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Recently two distinct small molecule inhibitors
2024-04-18
Recently, two distinct small-molecule inhibitors of PHGDH were identified using high-throughput screens, both of which inhibit de novo serine biosynthesis and show selective toxicity to cancer Melittin with high SSP flux [50,51]. The inhibitor NCT-503, which has an IC50 of 2.5μM, reduces the growth
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br Results and discussion br Conclusion The
2024-04-18
Results and discussion Conclusion The tyrosine kinase ALK represents one of the most successful molecular targets for the development of precise medicine to treat stratified subgroups of cancer patients. Three generations of ALK inhibitors have been awarded the FDA's approval or are being exte
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As an alternative to chronic receptor blockade we
2024-04-18
As an alternative to chronic receptor blockade, we have been targeting adenosine kinase (ADK) – an astrocyte-based enzyme that catalyses the phosphorylation of adenosine, as a means to modify Caspase-6, human recombinant protein adenosinergic signalling (Boison, 2006, Etherington et al., 2009). Up-r
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Ultraviolet UV spectroscopy is commonly
2024-04-18
Ultraviolet (UV) spectroscopy is commonly used for screening potential ADA inhibitors [15]. In the UV method, the ADA reaction is calculated by measuring the decrease in absorbance of the substrate at 265 nm or increase in absorbance of the product at 248 nm. However, AD and inosine share a very clo
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beta amyloid Earlier studies revealed an interaction between
2024-04-18
Earlier studies revealed an interaction between HSP90β and ACK1 [15]. In the proteomic approach, we show that ACK1 associates with HSP90α and HSP90β. Additionally, we confirm the existence of a HSP90-ACK1 complex with co-IP experiments. We further analysed whether an inhibition of HSP90 affected the
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We demonstrate a role for low oxygen to
2024-04-18
We demonstrate a role for low oxygen to regulate ATX mRNA in hepatocyte-derived HuH7 GW 6471 mg and human liver slices, consistent with reports of increased ATX expression in a variety of tumours that are frequently hypoxic. Importantly, we show a positive association between elevated ATX mRNA leve
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The diagnosis of ICP is currently based
2024-04-18
The diagnosis of ICP is currently based on the presence of pruritus, raised fasting serum TBS levels above 10μmol/L, and/or elevated serum transaminases (in the absence of diseases that cause cholestasis or pruritus) as well as spontaneous relief of signs and symptoms within four to six weeks after
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br Discussion In our current
2024-04-18
Discussion In our current study, we demonstrated that both the metastatic and recurrent ovarian cancer tissues expressed lower levels of p62 when compared with the patient-matched primary tumor samples. High GSK621 levels of p62 were associated with long progression-free survival of patients wit
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Stroke also known as a cerebrovascular accident or brain
2024-04-18
Stroke, also known as a cerebrovascular accident or DMP 777 attack, is one of the leading causes of death and disability worldwide (Haley et al., 2017; Hankey, 2017; Lie et al., 2017). According to the data released by the World Health Organization (WHO), stroke occurs every 5 s worldwide (WHO, 2016
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The acidification of endocytic compartments
2024-04-18
The acidification of endocytic compartments is closely related to endocytic activity, although the mechanism linking acidification and membrane dynamics is largely unknown. In a recent RNA interference (RNAi)-based screen, V-ATPase depletion blocked the formation of clathrin-coated vesicles, an effe
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br Materials and methods br Results A first series of
2024-04-17
Materials and methods Results A first series of experiments explored whether the Ampkα1 isoform is involved in the regulation of cardiac Pkcζ. To this end, HL-1 cardiomyocytes were transfected with a construct encoding constitutively active Prkaa1T183D (CAα1) or with the empty vector as contro
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Formation of SAHFs in human cells
2024-04-17
Formation of SAHFs in human duvelisib is a dynamic and multifaceted process that is largely dependent on the p16/pRB ras-induced senescence pathway [108]. Many details remain to be elucidated but formation appears to be driven by a complex of histone chaperones (HIRA and ASF1a), a pRB/hBrm/HDAC1/HP
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br Introduction Sustained over activation of neurohormonal s
2024-04-17
Introduction Sustained over-activation of neurohormonal systems is a hallmark in the pathophysiology of cardiac dysfunction following myocardial infarction (MI) and heart failure (HF). Inhibitors of the renin-angiotensin Perhexiline maleate system (RAAS) constitute cornerstones of pharmacotherap
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Aconitase clusters are prone to oxidations and are among the
2024-04-17
Aconitase clusters are prone to oxidations and are among the first to undergo a change in transition state during stages of electrophilic stress rendering them inactive [31]. Aconitase activity in LETO and OLETF did not differ at T0 suggesting that the early onset of insulin resistance may not be at
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Perhaps the first evidence of AMPKs therapeutic ability
2024-04-17
Perhaps the first evidence of AMPKs therapeutic ability in DM1 came from Thomas Cooper’s laboratory where they demonstrated that insulin-independent glucose uptake was unaffected in human DM1 muscle 2750 receptor treated with MET, an AMPK activator and first-line therapy for type 2 diabetes mellitu
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