Ulinastatin alleviates cerebral ischemia-reperfusion injury in rats by activating the Nrf-2/HO-1 signaling pathway

Cui, Lei; Cao, Wei; Xia, Yanmin; Li, Xiaofang

doi:10.21037/atm-20-5115

Cited by 27 publications

(20 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the expression level of several stroke-associated inflammatory genes, such as VCAM-1, SMAHD-1, and DDAH1, were significantly upregulated in COVID-19 positive patients, indicating that the inflammatory response may play potential roles in mediating COVID-19-associated stroke. As mentioned above, the expression levels of HMOX1, LTC4S, and ACTB seem to have negative correlation relationships with the risk of cerebral ischemia ( Freiberg et al, 2010 ; Nitti et al, 2018 ; Cui et al, 2020 ; Yang et al, 2020 ), the significant downregulation of HMOX1, LTC4S, and ACTB in PBMC samples from COVID-19 positive patients may indicate possible molecular mechanisms between COVID-19 and stroke. However, further clinical and functional studies using COVID-19 patient samples or animal models are highly needed to investigate direct viral infection effects and indirect inflammatory effects on human brains by SARS-CoV-2.…”

Section: Resultsmentioning

confidence: 78%

“…Numerous studies have reported the effectiveness of HMOX1, a stress-responsive protein induced by various oxidative agents, in cardiology by aspects such as inflammation, antioxidant function, apoptosis, hypoxia, and ischemia/reperfusion injury ( Wan et al, 2020 ). The upregulation of HMOX1 during cerebral ischemia revealed a protective effect on neuronal cell against oxidative stress ( Nitti et al, 2018 ; Cui et al, 2020 ). A previous study also showed that the dysfunction or downregulation of LTC4S, one of the key enzymes of the 5-lipoxygenase pathway, was associated with increased risk of venous thromboembolism and ischemic stroke ( Freiberg et al, 2010 ).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The Epidemiological and Mechanistic Understanding of the Neurological Manifestations of COVID-19: A Comprehensive Meta-Analysis and a Network Medicine Observation

et al. 2021

View full text Add to dashboard Cite

The clinical characteristics and biological effects on the nervous system of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain poorly understood. The aim of this study is to advance epidemiological and mechanistic understanding of the neurological manifestations of coronavirus disease 2019 (COVID-19) using stroke as a case study. In this study, we performed a meta-analysis of clinical studies reporting stroke history, intensive inflammatory response, and procoagulant state C-reactive protein (CRP), Procalcitonin (PCT), and coagulation indicator (D-dimer) in patients with COVID-19. Via network-based analysis of SARS-CoV-2 host genes and stroke-associated genes in the human protein-protein interactome, we inspected the underlying inflammatory mechanisms between COVID-19 and stroke. Finally, we further verified the network-based findings using three RNA-sequencing datasets generated from SARS-CoV-2 infected populations. We found that the overall pooled prevalence of stroke history was 2.98% (95% CI, 1.89–4.68; I2=69.2%) in the COVID-19 population. Notably, the severe group had a higher prevalence of stroke (6.06%; 95% CI 3.80–9.52; I2 = 42.6%) compare to the non-severe group (1.1%, 95% CI 0.72–1.71; I2 = 0.0%). There were increased levels of CRP, PCT, and D-dimer in severe illness, and the pooled mean difference was 40.7 mg/L (95% CI, 24.3–57.1), 0.07 μg/L (95% CI, 0.04–0.10) and 0.63 mg/L (95% CI, 0.28–0.97), respectively. Vascular cell adhesion molecule 1 (VCAM-1), one of the leukocyte adhesion molecules, is suspected to play a vital role of SARS-CoV-2 mediated inflammatory responses. RNA-sequencing data analyses of the SARS-CoV-2 infected patients further revealed the relative importance of inflammatory responses in COVID-19-associated neurological manifestations. In summary, we identified an elevated vulnerability of those with a history of stroke to severe COVID-19 underlying inflammatory responses (i.e., VCAM-1) and procoagulant pathways, suggesting monotonic relationships, thus implicating causality.

show abstract

Section: Resultsmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 99%

The Epidemiological and Mechanistic Understanding of the Neurological Manifestations of COVID-19: A Comprehensive Meta-Analysis and a Network Medicine Observation

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The Nrf2‐sMaf heterodimer then binds to AREs to activate hundreds of genes in the nucleus that regulate energy metabolism, anti‐inflammatory signal transduction and exogenous detoxification enzymes. Among these genes, the expression of many antioxidant enzymes, such as HO‐1, NQO1, SOD, glucuronyltransferase and glutathione s‐transferase, is the most closely related to oxidative damage 47–49 . Downstream antioxidant genes activated by Nrf2 transcription, particularly HO‐1, are an extremely important response to oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Triclosan regulates the Nrf2/HO‐1 pathway through the PI3K/Akt/JNK signaling cascade to induce oxidative damage in neurons

Wang

Liu

Jiang

2021

Environmental Toxicology

View full text Add to dashboard Cite

Triclosan (TCS), a broad‐spectrum antimicrobial agent, is recognized as an environmental endocrine disruptor. TCS has caused a wide range of environmental, water and soil pollution. TCS is also still detected in food. Due to its high lipophilicity and stability, TCS can enter the human body through biological enrichment and potentially threatenes human health. In recent years, the neurotoxic effects caused by TCS contamination have attracted increasing attention. This study was designed to investigate the mechanism underlying TCS‐induced HT‐22 cells injury and to explore the effect of TCS on the PI3K/Akt, MAPK, and Nrf2/HO‐1 signaling pathways in HT‐22 cells. In this study, we examined the adverse effects of TCS treatment on ROS generation, and MDA, GSH‐Px, and SOD activities. The expression levels of proteins in the Nrf2, PI3K/Akt, MAPK pathways and Caspase‐3, BAX, Bcl‐2 were measured and quantified by Western blotting. The results showed that TCS could significantly reduce the activity of HT‐22 cells, increase the production of intracellular ROS and upregulate the expression of proapoptotic proteins. In addition, TCS promoted an increase in the MDA and SOD levels, and downregulated the GSH‐Px activity, and oxidative damage occurred in neurons. The mechanism underlying this toxicity was related to TCS‐induced PI3K/Akt/JNK‐mediated regulation of the Nrf2/HO‐1 signaling pathway. This result was further confirmed by the specific inhibitors LY294002 and SP600125. In summary, TCS could induce oxidative damage in HT‐22 neurons, and activation of the PI3K/Akt/JNK/ Nrf2 /HO‐1 signaling cascade was the main mechanism underlying the TCS‐induced HT‐22 neuronal toxicity.

show abstract

“…The pathological histological damage of the whole brain in mice was evaluated by using Hematoxylin and eosin (HE) staining as previously described. 23 Briefly, after 24 h of reperfusion, the brain tissues were fixed with 4% paraformaldehyde, dehydrated by alcohol and embedded in paraffin. The brains were cut into 5-μm-thick sections and incubated with HE reagents, followed by photographed under a light microscopy in five randomly selected fields.…”

Section: Methodsmentioning

confidence: 99%

MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway

Ren¹,

Wang²,

Guo³

2021

NDT

View full text Add to dashboard Cite

Background MiR-195-5p has been shown to play crucial roles in tumor inhibition, but its biological functions in cerebral ischemia-reperfusion (I/R) injury are unclear. Methods To mimic cerebral I/R injury, mice were induced by transient middle cerebral artery occlusion (MCAO). Human brain microvascular endothelial cells (HBMVECs) were treated with oxygen-glucose deprivation (OGD) to mimic I/R injury in vitro. The expression of miR-195-5p and PTEN was detected by qRT-PCR or Western blot. Cell viability was evaluated by CCK-8 assay. Cell apoptosis was detected by flow cytometer. Cell death was detected using specific lactate dehydrogenase (LDH) cytotoxicity kit. Infarct volume in mice brains was evaluated by TTC staining. Histopathological analysis was performed by HE staining and TUNEL staining. The interaction between miR-195-5p and PTEN was determined by TargetScan and luciferase reporter assay. Results MiR-195-5p was significantly downregulated and PTEN was upregulated during cerebral I/R injury both in vitro and in vivo. Overexpression of miR-195-5p efficiently enhanced cell viability, while reduced LDH release and apoptotic rate of OGD-treated HBMVECs in vitro. MiR-195-5p could negatively regulate the expression of PTEN by directly binding to its 3′-UTR. Overexpression of PTEN obviously attenuated the protective effect of miR-195-5p mimics on cell viability, LDH release and apoptosis in OGD-treated HBMVECs. Meanwhile, overexpression of miR-195-5p increased the expression levels of p-AKT in OGD-treated HBMVECs, while this effect was reversed by overexpression of PTEN. Moreover, overexpression of miR-195-5p efficiently ameliorated brain injury of mice after MCAO treatment in vivo. Conclusion Overexpression of miR-195-5p ameliorated cerebral I/R injury by regulating the PTEN-AKT signaling pathway, providing a potential therapeutic target for cerebral I/R injury.

show abstract

Ulinastatin alleviates cerebral ischemia-reperfusion injury in rats by activating the Nrf-2/HO-1 signaling pathway

Cited by 27 publications

References 29 publications

The Epidemiological and Mechanistic Understanding of the Neurological Manifestations of COVID-19: A Comprehensive Meta-Analysis and a Network Medicine Observation

The Epidemiological and Mechanistic Understanding of the Neurological Manifestations of COVID-19: A Comprehensive Meta-Analysis and a Network Medicine Observation

Triclosan regulates the Nrf2/HO‐1 pathway through the PI3K/Akt/JNK signaling cascade to induce oxidative damage in neurons

MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway

Contact Info

Product

Resources

About