The incidence of premature ovarian failure (POF), also known as ovarian insufficiency, has been increasing in recent years. Although some treatments are currently available, improved treatment strategies are urgently required. Many researchers have reported that human endometrial stem cells (HuMenSCs), which exhibit stem/progenitor cell properties in vitro repaired damaged cells in vivo. Thus, we aimed to determine whether HuMenSCs can serve as cell therapy tools and be used for the treatment of POF. After treating with cyclophosphamide, on the first estrus period (we predicted mouse estrus cycle was generally 5 days), HuMenSCs were injected into a cyclophosphamide-induced mouse model of POF. The results revealed that the HuMenSCs could survive within POF mouse ovaries for at least 14 days in vivo; further, ovaries of the HuMenSCs-transplanted group expressed higher levels of ovarian markers [AMH, inhibin α/β, and follicle-stimulating hormone receptor (FSHR)], and the proliferative marker Ki67. In addition, the ovarian weight, plasma E2 level, and the number of normal follicles increased over time in the HuMenSC group compared with the control group. Further, microarray analysis of cDNA expression patterns revealed that, after HuMenSC transplantation, the gene mRNA expression patterns in the ovarian cells following stimulation of the host ovarian niche became increasingly similar to those observed in human ovarian tissue compared with the pretransplantation mRNA expression pattern in HuMenSCs. Hence, we can safely conclude that the mesenchymal stem cell properties and in vivo survival of HuMenSCs make them ideal seed cells for stem cell transplantation in the treatment of POF.

As the brain-resident innate immune cells, reactive microglia are a major pathological feature of Alzheimer's disease (AD). However, the exact role of microglia is still unclear in AD pathogenesis. Here, using metabolic profiling, we show that microglia energy metabolism is significantly suppressed during chronic Ab-tolerant processes including oxidative phosphorylation and aerobic glycolysis via the mTOR-AKT-HIF-1a pathway. Pharmacological activation of TRPV1 rescues Ab-tolerant microglial dysfunction, the AKT/mTOR pathway activity, and metabolic impairments and restores the immune responses including phagocytic activity and autophagy function. Amyloid pathology and memory impairment are accelerated in microglia-specific TRPV1-knockout APP/PS1 mice. Finally, we showed that metabolic boosting with TRPV1 agonist decreases amyloid pathology and reverses memory deficits in AD mice model. These results indicate that TRPV1 is an important target regulating metabolic reprogramming for microglial functions in AD treatment.

Freezing tolerance in plants is a complex trait that occurs in many plant species during growth at low, nonfreezing temperatures, a process known as cold acclimation. This process is regulated by a multigenic system expressing broad variation in the degree of freezing tolerance among wheat cultivars. Microarray analysis is a powerful and rapid approach to gene discovery. In species such as wheat, for which large scale mutant screening and transgenic studies are not currently practical, genotype comparison by this methodology represents an essential approach to identifying key genes in the acquisition of freezing tolerance. A microarray was constructed with PCR amplified cDNA inserts from 1184 wheat expressed sequence tags (ESTs) that represent 947 genes. Gene expression during cold acclimation was compared in 2 cultivars with marked differences in freezing tolerance. Transcript levels of more than 300 genes were altered by cold. Among these, 65 genes were regulated differently between the 2 cultivars for at least 1 time point. These include genes that encode potential regulatory proteins and proteins that act in plant metabolism, including protein kinases, putative transcription factors, Ca2+ binding proteins, a Golgi localized protein, an inorganic pyrophosphatase, a cell wall associated hydrolase, and proteins involved in photosynthesis.Key words: wheat microarray, expression profile, plant transcription, cold-regulated genes, freezing tolerance, cold acclimation, winter hardiness, stress genes, gene regulation, wheat transcriptome.

Although large numbers of long noncoding RNAs (lncRNAs) expressed in the mammalian nervous system have been detected, their functions and mechanisms of regulation remain to be fully clarified. It has been reported that the lncRNA antisense transcript for β-secretase-1 (BACE1-AS) is elevated in Alzheimer’s disease (AD) and drives the rapid feed-forward regulation of β-secretase, suggesting that it is critical in AD development. In the present study, the senile plaque (SP) AD SH-SY5Y cell model was established using the synthetic amyloid β-protein (Aβ) 1–42 in vitro. Using this model, the potential of siRNA-mediated silencing of lncRNA BACE1-AS expression to attenuate the ability of β-secretase-1 (BACE1) to cleave amyloid precursor protein (APP) and to reduce the production of Aβ1–42 oligomers was investigated. MTT assays demonstrated that exogenous Aβ1–42 suppressed SH-SY5Y cell proliferation and induced APP-related factor expression and SP formation. Furthermore, quantitative polymerase chain reaction and western blot analysis revealed that the mRNA and protein expression of Aβ1–42 and Aβ1–40 was significantly increased in the AD model group, with a marked decrease in Ki-67 expression at day six. RNase protection assays (RPA) and northern blotting analysis confirmed that exogenous Aβ1–42 not only promoted the expression of the APP-cleaving enzyme BACE1, but also induced lncRNA BACE1-AS expression. Furthermore, lncRNA BACE1-AS formed RNA duplexes and increased the stability of BACE1 mRNA. Downregulation of lncRNA BACE1-AS expression in SH-SY5Y cells by siRNA silencing resulted in the attenuation of the ability of BACE1 to cleave APP and delayed the induction of SP formation in the SP AD SH-SY5Y cell model.

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