Clinics
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2025
·
IF 2.4
Jingwei Liu,Xujie Sun,Junfeng Liang,Shiqiang Song
Introduction Renal Ischemia-Reperfusion Injury (RIRI) often arises due to heightened oxidative stress, rendering it a central focus of research. Sestrin2 plays a pivotal role in regulating oxidative stress; nevertheless, its impact on the renoprotective properties of Eugenol (EU) during RIRI warrants further investigation. Methods Mice and TCMK-1 cells were categorically assigned into six groups: Sham/Control, Ischemia-Reperfusion (IR)/HR (Hypoxia-Reoxygenation), IR/HR+EU, Sham/Control+Sestrin2-KO, IR/HR+Sestrin2-KO, and IR/HR+EU+Sestrin2-KO. The effects of EU and the involvement of Sestrin2 in RIRI/HR were evaluated using Urea Nitrogen (BUN), Creatinine (Scr), Superoxide Dismutase (SOD), Glutathione (GSH), Catalase (CAT), and Malondialdehyde (MDA) assay kits; western blotting; cell viability assays; HE-staining; and Reactive Oxygen Species (ROS) detection. Results Following RIRI/HR, a marked deterioration in kidney function and a significant surge in oxidative stress levels were observed. However, EU treatment ameliorated renal injury and inhibited oxidative stress. Additionally, EU upregulated Sestrin2 expression, and the renoprotective effects of EU were reversed upon Sestrin2 knockdown. Conclusion The present study posits that EU effectively mitigates RIRI/HRI (Hypoxia-Reoxygenation Injury), and its mechanism of renal protection potentially involves the upregulation of Sestrin2, coupled with the inhibition of oxidative and Endoplasmic Reticulum Stress (ERS).
研究领域:
药理学
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分子生物学
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2025
·
IF 3.5
Nan Wang,Zhengshan Gao,Honghong Zhan,Lin Jing,Fancheng Meng,Min Chen
Doxorubicin (DOX) is a potent anticancer drug, while its toxic side effects involve multi-organ toxicity, including hepatotoxicity. This study aims to investigate the therapeutic potential of salidroside against DOX-induced hepatotoxicity and elucidate its underlying mechanisms. Result showed that salidroside exhibited a liver protective effect in DOX-induced hepatotoxicity in mice, represented by the decreased serum ALT, AST and LDH levels, as well as the rescue of pathological changes in mice livers. Further study showed salidroside reduced the expression level of pyroptosis-associated proteins, including NLRP3, cleaved- caspase 1, gasdermin D (GSDMD-N) and mature IL-1β in mice liver tissues. In vitro study confirmed salidroside exerted a similar effect in AML12 cells. Mechanistically, salidroside alleviated mitochondrial dysfunction by activating the PGC-1α /Mfn2 signaling pathway, and restrained the endoplasmic reticulum (ER) stress, represented by the downregulation of GRP78 and p-PERK/PERK level. Subsequent investigations revealed that salidroside activated the Sestrin2/AMPK pathway, while the application of AMPK inhibitors, PGC-1α siRNA or Sestrain2 siRNA reversed the effects of salidroside on ameliorating mitochondrial dysfunction and ER stress, suggesting salidroside could be a promising therapeutic strategy for alleviating DOX-induced hepatotoxicity.
研究领域:
药理学
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毒理学
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分子生物学
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PubMed
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STEM CELLS AND DEVELOPMENT
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2026
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IF 1.9
Rui Chen,Lina Ren,Sen Xu,Yian Guan,Xuan Zhang,Yi Li,Ping Zhou,Dongyang Ma,Liling Ren
Prevascularized cell sheets are widely used in tissue engineering; however, enhancing their angiogenic potential within hypoxic microenvironments remains a significant challenge. In this study, we employed genetic manipulation to upregulate Sestrin2 (SESN2) expression in human umbilical vein endothelial cells (HUVECs) and investigated its effect on their angiogenic potential under hypoxic conditions. Transwell migration and Matrigel tube formation assays confirmed that SESN2 significantly promoted proliferation, migration, and tube formation of HUVECs under hypoxia, thereby enhancing angiogenesis. Furthermore, HUVECs overexpressing SESN2 were seeded onto cell sheets, and immunofluorescence staining for CD31 revealed increased lumen formation compared with the control group. SESN2 was also found to promote the secretion of vascular endothelial growth factor A and platelet-derived growth factor BB in vitro. Subsequent subcutaneous implantation studies demonstrated that prevascularized cell sheets with SESN2 overexpression enhanced angiogenesis and promoted the formation of functional blood vessels. In conclusion, SESN2 improves the vascularization capacity of tissue-engineered grafts in hypoxic environments, thereby facilitating successful transplantation of engineered tissues.
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PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2022
·Vol. 48
·期 2
·658-670
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IF 4.414
Yang Jinghui,Guo Qian,Wang Lu,Yu Shan
Cerebral ischemia reperfusion injury (CIRI) is the commonest cause of brain dysfunction. Up-regulation of POU domain class 2 transcription factor 2 (POU2F2) has been reported in patients with cerebral ischemia, while the role of POU2F2 in CIRI remains elusive. Middle cerebral artery occlusion/reperfusion (MCAO/R) in mice and oxygen and glucose deprivation/reperfusion (OGD/R) in mouse primary cortical neurons were used as models of CIRI injury in vivo and in vitro. Lentivirus-mediated POU2F2 knockdown further impaired CIRI induced by MCAO/R in mice, which was accompanied by increased-neurological deficits, cerebral infarct volume and neuronal loss. Our evidence suggested that POU2F2 deficiency deteriorated oxidative stress and ferroptosis according to the phenomenon such as the abatement of SOD, GSH, glutathione peroxidase 4 (GPX4) activity and accumulation of ROS, lipid ROS, 4-hydroxynonenal (4-HNE) and MDA. In vivo, primary cortical neurons with POU2F2 knockdown also showed worse neuronal damage, oxidative stress and ferroptosis. Sestrin2 (Sesn2) was reported as a neuroprotection gene and involved in ferroptosis mechanism. Up-regulation of Sesn2 was observed in the ischemic penumbra and OGD/R-induced neuronal cells. Further, we proved that POU2F2, as a transcription factor, could bind to Sesn2 promoter and positively regulate its expression. Sesn2 overexpression relieved oxidative stress and ferroptosis induced by POU2F2 knockdown in OGD/R-treated neurons. This research demonstrated that CIRI induced a compensatory increase of POU2F2 and Sesn2. Down-regulated POU2F2 exacerbated CIRI through the acceleration of oxidative stress and ferroptosis possibly by decreasing Sesn2 expression, which offers new sights into therapeutic mechanisms for CIRI.
研究领域:
神经科学
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分子生物学
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细胞生物学
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转录因子
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神经退行性疾病
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PubMed
高影响因子
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