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We next sought to determine the
2023-04-17
We next sought to determine the kinase responsible for IR-induced phosphorylation of 53BP1. Because the sites under investigation all lie in a consensus sequence for ATM, ATR and DNA-PK, that are all activated by IR, the involvement of each of these kinases was investigated. Preincubation of SB 2587
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TUNEL assay Apoptotic DNA fragmentation
2023-04-17
TUNEL assay. Apoptotic DNA fragmentation in Cy5 amine (non-sulfonated) was measured using a commercially available TUNEL assay kit (Thermo Fisher). Frozen cells were fixed with 10% paraformaldehyde/PBS. Apoptosis was determined by staining the 3′-OH ends of fragmented DNA with biotin-dNTP using DNA
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Recent studies have supported the
2023-04-17
Recent studies have supported the existence of an inward RAS regulatory mechanism in which AT1 receptors downregulate angiotensin-converting enzyme 2 (ACE2) and subsequently impair angiotensin-(1-7) generation and MAS functionality (Jessup et al., 2006, Gallagher et al., 2008, Xia et al., 2009, Pern
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Inhibition of autophagy has been shown
2023-04-14
Inhibition of autophagy has been shown to alleviate neuronal damage after cerebral ischemia, both in cell culture and rodent models (Koike et al., 2008, Li et al., 2015, Wang et al., 2016, Zhang et al., 2014, Zheng et al., 2014). Therefore, blockage of autophagy is a potential target for prevention
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Thus far clinical data indicate that IDO inhibitors
2023-04-14
Thus far, clinical data indicate that IDO1 inhibitors have manageable toxicity, albeit with a relatively short period of treatment in a small number of patients. KYN is a pluripotent mediator and key intermediate for the synthesis of a host of downstream KP metabolites that are implicated in inflamm
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Application of the broad acting HTR antagonist methiothepin
2023-04-14
Application of the broad-acting 5-HTR antagonist methiothepin (Bard et al., 1996, Hoyer et al., 1994, Peroutka, 1990) converted the TBS-induced response of both thalamocortical and intracortical A1 synapses from LTP to LTD, an effect that was mimicked by the selective 5-HT2R antagonist ketanserin (L
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Apoptosis or programmed cell death is
2023-04-14
Apoptosis or programmed cell death is a function of biochemical mechanisms, which are energy-dependent. It is considered to be a vital component of many processes such as normal cell cycle, immune mechanism, atrophy, embryonic development and toxin-induced cell death (Elmore, 2007). In addition, apo
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The most potent compounds within
2023-04-14
The most potent compounds within the current series of compounds were therefore , , , , and , with Caspase-6, human recombinant protein possessing the best selectivity towards the lyase reaction in comparison to the hydroxylase reaction, indeed, this compound was found to possess an IC value of 1
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Human leukemic blasts from both AML
2023-04-14
Human leukemic blasts from both AML and ALL patients demonstrated 5-, 12-, and 15-LOX expression [54]; however, using quantitative PCR, 5-LOX was much more prevalent than 15-LOX. When 15-HETE, 12-HETE, and LTB4 were tested for a direct effect on leukemic blasts, none induced apoptosis [54]. In contr
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br The role of apelin in hypertension diseases The
2023-04-14
The role of apelin in hypertension diseases The role of apelin and its receptor APJ in cardiovascular diseases has been described in numerous studies (Table 2) [36,37]. It has been revealed that exogenous apelin may lower blood pressure. Tatemoto et al. [6] have discovered that different forms of
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Although the interactions of PhLP with G and its
2023-04-14
Although the interactions of PhLP with Gβγ and its other partners have been convincingly documented through in vitro studies, it is not clear how PhLP controls WM-2474 signaling in vivo. C. elegans provides a powerful genetic model to analyze Phosducin function and study its interacting partners in
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Previous studies have thus demonstrated that AR activation g
2023-04-13
Previous studies have thus demonstrated that AR activation generally correlates with the promotion of urothelial carcinogenesis and cancer growth. In this article, we review available data suggesting their modulation through the AR pathway as well as correlations of AR signals with sensitivity to co
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In view of the ubiquitous distribution of the arachidonate
2023-04-13
In view of the ubiquitous distribution of the arachidonate 12S-lipoxygenase isoforms and the variety of cellular reactions influenced by the resulting arachidonate metabolites, these products widely play important roles in many biological systems. The development of new type-specific inhibitors of t
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These findings suggest that eventually more
2023-04-13
These findings suggest that eventually more than one 12/15-lipoxygenase isoform may play a role in human atherosclerosis. Humans have two 12-lipoxygenases and two 15-lipoxygenases which show different expression patterns, substrate specificities and stereo-selective metabolism [1]. However, in Pomal
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Lorlatinib is an orally active
2023-04-13
Lorlatinib is an orally active brain penetrant cyclic 2-aminopyridine derivative that is a type I½ B ALK inhibitor (Fig. 5F) [61]. This medicinal is an effective antagonist against the more common L1196M and G1269A crizotinib-resistant mutations as well as the less common T1151Ins, L1152R, C1156Y, F
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