TOXICOLOGY AND APPLIED PHARMACOLOGY
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2023
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IF 3.8
Hao Zhao,Xin Lin,Qingfeng Chen,Xiaoyue Wang,Yongya Wu,Xiaoxia Zhao
Sepsis-induced cardiomyopathy (SIC) has high morbidity and mortality. Quercetin (QUE) has been used to treat many inflammatory diseases related to pyroptosis . However, its effect on SIC has not been reported before. We aimed to explore the therapeutic mechanism of QUE on SIC. We found that the expression levels of NOX2, markers of myocardial injury and inflammatory factors related to pyroptosis were upregulated in the serum of SIC patients. QUE improved the viability and reduced the death rate of LPS-treated H9C2 cells. It could downregulate the expression level of NOX2 and alleviate NOX2-induced mitochondrial damage to inhibit the ROS-mediated NF-κB/TXNIP pathway thus ameliorating cell pyroptosis. Overexpression of NOX2 partially attenuated the anti-pyroptotic effects of QUE on LPS-treated H9C2 cells in vitro. Besides, the results of animal experiments reported that the mitochondrial damage was reduced by QUE treatment, which subsequently inhibited the ROS-mediated NF-κB/TXNIP pathway to ameliorate cell pyroptosis to further alleviate myocardial injury in CLP-induced rats in vivo. To conclude, QUE suppressed the NOX2/ROS-mediated NF-κB/TXNIP signaling pathway to ameliorate pyroptosis of cardiomyocytes to relieve SIC.
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COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2023
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IF 3.9
Liping Cao,Nailin Shao,Jinliang Du,Haojun Zhu,Jiancao Gao,Quanjie Li,Yi Sun,Jiawen Hu,Guojun Yin,Gangchun Xu
There is limited knowledge about the toxicity of Microcystin-LR (MC-LR) in crustaceans, despite its high toxicity to aquatic organisms . This research aimed to explore the effects of MC-LR on cytotoxicity, oxidative stress , and apoptosis in the hepatopancreas of Eriocheir sinensis , as well as elucidate the involvement of reactive oxygen species (ROS) and potential mechanisms of toxicity. In vivo and in vitro exposures of crabs to MC-LR and N -acetylcysteine (NAC) were performed, followed by assessments of cell morphology, viability, tissue pathology, biochemical indicators, gene expression, and hepatopancreatic transcriptome . Results revealed that MC-LR facilitated the entry of the MC-LR transporter oatp3a into hepatopancreatic cells, leading to upregulated expression of phase I detoxification enzyme genes ( cyp4c , cyp2e1 , and cyp3 ) and downregulated the phase II enzyme genes ( gst1 , gpx , gsr2 , gclc , and nqo1 ), resulting in increased ROS levels and cytotoxic effects. MC-LR exhibited cytotoxicity, reducing cell viability and inducing abnormal nuclear morphology with a 48 h- IC 50 value of approximately 120 μm. MC-LR exposure caused biochemical changes indicative of oxidative stress damage and evident hepatopancreatic lesions. Additionally, MC-LR exposure regulated the levels of bax and bcl-2 expression, activating caspase 3 and 6 to induce cell apoptosis. Intervention with NAC attenuated MC-LR-induced ROS production and associated toxic effects. Transcriptome analysis revealed enrichment of differentially expressed genes in pathways related to cytochrome P450-mediated xenobiotic metabolism and the FoxO signaling pathway . These findings shed light on the potential mechanisms underlying MC-LR toxicity and provide valuable references for further research and conservation efforts regarding the health of aquatic animals.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2023
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IF 6.7
Si-Han Zhou,Rui-Dong Wang,Tian-Tian Wu,Shi-Hui Deng,Ji-Chao Guo,Shu-Min Zhou,Xuan Zhou,Jiajia Du,Qi-Hua Zhao,Xiaoxia Ren,Ming-jin Xie
As many of the disadvantages of traditional single therapy can be avoided with combination therapy, combination therapy has become a new treatment method. Herein, a long rod-shaped gallium composite multifunctional material (CP–Au-PEG-FA@BSA@IR780) based on chemotherapy therapy (CT), photothermal therapy (PTT) and photodynamic therapy (PDT) is constructed to increase reactive oxygen species (ROS) levels and Au NP release. CP-Au-PEG-FA@BSA@IR780 has fluorescence localization characteristics and can combine with CT-DNA to cause cancer cell apoptosis. The in vitro cytotoxicity experiments showed the excellent biocompatibility and great therapeutic efficacy of the designed nanoplatform compared to those of the IR780 group, which had weak red fluorescence. The in vivo experiments also showed that the designed micro/nano platform can effectively eliminate HCT116 tumors by allowing the temperature of the tumor site to exceed 55 °C (thermal ablation) under light irradiation . The main mechanism of chemotherapy indicated that the presence of Fe 2+ /Fe 3+ can disrupt the rod-shaped structure of the original material and increase the content of Ga 3+ . Overall, CP-Au-PEG-FA@BSA@IR780 is a promising cancer therapy strategy that combines CT, PTT, and PDT and provides new insights into the synthesis method of enhancing composite materials with photothermal properties.
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JOURNAL OF NANOBIOTECHNOLOGY
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2023
·Vol. 21
·期 1
·1-21
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IF 10.2
Han Xiaoqin,Luo Ruifeng,Qi Shanshan,Wang Yanli,Dai Linxin,Nie Wenbiao,Lin Meisi,He Haoqi,Ye Naijing,Fu Chaomei,You Yu,Fu Shu,Gao Fei
Ulcerative colitis (UC) faces some barriers in oral therapy, such as how to safely deliver drugs to the colon and accumulate in the colon lesions. Hence, we report an advanced yeast particles system loaded with supramolecular nanoparticles with ROS scavenger (curcumin) to treat UC by reducing oxidative stress state and inflammatory response and accelerating the reprogramming of macrophages. In this study, the dual-sensitive materials are bonded on β-cyclodextrin (β-CD), the D-mannose (Man) is modified to adamantane (ADA), and then loaded with curcumin (CUR), to form a functional supramolecular nano-delivery system (Man-CUR NPs) through the host-guest interaction. To improve gastrointestinal stability and colonic accumulation of Man-CUR NPs, yeast cell wall microparticles (YPs) encapsulated Man-CUR NPs to form Man-CUR NYPs via electrostatic adsorption and vacuum extrusion technologies. As expected, the YPs showed the strong stability in complex gastrointestinal environment. In addition, the Man modified supramolecular nanoparticles demonstrated excellent targeting ability to macrophages in the in vitro cellular uptake study and the pH/ROS sensitive effect of Man-CUR NPs was confirmed by the pH/ROS-dual stimulation evaluation. They also enhanced lipopolysaccharide (LPS)-induced inflammatory model in macrophages through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and scavenging the excess ROS. Notably, in DSS-induced mice colitis model, Man-CUR NYPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways, alleviate oxidative stress by Nrf2/HO-1 signaling pathway, promote macrophages reprogramming and improve the favorable recovery of the damaged colonic tissue. Taken together, this study not only provides strategy for “supramolecular curcumin nanoparticles with pH/ROS sensitive and multistage therapeutic effects” in “advanced yeast particles”, but also provided strong theoretical support multi-effect therapy for UC.
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Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Wu Xiaodong,Li Pengpeng,Cheng Jian,Xu Qiang,Lu Beiji,Han Conghui,Huo Weiling
Objective: Osteoarthritis (OA) is a common subtype of arthritis. To date, treatment of OA focuses primarily on alleviating pain and improving joint function. The lack of a vascular system within synovial joints and the rapid removal of agents due to synovial exchange hinder continuous delivery of OA drugs. However, these obstacles are being addressed by promising nanoscale drugs.Methods: We synthesize and assemble a hydrogen peroxide [H2O2, belongs to the category of active oxygen species (ROS)]-sensitive nanomicelle, which is loaded with the anti-inflammation drug dexamethasone and chondrogenic differentiation factor cartilage-derivedmor-phogeneticprotein-1. The micelle can induce bone marrow mesenchymal stem cells to repair cartilage while inhibiting joint inflammation.Results: The prepared nanoparticles were of uniform size and displayed an obvious core-shell structure. Under H2O2 stimulation, the shell layer could be removed gradually. The drug-loaded micelle effectively inhibited proliferation of activated macrophages, induced macrophage apoptosis with an anti-inflammatory effect, and caused the BMSCs to differentiate into chondrocytes.Conclusion: This work provides an experimental and theoretical basis for further development of a drug-loaded micelle in the healing of osteoarthritis.
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
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2021
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IF 4.86
Jie Tang,Mingrong Bei,Jia Zhu,Guangtao Xu,Deqing Chen,Xin Jin,Jianzhong Huang,Jingjian Dong,Lili Shi,Long Xu,Bo Hu
Cadmium (Cd) exposure can exert an impact on carcinogenicity of breast cancer, however, the mechanism is not fully understood in triple-negative breast cancer (TNBC). We performed a TNBC MDA-MB-231 cell model and assessed the toxic effect of Cd exposure (0, 10, 20, 50, 60, 80 μM). Cd reduced cell viability in a time- and dose-dependent manner, followed by cell cycle arrest in S phase with alterations of cyclin 1A1, cyclin 1D1 and CDK2. Lactate dehydrogenase (LDH) release, apoptosis and pyroptosis were increased, which were relieved by z-VAD. Elevated ROS and NLRP3, caspase-1, IL-1β and IL-18 were detected, which was attenuated by N-acetylcysteine. Increased bax and decreased caspase-8, caspase-9 and caspase-3 were found. gasdermin E (GSDME) was activated with cleavage of GSDME-NT, which was retarded by z-VAD. Additionally, p38 MAPK signaling pathway was activated. Our data demonstrate GSDME-activated pyroptosis in Cd toxicity, implying a potential impact on TNBC.
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Frontiers in Cell and Developmental Biology
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2020
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IF 5.186
Hong Lin,Chen Jundixia,Wu Fang,Wu Fengjiao,Shen Xin,Zheng Peisen,Shao Rongrong,Lu Kongqin,Liu Zhiguo,Chen Daoxing,Liang Guang,Cai Yuepiao,Zou Peng,Xia Yiqun
Colon cancer is one of the leading causes of cancer-related death in the world. The development of new drugs and therapeutic strategies for patients with colon cancer are urgently needed. Isodeoxyelephantopin (ESI), a sesquiterpene lactone isolated from the medicinal plant Elephantopus scaber L., has been reported to exert antitumor effects on several cancer cells. However, the molecular mechanisms underlying the action of ESI is still elusive. In the present study, we found that ESI potently suppressed cell proliferation in human colon cancer cells. Furthermore, our results showed that ESI treatment markedly increased cellular reactive oxygen species (ROS) levels by inhibiting thioredoxin reductase 1 (TrxR1) activity, which leads to activation of the JNK signaling pathway and eventually cell death in HCT116 and RKO cells. Importantly, we found that ESI markedly enhanced cisplatin-induced cytotoxicity in HCT116 and RKO cells. Combination of ESI and cisplatin significantly increased the production of ROS, resulting in activation of the JNK signaling pathway in HCT116 and RKO cells. In vivo, we found that ESI combined with cisplatin significantly suppressed tumor growth in HCT116 xenograft models. Together, our study provide a preclinical proof-of-concept for ESI as a potential strategy for colon cancer treatment.
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LABORATORY INVESTIGATION
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2021
·Vol. 102
·期 1
·90-101
·
IF 5.662
Zhang Kailun,Chai Bo,Ji Hao,Chen liuqing,Ma Yanbing,Zhu Lifei,Xu Jingyu,Wu Yanqing,Lan Yinan,Li Hao,Feng Zhiguo,Xiao Jian,Zhang Hongyu,Xu Ke
Bioactive glass (BG) has recently shown great promise in soft tissue repair, especially in wound healing; however, the underlying mechanism remains unclear. Pyroptosis is a novel type of programmed cell death that is involved in various traumatic injury diseases. Here, we hypothesized that BG may promote wound healing through suppression of pyroptosis. To test this scenario, we investigated the possible effect of BG on pyroptosis in wound healing both in vivo and in vitro. This study showed that BG can accelerate wound closure, granulation formation, collagen deposition, and angiogenesis. Moreover, western blot analysis and immunofluorescence staining revealed that BG inhibited the expression of pyroptosis-related proteins in vivo and in vitro. In addition, while BG regulated the expression of connexin43 (Cx43), it inhibited reactive oxygen species (ROS) production. Cx43 activation and inhibition experiments further indicate that BG inhibited pyroptosis in endothelial cells by decreasing Cx43 expression and ROS levels. Taken together, these studies suggest that BG promotes wound healing by inhibiting pyroptosis via Cx43/ROS signaling pathway.
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JOURNAL OF DRUG TARGETING
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2018
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IF 3.408
Xuefei Zhou,Zimo Liu,Huifang Wang,Xin Liu,Zhuxian Zhou,Jianbin Tang,Xiangrui Liu,Min Zheng,Youqing Shen
Non-viral gene delivery is an attractive approach for the treatment of many diseases including cancer, benefiting from its safety and large-scale production concerns. However, the relatively low transfection efficacy compared with viral vectors restricts the clinical applications of non-viral gene vectors. Reactive oxygen species (ROS) triggered charge reversal polymers (named B-PDEAEA) presented improved transfection efficacy, because of fast release of plasmid DNA responding to enhanced oxidative stress in cancer cells. But inadequate dissociation can still occur owing to the insufficient intracellular ROS generation. Here, we report SAHA (vorinostat), which is a clinical histone deacetylase inhibitor and anticancer drug, induces the ROS accumulation in cancer cells, and facilitates the charge reversal process of B-PDEAEA and the cellular dissociation of the delivered gene from the vectors. As a result, SAHA remarkably increases the gene transfection efficacy in an ROS-dependent manner. Importantly, SAHA synergizes with B-PDEAEA mediated therapeutic gene TNF-related apoptosis-inducing ligand (TRAIL) delivery in inducing apoptosis of cancer cells. These findings support the first concept of improving the gene delivery efficacy of stimuli-responsive vectors through upregulating the cellular ROS via an FDA approved anticancer agent. Additionally, combination of SAHA and TRAIL gene therapy could be a potential strategy for cancer treatment.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
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IF 9.7
Longhao Lv,Yong Liu,Chengsong Cao,Yong Li,Zhengshuai Tang,Jinliang Liu
The tumor microenvironment (TME) is characterized by several key features, including hypoxia, elevated levels of hydrogen peroxide (H 2 O 2 ), high concentrations of glutathione (GSH), and an acidic pH. Recent research has increasingly focused on harnessing or targeting these characteristics for effective cancer therapy. In this study, we developed an innovative composite bio-reactor that integrates genetically engineered bacteria with upconversion nanoparticles (UCNPs) and nano-copper manganese materials for lung cancer treatment. The nano-copper manganese materials function as catalysts in Fenton-like reactions, facilitating the decomposition of hydrogen peroxide into harmful hydroxyl radicals and oxygen, which can effectively target tumors and reduce hypoxia. To circumvent the challenge of insufficient endogenous hydrogen peroxide during treatment, we employed UCNPs capable of converting near-infrared laser irradiation, known for its deep tissue penetration, into visible light. This conversion activates the genetically engineered bacteria to generate exogenous hydrogen peroxide directly within the tumor microenvironment, enabling prolonged therapeutic effects. Our findings suggest that this composite bio-reactor can achieve effective lung cancer therapy without the need for external hydrogen peroxide supplementation, representing a significant advancement in the design of targeted cancer treatments.
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Acta Biomaterialia
·
2024
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IF 9.4
Jianxun Shangguan,Fengnan Yu,Bingyu Ding,Zhijiang Jiang,Jie Wang,Dingwei Li,Yi Chen,Yingzheng Zhao,Sunkuan Hu,Helin Xu
The disrupted oxidative redox homeostasis plays a critical role in the progress of ulcerative colitis (UC). Herein, hydrogel-forming viscous liquid (HSD) composed of cysteamine-grafted hyaluronic acid (HS) and superoxide dismutase (SOD) has been designed for UC. When the viscous HSD liquid was infused into colitis colon, SOD would convert the pathological superoxide (O 2 ·− ) to hydrogen peroxides (H 2 O 2 ), which was subsequently scavenged by HS. Accordingly, the sol-gel transition of HSD was initiated by scavenging H 2 O 2 , enhancing its adhesion toward colitis colon. H 2 O 2 -treated HSD presented the higher storage modulus and stronger adhesion force toward porcine colon than the untreated HSD. Besides, H 2 O 2 -treated HSD presented the slower erosion profile in the colitis-mimicking medium (pH 3-5), while its rapid degradation was displayed in physiologic condition (pH7.4). The combination of pH-resistant erosion and ROS-responsive adhesion for HSD rendered it with the specifical retention on the inflamed colonic mucosa of DSS-induced colitis mice. Rectally administrating HSD could effectively hinder the body weight loss, reduce the disease activity index and improve the colonic shorting of DSS-induced colitis mice. Moreover, the pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were substantially decreased, the colonic epitheliums were well rearranged and the tight junction proteins were greatly recovered after HSD treatment. Besides, HSD also modulated the gut flora, markedly augmenting the abundance of Firmicutes, Barnesiella and Lachnospiraceae . Moreover, HSD treatment could regulate oxidative redox homeostasis via activating Nrf2-HO-1 pathway to reduce ROS and malondialdehyde and upregulate antioxidant enzymes (SOD, GPx and GSH). Collectively, HSD might be a promising therapy for UC treatments. Statement of Significance Herein, a hydrogel-forming viscous liquid (HSD) was designed by cysteamine-grafted hyaluronic acid (HS) and superoxide dismutase (SOD) for UC treatments. When the viscous HSD liquid was infused into a colitis colon, SOD would convert the pathological superoxide to hydrogen peroxides (H 2 O 2 ), which was subsequently scavenged by HS. Accordingly, the sol-gel transition of HSD was initiated by scavenging H 2 O 2 , enhancing its adhesion to the colitis colon. The colonic epitheliums of DSS-induced colitis mice were well rearranged and the tight junction proteins (Zonula-1 and Claudin-5) were greatly recovered after the HSD treatment. Moreover, the HSD treatment could regulate oxidative redox homeostasis via activating the Nrf2-HO-1 pathway to reduce ROS and malondialdehyde and upregulate antioxidant enzymes (SOD, GPx and GSH).
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JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-31
·
IF 12.6
Zhu Yujing,Xiu Ziliang,Jiang Xiaoxi,Zhang Huifang,Li Xiaofeng,Feng Yunru,Li Bojiang,Cai Rui,Li Chunhui,Tao Gang
Periodontitis, a chronic inflammatory disease caused by bacteria, is characterized by localized reactive oxygen species (ROS) accumulation, leading to an inflammatory response, which in turn leads to the destruction of periodontal supporting tissues. Therefore, antibacterial, scavenging ROS, reducing the inflammatory response, regulating periodontal microenvironment, and alleviating alveolar bone resorption are effective methods to treat periodontitis. In this study, we developed a ROS-responsive injectable hydrogel by modifying hyaluronic acid with 3-amino phenylboronic acid (PBA) and reacting it with poly(vinyl alcohol) (PVA) to form a borate bond. In addition, the ROS-responsive hydrogel encapsulated the antibacterial agent minocycline hydrochloride (MH) and Fe-Quercetin anti-inflammatory nanoparticles (Fe-Que NPs) for on-demand drug release in response to the periodontitis microenvironment. This hydrogel (HP-PVA@MH/Fe-Que) exhibited highly effective antibacterial properties. Moreover, by modulating the Nrf2/NF-κB pathway, it effectively eliminated ROS and promoted macrophage polarization to the M2 phenotype, reducing inflammation and enhancing the osteogenic differentiation potential of human periodontal ligament stem cells (hPDLSCs) in the periodontal microenvironment. Animal studies showed that HP-PVA@MH/Fe-Que significantly reduced alveolar bone loss and enhanced osteogenic factor expression by killing bacteria and inhibiting inflammation. Thus, HP-PVA@MH/Fe-Que hydrogel had efficient antibacterial, ROS-scavenging, anti-inflammatory, and alveolar bone resorption-alleviation abilities, showing excellent application potential for periodontitis healing. Graphical abstract
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