releasing only about 15%. An observed (inverse) isotope effect suggests that statistical decomposition on S(0) is unimportant. High level ab initio quantum chemical calculations reveal a transition state to cyclization of the N(3) moiety in H(D)N(3) on the first excited singlet (S(1)) surface that is close in energy to the experimentally observed threshold energy for this "slow channel". Furthermore, the translational energy release of the "slow channel" is energetically consistent with cyclic-N(3) formation. This work provides the clearest presently available insights into how ring closure can occur in azide photochemistry.