ACS Applied Bio Materials
·
2025
·
IF 4.7
Ji Xia,Jin Huang,Yixiao Yan,Chenxin Jian,Jiansheng He,Nisha Wang,Lei Shi,Qiyang Ding,Hao Tian,Wei Gao
Mitochondrial damage occurs as an initial event following ischemic onset, and the extent of mitochondrial dysfunction is highly correlated to the severity of ischemia-induced cell death. Once appropriate therapeutic interventions are provided, the ischemic tissue can be salvaged, which is of great significance in achieving better neurological outcomes. Herein, we developed a nanosized starch as a targeting nanoplatform, featuring effective blood-brain barrier (BBB) penetration through lactoferrin-mediated transcytosis. Notably, the nanostarch-based delivery of Mdivi-1 and Alda-1 enables controlled release in the acidic lysosome of neurons, effectively inhibiting the pathological mitochondrial fission and metabolizing toxic aldehydes, thereby creating protective effects on maintaining mitochondrial function. Moreover, we demonstrated that mitochondrial protection induces a transition from activated pro-death responses to a pro-survival state by reducing the release of pro-apoptotic proteins, significantly contributing to the long-term recovery of neurological function. Overall, our nanostarch provided an in-depth understanding of the delivery of mitochondrial protectants and underscored the potential and utility of mitochondrial protection for ischemic stroke via minimizing neuronal apoptosis.
研究领域:
神经科学
·
药理学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Ophthalmology
·
2020
·Vol. 20
·期 1
·1-10
·
IF 1.413
Yan Weiming,Long Pan,Wei Dongyu,Yan Weihua,Zheng Xiangrong,Chen Guocang,Wang Jiancong,Zhang Zuoming,Chen Tao,Chen Meizhu
Background Retinitis pigmentosa (RP) is a kind of inherited retinal degenerative diseases characterized by the progressive loss of photoreceptors. RP has been a conundrum without satisfactory countermeasures in clinic until now. Acetaldehyde dehydrogenase 2 (ALDH2), a major enzyme involved in aldehyde detoxification, has been demonstrated to be beneficial for a growing number of human diseases, such as cardiovascular dysfunction, diabetes mellitus and neurodegeneration. However, its protective effect against RP remains unknown. Our study explored the impact of ALDH2 on retinal function and structure in N-methyl-N-nitrosourea (MNU)-induced RP rats.Methods Rats were gavaged with 5 mg/kg Alda-1, an ALDH2 agonist, 5 days before and 3 days after MNU administration. Assessments of retinal function and morphology as well as measurement of specific proteins expression level were conducted.Results Electroretinogram recordings showed that Alda-1 administration alleviated the decrease in amplitude caused by MNU, rendering protection of retinal function. Mitigation of photoreceptor degeneration in MNU-treated retinas was observed by optical coherence tomography and retinal histological examination. In addition, Western blotting results revealed that ALDH2 protein expression level was upregulatedwith increased expression of SIRT1 protein after the Alda-1 intervention. Besides, endoplasmic reticulum stress (ERS) was reduced according to the significant downregulation of GRP78 protein, while apoptosis was ameliorated as shown by the decreased expression of PARP1 protein.Conclusion sTogether, our data demonstrated that ALDH2 could provide preservation of retinal function and morphology against MNU-induced RP, with the underlying mechanism at least partly related to the modulation of SIRT1, ERS and apoptosis.
研究领域:
眼科学
·
药理学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2023
·
IF 3.5
Qi Luo,Yang Shen,Guohong Zhai,Lin Chen,Furong Ou,Luxi Yi,Danli Yang,Hong Pan,Fuguo Shi
Dictamnine is a representative furan-containing hepatotoxic compound. Administration of dictamnine caused acute liver injury in mice and the metabolic activation of furan to reactive epoxy intermediate was responsible for the hepatotoxicity. This study aimed to characterize the protein adduction by endogenous hepatic aldehydes and investigate its role in dictamnine-induced hepatotoxicity. In the liver sample of dictamnine-treated mice, the protein adduction by five aldehydes was characterized as lysine residue-aldehyde adducts using high-resolution UPLC-Q/Orbitrap MS after exhaustive proteolytic digestion. The levels of protein adduct were increased at 2–3 h after the treatment with dictamnine. The formation of protein adduction increased with increasing doses of dictamnine. Inhibition of the bioactivation by CYP3A inhibitor ketoconazole prevented the protein adduction. Treatment with 2,3-dihydro-dictamnine, an analog of dictamnine that was unable to form the epoxy intermediate, did not lead to an increase in protein adduction. Application of aldehyde dehydrogenase-2 activator ALDA-1 or nucleophilic trapping reagent N -acetyl-L-lysine significantly reduced the protein adduction and attenuated dictamnine-induced liver injury without affecting the bioactivation. In conclusion, the metabolic activation of the furan ring of dictamnine resulted in the protein adduction by multiple hepatic aldehydes and the protein modification played a crucial role in dictamnine-induced liver injury.
研究领域:
药理学
·
毒理学
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Qiuyan Zhang,Jun Tong,Wei Zhou,Zibiao Zhong,Qianchao Hu,Qiang Ma,Haitao Long,Shuangquan Wu,Xiaowen Shi,Qifa Ye
Hypothermic machine perfusion (HMP) is a preferable measure to preserve kidneys from donation after cardiac death (DCD), while the current standard perfusate is imperfect. We synthesized amphiphilic chitosan, N-alkylated-O-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (N-alkyl-O-HTCC) as additive in the perfusate, which can self-assembly into micelles in water (size 133 ± 8.48 nm) (ζ-potential 43.9 ± 2.06 mV), with good antibacterial activity for Escherichia coli and Staphylococcus aureus . The derivates can also deliver hydrophobic drug Alda-1 into kidneys through HMP, with drug loading ratio (~42.14%). The delivery system specifically activated mitochondrial acetaldehyde dehydrogenase 2 in kidneys and reduced the ischemic injury. What's more, the addition of N-alkyl-O-HTCC in HMP also activated mitochondria superoxide dismutase 2, presented nice antioxidant activity . These all helped to improve the quality of DCD kidneys. This study provides a feasible amphiphilic carrier for hydrophobic drugs, and provides efficient guidance for perfusate improvement.
研究领域:
药学
·
生物医学工程
·
移植医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）