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However the clinical development of
2021-11-09
However, the clinical development of was terminated in 2013 due to the concerns over liver toxicity, raising important questions regarding the long-term safety and viability of targeting GPR40 and, more specifically, about our understanding of the pharmacobiology and signaling spectrum of this rece
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C prevents the glutamate and erastin induced ROS accumulatio
2021-11-09
C16 prevents the glutamate- and erastin-induced ROS accumulation but does not affect the decrease in GSH, indicating that prevention of ROS accumulation by C16 is not due to the restoration of GSH levels. Instead, C16 itself possessed superoxide anion scavenging activity in vitro at similar concentr
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br Introduction The term autophagy was
2021-11-09
Introduction The term “autophagy” was coined by Christian de Duve in 1963 to describe the process of removing and degrading intracellular components such as unused proteins and damaged organelles through lysosomes [1,2]. Autophagy has been divided into three main types, namely, macroautophagy, mi
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br Declarations of interest br Founding information
2021-11-09
Declarations of interest Founding information This work was partially supported by the New Energy and Industrial Technology Development Organization (NEDO) Japan [grant number P03043]; and Grants-in-Aid for Scientific Research [grant number 16H00738 to H.M.] from the Japan Society for the Prom
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Over of all melanomas have activating BRAF mutations
2021-11-09
Over 50% of all melanomas have activating BRAF mutations [29] and inhibition of the Ras/Raf/MEK/ERK signaling pathways is one of the most promising treatments for malignant melanoma [30]. However, studies using BRAF inhibitors have identified various feedback mechanisms to activate BRAF pathway in m
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Intestinal epithelium renewal is tightly controlled by Hedge
2021-11-08
Intestinal epithelium renewal is tightly controlled by Hedgehog genes. Three Hedgehog genes are highly conserved in mouse and human, including Sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog (Dhh) [13]. Hedgehogs bind to Patched (PTCH) [[14], [15], [16]], which unlike conventional r
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br Conclusion and future perspectives In the setting
2021-11-08
Conclusion and future perspectives In the setting of myocardial I/R stress, HDAC activity is induced and contributes to myocardial injury. HDAC inhibition appears to protect the our from I/R injury by activating a variety of pro-survival molecular pathways. From a clinical relevance standpoint, i
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The prevalence of hepatitis C virus HCV infection in p
2021-11-08
The prevalence of hepatitis C virus (HCV) infection in p.C282Y homozygotes in North America is unknown. We determined the prevalence of anti-HCV antibody and HFE genotype and serum ferritin (SF) associations in non-Hispanic white participants in the Hemochromatosis and Iron Overload Screening (HEIRS
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Not all metals are susceptible of
2021-11-08
Not all metals are susceptible of being accumulated by insects. Tissue concentrations of essential metals like Cu and Zn are regulated in many insects and hence cannot be used to biomonitor metal pollution (Hare, 1992). A similar behaviour could explain the observed stability of Zn and Cu relative t
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br Future perspectives sGC signaling is important in
2021-11-08
Future perspectives sGC signaling is important in the maintenance of multiple physiological functions. sGC is localized to cell membranes with both sGC Cys modifications and heme regulation identified as the crucial components in regulating sGC activity. Specifically, S-nitrosation of several com
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FFAR is highly expressed not only
2021-11-08
FFAR1 is highly expressed not only in β cells but also in α nae inhibitor (Segerstolpe et al., 2016), which gives the interesting perspective that 20-HETE may function both as an autocrine and as a paracrine regulator of islet cell function (Figure 1A), i.e., acting in symphony with the many other
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Injury to oligodendrocyte progenitors caused in part
2021-11-08
Injury to oligodendrocyte progenitors caused in part by glutamate contributes to the pathogenesis of myelination disturbances in PVL [5]. In the immature human brain, the susceptibility of developing oligodendrocytes to hypoxia-ischemia correlates with their expression of glutamate receptors of the
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br The concept of the axo myelin synapse
2021-11-08
The concept of the axo-myelin ‘synapse’ Axons can release glutamate in a Ca+-dependent and independent manner (reviewed in [13,69]). Glutamate released from axons activates GluRs located in myelin, a feature that gave rise to the idea of the axo-myelin ‘synapse’ by analogy with classical synaptic
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br Glucose metabolism and diet Glucokinase is essential for
2021-11-08
Glucose metabolism and diet Glucokinase is essential for sensing blood glucose levels, thus controls metabolism (Iynedjian, 1993, Iynedjian, 2009, Postic et al., 2001, Agius, 2008). Loss of glucokinase activity in humans and mice leads to diabetes (Printz et al., 1993b, Postic et al., 2001, Agius
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The role of the ER EK variant
2021-11-08
The role of the ER22/23EK variant which is associated with relative resistance to GC, as shown by a reduction of transactivating capacity in vitro and less suppression of DMOG mg levels after 1mg DST in vivo. Relative GC resistance associated with the ER22/23EK polymorphism might protect from the d
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