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We conclude that a combination of GD
2022-06-07

We conclude that a combination of GD2-specific CAR T cell therapy with pharmacological EZH2 inhibition deserves investigation as a new therapeutic strategy in EwS and potentially other cancers with heterogeneous GD2 expression, including osteosarcoma, various soft tissue sarcomas, melanoma, lung can
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Kinases belonging to the Thousand and one
2022-06-07

Kinases belonging to the Thousand and one (Tao) family are conserved throughout evolution. Three Tao proteins are encoded in the human genome (TAO1, TAO2, and TAO3), while D. melanogaster possesses a single ancestral Tao kinase (Tao-1). Like Hpo and GckIII, Tao kinases belong to the Sterile 20-like
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A complimentary approach with Per Luc cells exposed
2022-06-07

A complimentary approach with Per2:Luc VX-661 receptor exposed to hypoxia as well as with mBmal1:Luc circadian reporter cells in which we overexpressed variants of HIF-1α and HIF-2α revealed that hypoxia and HIFs can not only shorten the period but also decrease the amplitude of the clock (Figures
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Since we found miR b p to be differentially expressed
2022-06-07

Since we found miR-15b-5p to be differentially expressed along the porcine intestine in 31 day old piglets in a former study [10], the entire miRNA family was analyzed in terms of interaction with potential target-genes. In silico analysis predicted miR-15 family members to target the hedgehog signa
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br Mechanisms of Resistance As with other cancer treatments
2022-06-07

Mechanisms of Resistance As with other cancer treatments in development, resistance is a concern with HHIs. Most observations regarding HHI resistance originate from patients with BCC [78]. In the clinic, resistance to vismodegib and sonidegib were observed when used to treat advanced BCC [78], [
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In our previous study we designed and synthesized
2022-06-07

In our previous study, we designed and synthesized compounds of A series from the starting material 4-hydroxy-3-methoxycinnamic idasanutlin (ferulic acid). These compounds with R group being amino acid residues, fatty acyl group and sulfuryl group showed moderate HDAC inhibition and in vitro antitu
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Recently CFS has been included in
2022-06-07

Recently, CFS has been included in the group “low cystine and glutamine syndromes,” which are characterized by a combination of abnormally low plasma levels of these two aminoacids, as well as reduced natural killer cell activity, and increased rates of urea production [13]. Some studies indicated
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It is extremely difficult to
2022-06-07

It is extremely difficult to predict a plausible conformer of hsGCαβ heterodimer with right orientation of multiple domains. Even though the template identities in case of dimeric domains were not high enough but still we modelled the entire heterodimeric structure of hsGCαβ with a reasonable and ju
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The first report of GUCY D
2022-06-07

The first report of GUCY2D-related gene augmentation therapy in mammalians was also reported in 2006 in the KO mouse model (section 4.1.1). In this study, an AAV5 vector by using AAV5-mediated transfer of the bovine cDNA (the same used in the chicken study) was injected to the post-natal KO retina a
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Calcium mobilization FLIPR assay CHO K cells expressing
2022-06-07

Calcium mobilization (FLIPR) assay: CHO-K1 cells expressing an NFAT-β-lactamase reporter and the promiscuous Gα-subunit Gqi5 were stably transfected with either empty vector (pCDNA3.1, Invitrogen) or vector expressing HA-GPR81, GPR109A or GPR109B. Cells were seeded at 10,000cells/well in 384-well cu
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After brain injury adenosine levels rapidly increase in
2022-06-06

After brain injury, adenosine levels rapidly increase in the brain [9,10]. As shown in our previous studies, the increased adenosine concentration acts on adenosine A2A receptors (A2ARs), increasing post-traumatic glutamate levels in the brain and exacerbating the severity of injuries [11,12]. Accor
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In summary this study shows that
2022-06-06

In summary, this study shows that compound 4d has strong clinical potential as an efficient GLP-1/GCGR agonist exhibits weight-lowering, lipid-regulation and diabetes-protective effects and plays an important role in the prevention and therapy of diet induced obesity and dyslipidemia. The present st
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Importantly the levels of the
2022-06-06

Importantly, the levels of the pro-inflammatory cytokines TNF-α and IL-1β and Nf-κB, a key transcription factor in chronic inflammatory responses that is activated by pro-inflammatory cytokines, were also reduced by the drugs, confirming our previous results that demonstrated anti-inflammatory effec
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Polymerisation of HbS initiates the clinical complications
2022-06-06

Polymerisation of HbS initiates the clinical complications of SCD (Bunn and Forget, 1986). The resulting sequelae are multiple and diverse, and their individual impact on pathogenesis is difficult to elucidate. Early changes include altered red cell membrane permeability (Gibson and Ellory, 2002, L
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While the apparent complexity of
2022-06-06

While the apparent complexity of gap junction regulation presents challenges, new technologies continue to propel the field forward. Advances in microscopy are increasingly able to capture rapid dynamics at the plasma membrane (e.g., biosensors [67] and lattice light sheet microscopy [100]) and to d
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