INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Qi Liang,Rongjie Guo,Jia-Ruei Tsao,Yun He,Chenchen Wang,Jiaxuan Jiang,Di Zhang,Taige Chen,Tingting Yue,Kai Hu
Dry eye disease (DED) is a multifactorial disease, and oxidative stress plays a crucial role in its pathogenesis. Recently, multiple studies have shown that upregulation of autophagy can protect the cornea from oxidative stress damage. The present study investigated the therapeutic effects of salidroside, the main component of Rhodiola crenulata , in both in vivo and in vitro dry eye models. The results showed that topical eye drop treatment with salidroside restored corneal epithelium damage, increased tear secretion, and reduced cornea inflammation in the DED mice. Salidroside activated autophagy through AMP-activated protein kinase (AMPK)-sirtuin-1 (Sirt1) signaling pathway, which promoted the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and increased the expression of downstream antioxidant factors heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1). This process restored antioxidant enzyme activity, reduced reactive oxygen species (ROS) accumulation, and alleviated oxidative stress. The application of autophagy inhibitor chloroquine and AMPK inhibitor Compound C reversed the therapeutic efficacy of salidroside, validating the above findings. In conclusion, our data suggest that salidroside is a promising candidate for DED treatment.
研究领域:
药理学
·
眼科
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2020
·Vol. 96
·期 6
·1433-1446
·
IF 2.548
Yibing Guo,Liancheng Xu,Changchun Ling,Tao Yang,Wenjie Zheng,Jin Lv,Qingsong Guo,Bohua Chen
Eighteen new β-carboline-based indole-4,7-quinone derivatives ( 12a–i and 13a–i ) were designed and synthesized, and their in vitro and in vivo antiproliferative activities were studied. Most of target compounds showed strong inhibition on three human tumor cells' proliferation. In particular, the most active compound 13g not only displayed more prominent antiproliferative activities than β-lapachone, a clinical antitumor candidate, but also exerted significant NAD(P)H: quinone-oxidoreductase-1 (NQO1) inhibitory activity and NQO1-dependent cytotoxicity in HT29 cells. Furthermore, 13g dose-dependently induced high ROS levels in HT29 cells, and selectively inhibited cancer cell but not non-tumor colon cell proliferation in vitro. Importantly, 13g promoted HT29 cell apoptosis and DNA damage by regulating relative apoptotic proteins and H2AX expression. Finally, 13g displayed significant growth inhibition of HT29 human colorectal adenocarcinoma xenograft in mice without overt toxicity.
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Min Luo,Dan Luo,Jie Liu,Huailing Wang,Xiaoyu Liu,Min Yang,Fangfang Tian,Suofu Qin,Yuying Li
Probiotics are living bacteria that provide health benefits to the host when consumed in sufficient quantities. However, the protective effect of the bioactive peptides isolated from the probiotics against benzo(α)pyrene (BaP) induced gastrointestinal injury has never been investigated. The current work used a bio-assay guided technique to identify-four new cyclic peptides in BaP-induced Caco-2 cell culture and mouse colitis model. Lactobacillus rhamnosus cycle (Thr-His-Ala-Trp) peptide-1 (LRCP-1) effectively inhibited BaP-induced epithelial cytokine over-release and intracellular ROS over-production. Simultaneously, LRCP-1 attenuated BaP-induced NAD (P)H: oxidases (NOXs), Matrix metalloproteinases (MMPs) over-expression, respectively. Furthermore, increased NAD (P)H: quinone oxidoreductase 1 (NQO1)/heme oxygenase-1 (HO-1)/nuclear factor E2-related factor 2 (Nrf2) expression and aryl hydrocarbon receptor (AhR) pathway activation induced by the BaP-exposure were also inhibited after the LRCP-1 treatment. Notably, LRCP-1 is a promising agent protecting gastrointestinal epithelial cells from BaP-induced inflammatory and oxidative damages.
研究领域:
胃肠病学
·
免疫学
·
分子生物学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2023
·
IF 5.1
Tianyang Wang,Jian Zhang,Haokai Wei,Xi Wang,Minjuan Xie,Yinjie Jiang,Jie Zhou
Introduction Matrine (MT), an ingredient extracted from the Chinese herb Sophora flavescens , can result in nephrotoxicity because of long-term exposure. However, the underlying mechanism by which MT leads to kidney injury remains unclear. This study aimed to investigate the roles of oxidative stress and mitochondria in MT-induced kidney toxicity both in vitro and in vivo . Methods Mice were exposed to MT for 20 days, and NRK-52E cells were exposed to MT with or without LiCl (a GSK-3β inhibitor), tert-Butylhydroquinone (t-BHQ, an Nrf2 activator), or small interfering RNA . Results The results showed that MT caused nephrotoxicity accompanied by an increase in reactive oxygen species (ROS) accumulation and mitochondrial dysfunction. Meanwhile, MT significantly upregulated glycogen synthase kinase-3β (GSK-3β) activity, released cytochrome c (Cyt C) and cleaved caspase-3, decreased the activity of nuclear factor-erythroid 2-related Factor 2 (Nrf2), and reduced the expression of heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), which led to the inactivation of antioxidant enzymes and the activation of apoptosis . In addition, GSK-3β inhibition by LiCl or small interfering RNA pretreatment or Nrf2 activation by t-BHQ pretreatment attenuated the toxic effects of MT in NRK-52E cells. Conclusions Taken together, these results revealed that MT-induced apoptosis triggered kidney toxicity and that GSK-3β or Nrf2 might serve as a promising nephroprotective target for MT-induced kidney injury.
研究领域:
药理学
·
毒理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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 Environmental Chemical Engineering
·
2023
·
IF 7.7
Yuan Chen,Yuancai Chen,Yexia Qin
In the present study, we found that nanoparticles (Pd-NPs) were biosynthesized by Bacillus wiedmannii MSM ( B. wiedmannii MSM) with endogenous carbon under O 2 condition, and more favorablity under N 2 purging condition. XRD results indicated that crystal planes of Pd-NPs were attributed to Pd 0 (111), Pd 0 (200), Pd 0 (220), and Pd 0 (311), respectively. TEM and STEM-EDX results showed that the bio-reduction of Pd (II) ( k pd,1 =4.799 min −1 ) occurred predominately in periplasm space. FTIR results showed that the -COOH, -OH, and -NH 2 were the main groups participating in the removal of Pd (II). The aerobic reduction of Pd (II) by B. wiedmannii MSM was proposed, including extracellular superoxide radicals produced by NAD(P)H oxidases , endogenous electron donors, and O 2 -insensitive hydrogenase. These studies provide new methods and insights for reduction of Pd (II).
研究领域:
环境科学
·
材料科学
·
微生物学
·
化学
✓ 已验证
产品关联
DOI
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
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
Biotechnology Journal
·
2024
·Vol. 19
·期 3
·2300744
·
IF 3.2
Shuping Zou,Bing Zhang,Yuyue Han,Jinlong Liu,Kuo Zhao,Yaping Xue,Yuguo Zheng
NAD(P)H-dependent oxidoreductases are crucial biocatalysts for synthesizing chiral compounds. Yet, the industrial implementation of enzymatic redox reactions is often hampered by an insufficient supply of expensive nicotinamide cofactors. Here, a cofactor self-sufficient whole-cell biocatalyst was developed for the enzymatic asymmetric reduction of 2-oxo-4-[(hydroxy)(-methyl)phosphinyl] butyric acid (PPO) to L-phosphinothricin (L-PPT). The endogenous NADP + pool was significantly enhanced by regulating Preiss-Handler pathway toward NAD(H) synthesis and, in the meantime, introducing NAD kinase to phosphorylate NAD(H) toward NADP + . The intracellular NADP(H) concentration displayed a 2.97-fold increase with the strategy compared with the wild-type strain. Furthermore, a recombinant multi-enzyme cascade biocatalytic system was constructed based on the Escherichia coli chassis. In order to balance multi-enzyme co-expression levels, the strategy of modulating rate-limiting enzyme Pm GluDH by RBS strengths regulation successfully increased the catalytic efficiency of PPO conversion. Finally, the cofactor self-sufficient whole-cell biocatalyst effectively converted 300 mM PPO to L-PPT in 2 h without the need to add exogenous cofactors, resulting in a 2.3-fold increase in PPO conversion (%) from 43% to 100%, with a high space-time yield of 706.2 g L −1 d −1 and 99.9% ee . Overall, this work demonstrates a technological example for constructing a cofactor self-sufficient system for NADPH-dependent redox biocatalysis.
研究领域:
生物技术
·
生物化学
·
代谢工程
·
酶学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2021
·
IF 4.315
Hao Huang,Xielan Kuang,Xiaobo Zhu,Hao Cheng,Yuxiu Zou,Han Du,Han Tang,Linbin Zhou,Jingshu Zeng,Huijun Liu,Jianhua Yan,Chongde Long,Huangxuan Shen
Retinal ischemia-reperfusion (I/R) often results in intractable visual impairments, where blood retinal barrier (BRB) homeostasis mediated by retinal pigment epithelium (RPE) and retinal microvascular endothelium (RME) is crucial. However, strategies targeting the BRB are limited. Thus, we investigated the inconclusive effect of lycopene (LYC) in retinal protection under I/R. LYC elevated cellular viability and reversed oxidative stress in aRPE-19 cells/hRME cells under I/R conditions based on oxygen-glucose deprivation (OGD) in vitro . Molecular analysis showed that LYC promoted NRF2 expression and enhanced the downstream factors of the KEAP1/NRF2/ARE pathway: LYC increased the activities of antioxidants, including SOD and CAT , whereas it enhanced the mRNA expression of HO-1 ( ho-1 ) and NQO-1 ( nqo-1 ). The activation resulted in restrained ROS and MDA. On the other hand, LYC ameliorated the damage to retinal function and morphology in a mouse I/R model, which was established by unilateral ligation of the left pterygopalatine artery/external carotid artery and reperfusion . LYC promoted the expression of NRF2 in both the neural retina and the RPE choroid in vivo . This evidence revealed the potential of LYC in retinal protection under I/R, uncovering the pharmacological effect of the KEAP1/NRF2/ARE pathway in BRB targeting. The study generates new insights into scientific practices in retinal research.
研究领域:
眼科学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2022
·
IF 14.224
Zhiyan Yan,Chenrui Liu,Yun Liu,Xiaoqian Tan,Xinyue Li,Yan Shi,Chunlian Ding
Cr(VI) contaminated water usually contains other contaminants like engineered nanomaterials (ENMs). During the process of microbial treatment , the inevitable interaction of Cr(VI), ENMs, and microorganisms probably determines the efficiency of Cr(VI) biotransformation , however, the corresponding information remains elusive. This study investigated the interaction of ZnO nanoparticles (NPs), Cr(VI), and Pannonibacter phragmitetu s BB (hereafter BB), which changed the process of microbial Cr(VI) reduction. ZnO NPs inhibited Cr(VI) reduction, but had no effect on bacterial viability. In particular, Cr(VI) induced BB to produce organic acids and to drive Zn 2+ dissolution from ZnO NPs inside and outside of cells. The dissolved Zn 2+ not only promoted Cr(VI) reduction to Cr(V)/Cr(IV) by strengthening sugar metabolism and inducing increase in NAD(P)H production, but also hindered Cr(V)/Cr(IV) transformation to Cr(III) through down-regulating Cr(VI) reductase genes. A novel bacterial driven ROS scavenging mechanism leading to the inhibition of Cr(VI) reduction was elucidated. Specifically, the accumulated Cr(VI) and Cr(V)/Cr(IV) formed a redox dynamic equilibrium, which triggered the disproportionation of superoxide radicals mimicking superoxide dismutase through the flip-flop of Cr(VI) and Cr(V)/Cr(IV) in bacterial cells. This study provided a realistic insight into design the applicability of biological remediation technology for Cr(VI) contaminant and evaluating environmental risks of ENMs.
研究领域:
环境科学
·
微生物学
·
纳米技术
·
生物修复
✓ 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）