拟阵的瘦基运算和弃基

为更深入地用拟阵基系描述拟阵的性质,定义了拟阵的瘦基运算和弃基,即从拟阵基系的元素着手,使拟阵基的势减少或者使拟阵基系的势减少,得到一个新的拟阵基系,从而得到与它相对应的拟阵独立集系.利用所得结果证明了可以通过瘦基运算和弃基构造正则GV状模糊拟阵.

Leptin: a multifunctional hormone

Leptin is the protein product encoded by the obese (ob)gene. It is a circulating hormone produced primarily by the adipose tissue. ob/ob mice with mutations of the gene encoding leptin become morbidly obese, infertile, hyperphagic, hypothermic,and diabetic. Since the cloning of leptin in 1994, our knowledge in body weight regulation and the role played by leptin has increased substantially. We now know that leptin signals through its receptor, OB-R, which is a member of the cytokine receptor superfamily. Leptin serves as an adiposity signal to inform the brain the adipose tissue mass in a negative feedback loop regulating food intake and energy expenditure. Leptin also plays important roles in angiogenesis, immune function, fertility and bone formation. Humans with mutations in the gene encoding leptin are also morbidly obese and respond to leptin treatment,demonstrating that enhancing or inhibiting leptin’s activities in vivo may have potential therapeutic benefits.

Generation of obese rat model by transcription activator-like effector nucleases targeting the leptin receptor gene

The laboratory rat is a valuable mammalian model organism for basic research and drug discovery. Here we demonstrate an efficient methodology by applying transcription activator-like effector nucleases(TALENs) technology to generate Leptin receptor(Lepr) knockout rats on the Sprague Dawley(SD) genetic background. Through direct injection of in vitro transcribed m RNA of TALEN pairs into SD rat zygotes, somatic mutations were induced in two of three resulting pups. One of the founders carrying bi-allelic mutation exhibited early onset of obesity and infertility. The other founder carried a chimeric mutation which was efficiently transmitted to the progenies. Through phenotyping of the resulting three lines of rats bearing distinct mutations in the Lepr locus, we found that the strains with a frame-shifted or premature stop codon mutation led to obesity and metabolic disorders. However, no obvious defect was observed in a strain with an in-frame 57 bp deletion in the extracellular domain of Lepr. This suggests the deleted amino acids do not significantly affect Lepr structure and function. This is the first report of generating the Lepr mutant obese rat model in SD strain through a reverse genetic approach. This suggests that TALEN is an efficient and powerful gene editing technology for the generation of disease models.

Increased leptin by hypoxic-preconditioning promotes autophagy of mesenchymal stem cells and protects them from apoptosis

Autophagy is the basic catabolic progress involved in cell degradation of unnecessary or dysfunctional cellular components.It has been proven that autophagy could be utilized for cell survival under stresses.Hypoxic-preconditioning(HPC)could reduce apoptosis induced by ischemia and hypoxia/serum deprivation(H/SD)in bone marrow-derived mesenchymal stem cells(BMSCs).Previous studies have shown that both leptin signaling and autophagy activation were involved in the protection against apoptosis induced by various stress,including ischemia-reperfusion.However,it has never been fully understood how leptin was involved in the protective effects conferred by autophagy.In the present study,we demonstrated that HPC can induce autophagy in BMSCs by increased LC3-II/LC3-I ratio and autophagosome formation.Interestingly,similar effects were also observed when BMSCs were pretreated with rapamycin.The beneficial effects offered by HPC were absent when BMSCs were incubated with autophagy inhibitor,3-methyladenine(3-MA).In addition,down-regulated leptin expression by leptin-shRNA also attenuated HPC-induced autophagy in BMSCs,which in turn was associated with increased apoptosis after exposed to sustained H/SD.Furthermore,increased AMP-activated protein kinase phosphorylation and decreased mammalian target of rapamycin phosphorylation that were observed in HPC-treated BMSCs can also be attenuated by down-regulation of leptin expression.Our data suggests that leptin has impact on HPC-induced autophagy in BMSCs which confers protection against apoptosis under H/SD,possibly through modulating both AMPK and mTOR pathway.

Effect of quercetin on secretion and gene expression of leptin in breast cancer

OBJECTIVE: To investigate the possible inhibitory action of pure quercetin on secretion and gene expression of leptin in the T47 D breast cancer cell line.METHODS: In this experimental study, T47 D cells were cultured in monolayers in RPMI 1640. IC50 was determined by MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay after 24 h treatment at different concentrations of quercetin.The levels of leptin gene expression were measured by reverse-transcription real-time polymerase chain reaction(PCR). Secreted leptin was measured in the supernatant of cells by an enzyme-linked immuno sorbent assay.RESULTS: Analysis of MTT assay data showed that quercetin has a cytotoxic effect on T47 D breast cancer cells with 40 μM IC50 after 24 h exposure. Dataanalysis of real-time PCR showed that with increases in quercetin concentration, a decreasing trend was seen in m RNA levels of leptin of treated cells compared with the control cells(P < 0.05). Also,measurement of secreted leptin in the culture media showed a similar decreasing trend in the amount of leptin protein in the treated cells compared with the control cells(P < 0.05).CONCLUSION: Quercetin significantly inhibits the growth of T47 D cells through inhibition of leptin secretion and gene expression in T47 D breast cancer cells. Therefore, it might be an alternative approach to breast cancer therapy through leptin targeting.