Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious...Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious cycle leading to reactive oxygen species accumulation,resulting in progression of the pathological process.Therefore,breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage.Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4(NADPH oxidase 4,NOX4)led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage.The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress,mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage.We found that NOX4 knockdown by adeno-associated virus(AAV-NOX4)in rats enhanced neuronal tolerance to oxidative stress,enabling them to better resist the oxidative stress caused by intracerebral hemorrhage.Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria,relieved mitochondrial damage,prevented secondary reactive oxygen species accumulation,reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats.Finally,we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4.The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis,which is similar to the effect of AAV-NOX4.This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production,and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage.展开更多
BACKGROUND Twist is a repressor of E-cadherin transcription that induces epithelial-mesenchymal transition and cancer metastasis.However,the prognostic value of Twist expression in patients with esophageal cancer rema...BACKGROUND Twist is a repressor of E-cadherin transcription that induces epithelial-mesenchymal transition and cancer metastasis.However,the prognostic value of Twist expression in patients with esophageal cancer remains controversial.AIM To investigate the prognostic and clinicopathological value of Twist expression in esophageal cancer.METHODS Published literature in databases such as EMBASE,Web of Science,PubMed,China National Knowledge Infrastructure,Wanfang,and VIP databases was searched for eligible articles.Participants with esophageal cancer whose tumor tissues underwent immunohistochemistry to detect the expression of Twist were considered.Our meta-analysis was conducted using Stata version 12.0.The hazard ratio(HR) and relative ratio(RR) with their 95 % CI were pooled.Heterogeneity was estimated by I^(2) statistics.RESULTS Eleven articles published between 2009 and 2021 fulfilled the selection criteria.The pooled HR for overall survival was 1.88(95%CI:1.32-2.69,I^(2)=68.6%),and the pooled HR for disease-free survival/relapse-free survival/progression-free survival was 1.84(95 % CI:1.12-3.02,I^(2)=67.1%),suggesting that high Twist expression is associated with poor prognosis in esophageal cancer patients.In addition,overexpression of Twist was correlated with T stage(T3+T4 vs T1+T2,RR=1.38,95 % CI:1.14-1.67),lymph node metastasis(yes vs no,RR=1.34,95 % CI:1.11-1.60),distant metastasis(yes vs no,RR=1.18,95 % CI:1.02-1.35),tumor,node and metastasis(TNM) stage(Ⅲ+Ⅳ vs Ⅰ+Ⅱ,RR=1.35,95 % CI:1.14-1.60),and clinical stage(Ⅲ+Ⅳ vs Ⅰ+Ⅱ,RR=1.58,95 % CI:1.34-1.87).However,no correlation between Twist expression and age,gender,tumor location,differentiation,or venous invasion was observed.CONCLUSION High expression of Twist is associated with poor esophageal cancer prognosis.Moreover,Twist overexpression is correlated with T stage,lymph node metastasis,distant metastasis,TNM stage,and clinical stage,which indicates that Twist might accelerate esophageal cancer progression and metastasis.展开更多
基金supported by the National Natural Science Foundation of China,No.81671125the Natural Science Foundation of Guangdong Province,No.2021A1515011115Guangzhou Science and Technology Project,No.202102010346(all to YZC)。
文摘Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious cycle leading to reactive oxygen species accumulation,resulting in progression of the pathological process.Therefore,breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage.Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4(NADPH oxidase 4,NOX4)led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage.The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress,mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage.We found that NOX4 knockdown by adeno-associated virus(AAV-NOX4)in rats enhanced neuronal tolerance to oxidative stress,enabling them to better resist the oxidative stress caused by intracerebral hemorrhage.Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria,relieved mitochondrial damage,prevented secondary reactive oxygen species accumulation,reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats.Finally,we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4.The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis,which is similar to the effect of AAV-NOX4.This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production,and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage.
文摘BACKGROUND Twist is a repressor of E-cadherin transcription that induces epithelial-mesenchymal transition and cancer metastasis.However,the prognostic value of Twist expression in patients with esophageal cancer remains controversial.AIM To investigate the prognostic and clinicopathological value of Twist expression in esophageal cancer.METHODS Published literature in databases such as EMBASE,Web of Science,PubMed,China National Knowledge Infrastructure,Wanfang,and VIP databases was searched for eligible articles.Participants with esophageal cancer whose tumor tissues underwent immunohistochemistry to detect the expression of Twist were considered.Our meta-analysis was conducted using Stata version 12.0.The hazard ratio(HR) and relative ratio(RR) with their 95 % CI were pooled.Heterogeneity was estimated by I^(2) statistics.RESULTS Eleven articles published between 2009 and 2021 fulfilled the selection criteria.The pooled HR for overall survival was 1.88(95%CI:1.32-2.69,I^(2)=68.6%),and the pooled HR for disease-free survival/relapse-free survival/progression-free survival was 1.84(95 % CI:1.12-3.02,I^(2)=67.1%),suggesting that high Twist expression is associated with poor prognosis in esophageal cancer patients.In addition,overexpression of Twist was correlated with T stage(T3+T4 vs T1+T2,RR=1.38,95 % CI:1.14-1.67),lymph node metastasis(yes vs no,RR=1.34,95 % CI:1.11-1.60),distant metastasis(yes vs no,RR=1.18,95 % CI:1.02-1.35),tumor,node and metastasis(TNM) stage(Ⅲ+Ⅳ vs Ⅰ+Ⅱ,RR=1.35,95 % CI:1.14-1.60),and clinical stage(Ⅲ+Ⅳ vs Ⅰ+Ⅱ,RR=1.58,95 % CI:1.34-1.87).However,no correlation between Twist expression and age,gender,tumor location,differentiation,or venous invasion was observed.CONCLUSION High expression of Twist is associated with poor esophageal cancer prognosis.Moreover,Twist overexpression is correlated with T stage,lymph node metastasis,distant metastasis,TNM stage,and clinical stage,which indicates that Twist might accelerate esophageal cancer progression and metastasis.
