SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus responsible for the current COVID-19 (coronavirus disease 2019) pandemic, which has hit the world since December 2019. It has spread to about 216 countries worldwide, affecting more than 21.7 million people so far. Although clinical trials of a number of promising antiviral drugs and vaccines against COVID-19 are underway, it is hard to predict how successful these drug-or vaccine-based therapeutics are eventually going to be in combating COVID-19 because most of such therapeutic strategies have failed against human coronaviruses such as SARS-CoV and MERS-CoV (Middle East respiratory syndrome coronavirus) responsible for similar pandemics in the past. In that context, we would like to bring to scientific attention another group of endogenous regulatory molecules, the small non-coding RNAs, especially the microRNAs, which are found to regulate critical cellular pathways in a number of disease conditions, including RNA viral infections. This review will focus on understanding the effect of altered microRNA expression during coronavirus-mediated infections and how it may provide clues for further exploring the pathogenesis of SARS-CoV-2, with a view of developing RNAi-based therapeutics and biomarkers against COVID-19.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with the death of mid-brain dopaminergic neurons. Unfortunately, no effective cure or diagnostic biomarkers for PD are available yet. To address this, the present study focuses on brain-enriched small non-coding regulatory RNAs called microRNAs (miRNAs) that are released into the circulation packaged inside small extracellular vesicles called exosomes. We collected blood samples from PD patients and isolated exosomes from the plasma. qPCR-based detection revealed a particular neuron-enriched miR-128 to be significantly decreased in the patient-derived exosomes. Interestingly, a concomitant decreased expression of miR-128 was observed in the cellular models of PD. Fluorescent live cell imaging and flow-cytometry revealed that over-expression of miR-128 can prevent 6-OHDA-mediated mitochondrial superoxide production and induction of neuronal death respectively. This neuroprotective effect was found to be induced by miR-128-mediated inhibition of FoxO3a activation, a transcription factor involved in apoptosis. miR-128 over-expression also resulted in down-regulation of pro-apoptotic FoxO3a targets- FasL and PUMA, at both transcript and protein levels. Further downstream, miR-128 over-expression inhibited activation of caspases-8, -9 and -3, preventing both the intrinsic and extrinsic pathways of apoptosis. Additionally, over expression of miR-128 prevented down-regulation of synaptic proteins- Synaptophysin and PSD-95 and attenuated neurite shortening, thereby maintaining overall neuronal integrity. Thus, our study depicts the intracellular role of miR-128 in neuronal apoptosis and neurodegeneration and its implications as a biomarker being detectable in the circulating exosomes of PD patient blood. Thus, characterization of such exosomal brain-enriched miRNAs hold promise for effective detection and diagnosis of PD.
Gender and sexual violence is historically used as a weapon of war. Yazidi women resettled in Canada directly from northern Iraq after the 2014 Daesh-led attacks in the Sinjar region. This direct resettlement experience makes the Yazidi refugees a very distinct group from a resettlement perspective. The severe human rights violations and sexual and gender-based violence they have experienced has affected both their physical and mental health. However, research on pre-arrival trauma and its impact on resettlement has been limited to individual post-arrival psychological interventions without considering how pre-arrival trauma experiences may affect their overall settlement experience. Our paper focuses on the settlement challenges and needs of 21 Yazidi women resettled in the four Canadian cities with the largest Yazidi communities. Because the resettlement of the Yazidi often happened within weeks after their release from captivity, the structural deficiencies within the Canadian settlement network revealed challenges for resettlement organizations in terms of how they assist those with acute trauma. We argue that although the Canadian resettlement program is generous in many ways, it falls short of adequately addressing trauma at the acute stage, especially sexual and gender-based violence as experienced by the Yazidi women and children. Our analysis reveals that single-female-headed families, particularly those with young children, have a difficult time navigating the resettlement system in Canada. We have identified the resettlement experiences of Yazidi women and recommend resettlement to happen in three stages, to account for the acute level of trauma this particular group faces. The first stage lasts between six weeks and three months as many women require more dedicated support from settlement providers for housing, language, and health. The second stage is a period of adjustment which occurs within the next eighteen months, depending on the available support these refugee women have to navigate the different settlement services. The third stage begins sometime after the second year when many women can start navigating the social support, education and health systems independently. Thinking of how SGBV may influence the resettlement process in these three stages is a good way for us to consider the additional assistance that may be needed and how they may better access resettlement services.
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