TALANTA
·
2019
·
IF 4.916
Zhenwei Yuan,Mingjun Xu,Tianze Wu,Xinyi Zhang,Yuanzhi Shen,Umeorah Ernest,Lijuan Gui,Fei Wang,Qing He,Haiyan Chen
As an over-expressed flavoprotein in several kinds of tumor cells, NAD(P)H: quinone oxidoreductase-1 (NQO1) is considered as a potent biomarker in early-stage cancer diagnosis. Developing a fast, selective and sensitive method of monitoring NQO1 on cellular level will greatly promote cancer diagnosis in clinical practice. In this paper, a fast NQO1 responsive fluorescence probe SYZ-30 containing quinone acid and 7-nitro-2,1,3-benzoxadiazole (NBD) fluorophore is constructed. The probe could selectively respond to NQO1 and rapidly emit strong fluorescence in vitro within only 5 min. Notably, the peak fluorescent intensities at 550 nm showed a linear relationship with NQO1 concentrations in the range of 3–30 ng/ml and limit of detection (LOD) was 0.0667 ng/ml. Furthermore, it was validated that the probe has good biocompatibility and could be applied for bio-imaging in NQO1 over-expressed cancer cells, together with its mitochondria targeting ability. Importantly, confocal fluorescence imaging confirmed the NQO1 detection ability on cellular level, which can be used for real-time detection of several cancer subtypes like adenocarcinoma. To conclude, the probe is rapidly responsive, highly sensitive and selective which will potentially become a practical tool for early cancer detection and diagnosis.
研究领域:
癌症生物学
·
生物化学
·
分子生物学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2015
·
IF 2.912
Chuanyang Su,Xiaomin Xia,Qiong Shi,Xiufang Song,Juanli Fu,Congxue Xiao,Hongjun Chen,Bin Lu,Zhiyin Sun,Shanmei Wu,Siyu Yang,Xuegang Li,Xiaoli Ye,Erqun Song,Yang Song
Neohesperidin dihydrochalcone (NHDC), a sweetener derived from citrus, belongs to the family of bycyclic flavonoids dihydrochalcones. NHDC has been reported to act against CCl4-induced hepatic injury, but its mechanism is still unclear. We first discovered that NHDC showed a strong ability to scavenge free radicals. In addition, NHDC induces the phase II antioxidant enzymes heme oxygenase 1 (HO-1) and NAD(P)H/quinone oxidoreductase 1 (NQO1) through the activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) signaling. Further assays demonstrated that NHDC induces accumulation of Nrf2 in the nucleus and augmented Nrf2-ARE binding activity. Moreover, NHDC inhibits the ubiquitination of Nrf2 and suggests the modification of Kelch-like ECH-associated protein 1 (Keap1) and the disruption of the Keap1/Nrf2 complex. c-Jun N-terminal kinase (JNK) and p38 but not extracellular signal-regulated protein kinase (ERK) phosphorylations were up-regulated by NHDC treatment. Taken together, NHDC showed its protective antioxidant effect against CCl4-induced oxidative damage via the direct free radical scavenging and indirect Nrf2/ARE signaling pathway.
研究领域:
药理学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Xueping Yan,Peng Jing,Zitian Zhuang,Jianing Zhang,Haiming Chen,Tifeng Xia,Ke Jiang
As an alternative to chemotherapy, emerging gas therapy is considered a “green” treatment due to its minimal side effects. However, even typical gas molecules like nitric oxide (NO) face challenges such as a very short half-life (1.5–6 min), poor targeting, and limited therapeutic effects. This study employs a one-pot method to simultaneously encapsulate the NO donor L-arginine (L-Arg) and the H 2 O 2 precursor Vitamin K3 (VK3) into the pores of zeolitic imidazolate framework-8 (ZIF-8), achieving their co-delivery to tumor sites to address these issues. Furthermore, ZIF-8 is functionalized with hyaluronic acid (HA) to impart active targeting properties to tumor tissues. In the acidic tumor microenvironment, pH-sensitive ZIF-8 degrades, releasing VK3 and L-Arg. Under the action of the NAD(P)H quinone oxidoreductase-1 (NQO1) enzyme, VK3 generates H 2 O 2 , increasing oxidative stress levels in the tumor microenvironment, and reacts with L-Arg to produce NO, thereby achieving tumor oxidative stress-based gas therapy. Both in vitro and in vivo experiments showed good tumor treatment effects, with a tumor inhibition rate of up to 90.5 % and minimal impact on normal tissues and organs. This approach demonstrates efficient loading, controlled release, and significant anti-tumor performance, offering new insights into gas and reactive oxygen species (ROS) synergistic therapy.
研究领域:
癌症治疗
·
药物递送系统
·
材料科学
·
生物医学工程
·
药学化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-11
·
IF 4.259
Zhao Hongting,Li Huihui,Hao Shuangying,Chen Jiping,Wu Jing,Song Chuanhui,Zhang Meng,Qiao Tong,Li Kuanyu
Friedreich ataxia is a progressive neurodegenerative disease caused by the expansion of GAA trinucleotide repeats within the first intron of the FXN gene, which encodes frataxin. The pathophysiology of the disease is thought to be derived from the decrease of Fe-S cluster biogenesis due to frataxin deficiency. There is currently no effective treatment for the disease. In our study, we demonstrated that treatment with the mitochondrion-targeted peptide SS-31 reduced frataxin deficiency-induced oxidative stress in lymphoblasts and fibroblasts derived from patients. Interestingly, SS-31 treatment translationally upregulated the protein level of frataxin in a dose-dependent manner. Furthermore, SS-31 treatment increased the enzymatic activities of the iron-sulphur enzymes, including aconitase and complex II and III of the respiratory chain. Further evaluation of the quality of mitochondria showed that mitochondrial membrane potential, ATP content, NAD + /NADH, and the morphology of mitochondria all improved. Our results suggest that SS-31 might potentially be a new drug for the early treatment of Friedreich ataxia.
研究领域:
神经退行性疾病
·
分子生物学
·
线粒体生物学
·
遗传病
✓ 已验证
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Lihua Chen,Hui Ming,Bowen Li,Chen Yang,Shanshan Liu,Yajie Gao,Tingting Zhang,Canhua Huang,Tingyuan Lang,Zhuo Yang
Cancer metastasis poses significant challenges in current clinical therapy. Osthole (OST) has demonstrated efficacy in treating cervical cancer and inhibiting metastasis. Despite these positive results, its limited solubility, poor oral absorption, low bioavailability, and photosensitivity hinder its clinical application. To address this limitation, a glutathione (GSH)-responded nano-herb delivery system (HA/MOS@OST&L-Arg nanoparticles, HMOA NPs) is devised for the targeted delivery of OST with cascade-activatable nitric oxide (NO) release. The HMOA NPs system is engineered utilizing enhanced permeability and retention (EPR) effects and active targeting mediated by hyaluronic acid (HA) binding to glycoprotein CD44. The cargoes, including OST and L-Arginine (L-Arg), are released rapidly due to the degradation of GSH-responsive mesoporous organic silica (MOS). Then abundant reactive oxygen species (ROS) are produced from OST in the presence of high concentrations of NAD(P)H quinone oxidoreductase 1 (NQO1), resulting in the generation of NO and subsequently highly toxic peroxynitrite (ONOO − ) by catalyzing guanidine groups of L-Arg. These ROS, NO, and ONOO − molecules have a direct impact on mitochondrial function by reducing mitochondrial membrane potential and inhibiting adenosine triphosphate (ATP) production, thereby promoting increased apoptosis and inhibiting metastasis. Overall, the results indicated that HMOA NPs has great potential as a promising alternative for the clinical treatment of cervical cancer.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Shiyao Guo,Mingyue Zhang,Ke Zhang,Xiaotong Lu,Peiran Chen,Bangliu Yang,Xueqian Wang,Yuhong Zhuo,Dongqin Yu,Chao Qi,Kaiyong Cai
Osteoporosis compromises bone repair by generating a dysregulated microenvironment marked by excessive accumulation of reactive oxygen species (ROS) and a reduced pH. This pathological state leads to mitochondrial dysfunction, impaired osteogenic differentiation, and excessive activation of osteoclasts. In this study, a ROS-responsive titanium implant coating composed of calcium carbonate-mineralized nicotinamide mononucleotide (NMN) nanoparticles, lipoic acid-modified gelatin (LAMG), and sodium alginate (SA) is developed, designed to enhance osseointegration through dual synergistic mechanisms. First, the LAMG hydrogel effectively scavenges excess ROS, while calcium carbonate neutralizes H + ions and restores physiological pH levels, thereby reducing acid-induced bone resorption and inhibiting osteoclast activity. Second, ROS and H + ions-triggered release of NMN enhances the intracellular NAD⁺/NADH ratio in bone marrow mesenchymal stem cells, activates the SIRT1 signaling pathway, restores mitochondrial function, and promotes osteogenic differentiation. By concurrently remodeling the pathological bone microenvironment and repairing mitochondrial dysfunction, this multifunctional coating suppresses osteoclast-mediated bone resorption while facilitating osteoblast formation, thereby enhancing peri-implant osseointegration under osteoporotic conditions. This strategy not only presents a promising therapeutic approach for functionalizing titanium implants but also offers a potentially translatable platform for treating osteoporotic bone defects.
研究领域:
生物材料
·
组织工程
·
骨科
·
再生医学
·
纳米医学
·
骨骼生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Fang Liu,Yaru Li,Yao Li,Zheng Wang,Xin Li,Yancheng Liu,Yanjun Zhao
The clinical translation of the anticancer drug β -lapachone (LAP) has been limited by the narrow therapeutic window. Stimuli-responsive anticancer drug delivery systems have gained tremendous attention in recent years to alleviate adverse effects and enhance therapeutic efficacy. Here, we report a dual pH- and enzyme-responsive nanocarrier to address the above issue of LAP. In detail, the epigallocatechin gallate (EGCG) and ferric ions were employed to engineer nanoscale ferric ion-polyphenol complexes where LAP was physically encapsulated therein. The coordination bond between Fe 3+ and the catechol moiety of EGCG was sensitive to the low pH, enabling the triggered cargo release in the acidic endosomes/lysosomes. Afterward, the released LAP was activated by the overexpressed NAD(P)H: quinone oxidoreductase 1 (NQO1) and ferroptosis suppressor protein 1 (FSP1) in the tumor cells, followed by the generation of reactive oxygen species (ROS), and the induction of oxidative stress and apoptotic cell death. Meanwhile, EGCG could upregulate gasdermin E (GSDME), and ferric ions were involved in the Fenton reaction. Hence, EGCG and ferric ions could sensitize the toxicity of LAP through the induction of multiple cell death pathways ( e.g ., pyroptosis, ferroptosis, apoptosis, and necroptosis). The current work enlarged the LAP’s therapeutic window via controlled cargo release and vehicle sensitization.
研究领域:
药学
·
纳米技术
·
癌症治疗
·
药物递送系统
·
细胞死亡机制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Fuqiang Liang,Yajing Fang,Weiwei Cao,Zhuo Zhang,Siyi Pan,Xiaoyun Xu
The current study evaluates the protective effects of tangeretin, a representative polymethoxyflavone (PMF) mainly isolated from the peels of citrus fruits, against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells and the potential mechanisms of this protection. Tangeretin suppressed t-BHP-induced oxidative damage, as evaluated by cell viability, reactive-oxygen-species (ROS) levels, lactate dehydrogenase (LDH) leakage and glutathione (GSH) levels. Further mechanistic studies showed that tangeretin up-regulated the expression of heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Moreover, tangeretin induced antioxidant-responsive-element (ARE)-dependent luciferase activation, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation, and mitogen-activated-protein-kinase (MAPK) phosphorylation. Results in the study indicate that the protective effects of tangeretin may be at least partly due to its capacity to up-regulate the antioxidant enzymes NQO1 and HO-1 via the MAPK–Nrf2–ARE signaling pathway. Tangeretin may play an effective protective role in liver injury.
研究领域:
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROPHARMACOLOGY
·
2024
·
IF 4.6
Peng Chen,Yulai Wang,Jing Xie,Jiexin Lei,Benhong Zhou
Effective therapeutic interventions for elderly patients are lacking, despite advances in pharmacotherapy. Methylated urolithin A (mUro A), a modified ellagitannin (ET)-derived metabolite, exhibits anti-inflammatory, antioxidative, and anti-apoptotic effects. Current research has primarily investigated the neuroprotective effects of mUroA in aging mice and explored the underlying mechanisms. Our study used an in vivo aging model induced by d -galactose (D-gal) to show that mUro A notably improved learning and memory, prevented synaptic impairments by enhancing synaptic protein expression and increasing EPSCs, and reduced oxidative damage in aging mice. mUro A alleviated the activation of the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome, leading to reduced glial cell activity and neuroinflammation in both accelerated aging and naturally senescent mouse models. Moreover, mUroA enhanced the activity of TCA cycle enzymes (PDH, CS, and OGDH), decreased 8-OHdG levels, and raised ATP and NAD + levels within the mitochondria. At the molecular level, mUro A decreased phosphorylated p53 levels and increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), thus enhancing mitochondrial function. In conclusion, mUro A alleviates cognitive impairment in aging mice by suppressing neuroinflammation through NLRP3 inflammasome inhibition and restoring mitochondrial function via the p53-PGC-1α pathway. This suggests its potential therapeutic agent for brain aging and aging-related diseases.
研究领域:
神经科学
·
老年学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2018
·
IF 3.04
Yuxin Wang,Linyao Li,Yawen Wang,Xiaokang Zhu,Mingdong Jiang,Erqun Song,Yang Song
A large population of drug candidates have failed “from bench to bed” due to unwanted toxicities. We intend to develop an alternative approach for drug discovery, that is, to seek candidates from “safe” compounds. Rebaudioside A (Reb-A) is an approved commercial sweetener from Stevia rebaudiana Bertoni. We found that Reb-A protects against carbon tetrachloride (CCl 4 )-induced oxidative injury in human liver hepatocellular carcinoma (HepG2) cells. Reb-A showed antioxidant activity on reducing cellular reactive oxygen species and malondialdehyde levels while increasing glutathione levels and superoxide dismutase and catalase activities. Reb-A treatment induced nuclear factor erythroid-derived 2-like 2 (Nrf2) activation and antioxidant response element activity, as well as the expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Further mechanistic studies indicated that c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), mitogen-active protein kinase (MAPK) and protein kinase C epsilon (PKCε) signaling was upregulated. Thus, the present in vitro study conclusively demonstrated that Reb-A is an activator of Nrf2 and is a potential candidate hepatoprotective agent. More importantly, the present study illustrated that seeking drug candidates from “safe” compounds is a promising strategy.
研究领域:
药理学
·
毒理学
·
细胞生物学
·
分子生物学
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Panpan Xue,Huilan Zhuang,Sijie Shao,Tingjie Bai,Xuemei Zeng,Shuangqian Yan
The activation of cellular ferroptosis is promising in tumor therapy. However, ferroptosis is parallelly inhibited by antiferroptotic substances, including glutathione peroxidase 4 (GPX4), dihydroorotate dehydrogenase (DHODH), and ferroptosis suppressor protein 1 (FSP1). Thus, it is highly desirable, yet challenging, to simultaneously suppress these three antiferroptotic substances for activating ferroptosis. Here, we rationally designed a hollow iron-doped SiO2-based nanozyme (FeSHS) loaded with brequinar (BQR) and lificiguat (YC-1), named FeSHS/BQR/YC-1-PEG, for tumor ferroptosis activation. FeSHS were developed through the continuous etching of SiO2 nanoparticles by iron ions, which exhibit pH/glutathione-responsive biodegradability, along with mimicking the activities of peroxidase, glutathione oxidase, and NAD(P)H oxidase. Specifically, glutathione depletion and NAD(P)H oxidation by FeSHS will suppress the expression of GPX4 and inhibit FSP1 by disrupting the NAD(P)H/FSP1/ubiquinone axis. In addition, the released BQR can suppress the expression of DHODH. Meanwhile, YC-1 is able to increase the cellular polyunsaturated fatty acids (PUFAs) by destroying the HIF-1α/lipid droplet axis. The elevation of levels of iron and PUFAs while simultaneously disrupting the GPX4/DHODH/FSP1 inhibitory pathways by our designed nanoplatform displayed high therapeutic efficacy both in vitro and in vivo. This work elucidates rationally designing smart nanoplatforms for ferroptosis activation and future tumor treatments.
研究领域:
纳米技术
·
癌症治疗
·
生物化学
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Maoxing Pan,Yuanjun Deng,Yebei Qiu,Dajin Pi,Chuiyang Zheng,Zheng Liang,Jianwei Zhen,Wen Fan,Qingliang Song,Jinyue Pan,Yuanyou Li,Haizhen Yan,Qinhe Yang,Yupei Zhang
Background Non-alcoholic fatty liver disease (NAFLD) has emerged as a burgeoning health problem worldwide, but no specific drug has been approved for its treatment. Shenling Baizhu powder (SL) is extensively used to treat NAFLD in Chinese clinical practice. However, the therapeutic components and pharmacological mechanisms of SL against NAFLD have not been thoroughly investigated. Purpose This study aimed to investigate the pharmacological impact and molecular mechanism of SL on NAFLD. Methods First, we established an animal model of NAFLD by high-fat diet (HFD) feeding, and evaluated the therapeutic efficacy of SL on NAFLD by physiological, biochemical, pathological, and body composition analysis. Next, the effect of SL on autophagic flow in NAFLD rats was evaluated by ultrastructure, immunofluorescence staining, and western blotting. Moreover, an integrated strategy of targeted energy metabolomics and network pharmacology was performed to characterize autophagy-related genes and explore the synergistic effects of SL active compounds. UPLC-MS/MS, molecular docking combined with in vivo and in vitro experiments were conducted to verify the key compounds and genes. Finally, a network was established among SL-herb-compound-genes-energy metabolites-NAFLD, which explains the complicated regulating mechanism of SL on NAFLD. Results We discovered that SL decreased hepatic lipid accumulation, hepatic steatosis, and insulin resistance, and improved systemic metabolic disorders and pathological abnormalities. Subsequently, an integrated strategy of targeted energy metabolomics and network pharmacology identified quercetin, ellagic acid, kaempferol, formononetin, stigmasterol, isorhamnetin and luteolin as key compounds; catalase (CAT), AKT serine/threonine kinase 1 (AKT), nitric oxide synthase 3 (eNOS), NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1) and hypoxia-inducible factor 1 subunit alpha (HIF-1α) were identified as key genes; while nicotinamide adenine dinucleotide phosphate (NADP) and succinate emerged as key energy metabolites. Mechanistically, we revealed that SL may exert its anti-NAFLD effect by inducing autophagy activation and forming a comprehensive regulatory network involving key compounds, key genes, and key energy metabolites, ultimately alleviating oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction. Conclusion Our study demonstrated the therapeutic effect of SL in NAFLD models, and establishes a basis for the development of potential products from SL plant materials for the treatment of NAFLD.
研究领域:
药理学
·
分子生物学
·
代谢组学
·
营养学
✓ 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）