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The differential tissue and ligand dependent signaling descr
2022-06-17
The differential tissue- and ligand-dependent signaling described here has important implications for the therapeutic potential of synthetic GPR109A agonists for the treatment of atherosclerosis. The failure of MK-0354, a biased, partial GPR109A agonist, to activate signaling pathways upstream of va
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The top concern for the clinical use
2022-06-17
The top concern for the clinical use of CRISPR-Cas9 technology is safety. Off-target alterations must be avoided to ensure genome integrity and proper cellular function. WGS found no off-target effects among the top 49 predicted off-target sites. WGS did find 4,658 indels and 1,891 SNVs in sgRNA1/2-
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In this study we further expanded the
2022-06-17
In this study, we further expanded the antitumor bioactivity, with the BALB/c S-180 tumor model, which is long-established due to its highly aggressive in all strains of laboratory mice and rats (Cui et al., 2003). We investigated the tumor-regressing ability of β-glucan by different modes of admini
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ARCA The activation of the ERK
2022-06-17
The activation of the ERK pathway may participate in the sensitization of primary afferents in pain transmission (Ji et al., 2009, Lai et al., 2011); the blockade of ERK activation in the DRG can decrease mechanical and heat hypersensitivity in inflammatory pain. IL-10 can inhibit phosphorylation of
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So far GnRH receptors have been detected
2022-06-17
So far, GnRH receptors have been detected in the human ovary, but their physiological importance is still unclear (). In particular, GnRH receptors as well as GnRH types I and II have been localized in the granulosa AS1842856 of pre-ovulatory follicles, but not of follicles from the primordial to t
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br Regulation of gonadotropins by GnRH GnRH is
2022-06-17
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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br Transporter based brain targeting nano DDS Drug
2022-06-17
Transporter-based brain-targeting nano-DDS Drug delivery to the central nervous system (CNS) is still challenging due to the bloodbrain barrier (BBB)53., 54.. The BBB is a natural defense barrier protecting the Celecoxib from harmful substances. Since only selected, neutral, lipophilic small mol
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Our data suggest that Slc a is important for amino
2022-06-17
Our data suggest that Slc38a5 is important for amino-acid-induced α cell proliferation and expansion of α cell mass following GCGR inhibition, but not for formation and maintenance of α cell mass. This is supported by the finding that Slc38a5−/− mice have normal α cell mass. This is interesting sinc
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br Introduction When human red
2022-06-17
Introduction When human red blood uncouplers of oxidative phosphorylation (hRBC) are suspended in depolarising Ringers, they respond by opening a non-selective voltage-dependent cation pathway, the NSVDC channel, which is permeable to mono- and divalent cations [1], [2], [3]. In patch clamp exper
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Human GS is a multi subunit complex consisting of four
2022-06-17
Human GS is a multi-subunit complex consisting of four components: presenilin 1 (PS1), presenilin enhancer 2 (PEN-2), anterior pharynx-defective 1A (APH-1A) and nicastrin (NCT) (Fig. 1a) [5,6]. PS1 comprise nine transmembrane helices (TM 1–9) and contains the catalytic aspartate residues in its TM6
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p16 Recently accumulated evidence has revealed a close link
2022-06-17
Recently, accumulated evidence has revealed a close link of FXR to gluconeogenesis. For example, activation of FXR by its agonist GW4064 improved hyperglycemia in db/db mice by repressing gluconeogenesis [15], and FXR agonist CDCA decreased transactivation activity of key gluconeogenic genes by indu
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Recent evidence indicates that prolonged vasoconstriction of
2022-06-17
Recent evidence indicates that prolonged vasoconstriction of conductance and resistance arteries involves VSMCs HU 308 australia polymerization, through activation of small GTPases [4] and a subsequently transition to a more solid rheology [5]. Actin polymerization occurs in two steps, nucleation a
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Sirolimus rapamycin and everolimus both of which are mTOR
2022-06-17
Sirolimus (rapamycin) and everolimus, both of which are mTOR inhibitors, are released by commonly used first- and second-generation DES. Considering the relatively high rates of the target vessel failure with currently available DES [12,14,16,45,46], there is a need for a novel drug strategy that pr
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The molecular target of N BPs is farnesyl diphosphate syntha
2022-06-17
The molecular target of N-BPs is farnesyl diphosphate synthase (FPPS), a crucial enzyme at the branch point of cholesterol and isoprenoid synthesis in the mevalonate pathway [5]. Because they bind calcium ions, N-BPs accumulate quickly in the skeleton and are internalised by osteoclasts, leading to
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The product chain length determination mechanism of prenyltr
2022-06-17
The product chain-length determination mechanism of -prenyltransferases has not yet been elucidated, although mutational analyses of highly conserved residues and of characteristic amino KB SRC 4 residues in each subfamily of -prenyltransferases have enabled the understanding of the basic catalytic
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