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In pancreatic islets we found
2023-08-25
In pancreatic islets we found an increase in protein expression of leukocyte 12/15-LO that paralleled the metabolic decline characterized by severe hyperglycemia and reduced islet numbers. Similar increase in 12/15-LO expression by Western blot was found in the control mice, which have a normal meta
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At the outset of targeting the two Gln side chain
2023-08-25
At the outset of targeting the two Gln756 side-chain rotamers, it was unclear which rotational isomer would lead to more potent ASK1 inhibitors. While such a preference might have been anticipated, the cohort of ASK1 inhibitors in Table 3 did not provide any guidance regarding which of the Gln756 am
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br Aromatase inhibitors The aromatase enzyme P arom belongs
2023-08-25
Aromatase inhibitors The aromatase enzyme, P450arom, belongs to the super-family of P450 proteins which includes more than 480 members divided in 74 different families. P450arom is a unique member of family 19 [39], and is located in the endoplasmic reticulum of mammalian Copanlisib that express
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Introduction Preeclampsia a serious hypertensive disorder th
2023-08-25
Introduction Preeclampsia, a serious hypertensive disorder that can occur during pregnancy, is a pregnancy-related disease characterized by the onset of EHop-016 australia and proteinuria after the 20 t h week of gestation, and it occurs in about 5% of all pregnancies [1]. If left untreated, preec
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Melphalan The physiologic conditions and signaling mechanism
2023-08-25
The physiologic conditions and signaling mechanisms that regulate apelin secretion and APLNR expression in malignant tissues appear to be multifactorial. Previous studies have shown that hyperplastic and neoplastic cholangiocytes secrete a variety of hormones, peptides, and growth factors that help
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br Possible complementarity of trimming pathways Determining
2023-08-25
Possible complementarity of trimming pathways Determining the exact pathway for the generation or destruction of MHCI peptide ligands by ERAP1 is important for our understanding of the shaping of the immunopeptidome and for designing inhibitors that can manipulate it. It is also possible however
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br Development of lorlatinib from crizotinib to a clinical c
2023-08-25
Development of lorlatinib from crizotinib (1) to a clinical candidate (6) Xalkori (1, PF-02341066, crizotinib), was the first-in-class ALK inhibitor approved by the Unites States Food and Drug Administration (FDA) in 2011 as a first-line treatment for ALK+- NSCLC patients. This section describes
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The current guidelines are designed to optimize the detectio
2023-08-25
The current guidelines are designed to optimize the detection of IHC+FISH+ cases, most of which (but not all encountered in our study) being classically good responders to crizotinib therapy (resistance mechanisms to crizotinib therapy were not investigated in our study). In addition to the current
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The importance of insulin in
2023-08-24
The importance of insulin in controlling lipolysis and fat mass is further emphasized by mouse models with alterations in the insulin signaling pathway of adipocytes. For example, mice with a tamoxifen-inducible knockout of the insulin receptor in mature adipocytes reveal a substantial decrease of a
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Metformin s pluripotent roles are alluded to in terms of
2023-08-23
Metformin's pluripotent roles are alluded to in terms of its antitumorigenic, glucose-lowering, and cardioprotective effects, which are due in part to its upregulation of AMPK activity [39,40]. Metformin's glucose-lowering effect is a result of reduced hepatic gluconeogenesis, whereas improved insul
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Adenosine is a ubiquitous homeostatic purine nucleoside that
2023-08-23
Adenosine is a ubiquitous homeostatic purine nucleoside that accumulates extracellularly in response to metabolic stresses such as hypoxia and inflammation. Activation of either G protein-coupled adenosine receptors (ARs; A1R, A2AR, A2BR, and A3R) by extracellular adenosine can modulate cell signali
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br Methods br Transparency document br Introduction Epinephr
2023-08-23
Methods Transparency document Introduction Epinephrine (EP) is a critical hormone and catecholamine neurotransmitter in nervous system of mammals.1, 2, 3 It has been known to accelerate and regulate heartbeat, blood pressure, bronchodilation, mydriasis, blood sugar and lipolysis, and can he
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The structure of LO is divided in two
2023-08-23
The structure of 5-LO is divided in two domains, the catalytic C-terminal domain and the N-terminal regulatory C2-like domain (C2ld) [59,60]. The C2ld spans the EPZ5676 1-114 and is responsible for translocation and binding of calcium and membranes [61–63]. The catalytic domain is primarily an α-he
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br LOX in colorectal cancer Colorectal
2023-08-23
5-LOX in colorectal cancer Colorectal cancer (CRC) like other malignancies exhibits an overexpression of 5-LOX. Ohd et al. (Ohd et al., 2003) revealed in a study that malignant colon tissues overexpress 5-LOX activity and retain elevated levels of inflammatory mediators, leukotrienes. Additionall
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br Acknowledgements MC and PD were funded by
2023-08-23
Acknowledgements MC and PD were funded by the Michael J Fox Foundation (Grant ID 9969). We would like to thank Pierluigi Saba, Francesco Traccis and Barbara Tuveri for their technical assistance. Introduction In the prostate, androgens play a crucial role in normal, BPH and cancerous growth b
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