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For the NSCLC patients with
2023-07-18
For the NSCLC patients with EGFR-activating mutations, EGFR-TKIs (gefitinib and erlotinib) are effective clinical therapies [21], [22]. However, approximately 10% of patients harboring EGFR-sensitizing mutations exhibit intrinsic resistance, and up to 40% do not attain a major response to treatment
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HCC aetiology is multifactorial and the disease
2023-07-18
HCC aetiology is multifactorial and the disease is often preceded by other conditions including liver fibrosis and cirrhosis that are associated with HCV, HBV, alcoholic and non-alcoholic hepatitis. The discovery of new therapeutic targets will require a greater understanding of the pathogenic mecha
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br Aurora A Aurora B and Aurora
2023-07-18
Aurora-A, Aurora-B and Aurora-C small molecule inhibitors Nicholas et al. described phenotypic cellular screening of new highly potent and selective class of Aurora kinase inhibitors. Fragment based approach was utilized; core structure of 57 (Fig. 5) was optimized and selective inhibitor 58 (Fig
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br Disclaimer Statement br Acknowledgments br
2023-07-18
Disclaimer Statement Acknowledgments Introduction Metabolic changes are a common feature of cancerous tissues. Mutations in oncogenes and tumor suppressor genes cause alterations to multiple intracellular signaling pathways that rewire tumor cell metabolism and re-engineer it to allow enhan
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Hydrogen sulfide H S a colorless and water soluble
2023-07-18
Hydrogen sulfide (H2S) [33], a colorless and water-soluble gas with the smell of rotten eggs, is now recognized as an important gasotransmitter, after the extensive study of nitric oxide (NO) and carbon monoxide (CO). H2S is produced endogenously via enzymatic reactions of cysteine, homocysteine and
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br Materials and methods br Results br Discussion
2023-07-18
Materials and methods Results Discussion In this study, the orphan receptor GPR25 was cloned from several representative vertebrate species including zebrafish. Although the overall amino H-Lys(Z)-OH sequence identity among these species is not high (38–52%), our synteny analysis clearly i
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Apelin is involved in various physiological functions includ
2023-07-18
Apelin is involved in various physiological functions, including TAK-285 contraction (Ashley et al., 2005), vasodilatation (Jia et al., 2007), feeding control (Valle et al., 2008), and metabolic homeostasis (Higuchi et al., 2007, Dray et al., 2008, Attane et al., 2010). Its plasma level is elevated
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In recent years the higher
2023-07-18
In recent years, the ‘higher lipophilicity’-thus-‘better performance’ tenet, derived from the polar paradox theory applied to micro-structured media, was challenged by novel and unexpected experimental results. In particular, the synthesis of many complete series of fatty Boc-D-Asp(OtBu)-OH.DCHA es
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Dual acting RAAS blockade and neprilysin inhibition
2023-07-18
Dual-acting RAAS blockade and neprilysin inhibition has been evaluated in several clinical HF trials. In PARADIGM-HF [6,7], LCZ696 was superior to enalapril in reducing mortality and HF hospitalizations in symptomatic patients with HF with reduced EF. Augmented benefits on maladaptive cardiac remode
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Therefore in the present study we first examined the ATRAP
2023-07-18
Therefore, in the present study, we first examined the ATRAP 745 australia in human leukocytes of healthy subjects. We next analyzed possible relevant clinical factors affecting ATRAP expression in leukocytes of patients with NCDs. Furthermore, we examined the possible effect of ATRAP downregulatio
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While there is much in vivo work on prion
2023-07-18
While there is much in vivo work on prion-like Aβ, it has not been shown that one can induce inclusions of Aβ in cultured cells as has been shown for tau and α-synuclein. One reason is practical; Aβ is a low molecular weight metabolite cleaved from within the larger amyloid precursor protein (APP) a
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The chronic induction of skeletal muscle AMPK activity is
2023-07-18
The chronic induction of skeletal muscle AMPK activity is an attractive therapeutic approach for DMD, as it addresses multiple cellular pathways needed for powerful phenotypic plasticity, including activation of the slow oxidative myofiber program, corrective autophagic signaling, as well as regulat
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br Results br Discussion Cardiac dysfunction common complica
2023-07-18
Results Discussion Cardiac dysfunction, common complication of severe sepsis, is one cause of death in intensive care units. Accumulated evidence revealed the regulatory effect of autophagy on sepsis-induced cardiac dysfunction [15], [22], although the mechanisms in young and aging are not elu
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The molecular mechanisms that mediate the
2023-07-18
The molecular mechanisms that mediate the plasticity of the NMJ are not well understood. PGC-1α is a master regulator of the NMJ gene expression program 23, 24, and thus AMPK might indirectly regulate the NMJ via its broad influence on the coactivator. Cerveró et al.[6] recently provided more direct
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br Functional repercussions of each trimming pathway
2023-07-17
Functional repercussions of each trimming pathway A main difference between the two pathways presented in Fig. 1 lies in enzyme kinetics and selectivity. In pathway #1, the substrate for ERAP1 is free peptide, and so both kinetics and selectivity are determined by interactions between the peptide
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