• The focused set of additional pyrazole analogs allowed

  2021-12-14

  

  The focused set of additional pyrazole analogs allowed the identification of three additional moderately potent γ-secretase modulators, , and which were subsequently screened in a kinetic solubility assay. Unfortunately, neither the architectural changes in analog nor the integration of trifluoro

• Because of its role in

  2021-12-14

  

  Because of its role in the cleavage of Aβ and the fact that many genetic forms of AD are caused by mutations in the enzyme, GS has long been a target for drug development, though previous clinical trials of Semagacestat, a GS inhibitor, have failed due to an increase in skin cancer, and a decrease i

• LEE011 Until recently the mechanism of

  2021-12-14

  

  Until recently the mechanism of how GSMs shifted γ-secretase cleavage was poorly understood. Today, building on the sequential cleavage model developed by Ihara and colleagues [14], there is evidence that GSMs act as processivity enhancers, and iGSMs as inhibitors of processivity [120]. At least for

• In the last thirty years

  2021-12-14

  

  In the last thirty years, accumulating data have addressed a role for GABA in the modulation of gastrointestinal (GI) functions via its possible involvement in the circuitry of the enteric nervous system (ENS). The ENS is a complex neuronal network located within the gut wall, capable of regulating,

• The Hippo pathway has been well established as a tumor

  2021-12-14

  

  The Hippo pathway has been well established as a tumor suppressor pathway and is involved in many diverse biologic processes including cell growth, cell death, and organ size control in organisms, ranging from Drosophila to mammals [4]. Central to this pathway is a kinase cascade in which the Ste20-

• Another lever to efficiently eradicate tumors including ovar

  2021-12-14

  

  Another lever to efficiently eradicate tumors including ovarian cancer might rely on their high addiction to iron [34]. In fact, ultrasmall silica-based nanoparticles, functionalized with melanoma-targeting peptide, efficiently triggered ferroptosis not only in cell culture but also in tumor bearing

• To date three other allosteric binding sites

  2021-12-13

  

  To date, three other allosteric binding sites of HIV-1 IN have also been reported. In the work of Wielens and co-workers [33], a pocket formed by the residues Tyr83, Trp108, Asn184, Ile200 and Val201 was found, which can be bound by small molecules. In the work by Rhodes et al. [34], a small-molecul

• One class of microbial derived metabolites

  2021-12-13

  

  One class of microbial-derived metabolites that have received significant attention are the short-chain fatty acids (SCFA), which include butyrate, acetate and propionate. The production of SCFA occurs in the colon following microbial fermentation of dietary fibers and SCFA can also be consumed in c

• br Introduction Topological hedgehogs keep generating intere

  2021-12-13

  

  Introduction Topological hedgehogs keep generating interest in point-set topology as they are a rich source of counterexamples and applications (for a comprehensive survey on topological hedgehogs we refer to [1]; see also [9]). They may be described as a set of spines identified at a single poin

• Some data also suggested that CCR could influence the progre

  2021-12-13

  

  Some data also suggested that CCR5Δ32 could influence the progression of HCV-related liver diseases (Goulding et al., 2005; Hellier et al., 2003; Wald et al., 2004). However, after stratifying HCV+ individuals according to clinical/histological criteria, no association of CCR5Δ32 with these HCV-rela

• The frequency of GSTM and GSTT null genotypes

  2021-12-13

  

  The frequency of GSTM1 and GSTT1 null genotypes vary in different populations. For example, Hiragi et al. (2007) reported a frequency of 17–35% for the GSTM1 null genotype and 22–44% for the GSTT1 null genotype in Brazilians of African descent (Hiragi et al., 2007). Chen, Liu, and Relling (1996) rep

• A similar symbiotic relationship has been

  2021-12-13

  

  A similar symbiotic relationship has been reported in the brain, where increased gradients of lactate secreted by astrocytes enables neurons to import and use this nutrient, a process referred to the ‘neuron–astrocyte lactate shuttle’ [16]. Similarly, lactate-based metabolic coupling established by

• br Materials and methods br Results Using

  2021-12-13

  

  Materials and methods Results Using an 84 gene Th1-Th2-Th3 cytokine profile, 17 genes were significantly up-regulated in PBMC one week post-marathon compared to pre-marathon samples (Table 1). Eight genes were down-regulated among various subjects but none consistently enough to achieve statis

• One of the most common dietary approaches against obesity as

  2021-12-13

  

  One of the most common dietary approaches against obesity-associated diseases is the increase in the consumption of ω3 polyunsaturated fatty acids [18], [19]. Since seminal paper by Bang and Dyeberg in which the low prevalence of coronary heart disease among the Inuit was associated with the high ma

• Hesperidin is an abundant and

  2021-12-13

  

  Hesperidin is an abundant and inexpensive plant flavonoid, largely derived from citrus species including sweet orange and lemon. Hesperetin (Hst) is the aglycone of hesperidin. Hesperidin and hesperetin have been reported to show a battery of pharmacological properties, including anti-hyperlipidemic

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