scholarly journals NSAIDs Immunomodulation in COVID-19 Might Inhibit SARS CoV-2 ORF Proteins Induced Caspase Activation, Necroptosis and Endoplasmic Reticulum Stress.

Author(s):  
Mina Kelleni

We have previously suggested numerous immunomodulatory and anti-inflammatory benefits when NSAIDs are administered to manage COVID-19 and in this commentary, we add other potential benefits related to SARS CoV-2 ORF proteins dependent activation of caspases with subsequent mitochondrial dysfunction, endoplasmic reticulum stress and necroptosis that were described with complicated COVID-19 as NSAIDs are known to be caspase inhibitors. Moreover, NSAIDs might independently inhibit other COVID-19 associated downstream pathological signaling mechanisms. We also postulate that CARD-14, a caspase recruitment domain-containing protein, polymorphisms might play a role in development of severe and critical COVID-19. We believe that it is very unfortunate that for more than one year of relentless struggle, our recommendation to adopt NSAIDs as first choice COVID-19 therapy has not adopted while lives are lost are succumbed every day.

Author(s):  
Mina Kelleni

We have previously suggested numerous immunomodulatory and anti-inflammatory benefits when NSAIDs are administered to manage COVID-19 and in this commentary, we add other potential benefits related to SARS CoV-2 ORF proteins dependent activation of caspases with subsequent mitochondrial dysfunction, endoplasmic reticulum stress and necroptosis that were described with complicated COVID-19 as NSAIDs are known to be caspase inhibitors. Moreover, NSAIDs might independently inhibit other COVID-19 associated downstream pathological signaling mechanisms. We also postulate that CARD-14, a caspase recruitment domain-containing protein, polymorphisms might play a role in development of severe and critical COVID-19. We believe that it is very unfortunate that for more than one year of relentless struggle, our recommendation to adopt NSAIDs as first choice COVID-19 therapy has not adopted while lives are lost are succumbed every day.


Author(s):  
Mina Kelleni

We have previously suggested numerous immunomodulatory and anti-inflammatory benefits when NSAIDs are administered to manage COVID-19 and in this commentary, we add other potential benefits related to SARS CoV-2 ORF proteins dependent activation of caspases with subsequent mitochondrial dysfunction, endoplasmic reticulum stress and necroptosis that were described with complicated COVID-19 as NSAIDs are known to be caspase inhibitors. Moreover, NSAIDs might independently inhibit other COVID-19 associated downstream pathological signaling mechanisms. We also postulate that CARD-14, a caspase recruitment domain-containing protein, polymorphisms might play a role in development of severe and critical COVID-19. We believe that it is very unfortunate that for more than one year of relentless struggle, our recommendation to adopt NSAIDs as first choice COVID-19 therapy has not adopted while lives are lost are succumbed every day.


2021 ◽  
Author(s):  
Mina Kelleni

We have previously suggested numerous immunomodulatory and anti-inflammatory benefits when NSAIDs are administered as first choice therapy early in management of COVID-19 and in this manuscript we add several additional clues and it is really unfortunate that for more than one year of relentless struggle, this call is not yet adopted to save precious lives that are succumbed every day.


2021 ◽  
Vol 22 (9) ◽  
pp. 4646
Author(s):  
Alexey A. Tinkov ◽  
Monica M. B. Paoliello ◽  
Aksana N. Mazilina ◽  
Anatoly V. Skalny ◽  
Airton C. Martins ◽  
...  

Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. We provide, here, a brief review of pertinent discoveries related to Mn-induced neurotoxicity research from the last five years. Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling. Genetic analysis identified multiple metabolic pathways that could be considered as Mn neurotoxicity targets, including oxidative stress, endoplasmic reticulum stress, apoptosis, neuroinflammation, cell signaling pathways, and interference with neurotransmitter metabolism, to name a few. Recent findings have also demonstrated the impact of Mn exposure on transcriptional regulation of these pathways. There is a significant role of autophagy as a protective mechanism against cytotoxic Mn neurotoxicity, yet also a role for Mn to induce autophagic flux itself and autophagic dysfunction under conditions of decreased Mn bioavailability. This ambivalent role may be at the crossroad of mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. Yet very recent evidence suggests Mn can have toxic impacts below the no observed adverse effect of Mn-induced mitochondrial dysfunction. The impact of Mn exposure on supramolecular complexes SNARE and NLRP3 inflammasome greatly contributes to Mn-induced synaptic dysfunction and neuroinflammation, respectively. The aforementioned effects might be at least partially mediated by the impact of Mn on α-synuclein accumulation. In addition to Mn-induced synaptic dysfunction, impaired neurotransmission is shown to be mediated by the effects of Mn on neurotransmitter systems and their complex interplay. Although multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity.


2012 ◽  
Vol 24 (1) ◽  
pp. 29 ◽  
Author(s):  
Linda L.-Y. Wu ◽  
Robert J. Norman ◽  
Rebecca L. Robker

Obesity can have detrimental effects on pregnancy rates in natural conceptions and also in women undergoing IVF or intracytoplasmic sperm injection (ICSI). This review summarises the most recent clinical literature investigating whether obesity impacts oocyte quality and early embryo growth. In other tissues, obesity leads to lipotoxicity responses including endoplasmic reticulum stress, mitochondrial dysfunction and apoptosis. Recent reports indicate that lipotoxicity is a mechanism by which obesity may impact oocyte quality.


2019 ◽  
Vol 19 ◽  
pp. 24-33 ◽  
Author(s):  
Sandra López-Domènech ◽  
Zaida Abad-Jiménez ◽  
Francesca Iannantuoni ◽  
Aranzazu M. de Marañón ◽  
Susana Rovira-Llopis ◽  
...  

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