MOLECULES
·
2016
·Vol. 21
·期 8
·1061
·
IF 2.465
Chongshan Dai,Daowen Li,Lijing Gong,Xilong Xiao,Shusheng Tang
Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced cytotoxicity and the underlying mechanism in human hepatocyte L02 cells. The results showed that curcumin pre-treatment significantly ameliorated FZD-induced oxidative stress, characterized by decreased reactive oxygen species (ROS) and malondialdehyde formation, and increased superoxide dismutase, catalase activities and glutathione contents. In addition, curcumin pre-treatment significantly ameliorated the loss of mitochondrial membrane potential, the activations of caspase-9 and -3, and apoptosis caused by FZD. Alkaline comet assay showed that curcumin markedly reduced FZD-induced DNA damage in a dose-dependent manner. Curcumin pre-treatment consistently and markedly down-regulated the mRNA expression levels of p53, Bax, caspase-9 and -3 and up-regulated the mRNA expression level of Bcl-2. Taken together, these results reveal that curcumin protects against FZD-induced DNA damage and apoptosis by inhibiting oxidative stress and mitochondrial pathway. Our study indicated that curcumin may be a promising combiner with FZD to reduce FZD-related toxicity in clinical applications.Keywords:curcumin;furazolidone;oxidative stress;DNA damage;mitochondrial pathway
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Environmental Technology & Innovation
·
2024
·
IF 6.7
Yan Li,Hongyu Sun,Zewei Liu,Yutan Chu,Yizong Huang,Qiongli Bao
The remediation of soil contaminated with cadmium (Cd) and arsenic (As) has consistently been a complex issue. Foliar application of jasmonic acid (JA) could be a promising agronomic practice for reducing heavy metal accumulations. However, the combined reduction effects and mechanisms of Cd and As in rice through foliar JA application have not been fully explored. In this study, a pot experiment was conducted to investigate rice yield, Cd and As accumulations and translocations, photosynthesis, and ROS-scavenging attributes in Huanghuazhan (HHZ) and Huarun No.2 (HR). The results revealed that 1 μM JA treatment significantly decreased the concentrations of Cd (by 34.6% in HHZ and 38.3% in HR) and As (by 30.8% in HHZ and 40.8% in HR) in the grains, and increased the percentage of filled-grain and 1000-grain weight in HHZ. The structural equation model (SEM) indicated that grain Cd was directly and positively affected by panicle Cd and leaf sheath Cd, while grain As was directly and positively affected by panicle As, leaf blade As and leaf sheath As. JA application enhanced the net photosynthetic rate and chlorophyll content (both a and b). Additionally, it scavenged levels of H 2 O 2 and O 2 .- , reduced lipid peroxidation damage by promoting the activities of antioxidant enzymes and altering the cellular redox status in the flag leaves of rice. Overall, these results suggest that foliar JA application of could be an effective strategy for preventing Cd and As accumulations in rice grains in paddy soils with low to medium contamination risks.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2024
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IF 4.9
Yue Wang,Yaning Li,Meiwen Cao,Zeyu Yan,Fenggang Wei,Tianhao Ma,Ruochen Xie,Hongchao Ma
Tumor hypoxia, limited H 2 O 2 levels, and abundant glutathione (GSH) in the tumor microenvironment (TME) pose challenges for high-efficiency reactive oxygen species (ROS)-mediated therapies. To address these limitations, an intelligent ROS-mediated nanoplatform, Ce6@ZIF-8/PDA/CuO 2 /HA (CZPCH), with photodynamic activity, self-supplied H 2 O 2 , Fenton-like reaction, GSH-depletion and photothermal activity was designed for efficient tumor treatment. In the acidic TME, CuO 2 in CZPCH deposits into Cu 2+ and H 2 O 2 , consuming GSH and triggering Fenton-like reactions to generate hydroxyl radical (•OH), enabling efficient chemodynamic therapy (CDT). Moreover, the presence of Ce6 and PDA enables CZPCH to exhibit excellent singlet oxygen ( 1 O 2 ) and temperature increase performance 660 nm and 808 nm laser irradiation, respectively, resulting in efficient photodynamic therapy (PDT) and photothermal therapy (PTT) efficacy. Interestingly, the temperature increase from PTT significantly enhances •OH and 1 O 2 generation, achieving high-efficiency ROS-based therapeutic efficacy. This synergistic CDT/PDT/PTT treatment demonstrates excellent anti-tumor efficacy and illuminates novel ROS-based therapeutic strategy design.
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International Journal of Nanomedicine
·
2024
·
IF 6.6
Licai Miao,Zihao Xu,Junhao Sui,Xiangyu Meng,Shicheng Huo,Shu Liu,Mengchen Chen,Zhong Zheng,Xiaobin Cai,Hao Zhang
Purpose Skin injury, often caused by physical or medical mishaps, presents a significant challenge as wound healing is critical to restore skin integrity and tissue function. However, external factors such as infection and inflammation can hinder wound healing, highlighting the importance of developing biomaterials with antibiotic and wound healing properties to treat infections and inflammation. In this study, a novel photothermal nanomaterial (MMPI) was synthesized for infected wound healing by loading indocyanine green (ICG) on magnesium-incorporated mesoporous bioactive glass (Mg-MBG) and coating its surface with polydopamine (PDA).Results In this study, Mg-MBG and MMPI was synthesized via the sol-gel method and characterized it using various techniques such as scanning electron microscopy (SEM), the energy dispersive X-ray spectrometry (EDS) system and X-ray diffraction (XRD). The cytocompatibility of MMPI was evaluated by confocal laser scanning microscopy (CLSM), CCK8 assay, live/dead staining and F-actin staining of the cytoskeleton. The antibacterial efficiency was assessed using bacterial dead-acting staining, spread plate method (SPM) and TEM. The impact of MMPI on macrophage polarization was initially evaluated through flow cytometry, qPCR and ELISA. Additionally, an in vivo experiment was performed on a mouse model with skin excision infected. Histological analysis and RNA-seq analysis were utilized to analyze the in vivo wound healing and immunomodulation effect.Conclusion Collectively, the new photothermal and photodynamic nanomaterial (MMPI) can achieve low-temperature antibacterial activity while accelerating wound healing, holds broad application prospects.
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Theranostics
·
2025
·Vol. 15
·期 10
·4734
·
IF 13.3
Zi-Yue Xi,Chuan-Yong Fan,Ying-Ying Jiang,Xin-Ran Xi,Gan-Yu Nie,Shuang Zhu,Jun-Jie Zhang,Lu Xu
Background: Traditional programmed cell death, including ferroptosis, cuproptosis, and apoptosis, has demonstrated excellent anti-tumor effects and declared their complete mechanisms, however, the zinc ion-mediated tumor inhibiting mechanisms remain insufficiently explored. In this study, a self-generated oxygen nanocatalytic system (ZnO@COF@EM, ZCE) was developed to stimulate cascade amplified effect (CAE) of reactive oxygen species (ROS) generation leading to Znproptosis. The underlying Znproptosis mechanism to disrupt mitochondrial (Mito) metabolism was also investigated. Methods: Specifically, the principle of Znproptosis caused by accumulated zinc and ROS, which served as key factors, was declared through western blot analysis and genetic testing. The mechanism of generated ROS (·OH and 1 O 2 ) under NIR irradiation by ZCE was detected by UV scanning curves, confocal laser scanning microscopy (CLSM) images, and density functional analysis. The injury condition of Fe-S protein of mitochondria metabolism, which triggered Znproptosis with FDX2/LIAS pathway by zinc and ROS, was examined by PCR test and MTT assay. Notably, a Mito-targeting strategy for ZCE was proposed by using molecular docking technology, wherein Zn 2+ was recognized by zinc finger proteins (ZFPs) with the Mito. Results: ZCE, along with CAE, produced abundant ROS (2.42-time more than control group). At the quantum chemical level, the CAE mechanism was associated with a narrower highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gap and increased electronic energy motion within ZCE, which prolonged the excited triplet state (ETS). At the gene level, Znproptosis was achieved by regulating FDX2 and ZIP7 proteins to damage Fe-S protein. The cell cycle was interrupted by Chk2/Cdc25C/Cdc2 and Chk2/p21/Cyclin B1 pathways, leading to the arrest of G1/S and G2/M phases of the cell cycle and inhibition of the Akt/mTOR signaling pathway. Moreover, Znproptosis induced by overloading zinc ions and ROS resulted in a significant antitumor effect (up to 83.81%). Conclusion: Hence, the research reveals a detailed Znproptosis mechanism in nanocatalytic system. Through regulating FDX2/LIAS pathway, Znproptosis could improve the death rate of mitochondria by decreasing the production of Fe-S protein, contributing to advancements in the field of antitumor therapy.
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JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Xiaoye Yang,Xiaoqun Shi,Yanan Zhang,Jiangkang Xu,Jianbo Ji,Lei Ye,Fan Yi,Guangxi Zhai
To improve the anti-cancer therapeutic effect of nanosystems for chemo-photodynamic therapy, there remain several hurdles to be addressed, e.g. , limited co-loading efficiency, insufficient stimulus-responsiveness and lack of synergetic effect. This work reported novel reactive‑oxygen-species (ROS)-responsive chlorin e6 (Ce6) and paclitaxel (PTX) co -encapsulated chondroitin sulfate- g -poly (propylene sulfide) nanoparticles (CP/ChS- g -PPS NPs), wherein the drug loading efficiencies of Ce6 and PTX were as high as 14.93% and 24.31%, respectively. To enlarge the ROS signal at tumor sites thus enhancing the ROS-responsiveness of ChS- g -PPS NPs, near-infrared (NIR) light was utilized to induce Ce6 to produce more ROS to destruct the NPs. Our data showed that the photo-triggered self-destructive property of NPs helped drugs to spread deeper in tumors upon laser irradiation, making the NPs promising to thoroughly remove tumor cells. CP/ChS- g -PPS NPs exhibited a synergetic chemo-photodynamic therapy effect in vitro , which was suggested by the combination indexes of PTX and Ce6 lower than 1 when 20–80% inhibition rates of MCF-7 cells were achieved. As for the in vivo antitumor activity , the tumor inhibition rates of CP/ChS- g -PPS NPs (with laser irradiation) were as high as 92.76% and 88.57% in 4T1 bearing BALB/c mice and MCF-7 bearing BALB/c nude mice, respectively, which were significantly higher than those of other treatment groups. This work provided a simple yet effective strategy to develop photo-triggered ROS-responsive NPs for synergetic chemo-photodynamic therapy with quick ROS-responsive self-destruction, spatiotemporally controllability, reduced off-target toxicity, and desirable therapeutic effect.
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CTS-Clinical and Translational Science
·
2024
·Vol. 17
·期 3
·e13748
·
IF 3.1
Chenyu Song,Kaiyang Wang,Bangping Qian,Jingshun Lu,Mu Qiao,Yong Qiu,Bin Wang,Yang Yu
Ankylosing spondylitis (AS) is an immune chronic inflammatory disease, resulting in back pain, stiffness, and thoracolumbar kyphotic deformity. Based on the reported anti-inflammatory and antioxidant capacities of cynarin (Cyn), this study explored its protective role and molecular mechanisms in mesenchymal stem cells (MSCs) from AS. The target pathways and genes were verified using Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescent staining, while molecular docking analysis was conducted. In AS-MSCs, we found that the expression levels of p-NF-κB, IL-6, IL-1β, and TNF-α were higher and IκB-α, Nrf-2, and HO-1 were lower compared with healthy control (HC)-MSCs. With molecular docking analysis, the biding affinities between Cyn and Keap1-Nrf-2 and p65-IκB-α were predicted. The mRNA and protein expression of p-NF-κB, IL-6, IL-1β, and TNF-α and the reactive oxygen species (ROS) generation were downregulated following Cyn administration. Meanwhile, the expression level of IκB-α, Nrf-2, and HO-1 were significantly increased after Cyn pretreatment. The results suggested that the protective mechanisms of Cyn in AS-MSCs were based on enhancing the antioxidation and suppression of excessive inflammatory responses via Nrf-2/ROS/NF-κB axis. Our findings demonstrate that Cyn is a potential candidate for alleviating inflammation in AS.
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CHEMICAL ENGINEERING JOURNAL
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2024
·
IF 13.3
Qian Luo,Jiao Zhang,Samira Batur,Chuansheng Fu,Wei Chen,Qi Xie,Conglian Yang,Zhiping Zhang
Androgenic alopecia (AGA) is the most common type of hair loss, causing serious physical and mental distress to patients. The key factors contributing to AGA include oxidative stress and insufficient vascularization in the microenvironment around hair follicles. Currently, the available treatment options are limited, and there is no comprehensive treatment strategy with minimal side effects and optimal efficacy. Herein, we developed a novel minoxidil and epigallocatechin gallate co-loaded ionic liquids drug delivery system (ME@CGIL), which was simple to prepare and could effectively regulate hair follicle microenvironment homeostasis. After topical application, the ionic liquids, which had a certain function of promoting hair regrowth, facilitated drugs delivery into the epidermis and dermis while prolonging their retention time, so as to reduce the frequency and dosage requirements. ME@CGIL promoted hair regrowth by activating hair follicle stem cells, scavenging excessive reactive oxygen species and promoting neovascularization in the AGA mouse model, showing superior efficacy than commercially available minoxidil products. Altogether, this study may provide a simple and ingenious treatment strategy for AGA, which has great potential for clinical application.
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CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Jinhong Cai,Shuhan Liu,Qiuling Zhong,Yifeng Shang,Zhengrong Chen,Yi Yao,Bo Zhou,Feiying Yin,Jinmin Zhao,Li Zheng
An ideal wound dressing has both efficient antimicrobial and anti-inflammatory properties, as well as the potential to regulate the immune microenvironment for the treatment of chronically infected wounds. Herein, a novel multifunctional hydrogel wound dressing (HPZ8) was developed for wound healing by incorporating polydopamine Zeolite Imidazole Framework 8 (PDA-ZIF8) nanoparticles into a dynamic cross-linked network consisting of hydrazide-modified hyaluronic acid (HA-CDH) and oxidized hyaluronic acid (HA-CHO). The results suggested that the HPZ8 hydrogel could be injected into the wound to form a barrier, facilitating tissue adhesion and rapid hemostasis. After loaded with PDA-ZIF8 nanoparticles, the hydrogel exhibited excellent antioxidant and photothermal antimicrobial properties, which could effectively scavenge ROS, reduce oxidative stress and eliminate bacterial infections. Especially, near-infrared (NIR) irradiation strengthened the photothermal therapy (PTT). Besides, HPZ8 hydrogel could release zinc ions to promote cell migration, angiogenesis and M2 polarization of macrophages, accelerating macrophage transition from inflammation to proliferation stages, thus promoting infected wound healing. Therefore, the HPZ8 multifunctional hydrogel dressing has application prospects for the therapy of chronic infected wounds.
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BIOMATERIALS
·
2024
·
IF 12.8
Xiaolan Ou,Ze Wang,Daojiang Yu,Wenlai Guo,Andrei V. Zvyagin,Quan lin,Wenrui Qu
ABSTRACT Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus (DM), significantly contributing to the risk of amputation and mortality. Reactive oxygen species (ROS) can induce both neurological and structural harm through direct impact and pyroptosis, underscoring the critical role of ROS regulation in mitigating DPN. In this research endeavor, we propose harnessing the inherent antioxidant properties of sulfhydryl groups by grafting them onto gold nanodots through an amidation reaction, resulting in the creation of ROS-responsive AuNDs. Additionally, we aim to synthesize AuNDs-VEGF, wherein VEGF is attached to AuNDs via electrostatic interactions, as a therapeutic strategy for addressing DPN in rat models. The results of in vivo experiments showed that AuNDs and AuNDs-VEGF nanoparticles could increase the nerve conduction velocity, shorten the latency of nerve conduction in the sciatic nerve, promote the regeneration of nerve trophectodermal vessels, improve the structure and function of the sciatic nerve, reduce the apoptosis of neural cells, and alleviate the atrophy of the gastrocnemius muscle. Thus, VEGF-loaded ROS-responsive nanodots present a promising avenue for ameliorating diabetic peripheral neuropathy. This innovative approach not only extends the application possibilities of nanodots but also introduces a novel avenue for the treatment of diabetic neuropathy.
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Pharmaceutics
·
2025
·Vol. 17
·期 7
·940
·
IF 5.5
Xin Zhang,Ruonan Lian,Bingbing Fan,Lei Meng,Pengxia Zhang,Yu Zhang,Weitong Sun
Objectives:Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by chronic inflammation, gut microbiota dysbiosis, and complex tumor microenvironment interactions. Current therapies are limited by systemic toxicity and poor tumor accumulation. This study aimed to develop a ROS/enzyme dual-responsive oral drug delivery system, KGM-CUR/PSM microspheres, to achieve precise drug release in CRC and enhance tumor-specific drug accumulation, which leverages high ROS levels in CRC and the β-mannanase overexpression in colorectal tissues.Methods:In this study, we synthesized a ROS-responsive prodrug polymer (PSM) by conjugating polyethylene glycol monomethyl ether (mPEG) and mesalazine (MSL) via a thioether bond. CUR was then encapsulated into PSM using thin-film hydration to form tumor microenvironment-responsive micelles (CUR/PSM). Subsequently, konjac glucomannan (KGM) was employed to fabricate KGM-CUR/PSM microspheres, enabling targeted delivery for colorectal cancer therapy. The ROS/enzyme dual-response properties were confirmed through in vitro drug release studies. Cytotoxicity, cellular uptake, and cell migration were assessed in SW480 cells. In vivo efficacy was evaluated in AOM/DSS-induced CRC mice, monitoring tumor growth, inflammatory markers (TNF-α, IL-1β, IL-6, MPO), and gut microbiota composition.Results:In vitro drug release studies demonstrated that KGM-CUR/PSM microspheres exhibited ROS/enzyme-responsive release profiles. CUR/PSM micelles demonstrated significant anti-CRC efficacy in cytotoxicity assays, cellular uptake studies, and cell migration assays. In AOM/DSS-induced CRC mice, KGM-CUR/PSM microspheres significantly improved survival and inhibited CRC tumor growth, and effectively reduced the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and myeloperoxidase (MPO). Histopathological and microbiological analyses revealed near-normal colon architecture and microbial diversity in the KGM-CUR/PSM group, confirming the system’s ability to disrupt the “inflammation-microbiota-tumor” axis.Conclusions:The KGM-CUR/PSM microspheres demonstrated a synergistic enhancement of anti-tumor efficacy by inducing apoptosis, alleviating inflammation, and modulating the intestinal microbiota, which offers a promising stimuli-responsive drug delivery system for future clinical treatment of CRC.
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ENVIRONMENTAL POLLUTION
·
2025
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IF 7.3
Mengqiang He,Xiaolei Teng,Junyan Wei,Xiaoyu Li,Zunyao Wang
o,p’-dichlorodiphenyltrichloroethane (2,4′-DDT) is a typical persistent organic pollutant (POP) characterized by environmental persistence and acute toxicity. Its pronounced hydrophobicity drives preferential adsorption onto suspended particulate matter (SPM) in aquatic systems. This study systematically investigated the photochemical transformation mechanism of 2,4′-DDT in the Pearl River SPM-water system. Environmental factor analysis revealed negligible effects from pH and cations on 2,4′-DDT photodegradation, while NO 3 − and HCO 3 − inhibited degradation via competitive UV absorption and reactive species quenching. Reaction mechanisms were probed through H 2 O 2 -enhanced hydrophilic reactive oxygen species (ROS) generation, revealing dual photosensitizing and ROS-quenching roles of dissolved organic matter (DOM) in SPM. Hydrophobicity-dependent degradation patterns were revealed through quenching experiments and comparative POPs studies, demonstrating that hydrophilic-region ROS (particularly •OH) contributed dominantly to 2,4′-DDT degradation compared to hydrophobic-region ROS. The LC-MS and GC-MS analyses identified three transformation pathways: dechlorination, elimination, and hydroxylation. Theoretical calculations confirmed C-Cl bond cleavage and elimination feasibility, with •OH attacking benzene-ring carbons at minimal energies, explaining the formation of hydroxylated products. Notably, toxicity assessments revealed enhanced hazards of dechlorination and elimination photoproducts to humans and aquatic organisms than the parent compound.
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