• Clinical trials of all GSIs have ended prematurely raising

  2021-11-01

  

  Clinical trials of all GSIs have ended prematurely, raising the question on our understanding of their target, the γ-secretase/presenilin. Development of compounds to target γ-secretase and reduce Aβ production is complicated by the fact that γ-secretase/presenilin has critical biological function,

• br Acknowledgments We apologize for the omission of primary

  2021-11-01

  

  Acknowledgments We apologize for the omission of primary citations owing to space limitations. This work was supported by grants from National Natural Science Foundation of China (81772801 and 81472455 to C.D.), the Key Program of Zhejiang Provincial Natural Science Foundation (LZ17H160002 to C.D

• The present study was therefore conducted with

  2021-11-01

  

  The present study was therefore conducted with three aims; (1) we tested the effect of IRL-1620, a selective ETB receptor agonist, on the analgesic tolerance to morphine and oxycodone in mice; (2) we determined the expression of ETA receptors and ETB receptors in the CX-5461 of morphine and oxycodo

• In an RNAi screen to interrogate the function of transmembra

  2021-11-01

  

  In an RNAi screen to interrogate the function of transmembrane proteins in ISCs/EBs, we identified the SJ protein tetraspanin 2A (Tsp2A) as a tumor suppressor. Further characterization reveals that Tsp2A expression initiates in ISCs and Tsp2A protein assembles at the SJs in the progenitor ascorbic a

• While the binding of HK to VDAC is

  2021-11-01

  

  While the binding of HK1 to VDAC1 is strong and continuous, the binding of HK2 to VDAC1 is much weaker, and alternates between a cytoplasmic and a mitochondrial-bound states (John et al., 2011). This dynamic process is regulated by the metabolic and energetic requirements of the LY2603618 synthesis

• Immunohistochemical evaluation of gastric cancer tumor

  2021-11-01

  

  Immunohistochemical evaluation of gastric cancer tumor samples revealed that 57.8% (59/101) were positive for GLI1, and 71.3% (72/101) stained positive for SHH [27]. Overexpression of SHH and GLI1 protein were significantly associated with larger tumor size, tumor aggressiveness, and less differenti

• br Materials and methods br Results br Discussion Myocardium

  2021-11-01

  

  Materials and methods Results Discussion Myocardium reperfusion injury contributes almost half of myocardial infarct size in myocardial infarction patients, and infarct size is closely correlated with the probability of developing Schizandrin A receptor failure [1]. Despite this knowledge,

• Gp induces cell death by

  2021-10-29

  

  Gp120 induces cell death by apoptotic mechanisms and increases intracellular Ca, and activates messengers related to cell death. Intracellular mechanisms of neuronal damage are mainly a consequence of the activation of the N-methyl-d-aspartate receptor (NMDAR) [2], [5], which induces excitotoxicity

• In three groups independently proposed two

  2021-10-29

  

  In 2001, three groups independently proposed two different mechanisms for the catalytic reaction of GlxI [5], [6], [7]. Richter and Krauss (RK) used HF/4–31G calculations of the active site, coupled with a frozen effective fragment potential description [8], [9] of eleven residues in the binding sit

• Apart from a few mutations which affect

  2021-10-29

  

  Apart from a few mutations, which affect intracellular and extracellular loops of hCRT-1, the mutations are primarily found in the hydrophobic core of the transporter; in fact, TMDs 7 and 8 appear to be a hot spot for mutations (Freissmuth et al., 2018). Several mutations are found at positions, whi

• Here we examined whether complete ablation

  2021-10-29

  

  Here, we examined whether complete ablation of GIP production could reduce weight gain in the absence of the adipocyte hormone leptin, a condition that results in extreme hyperphagia, obesity, hyperinsulinemia, and insulin resistance, in both mice [24] and humans [25]. We found that Lepob/ob mice be

• Previous research has suggested that differences in spatiote

  2021-10-29

  

  Previous research has suggested that differences in spatiotemporal regulation of intracellular signaling pathways can confer specificity to cellular responses (Marshall, 1995). Conventional approaches based on gain- or loss-of-function genetic manipulations or small-molecule inhibitors, however, lac

• The ability of GPX and other

  2021-10-29

  

  The ability of GPX4 and other selenoproteins to be selectively induced by ferroptotic stimuli suggests that the stress-induced increase in the transcription of a number of putative, “antioxidant” selenoproteins is an adaptive homeostatic, but insufficient response to prevent cell death in the face o

• The root of Danshen has been widely used

  2021-10-29

  

  The root of (Danshen) has been widely used as traditional Chinese medicine for many years and shown to exhibit significant pharmacological activities for a variety of human diseases including cancers. Tanshinones, the major active components, belong to a group of an abietane-type diterpenes contain

• The Jumonji JmjC domain containing KDM family members can

  2021-10-29

  

  The Jumonji (JmjC) domain-containing KDM family members can be clustered into seven subfamilies (KDM2 – KDM8). The KDM2 cluster catalyzes H3K36me2/me1 demethylation; in addition, KDM2B/JHDM1B/FBXL10 has been suggested to catalyze demethylation of H3K4me3 [3]. Cell culture studies support that KDM2

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