The protective effect of cycloastragenol on aging mouse circadian rhythmic disorder induced by d-galactose

Aging process in mammals is associated with a decline in amplitude and a long period of circadian behaviors which are regulated by a central circadian regulator in the suprachiasmatic nucleus (SCN) and local oscillators in peripheral tissues. It is unclear whether enhancing clock function can retard aging. Using fibroblasts expressing per2::lucSV and senescent cells, we revealed cycloastragenol (CAG), a natural aglycone derivative from astragaloside IV, as a clock amplitude enhancing small molecule. CAG could activate telomerase to antiaging, but no reports focused on its effects on circadian rhythm disorders in aging mice. Here we analyze the potential effects of CAG on d -galactose-induced aging mice on the circadian behavior and expression of clock genes. For this purpose, CAG (20 mg/kg orally), was administered daily to d -galactose (150 mg/kg, subcutaneous) mice model of aging for 6 weeks. An actogram analysis of free-running activity of these mice showed that CAG significantly enhances the locomotor activity. We further found that CAG increase expressions of per2 and bmal1 genes in liver and kidney of aging mouse. Furthermore, CAG enhanced clock protein BMAL1 and PER2 levels in aging mouse liver and SCN. Our results indicated that the CAG could restore the behavior of circadian rhythm in aging mice induced by d -galactose. These data of present study suggested that CAG could be used as a novel therapeutic strategy for the treatment of age-related circadian rhythm disruption.     

Comparative Analysis of Endogenous Hormones and Metabolite Profiles in Early-Spring Flowering Plants and Unflowered Plants Revealing the Strategy of Blossom

Journal of Plant Growth Regulation - Early-spring plants are a special type of plant that complete their life cycle promptly in cold, early spring. Very little effort has been made into researching...     

Extracellular vesicles in bone and tooth: A state-of-art paradigm in skeletal regeneration

Bone and tooth, fundamental parts of the craniofacial skeleton, are anatomically and developmentally interconnected structures. Notably, pathological processes in these tissues underwent together and progressed in multilevels. Extracellular vesicles (EVs) are cell-released small organelles and transfer proteins and genetic information into cells and tissues. Although EVs have been identified in bone and tooth, particularly EVs have been identified in the bone formation and resorption, the concrete roles of EVs in bone and tooth development and diseases remain elusive. As such, we review the recent progress of EVs in bone and tooth to highlight the novel findings of EVs in cellular communication, tissue homeostasis, and interventions. This will enhance our comprehension on the skeletal biology and shed new light on the modulation of skeletal disorders and the potential of genetic treatment.     

Evidence for Inbreeding and Genetic Differentiation among Geographic Populations of the Saprophytic Mushroom Trogia venenata from Southwestern China

During the past 40 years, more than 400 Sudden Unexplained Deaths (SUDs) have occurred in Yunnan, southwestern China. Epidemiological and toxicological analyses suggested that a newly discovered mushroom called Trogia venenata was the leading culprit for SUDs. At present, relatively little is known about the genetics and natural history of this mushroom. In this study, we analyzed the sequence variation at four DNA fragments among 232 fruiting bodies of T. venenata collected from seven locations. Our ITS sequence analyses confirmed that all the isolates belonged to the same species. The widespread presence of sequence heterozygosity within many strains at each of three protein-coding genes suggested that the fruiting bodies were diploid, dikaryotic or heterokaryotic. Within individual geographic populations, we found significant deviations of genotype frequencies from Hardy-Weinberg expectations, with the overall observed heterozygosity lower than that expected under random mating, consistent with prevalent inbreeding within local populations. The geographic populations were overall genetically differentiated. Interestingly, while a positive correlation was found between population genetic distance and geographic distance, there was little correlation between genetic distance and barium concentration difference for the geographic populations. Our results suggest frequent inbreeding, geographic structuring, and limited gene flow among geographic populations of T. venenata from southwestern China.     

Alpha‐fetoprotein accelerates the progression of hepatocellular carcinoma by promoting Bcl‐2 gene expression through an RA‐RAR signalling pathway

Previous studies have found that alpha‐fetoprotein (AFP) can promote the proliferation of hepatoma cells and accelerate the progression of hepatocellular carcinoma (HCC). However, the exact mechanism of action remains unclear. Recent bioinformatics studies have predicted the possible interaction between AFP and retinoic acid receptors (RARs). Thus, the purpose of this study was to investigate the molecular mechanism through which AFP promotes tumour cell proliferation by interfering with the RA‐RAR signal pathway. Our data indicated that AFP could significantly promote the proliferation and weaken ATRA‐induced apoptosis of hepatoma cells. Besides, cytoplasmic AFP interacts with RAR, disrupting its entrance into the nucleus, which in turn affects the expression of the Bcl‐2 gene. In addition, knockdown of AFP in HepG2 cells was synchronously associated with an incremental increase of RAR binding to DNA, as well as down‐regulation of Bcl‐2; the opposite effect was observed in AFP gene‐transfected HLE cells. Moreover, a similar effect of AFP was detected in tumour tissues with high serum AFP, but not in adjacent non‐cancerous liver tissues, or HCC tissues with low serum AFP levels. These results indicate that AFP acts as signalling molecule and prevents RAR from entering into the nucleus by interacting with RAR, thereby promoting the expression of Bcl‐2. Our data reveal a novel mechanism through which AFP regulates Bcl‐2 expression and further suggest that AFP may be used as a novel target for treating HCC.     

Intrinsic Migratory Properties of Cultured Schwann Cells Based on Single-Cell Migration Assay

The migration of Schwann cells is critical for development of peripheral nervous system and is essential for regeneration and remyelination after nerve injury. Although several factors have been identified to regulate Schwann cell migration, intrinsic migratory properties of Schwann cells remain elusive. In this study, based on time-lapse imaging of single isolated Schwann cells, we examined the intrinsic migratory properties of Schwann cells and the molecular cytoskeletal machinery of soma translocation during migration. We found that cultured Schwann cells displayed three motile phenotypes, which could transform into each other spontaneously during their migration. Local disruption of F-actin polymerization at leading front by a Cytochalasin D or Latrunculin A gradient induced collapse of leading front, and then inhibited soma translocation. Moreover, in migrating Schwann cells, myosin II activity displayed a polarized distribution, with the leading process exhibiting higher expression than the soma and trailing process. Decreasing this front-to-rear difference of myosin II activity by frontal application of a ML-7 or BDM (myosin II inhibitors) gradient induced the collapse of leading front and reversed soma translocation, whereas, increasing this front-to-rear difference of myosin II activity by rear application of a ML-7 or BDM gradient or frontal application of a Caly (myosin II activator) gradient accelerated soma translocation. Taken together, these results suggest that during migration, Schwann cells display malleable motile phenotypes and the extension of leading front dependent on F-actin polymerization pulls soma forward translocation mediated by myosin II activity.     

Characterization of MnpC, a Hydroquinone Dioxygenase Likely Involved in the meta-Nitrophenol Degradation by Cupriavidus necator JMP134

Cupriavidus necator JMP134 utilizes meta-nitrophenol (MNP) as the sole source of carbon, nitrogen, and energy. The metabolic reconstruction of MNP degradation performed in silico suggested that MnpC might have played an important role in MNP degradation. In order to experimentally confirm the prediction, we have now characterized the mnpC-encoded (amino)hydroquinone dioxygenase involved in the ring-cleavage reaction of MNP degradation. Real-time PCR analysis indicated that mnpC played an essential role in MNP degradation. MnpC was purified to homogeneity as an N-terminal six-His-tagged fusion protein, and it was proved to be a dimer as demonstrated by gel filtration. MnpC was a Fe²⁺- and Mn²⁺-dependent dioxygenase, catalyzing the ring-cleavage of hydroquinone to 4-hydroxymuconic semialdehyde in vitro and proposed as an aminohydroquinone dioxygenase involved in MNP degradation in vivo. Phylogenetic analysis suggested that MnpC diverged from the other (chloro)hydroquinone dioxygenases at an earlier point, which might result in the preference for its physiological substrate.