The international journal of biochemistry & cell biology
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Int. J. Biochem. Cell Biol. · Jun 2020
ReviewThe pivotal role of ubiquitin-activating enzyme E1 (UBA1) in neuronal health and neurodegeneration.
Ubiquitin-activating enzyme E1, UBA1, functions at the apex of the enzymatic ubiquitylation cascade, catalysing ubiquitin activation. UBA1 is thus of fundamental importance to the modulation of ubiquitin homeostasis and to all downstream ubiquitylation-dependent cellular processes, including proteolysis through the ubiquitin-proteasome system and selective autophagy. ⋯ Moreover, ubiquitylation-independent functions of UBA1 of importance to neuronal functioning have been proposed. Here, we summarise findings supporting the significant role of UBA1 in regulating neuronal functioning, and discuss the detrimental consequences of UBA1 impairment that contribute to neuronal dysfunction and degeneration.
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Int. J. Biochem. Cell Biol. · Sep 2019
ReviewVirtual Reality interventions for acute and chronic pain management.
Virtual Reality (VR) is now consumer ready and nearing ubiquity. In terms of clinical applications, several studies suggest that VR can be effective as a complementary adjunct or alternative non-pharmacologic analgesic in a range of pain-inducing procedures and in management of chronic pain. ⋯ However, further research is needed to establish its long-term benefits if VR is to be adopted into mainstream protocols for analgesia management. This research requires a range of study designs with collection of patient self-report and clinical data together to develop bespoke interventions for different cohorts.
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Int. J. Biochem. Cell Biol. · May 2019
ReviewAntisense oligonucleotide therapies for Amyotrophic Lateral Sclerosis: Existing and emerging targets.
Amyotrophic lateral sclerosis (ALS) is a disease with highly heterogenous causes, most of which remain unknown, a multitude of possible disease mechanisms, and no therapy currently available that can halt disease progression. However, recent advances in antisense oligonucleotides have made them a viable option for targeted therapeutics for patients. ⋯ Furthermore, biological pathways involved in the pathogenesis of disease also offer tantalizing targets for intervention using antisense oligonucleotides. Here we detail existing and potential targets for antisense oligonucleotides in ALS and briefly examine the requirements for these drugs to reach and be effective in clinic.
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Int. J. Biochem. Cell Biol. · Feb 2019
Tachykinin NK1 receptor antagonist L-733,060 and substance P deletion exert neuroprotection through inhibiting oxidative stress and cell death after traumatic brain injury in mice.
Substance P (SP) is believed to play a role in traumatic brain injury (TBI), and the inhibition of binding of SP to the tachykinin neurokinin-1 receptor (NK1R) using NK1R antagonists had made favorable effects on TBI. Our current study addresses the functional roles and underlying mechanisms of SP and NK1R antagonist L-733,060 following TBI. Adult male wild type C57BL/6 J and SP knock out (SPKO) mice received a controlled cortical impact and outcome parameters were assessed. ⋯ Together, the results of this study implicate a functional role for NK1-R antagonist L-733,060 and deletion of SP in TBI-induced neurological outcome, oxidative damage, neuroinflammation and cell death. Upregulation of NK1R maybe a consequence of TBI, independent of the levels of substance P. This study raises the possibility that targeting SP through its receptor NK1R or genetic deletion may have therapeutic efficacy in TBI.
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Int. J. Biochem. Cell Biol. · Nov 2018
Long non-coding RNA NIFK-AS1 inhibits M2 polarization of macrophages in endometrial cancer through targeting miR-146a.
Accumulating evidence suggested that tumor-associated macrophages played crucial roles in the progression of endometrial cancer. The aim of this study was to determine the role of lncRNA NIFK-AS1 in M2-like polarization of macrophages and further to investigate the effect of NIFK-AS1 modulating macrophage polarization on the proliferation, migration and invasion of endometrial cancer cells. Human peripheral blood mononuclear cells and tumor-associated macrophages were isolated from healthy volunteers and endometrial cancer patients, respectively. ⋯ Further experiments revealed that miR-146a overexpression attenuated the effect of NIFK-AS1 on suppressing the M2 polarization of macrophages and the estrogen-induced proliferation, migration and invasion of endometrial cancer cells. These findings indicated that NIFK-AS1 inhibited the M2-like polarization of macrophages via targeting miR-146a, thereby reducing the estrogen-induced proliferation, migration and invasion of endometrial cancer cells. Our study highlights the important role of NIFK-AS1 in regulating the polarization and function of tumor-associated macrophages in endometrial cancer and provides novel insight into the TAMs-mediated progression of endometrial cancer.