ANALYTICAL CHEMISTRY
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2025
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IF 6.7
Qing-Nan Li,Yun-Xi Cui,Zhi-Qi Dai,Zhi-Li Yao,Man-Ying Li,Qi-Liang Cai,De-Ming Kong
The CRISPR/Cas12a system has emerged as a powerful tool in biosensing due to its unique trans-cleavage activity. This study conducted an in-depth investigation of the modulatory capabilities of this system, particularly focusing on the 5′-end modifications of the activator strand, and found that introducing a hairpin structure (HP) at the 5′-end of the activator strand, which was designed based on the RESET effect, can effectively suppress the activator strand’s ability to activate the trans-cleavage activity of the CRISPR/Cas12a system. This suppression is independent of the HP’s relation to the activator strand and the type of linker used (DNA, RNA or peptide). Detaching the HP from the activator strand restores the system’s activity. These findings enrich the development of CRISPR/Cas12a-based biosensors, and expand their application beyond DNA-based target detection to peptide sequence-based target recognition. Based on this discovery, we constructed a sensitive biosensor for caspase-3 (Casp-3), a key executor in apoptosis, by linking the HP to the activator strand with a peptide linker containing a Casp-3 recognition site. The proposed biosensor has been validated for its sensitivity and specificity in detecting Casp-3, as well as for monitoring drug-induced apoptosis through the imaging of Casp-3 in living cells, providing a valuable tool for studying the apoptotic process, screening drugs, assessing drug efficacy, and evaluating treatment outcomes. This strategy also shows promise for detecting other peptide-based targets, broadening the horizons for early disease biomarker detection and timely therapeutic interventions.
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Xin Zheng,Xinyi Tang,Yinan Xu,Haiyan Zhu,Lianwei Zhong,Chen Chen,Jiajun Cui,Jie Zhou
Ethnopharmacological relevance The seed of Aesculus wilsonii Rehd., also known as Suoluozi in China, is a traditional Chinese herb included in the Pharmacopoeia of China (2020). Sodium aescinate (SA) is derived from the Aesculus wilsonii Rehd.’s seeds and is extensively used in clinical practice. Aim of the study The study investigated the involvement of the Nrf2/CTH pathway in SA-induced hepatotoxicity and explored potential strategies for alleviating SA-induced liver damage. Materials and methods The ICR mice and AML12 mouse hepatocytes were exposed to SA. The levels of Fe 2+ , cysteine (Cys), glutathione (GSH), hydrogen sulfide (H 2 S), ROS, lipid peroxides and caspase-3 activity were assessed. The effects of SA on signaling pathways related to ferroptosis and apoptosis were examined. Furthermore, genetic modification or agonists of Nrf2 and CTH were co-treated with SA. Results SA triggered ferroptosis and apoptosis in AML12 cells and mouse livers, characterized by a decline in Cys, GSH, and H 2 S levels, as well as accumulation of Fe 2+ , ROS and lipid peroxides, mitochondrial dysfunction, and chromatin condensation. SA decreased Nrf2, CTH, and Bcl-2 levels, elevated Bax levels, and activated caspase-9/3. Overexpression of Nrf2 or CTH, or NAC supplementation alleviated SA-induced ferroptosis by upregulating Cys and GSH levels. Overexpression of Nrf2 or CTH, or NaHS supplementation increased H 2 S levels, which reduced the interaction between p616-Drp1 and VDAC1 by enhancing Drp1 S-sulfenylation, thereby alleviating SA-induced mitochondrial-dependent apoptosis. Furthermore, DMF or Met mitigated SA-induced hepatotoxicity by activating the Nrf2/CTH pathway. Conclusions SA triggers oxidative stress, mitochondrial dysfunction, apoptosis, and ferroptosis, ultimately leading to liver damage by suppressing the Nrf2/CTH pathway.
研究领域:
药理学
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分子生物学
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医学
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高影响因子
JOURNAL OF CONTROLLED RELEASE
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2022
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IF 11.467
Mingbo Wu,Wenwu Ling,Jiaojun Wei,Ran Liao,Haiyue Sun,Dongqiu Li,Ye Zhao,Long Zhao
As a novel non-apoptotic cell death pathway, ferroptosis can effectively enhance the antitumor effects of photodynamic therapy (PDT) by disrupting intracellular redox homeostasis. However, the reported nanocomposites that combined the PDT and ferroptosis are cumbersome to prepare, and the unfavorable tumor microenvironment also severely interferes with their tumor suppressive effects. To address this inherent barrier, this study attempted to explore photosensitizers that could activate ferroptosis pathway and found that the photosensitizer aloe-emodin (AE) could induce cellular ferroptosis based on its specific inhibiting activity to Glutathione S-transferase P1(GSTP1), a key protein for ferroptosis. Herein, we prepared [email protected] /Fe nanocrystals (NCs) with synergistic PDT and ferroptosis therapeutic effects by one-step emulsification to obtain AE NCs cores and further modification of red blood cells (RBC) membranes and ferritin. Benefiting from the involvement of ferritin, the prepared [email protected] /Fe NCs provide not only sufficient oxygen for oxygen-dependent PDT, but also Fe 3+ for iron-dependent ferroptosis in tumor cells. Furthermore, the biomimetic surface functionalization facilitated the prolonged circulation and cancer targeting of [email protected] /Fe NCs in vivo . The in vitro and in vivo results demonstrate that [email protected] /Fe NCs exhibit significantly enhanced therapeutic effects for the combined two antitumor mechanisms and provide a promising prospect for achieving PDT/ferroptosis synergistic therapy.
研究领域:
癌症治疗
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纳米技术
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药理学
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肿瘤学
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高影响因子
MOLECULES
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2022
·Vol. 27
·期 20
·7099
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IF 4.927
Kuo Yong,Sidra Kaleem,Mingzhu Ma,Xiaoyuan Lian,Zhizhen Zhang
Marine-derivedPenicilliumfungi are one of the most important sources for the discovery of new bioactive natural products. This study characterized the isolation, structures, and antiglioma activities of twelve compounds, including three novel ones—penipyridinone B (1), 11S-(−)-penilloid A (2), and 11R,14E-(+)-penilloid A (3)—from the marine fungusPenicilliumsp. ZZ1750. The structures of the novel compounds were determined via extensive nuclear magnetic resonance (NMR) spectroscopic analyses, high-resolution electrospray ionization mass spectroscopy (HRESIMS) data, Mosher’s method, optical rotation (OR) calculations, and electronic circular dichroism (ECD) calculations. Penipyridinone B represents the first example of its structural type and showed potent antiglioma activity, with IC50values of 2.45 μM for U87MG cells and 11.40 μM for U251 cells. The known compounds of questiomycin A (9) and xanthocillin X (10) also showed antiproliferative activity against both U87MG and U251 cells, with IC50values of 13.65 μM to 22.56 μM. The antiglioma activity of questiomycin A and xanthocillin X may be related to the promotion of reactive oxygen species (ROS) production, the reduction of mitochondrial membrane potential (MMP), and the enhancement of caspase-3 enzyme activity.Keywords:marinePenicilliumsp. ZZ1750;penipyridinone B;11S-(−)-penilloid A;11R,14E-(+)-penilloid A;structure elucidation;antiglioma activity
研究领域:
天然产物化学
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药理学
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海洋生物学
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癌症研究
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高影响因子
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