Melatonin membrane receptors in peripheral tissues: distribution and functions

Many of melatonin's actions are mediated through interaction with the G-protein coupled membrane bound melatonin receptors type 1 and type 2 (MT1 and MT2, respectively) or, indirectly with nuclear orphan receptors from the RORα/RZR family. Melatonin also binds to the quinone reductase II enzyme, previously defined the MT3 receptor. Melatonin receptors are widely distributed in the body; herein we summarize their expression and actions in non-neural tissues. Several controversies still exist regarding, for example, whether melatonin binds the RORα/RZR family. Studies of the peripheral distribution of melatonin receptors are important since they are attractive targets for immunomodulation, regulation of endocrine, reproductive and cardiovascular functions, modulation of skin pigmentation, hair growth, cancerogenesis, and aging. Melatonin receptor agonists and antagonists have an exciting future since they could define multiple mechanisms by which melatonin modulates the complexity of such a wide variety of physiological and pathological processes.     

Keap1-Nrf2-ARE通路与脑缺血

Keap1 -Nrf2-ARE通路在抗肿瘤、抗应激、抗凋亡、抗炎症等方面具有广泛的细胞保护功能.其在神经系统疾病中的神经保护作用已成为目前的研究热点之一.文章综述了Keap1-Nrf2-ARE通路在脑缺血中的神经保护作用.     

The effect of RCTs on drug demand: Evidence from off-label cancer drugs

This paper investigates the effect of scientific information from randomized controlled clinical trials (RCTs) on the demand for off-label uses of cancer drugs. This is a unique setting where demand for a drug for a specific use is observable both before and after the first RCT results are released. Using variation in the timing of RCTs across off-label uses of drugs, I find that demand responds asymmetrically to the trial results based on the statistical significance of the clinically relevant endpoint. When this endpoint is statistically significant, there is a large and immediate increase in demand. When this end point is not statistically significant, physicians are relatively slow to abandon use of the drug.     

MicroRNA在胃癌中的调控机制及预后价值

作为非编码RNA (ncRNAs)的一种,微小RNA(microRNA,miRNA)在基因表达调控方面受到广泛关注.MiRNA参与细胞周期、细胞凋亡、细胞迁移等进程,在肿瘤发生发展过程中也发挥重要作用.中国胃癌发病率较高,但对胃癌的治疗未能取得突破性进展,进展期胃癌患者往往预后不佳.目前尚缺乏可对胃癌患者预后进行判断的有效生物学标志,胃癌耐药也是临床的棘手问题.如何根据有效的生物学标志来判断预后,并针对这些靶点展开治疗,如何改善胃癌化疗耐药问题.miRNA在基因调控方面的作用给攻破这些难题带来了可能.该文是近年来关于miRNA与胃癌患者预后关系,改善患者预后,化疗耐药调控等方面的最新研究的综合论述.     

The lipid connection–regulation of voltage-gated Ca2+ channels by phosphoinositides

Recent findings have revealed a pivotal role for phospholipids phosphatidylinositol -4,5-biphosphate (PIP₂) and phosphatidylinositol -3,4,5-trisphosphate (PIP₃) in the regulation of high voltage-activated (HVA) Ca²⁺ channels. PIP₂ exerts two opposing actions on HVA Ca²⁺ channels: It stabilizes their activity but also produces a voltage-dependent inhibition that can be antagonized by protein kinase A (PKA) phosphorylation. PIP₂ depletion and arachidonic acid together mediate the slow, voltage-independent inhibition of HVA Ca²⁺ channels by G _q/11 -coupled receptors in neurons. A sufficient level of plasma membrane PIP₂ also appears to be necessary for G _βγ -mediated inhibition. On the other hand, increased production of PIP₃ by PI-3 kinases promotes trafficking of HVA Ca²⁺ channels to the plasma membrane. This review discusses these findings and their implications.