Redox Biology
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2024
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IF 10.7
Yue-Yue Guo,Nan-Nan Liang,Xiao-Yi Zhang,Ya-Hui Ren,Wen-Zheng Wu,Zhi-Bing Liu,Yi-Zhang He,Yi-Hao Zhang,Yi-Chao Huang,Tao Zhang,De-Xiang Xu,Shen Xu
Increasing evidences demonstrate that environmental stressors are important inducers of acute kidney injury (AKI). This study aimed to investigate the impact of exposure to Cd, an environmental stressor, on renal cell ferroptosis. Transcriptomics analyses showed that arachidonic acid (ARA) metabolic pathway was disrupted in Cd-exposed mouse kidneys. Targeted metabolomics showed that renal oxidized ARA metabolites were increased in Cd-exposed mice. Renal 4-HNE, MDA, and ACSL4, were upregulated in Cd-exposed mouse kidneys. Consistent with animal experiments, the in vitro experiments showed that mitochondrial oxidized lipids were elevated in Cd-exposed HK-2 cells. Ultrastructure showed mitochondrial membrane rupture in Cd-exposed mouse kidneys. Mitochondrial cristae were accordingly reduced in Cd-exposed mouse kidneys. Mitochondrial SIRT3, an NAD + -dependent deacetylase that regulates mitochondrial protein stability, was reduced in Cd-exposed mouse kidneys. Subsequently, mitochondrial GPX4 acetylation was elevated and mitochondrial GPX4 protein was reduced in Cd-exposed mouse kidneys. Interestingly, Cd-induced mitochondrial GPX4 acetylation and renal cell ferroptosis were exacerbated in Sirt3 −/− mice. Conversely, Cd-induced mitochondrial oxidized lipids were attenuated in nicotinamide mononucleotide (NMN)-pretreated HK-2 cells. Moreover, Cd-evoked mitochondrial GPX4 acetylation and renal cell ferroptosis were alleviated in NMN-pretreated mouse kidneys. These results suggest that mitochondrial GPX4 acetylation, probably caused by SIRT3 downregulation, is involved in Cd-evoked renal cell ferroptosis.
研究领域:
毒理学
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肾脏生理学
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细胞生物化学
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PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2023
·Vol. 21
·期 1
·1-17
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IF 10.2
Wu Xinzhou,Jiao Zhouguang,Zhang Junying,Li Feng,Li Yuhua
Background Currently, high doses of cytarabine arabinoside (Ara-C)-based combined chemotherapy are commonly used in acute myeloid leukemia (AML) therapy, but severe adverse effects and poor suppression effects in leukemia cells limit the clinical therapeutic efficiency of Ara-C-based chemotherapy due to a lack of targeting selectivity. To improve the therapeutic effect of Ara-C in AML, here, since we confirmed that transferrin receptor 1 (TFRC) expression in AML cells was constant, we generated Ara-C@HFn by encapsulating free Ara-C into self-assembled heavy ferritin chain (HFn, the ligand of TFRC) nanocages.Results The analysis of clinically relevant data suggested that the high expression levels of TFRC from AML cells would not decrease significantly after treatment with Ara-C. Ara-C@HFn can be efficiently internalized by leukemia cells, showing stronger cytotoxic effects in vitro and reducing the burden of leukemia in AML mice more effectively in vivo than free Ara-C. Ara-C@HFn treatment showed no acute toxicity in visceral organs of mice. Moreover, the analysis of clinically relevant data also suggested that there are several drugs (such as tamibarotene and ABT199) that would not cause significant expression down-regulation of TFRC in AML cells (after treatment).Conclusion The above results suggested that TFRC can be used as a constant and effective target for drug targeting delivery of AML cells. Thus Ara-C@HFn treatment can become a safe and efficient strategy for AML therapy by specifically delivering Ara-C to AML cells. Besides, the HFn nanocages are promising for improving antineoplastic effect of other AML-related therapy drugs that do not cause downregulated expression of TFRC in AML cells.Graphical Abstract
研究领域:
肿瘤学
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药理学
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分子生物学
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血液学
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PubMed
高影响因子
FOOD CHEMISTRY
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2026
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IF 10.4
Yipeng Zhang,Shijia Wu,Yisheng Chen
A portable biosensor for the peanut allergen Ara h 1 was developed by integrating a polydopamine-functionalized pipette tip, CRISPR/Cas12a signal amplification, and a personal glucose meter. Ara h 1 binding induced partial displacement of a cDNA activator, which activated Cas12a trans-cleavage and released glucose oxidase from GOx–DNA conjugates. The released enzyme catalyzed glucose oxidation, producing a quantitative decrease in glucose concentration. Under optimized conditions, the assay showed a linear range of 50–1000 ng/mL and a solution-based limit of detection of 22.19 ng/mL. Post-extraction matrix-spike tests in commercial peanut-biscuit and peanut-beverage extracts yielded recoveries of 101.58–104.68% with relative standard deviations below 3.44%. These results demonstrate the analytical feasibility and preliminary matrix compatibility of the platform, although validation using pre-extraction fortified, incurred, and naturally contaminated foods is still required.
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高影响因子
FOOD CHEMISTRY
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2026
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IF 9.8
Shuo Yang,Jinglong Qu,Yang Qin,Shuaibing An,Kaiqiang Huang,Yaling Wei,Jun Xi
Ara h 3, a prevalent peanut allergy, presents a considerable risk to public health. Preventing exposure to food allergens is the paramount method for safeguarding those with allergies. Consequently, we devised a polydopamine (PDA)-modulated gold self-coupling technique to fabricate plasmonic blackbodies (AuNBs@PDA) featuring multibranched configurations. High-performance SERS labels are possible using AuNBs@PDA's PDA coating and multi-branched design. It detects Ara h 3 ultra-sensitively in lateral flow immunochromatographic test strips (LFIA). SERS-LFIA has outstanding specificity, stability, and reproducibility, with a test strip shelf life of over a year and a LOD of 72.2 pg/mL, 295 times higher than standard AuNPs-LFIA. Implementing this technology accurately detects food samples. This sensitive and reliable platform for Ara h 3 detection has great potential for food allergy monitoring.
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高影响因子
ACS Synthetic Biology
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2023
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IF 4.7
Qiuyan Sun,Fang Guo,Shichao Ren,Liang Zhang,Xinhe Liu,Chun Li,Xudong Feng
Glycosylation is an important method of modifying natural products and is usually catalyzed by uridine 5′-diphosphate (UDP)-glycosyltransferase. UDP-β-l-arabinose (UDP-Ara) confers specific functions to natural products such as pentacyclic triterpenoids. However, UDP-arabinosyltransferase with high regioselectivity toward pentacyclic triterpenoids has rarely been reported. In addition, UDP-Ara is mainly biosynthesized from UDP-α-d-glucose (UDP-Glc) through several reaction steps, resulting in the high cost of UDP-Ara. Herein, UGT99D1 was systematically characterized for specifically transferring one moiety of arabinose to the C-3 position of typical pentacyclic triterpenoids. Subsequently, 15 enzymes from plants, mammals, and microorganisms were characterized, and a four-enzyme cascade comprising sucrose synthase, UDP-Glc dehydrogenase, UDP-α-d-glucuronic acid decarboxylase, and UDP-Glc 4-epimerase was constructed to transform sucrose into UDP-Ara with UDP recycling. This system was demonstrated to efficiently produce the arabinosylated derivative (Ara-BA) of typical pentacyclic triterpenoid betulinic acid (BA). Finally, the in vitro cytotoxicity tests indicated that Ara-BA showed much higher anticancer activities than BA. The established arabinosylation platform shows the potential to enhance the pharmacological activity of natural products.
研究领域:
生物化学
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生物技术
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药理学
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酶学
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高影响因子
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