Interplay between nuclear factor erythroid 2-related factor 2 and inflammatory mediators in COVID-19-related liver injury.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 is a global pandemic and poses a major threat to human health worldwide. In addition to respiratory symptoms, COVID-19 is usually accompanied by systemic inflammation and liver damage in moderate and severe cases. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that regulates the expression of antioxidant proteins, participating in COVID-19-mediated inflammation and liver injury. Here, we show the novel reciprocal regulation between NRF2 and inflammatory mediators associated with COVID-19-related liver injury. Additionally, we describe some mechanisms and treatment strategies.

Selective Ferroptosis Inhibitor Liproxstatin-1 Attenuates Neurological Deficits and Neuroinflammation After Subarachnoid Hemorrhage / 神经科学通报·英文版

Ferroptosis is a form of iron-dependent regulated cell death. Evidence of its existence and the effects of its inhibitors on subarachnoid hemorrhage (SAH) is still lacking. In the present study, we found that liproxstatin-1 protected HT22 cells against hemin-induced injury by protecting mitochondrial functions and ameliorating lipid peroxidation. In in vivo experiments, we demonstrated the presence of characteristic shrunken mitochondria in ipsilateral cortical neurons after SAH. Moreover, liproxstatin-1 attenuated the neurological deficits and brain edema, reduced neuronal cell death, and restored the redox equilibrium after SAH. The inhibition of ferroptosis by liproxstatin-1 was associated with the preservation of glutathione peroxidase 4 and the downregulation of acyl-CoA synthetase long-chain family member 4 as well as cyclooxygenase 2. In addition, liproxstatin-1 decreased the activation of microglia and the release of IL-6, IL-1β, and TNF-α. These data enhance our understanding of cell death after SAH and shed light on future preclinical studies.

The relationship between hypoxia-inducible factor-1α expression and apoptosis in early brain injury after subarachnoid hemorrhage / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the association of hypoxia-inducible factor-1α (HIF-1α) expression and apoptosis in the cerebral cortex following subarachnoid hemorrhage (SAH).</p><p><b>METHODS</b>Subarachnoid hemorrhage was induced by modified monofilament puncture method in rats. Thirty-five adult male Sprague-Dawley rats were randomly assigned to five groups: sham-operated group, SAH 6 h, SAH 12 h, SAH 24 h and SAH 72 h groups. HIF-1α expression was assessed by immunofluorescence staining. TdT-mediated dUTP-biotin nick end-labeling (TUNEL) technique was adopted to detect apoptotic cells. Double immunolabeling was used to identify cell types with positive HIF-1α expression.</p><p><b>RESULTS</b>The expression of HIF-1α was increased at 6 h (4.65%±1.01%), peaked at 24 h (18.55%±4.23%), and decreased at 72 h (6.31%±1.15%) after SAH (P<0.05). TUNEL-positive cells were up-regulated in the brain at 6 h (7.09%±2.34%), peaked at 24 h (25.54%±7.36%), and down-regulated at 72 h (14.11%±3.03%) after SAH (P<0.05). A significant positive correlation was noted between HIF-1α positive rates and TUNEL positive rates following SAH (r=0.738, P<0.05). Double immunolabeling indicated that HIF-1α was expressed predominantly in neurons and some nuclei with positive HIF-1α were co-stained with TUNEL.</p><p><b>CONCLUSION</b>The data indicate that HIF-1α might participate in the pathological progression of early brain injury after SAH.</p>