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br Chemistry The methylsulfanyl dihydro H thieno g
2022-02-28
Chemistry The 8-methylsulfanyl-4,5-dihydro-1H-thieno[3,4-g]isothiadizaole scaffold was synthesized from commercially available 1,3-dioxolane-2,1′-cyclohexane-4-one 17 (Scheme 1). The isothiadizaole ring was formed with SOCl2 from N-carboxamide hydrazine imine 19, which was prepared from 17 and hy
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Introduction Glycogen synthase kinase GSK is an
2022-02-26
Introduction Glycogen synthase kinase-3 (GSK-3) is an enzyme playing multiple roles in animal tissues and organs, and Vacuolin-1 is not an exception. Apart from involvement in regulation of apoptosis and survival GSK-3 influences neuronal morphology, synapse formation, memory reconsolidation in ad
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In summary we have designed and optimized a
2022-02-26
In summary, we have designed and optimized a new series of 1,4-dioxycyclohexane GPR119 agonists. SAR studies led to the discovery of the preferred molecule that has potent and efficacious GPR119 activity across species. This lead compound exhibited an excellent ADME and safety profile, and demonstra
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Disrupting the dialog between microbiota and
2022-02-26
Disrupting the dialog between microbiota and the host, especially at the level of mucosal immunology, is expected to have profound effects on disease development. By using the AOM+DSS model of colitis-associated CRC, Singh et al. (2014) showed that development of inflammation and CRC are exacerbated
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br Conflict of interest statement br Acknowledgements We
2022-02-26
Conflict of interest statement Acknowledgements We acknowledge the support of Zoetis Animal Health, Estrotect, Select Sires and Texas A&M AgriLife Research. The assistance of Randle Franke and Ernest Soto is also gratefully acknowledged. Background Luteal phase deficiency (LPD) is caused b
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br Acknowledgements This work was supported by the
2022-02-26
Acknowledgements This work was supported by the grants from National key Basic Research Program of China (2012CB124702), 948 Program (2015-Z33), National Natural Science Foundation of China (31172093, 31301947), the National Science Foundation for Fostering Talents in Basic Research (J1103510), S
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Psoriasis is an inflammatory skin disease characterized by e
2022-02-26
Psoriasis is an inflammatory skin disease characterized by epidermal hyperplasia; micro-abscesses; neo-angiogenesis; a proinflammatory cytokine environment involving alterations of IL-17A, IL-23, and TNF-α; and activation of and infiltration by macrophages, mast cells, neutrophils, CD11c+ dendritic
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LY 294002 The molecular mechanism of gliotransmitter release
2022-02-26
The molecular mechanism of gliotransmitter release is not fully understood until now, and previous studies have emphasized that the elevation of [Ca2+]i triggers vesicular LY 294002 of glutamate. Parpura et al. reported that the essential role of Ca2+ release from internal stores in glutamate releas
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Silicristin br Acknowledgments br Introduction Histone deace
2022-02-25
Acknowledgments Introduction Histone deacetylases (HDACs) related to tumor suppressor genes have become promising targets for the treatment of cancer [1,2]. Under the normal physiological conditions, Histone acetyltransferases (HATs) and histone deacetylases (HDACs) together regulate the acety
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br Acknowledgments We thank Dr Kathleen Sullivan of Merck
2022-02-25
Acknowledgments We thank Dr Kathleen Sullivan of Merck Research Laboratories for providing the CHO-K1 norepinephrine bitartrate expressing an NFAT-β-lactamase reporter and the Gα subunit Gqi5, Dr. Chen Liaw (Arena Pharmaceutical), Ms. Rebecca Kaplan, Mr. Frank Xiaodong Gan for technical assistan
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Our synthetic approach to GPR antagonists was designed
2022-02-25
Our synthetic approach to GPR55 antagonists was designed so that many different structures could be accessed to rapidly explore initial SAR, along with validating or modifying our current model (). The synthesis begins with the coupling of a carboxylic ornidazole to 4-piperidone by first forming th
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In order to elucidate the mechanisms behind
2022-02-25
In order to elucidate the mechanisms behind the observed changes in metabolic activity in the cardiomyoblasts we investigated changes in gene and protein expression subsequent to treatment with PSN632408 with or without concurrent exposure to palmitate. Activating GPR119 in basal and high palmitate
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In vertebrates three cognate receptors or
2022-02-25
In vertebrates, three cognate receptors or receptor-like sequences have been identified with distinct distributions and functions (Millar, 2005, Neill et al., 2001). Only two types of GnRHR occur in mammals, though (Morgan and Millar, 2004). The mammalian type I GnRHR shares over 80% amino GSK265615
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br Regulation of gonadotropins by GnRH GnRH is released
2022-02-25
Regulation of gonadotropins by GnRH GnRH is released from the hypothalamus, and its release pattern is known to be pulsatile. That is, the pulse frequency and amplitude of GnRH release vary physiologically during reproductive cycles in females, and differentially stimulate the production and rele
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Hesperidin is an abundant and inexpensive plant
2022-02-25
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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