Aging-US
·
2020
·
IF 4.831
Yan Sun,Shiting Dai,Jin Tao,Yunlong Li,Ziqi He,Quan Liu,Jiawen Zhao,Yaoliang Deng,Juening Kang,Xuepei Zhang,Sixing Yang,Yunlong Liu
Oxidative stress and autophagy are the key promoters of calcium oxalate (CaOx) nephrolithiasis. Taurine is an antioxidant that plays a protective role in the pathogenesis of kidney disease. Previous studies found that taurine suppressed cellular oxidative stress, and inhibited autophagy activation. However, the effect of taurine on CaOx kidney stone formation remains unknown. In the present work, we explored the regulatory effects of taurine on CaOx crystals-induced HK-2 cell injury. Results showed that pretreatment with taurine significantly enhanced the viability of HK-2 cells and ameliorated kidney tissue injury induced by CaOx crystals. Taurine also markedly reduced the levels of inflammatory cytokines, apoptosis, and CaOx crystals deposition. Furthermore, we observed that taurine supplementation alleviated CaOx crystals-induced autophagy. Mechanism studies showed that taurine reduced oxidative stress via increasing SOD activity, reducing MDA concentration, alleviating mitochondrial oxidative injury, and decreasing the production of intracellular ROS. Taurine treatment also effectively activated Akt/mTOR signaling pathway in CaOx crystals-induced HK-2 cells both in vitro and in vivo . In summary, the current study shows that taurine inhibits ROS-dependent autophagy via activating Akt/mTOR signaling pathway in CaOx crystals-induced HK-2 cell and kidney injury, suggesting that taurine may serve as an effective therapeutic agent for the treatment of CaOx nephrolithiasis.
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高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 7.3
Zhikun Liu,Meng Wang,Rizhen Huang,Tianhui Hu,Yi Jing,Xiaochao Huang,Weiwei Hu,Guoxiu Cao,Hengshan Wang
Developing multifunctional platinum(IV) prodrugs via integrating bioactive pharmacophores into one entity is an attractive strategy to ameliorate the defects of platinum(II) drugs. Herein, a series of indole–chalcone derivative-ligated platinum(IV) complexes were synthesized and evaluated for their anticancer activities. Among them, optimal complex 17a exerted superior activity compared to that of cisplatin (CDDP) against the tested cells but showed lower cytotoxicity toward human normal lung cells. Detailed mechanisms demonstrated that 17a significantly enhanced intracellular accumulation, induced DNA damage, and inhibited migration in A549/CDDP cells. Furthermore, 17a efficiently disturbed the tubulin–microtubule system, initiated reactive oxygen species (ROS)-mediated endoplasmic reticulum stress, and activated a mitochondrion-dependent apoptosis signaling pathway. Besides, 17a was superior to free drugs or their combination in inhibiting cancer growth in A549/CDDP xenografts without inducing obvious side effects. The physical mixture of 16a and CDDP was almost identical to 17a but showed apparent systematic side effects. In summary, our studies may provide an efficient treatment regimen for CDDP resistance.
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RSC Advances
·
2025
·Vol. 15
·期 15
·11283-11292
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IF 4.6
Zixin Liang,Xinyi Xu,Ning Wang,Xintao He,Xingzhi Han,Liuqi Sang,Jing Hu,Xiaoping Qian
Colorectal cancer (CRC) remains a major global health challenge, particularly in advanced stages where drug resistance leads to high recurrence rates and poor survival outcomes. This study investigates a novel therapeutic approach combining gambogic acid (GA) with manganese dioxide (MnO2) nanoparticles (MBG NPs) to enhance anti-tumor efficacy in the acidic and hypoxic tumor microenvironment (TME). The development of MBG NPs involved conjugating MnO2 nanosheets with bovine serum albumin (BSA) for effective GA encapsulation, optimizing the delivery of both components. We explored the potential of Mn2+ ions released from MnO2 to synergize with GA to alleviate tumor hypoxia and modulate the TME, thereby improving immune response. In vitro assays demonstrated significant cytotoxicity of MBG NPs against mouse colon cancer cells (CT26 cells), with enhanced apoptosis and elevated reactive oxygen species (ROS) levels. In vivo studies using BALB/c mice showed that treatment with MBG NPs significantly reduced tumor volumes and improved survival rates compared to controls. Additionally, MBG NPs combined with programmed death-1 inhibitor (aPD-1) further augmented therapeutic effects. Histological analyses confirmed tumor necrosis and changes in TME composition, indicating the potential of this synergistic strategy to overcome drug resistance in microsatellite stable (MSS) CRC, inhibit tumor growth and benefit patient survival. These findings highlight the promising application of nanoparticle-based platforms in enhancing immunotherapy outcomes for advanced colorectal cancer.
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JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Hui Ren,Yu-Jue Wang,Xin-Ye Wang,Xiangyun Li,Zheng Han,Guxue Zhang,Liwei Gu,Ming Bai,Guo-Dong Yao,Qingbo Liu,Shao-Jiang Song
Thioredoxin reductase 1 (TrxR1) is an important therapeutic target for nonsmall cell lung cancer (NSCLC) treatment due to its overexpression in NSCLC cells. In this work, to address the deficiency that sesquiterpene lactone containing α-methylene-γ-lactone moiety was rapidly metabolized by endogenous nucleophiles, series of novel thioether derivatives were designed and synthesized based on a reactive oxygen species (ROS)-triggered prodrug strategy. Among them, prodrug 5u exhibited potent cytotoxicity against NSCLC cells and better release rates in response to ROS. The active compound 6a released from 5u covalently binds to Cys475 and Sec498 sites on TrxR1, resulting in inhibition on TrxR1 activity, which led to redox homeostasis disorder, and caused apoptosis and ferroptosis. Moreover, prodrug 5u exhibited significant antitumor efficiency in nude mice and NSCLC organoids. Our results deliver ROS-triggered prodrug 5u as a novel TrxR1 inhibitor for the treatment of NSCLC and provide a promising strategy of ROS-activated prodrug for covalent compounds in cancer therapy.
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高影响因子
PLANT AND CELL PHYSIOLOGY
·
2018
·Vol. 59
·期 9
·1889-1904
·
IF 4.059
Zhang Wei,Lu Li-Ying,Hu Li-Yan,Cao Wei,Sun Kai,Sun Qi-Biao,Siddikee Ashaduzzaman,Shi Run-Han,Dai Chuan-Chao
Allelopathy is mediated by plant-derived secondary metabolites (allelochemicals) which are released by donor plants and affect the growth and development of receptor plants. The plant root is the first organ which senses soil allelochemicals this results in the production of a shorter primary root. However, the mechanisms underlying this process remain elusive. Here, we report that a model allelochemical benzoic acid (BA) inhibited primary root elongation of Arabidopsis seedlings by reducing the sizes of both the meristem and elongation zones, and that auxin signaling affected this process. An increase in auxin level in the root tips was associated with increased expression of auxin biosynthesis genes and auxin polar transporter AUX1 and PIN2 genes under BA stress. Mutant analyses demonstrated that AUX1 and PIN2 rather than PIN1 were required for the inhibition of primary root elongation during BA exposure. Furthermore, BA stimulated ethylene evolution, whereas blocking BA-induced ethylene signaling with an ethylene biosynthesis inhibitor (Co2+), an ethylene perception antagonist (1-methylcyclopropene) or ethylene signaling mutant lines etr1-3 and ein3eil1 compromised BA-mediated inhibition of root elongation and up-regulation of auxin biosynthesis-related genes together with AUX1 and PIN2, indicating that ethylene signal was involved in auxin-mediated inhibition of primary root elongation during BA stress. Further analysis revealed that the BA-induced reactive oxygen species (ROS) burst contributed to BA-mediated root growth inhibition without affecting auxin and ethylene signals. Taken together, our results reveal that the allelochemical BA inhibits root elongation by increasing auxin accumulation via stimulation of auxin biosynthesis and AUX1/PIN2-mediated auxin transport via stimulation of ethylene production and an auxin/ethylene-independent ROS burst.
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Chemistry-An Asian Journal
·
2014
·Vol. 9
·期 8
·2295-2302
·
IF 3.935
Lingwu Zeng,Yang Li,Tianyu Li,Wei Cao,Yu Yi,Weijia Geng,Zhiwei Sun,Huaping Xu
Graphical Selenium helps target cancer : We report a selective anticancer system based on the coordination between selenide and cisplatin. The system induces cell apoptosis in a different way from cisplatin. By selectively inducing different reactive oxygen species (ROS) concentrations in cancer cells and normal cells, the system kills cancer cells 18 times faster than that of normal cells (see figure). en We report the preparation of selenium-containing platinum-based anticancer drug EG-Se/Pt. EG-Se/Pt was obtained from the coordination of selenium-containing molecules (EG-Se) with cisplatin (CDDP). The structure of EG-Se/Pt was characterized by 1 H and 77 Se NMR spectroscopy, XPS, ESI-MS, and MALDI-TOF. In aqueous solution, EG-Se/Pt self-assembles to form spherical aggregates. EG-Se/Pt shows enhanced stability against dilution and high salt concentration compared with EG-Se. EG-Se/Pt induces cell apoptosis via reactive oxygen species (ROS), which leads to high selectivity between cancer cells and normal cells in cytotoxicity assays. More importantly, EG-Se/Pt effectively inhibits tumor growth in vivo in tumor-bearing mice. It is anticipated that tuning the ROS level through the assembly of selenium-containing molecules can be a general method to realize anticancer selectivity. zh 1
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高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2025
·
IF 8.2
Xiao He,Zhongmin Wang,Huayang Bai,Yaqin Tang,Daimeng Feng,Shuyu Zhang,Robert J. Lee,Jing Xie,Yansun Sun
Breast cancer remains a major global health challenge, with triple-negative breast cancer (TNBC) posing a particular therapeutic dilemma due to its lack of targetable receptors and reliance on chemotherapy, which is often thwarted by drug resistance. To overcome these limitations, we developed a novel metal-polyphenol nano-platform (DLF@NPs) via a one-pot coordination assembly of L-dopa (L-DA), doxorubicin (DOX), and ferrous ions (Fe 2+ ). This GSH/pH-dual-responsive nanoparticle exploits the overexpression of L-type amino acid transporter 1 (LAT1) on breast cancer cells for targeted delivery and tumor-specific enrichment, effectively addressing the off-target toxicity and resistance associated with free DOX. Upon internalization into the acidic and high-GSH tumor microenvironment, DLF@NPs rapidly disassemble, releasing their payload. The liberated DOX not only exerts its apoptotic effect but also activates NADPH oxidases (NOXs) to elevate intracellular H 2 O 2 levels. This endogenous H 2 O 2 supply fuels a Fenton reaction catalyzed by the co-released Fe 2+ , generating highly toxic hydroxyl radicals. Furthermore, L-DA reduces the resultant Fe 3+ back to Fe 2+ , establishing a catalytic cycle that robustly amplifies reactive oxygen species (ROS). The resultant ROS burst synergizes with DOX by inducing severe mitochondrial damage, leading to potentiated apoptosis. In summary, this work proposes a novel targeted nanoplatform that utilizes the synergy between chemodynamic therapy and chemotherapy to provide a promising strategy for combating drug-resistant breast cancer.
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International Journal of Nanomedicine
·
2024
·
IF 6.6
Zixia Wu,Weibo Xia,Liling Ou,Ling Zheng,Bingying Hou,Tonghe Pan,Wenjie Sun,Leo H Koole,Yongqing Shao,Lei Qi
Purpose Patients afflicted with dry eye disease (DED) experience significant discomfort. The underlying cause of DED is the excessive accumulation of ROS on the ocular surface. Here, we investigated the nitrogen doped-graphene quantum dots (NGQDs), known for their ROS-scavenging capabilities, as a treatment for DED.Methods NGQDs were prepared by using citric acid and urea as precursors through hydrothermal method. The antioxidant abilities of NGQDs were evaluated through: scavenging the ROS both extracellular and intracellular, regulating the nuclear factor-erythroid 2-related factor (Nrf2) antioxidant pathway of human corneal epithelial cells (HCECs) and their transcription of inflammation related genes. Furthermore, NGQDs were modified by Arg-Gly-Asp-Ser (RGDS) peptides to obtain RGDS@NGQDs. In vivo, both the NGQDs and RGDS@NGQDs were suspended in 0.1% Pluronic F127 (w/v) and delivered as eye drops in the scopolamine hydrobromide-induced DED mouse model. Preclinical efficacy was compared to the healthy and DPBS treated DED mice.Results These NGQDs demonstrated pronounced antioxidant properties, efficiently neutralizing free radicals and activating the intracellular Nrf2 pathway. In vitro studies revealed that treatment of H2O2-exposed HCECs with NGQDs induced a preservation in cell viability. Additionally, there was a reduction in the transcription of inflammation-associated genes. To prolong the corneal residence time of NGQDs, they were further modified with RGDS peptides and suspended in 0.1% Pluronic F127 (w/v) to create RGDS@NGQDs F127 eye drops. RGDS@NGQDs exhibited superior intracellular antioxidant activity even at low concentrations (10 μg/mL). Subsequent in vivo studies revealed that RGDS@NGQDs F127 eye drops notably mitigated the symptoms of DED mouse model, primarily by reducing ocular ROS levels.Conclusion Our findings underscore the enhanced antioxidant benefits achieved by modifying GQDs through nitrogen doping and RGDS peptide tethering. Importantly, in a mouse model, our novel eye drops formulation effectively ameliorated DED symptoms, thereby representing a novel therapeutic pathway for DED management.
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高影响因子
CANCER LETTERS
·
2018
·
IF 6.491
Yingming Sun,Hongtao Miao,Shijing Ma,Lei Zhang,Chengcheng You,Fang Tang,Cui Yang,Xiaoli Tian,Feng Wang,Yuan Luo,Xiangjie Lin,Hui Wang,Chunyang Li,Zhijun Li,Hongnv Yu,Xuefeng Liu,Yu Xiao,Yan Gong,Junhong Zhang,Hong Quan,Conghua Xie
FePt-Cys nanoparticles (FePt-Cys NPs) have been well used in many fields, despite their poor solubility and stability. We synthetized a cysteine surface modified FePt NPs, which exhibited good solubility, stability and biocompatibility. We explored the insight mechanisms of the antitumor effects of this new nanoparticle system in lung cancer cells. In the in vitro study, FePt-Cys NPs induced a reactive oxygen species (ROS) burst, which suppressed the antioxidant protein expression and induced cell apoptosis. Furthermore, FePt-Cys NPs prevented the migration and invasion of H1975 and A549 cells. These changes were correlated with a dramatic decrease in MMP-2/9 expression and enhanced the cellular attachment. We demonstrated that FePt-Cys NPs promoted the effects of chemo-radiation through activation of the caspase system and impairment of DNA damage repair. In the in vivo study, no severe allergies or drug-related deaths were observed and FePt-Cys NPs showed a synergistic effect with cisplatin and radiation. In conclusion, with good safety and efficacy, FePt-Cys NPs could therefore be potential sensitizers for chemoradiotherapy.
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Small
·
2024
·
IF 13
Yu He,Ejun Peng,Xiaozhuo Ba,Jian Wu,Wen Deng,Qiu Huang,Yonghua Tong,Haojie Shang,Zichen Zhong,Xiao Liu,Yanlong Zhang,Tao Ye,Xiaoqi Yang,Kangyang Wang,Yabin Xie,Kehua Jiang,Ding Xia,Zhiqiang Chen,Kun Tang
Emerging studies have demonstrated that M1 macrophage polarization and oxidative stress play important roles in calcium oxalate (CaOx) induced kidney injury, which leads to increased crystals deposition. ROS scavenging nanozymes and kidney-targeted nanoparticles for antioxidant drugs delivery have emerged as an arisen methodology for kidney injury therapy. However, cell membrane biomimetic-modified nanozymes as anti-inflammatory drug delivery systems for the treatment of kidney injury is rarely reported. Herein, the ROS responsive red blood cell-membrane-coated resatorvid-loaded cerium oxide nanoparticles (RBCM@CeO 2 /TAK-242) are constructed to suppress CaOx induced kidney injury and crystals deposition. In vitro, RBCM@CeO 2 /TAK-242 shows effective internalization by renal tubular epithelial cells, along with demonstrated antioxidative, anti-inflammatory, and macrophage reprogramming effects. Glyoxalate(Gly)-induced renal CaOx crystals mouse model is established, RBCM@CeO 2 /TAK-242 shows excellent injured kidney targeting and biosafety, and could effectively suppress CaOx induced kidney injury and crystals deposition. RBCM@CeO 2 /TAK-242 has a dual protective effect by both inhibiting oxidative stress and modulating macrophage polarization in vivo. In addition, RNA seq analysis reveals that RBCM@CeO 2 /TAK-242 protects against CaOx induced kidney injury via suppressing the TLR4/NF-κB pathway. This study provides an innovative strategy for RBCM@CeO 2 /TAK-242 as injured kidney targeting and dual protective effects for the treatment of CaOx induced kidney injury and crystals deposition.
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BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Ke Wang,Xiaomin Xia,Nan Wang,Jie Liu,Xue Li
Macrophage extracellular traps (METs) are protein network structures released by macrophages during immune defense initiation and inflammation regulation. Evidence shows that these protein structures can help kill pathogens. However, overproduction of METs can harm organisms. Therefore, novel strategies to inhibit the excessive production of METs during immune reactions need to be developed. This study introduces a novel type of anti-inflammatory and antibacterial nanocomposites (i.e., ZIF-8/Ce@rutin NPs) developed by doping the nanozyme Ce into the antibacterial zeolitic imidazole framework-8 (ZIF-8) and then loading the reactive oxygen species (ROS) scavenger rutin via electrostatic adsorption. Results showed that ZIF-8/Ce@rutin exerted bactericidal effects on gram-positive and -negative bacteria, thereby inhibiting MET production from the source. Furthermore, ZIF-8/Ce@rutin scavenged ROS and induced macrophage polarization into the anti-inflammatory M2 type, thereby inhibiting MET progression. This research shows that ZIF-8/Ce@rutin can restrain MET overproduction, providing a theoretical basis for using ZIF-8/Ce@rutin to treat inflammatory and infectious diseases.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Jialin Zhuang,Yechen Wang,Liping Lin,Jiaying Xiao,Jiahui Cai,Yingmo Hu,Qi An
Reactive oxygen species (ROS) as highly oxidative substances play significant roles in environmental matter cycling. Despite their high potential in environmental regulation, effective artificial ROS generation techniques are still in the primary stage. In this study, we propose an effective piezo-photocatalytic film for ROS generation in water flow and under light irradiation. The high ROS generation capability stem from the special suprathin and highly porous structure obtained using our developed spray-drying technique to prepare the composite film. During the spray process, optimized component of graphene oxide, TiO 2 nanoparticles, and Poly(vinylidene fluoride- co -hexafluoropropylene) (PVDF-HFP) polymer chains self-organized to effective piezoelectrically and photocatalytically active assemblies, and highly porous structures are formed during the drying process. Especial mechanical sensibility to deform is realized in response to external force as weak as 0.2 N. The enhanced piezoelectricity of the PVDF-HFP microdomain, the narrowed band gap, and the electron transfer across the interfacial heterojunction between graphene and TiO 2 all contribute to the especially high piezo-photocatalytic capabilities. Water flow can effectively trigger the piezoelectric field generation in the film, which remarkably boost extractable charge carriers generated upon light irradiation. 88.05 % degradation efficiency of Rhodamine B during 15 min and 95.2 % degradation efficiency of ciprofloxacin in 120 min are realized, along with bacteriostat capabilities. The application potential of the composite are demonstrated in dest-top laundry process and the treated stained water can be used to cultivate plant. We expect the strategy to develop into a novel form of cleaning technique.
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危险品化学品经营许可证（带存储）