CHEMICAL RESEARCH IN TOXICOLOGY
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2018
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IF 3.432
Li-Long Jiang,Yan Jiang,Dong-Sheng Zhao,Ya-Xi Fan,Qiong Yu,Ping Li,Hui-Jun Li
1,3,8-Trihydroxy-6-methylanthraquinone (emodin), a widely existing natural product in herbal medicines, has been reported to be hepatotoxic, but the exact underlying mechanism is still not fully understood. The objective of the present study was to evaluate the role of CYP3A and glutathione (GSH) in emodin-induced liver injury. Primary human hepatocytes were exposed to emodin with and without addition of CYP3A inducer/inhibitor and GSH synthesis inhibitor. It was found that emodin-mediated cytotoxicity increased when CYP3A was activated and GSH was depleted. Hepatotoxicity induced by emodin in rats by activation/inhibition of CYP3A and depletion of GSH was further investigated. Administration of emodin in combination with l-buthionine sulfoximine (BSO) or dexamethasone (DEX) resulted in aggravated liver injury, whereas pretreatment with ketoconazole (KTZ) suppressed the side effects caused by emodin. In addition, plasma exposure of emodin and its glucuronide metabolite were measured by ultraperformance liquid chromatography triple quadrupole mass spectrometry. Emodin and its glucuronide were lower in BSO-, DEX-, and KTZ-co-treated rats compared with those administered with emodin alone. In conclusion, these mentioned results suggested that CYP3A induction and GSH depletion might be involved in hepatotoxicity induced by emodin. This study may help to understand the risk factors and the mechanism of hepatotoxicity of emodin in humans.
研究领域:
药理学
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毒理学
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药学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2025
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IF 9.6
Yi Zhou,Fengjiao Chen,Yutao Lin,Qiyao Wang,Yirui Hong,Sifang Zhao,Kangyang Gao,Hongze Liang,Wei Cui,Lingling Zhao
Ischemic stroke is a leading cause of mortality and disability, with ischemia-reperfusion injury exacerbating neuronal damage and neuroinflammation due to pathologically activated reactive oxygen species (ROS) production in the ischemic penumbra. Edaravone, a free radical scavenger, is approved for the clinical treatment of ischemic stroke. However, edaravone directly decreases ROS even at low concentrations, which may inhibit the physiological effects of ROS and largely limit the clinical application of edaravone. To overcome this challenge, a ROS-response nanoparticle system, edaravone-loaded DEX-CDIPBE (DEX-CDIPBE-ED), is developed for the selectively releasing edaravone in the ischemic penumbra during reperfusion, mitigating oxidative stress while minimizing off-target effects. DEX-CDIPBE-ED produces potent antioxidant and neuroprotective effects in neuronal cells mimicking ischemic and/or reperfusion phases of ischemic stroke. DEX-CDIPBE-ED further prevents behavioral deficits, reduces oxidative stress, and inhibites neuroinflammation with a higher potency than edaravone in the ischemic penumbra in middle cerebral artery occlusion/reperfusion (MCAO/R)-treated rats. These findings highlight the potential of DEX-CDIPBE-ED as a pathological activated antioxidative therapy for ischemic stroke, offering enhanced neuroprotection and reduced systemic toxicity.
研究领域:
纳米医学
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神经病学
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药学
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生物医学工程
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卒中研究
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自由基生物学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2024
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IF 9.4
Tao Zhou,Zhou Liu,Xudong Ma,Chaofeng Cen,Zhangwei Huang,Yi Lu,Tiantian Kong,Cheng Qi
The essence of compartmentalization in cells is the inspiration behind the engineering of synthetic counterparts, which has emerged as a significant engineering theme. Here, we report the formation of ultra-stable water-in-water (W/W) emulsion droplets. These W/W droplets demonstrate previously unattained stability across a broad pH spectrum and exhibit resilience at temperatures up to 80℃, overcoming the challenge of insufficient robustness in dispersed droplets of aqueous two-phase systems (ATPS). The exceptional robustness is attributed to the strong anchoring of micelle-like casein colloidal particles at the PEO/DEX interface, which maintains stability under varying environmental conditions. The increased surface hydrophobicity of these particles at high temperatures contributes to the formation of thermally-stable droplets, enduring temperatures as high as 80℃. Furthermore, our study illustrates the adaptable affinity of micelle-like casein colloidal particles towards the PEO/DEX-rich phase, enabling the formation of stable DEX-in-PEO emulsions at lower pH levels, and PEO-in-DEX emulsions as the pH rises above the isoelectric point. The robust nature of these W/W emulsions unlocks new possibilities for exploring various biochemical reactions within synthetic subcellular modules and lays a solid foundation for the development of novel biomimetic materials.
研究领域:
材料科学
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生物技术
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化学工程
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胶体科学
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生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
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2023
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IF 8.4
Susu Huang,Yuelin Fang,Boguang Yang,Prabhleen Kaur,Yanqing Wang,Jicheng Zhang,Qiaoying Hu,Xiaoye Yang,Yabin Zhang,Guangxi Zhai,Lei Ye
Postoperative adhesions are one of the most common complications post intraperitoneal surgery. Even after the adhesiolysis, the recurrence of adhesions is as high as 85%. Although zwitterionic-based materials have been reported for the application, unlike the conventional zwitterionic hydrogel, a series of poly (sulfobetaine methacrylate) grafted dextran derivatives (Dex-g-PSBMA) were synthesized by atom transfer radical polymerization (ATRP) reaction, making it fined controllable copolymer by its living polymerization property. Intriguingly, the Dex-g-PSBMA copolymer can self-assemble into a physical hydrogel under physiological conditions. When injected at the site of the lesions, it can immediately cover the wound area, and as the ion concentration increases, the chemical bonds dissociate and the hydrogel may degrade completely. In the abdominal wall-cecum injury adhesion model in rats, Dex-g-PSBMA hydrogel showed excellent anti-adhesion ability, effectively preventing postoperative abdominal wall-cecum adhesion. The mechanism exploration revealed that Dex-g-PSBMA hydrogel can take an effect on the TGF-β/Smad signaling pathway, which can inhibit the Smad3 and activate the Smad7 pathway, thereby reducing the probability of tissue fibrosis, reducing fibrin deposition, and resisting fibroblast adhesions. In conclusion, these findings demonstrated that this Dex-g-PSBMA physical hydrogel is a promising candidate for completely preventing post-surgical adhesions.
研究领域:
生物医学工程
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材料科学
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外科研究
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药剂学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2023
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IF 10.8
Yinjuan Lv,Chenggong Yu,Xiaodi Li,Hongying Bao,Shaoshuai Song,Xiaoling Cao,Haixia Lin,Jie Huang,Zhijun Zhang
Mesenchymal stem cell (MSC) transplantation is emerging as a promising approach in the treatment of idiopathic pulmonary fibrosis (IPF), while it is still impeded by several challenges, including unsatisfactory treatment outcomes due to the poor survival of transplanted MSCs, and the lack of non-invasive and long-term imaging modality for tracking the behavior of MSCs. Herein, copper-based nanozyme (Cu x O NPs) and gold nanoparticles (Au NPs) were encapsulated in oxidation-sensitive dextran (Oxi-Dex), a dextran derivative with reactive oxygen species (ROS)-responsiveness, forming a kind of novel nanocomposites (assigned as RSNPs) to act as ROS scavengers and computer tomography (CT) imaging tracers. After being internalized by MSCs, RSNPs enabled continuous CT imaging tracking of the transplanted MSCs for 21 days in IPF treatment, obtaining the location and distribution of the transplanted MSCs. Once MSCs were attacked by oxidative stress, the intracellular RSNPs could activate ROS clearance on demand by releasing Cu x O NPs, thereby enhancing the therapeutic efficacy against IPF by improving cell survival. Taken together, a novel multifunctional RSNP was fabricated to label MSCs for CT imaging tracking and clearing superfluous ROS, presenting a promising high-efficient IPF therapy.
研究领域:
纳米技术
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干细胞疗法
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医学成像
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呼吸病学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
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2024
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IF 14.3
Haochen Yao,Sheng Ma,Juanjuan Huang,Xinghui Si,Ming Yang,Wantong Song,Guoyue Lv,Guoqing Wang
Reversing the hepatic inflammatory and immunosuppressive microenvironment caused by gut microbiota-derived lipopolysaccharides (LPS), accumulating to the liver through the gut-liver axis, is crucial for suppressing hepatocellular carcinoma (HCC) and metastasis. However, synergistically manipulating LPS-induced inflammation and gut microbiota remains a daunting task. Herein, a Trojan-horse strategy is proposed using an oral dextran-carbenoxolone (DEX-CBX) conjugate, which combines prebiotic and glycyrrhetinic acid (GA) homologs, to targeted delivery GA to HCC through the gut-liver axis for simultaneous modulation of hepatic inflammation and gut microbiota. In the orthotopic HCC model, a 95–45% reduction in the relative abundances of LPS-associated microbiota is observed, especially Helicobacter , caused by DEX-CBX treatment over phosphate-buffered saline (PBS) treatment. Notably, a dramatic increase (37-fold over PBS) in the abundance of Akkermansia , which is known to strengthen systemic immune response, is detected. Furthermore, DEX-CBX significantly increased natural killer T cells (5.7-fold) and CD8 + T cells (3.9-fold) as well as decreased M2 macrophages (59% reduction) over PBS treatment, resulting in a tumor suppression rate of 85.4%. DEX-CBX is anticipated to offer a novel strategy to precisely modulate hepatic inflammation and the gut microbiota to address both the symptoms and root causes of LPS-induced immunosuppression in HCC.
研究领域:
癌症生物学
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免疫学
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微生物学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Chen Chu,Jianzhong Qiu,Qian Zhao,Xingxiang Xun,Hejing Wang,Rongtao Yuan,Xiao Xu
Adequate blood supply and thorough innervation are essential to the survival of tissue-engineered bones. Though great progress has been created in the application of bone tissue engineering technology to bone defect repair, many challenges remain, such as insufficient vascularisation and deficient innervation in newly regenerated bone. In the present study, we addressed these challenges by manipulating the bone regeneration microenvironment in terms of vascularisation and innervation. We used a novel injectable thermosensitive liposome-hydrogel composite scaffold as a sustained-release carrier for basic fibroblast growth factor (bFGF, which promotes angiogenesis and neurogenic differentiation) and dexamethasone (Dex, which promotes osteogenic differentiation). In vitro biological assessment demonstrated that the composite scaffold had sufficient cell compatibility; it enhanced the capacity for angiogenesis in human umbilical vein endothelial cells, and the capacity for neurogenic/osteogenic differentiation in human bone marrow mesenchymal stem cells. Moreover, the introduction of bFGF/Dex liposome-hydrogel composite scaffold to bone defect sites significantly improved vascularisation and innervated bone regeneration properties in a rabbit cranial defect model. Based on our findings, the regeneration of sufficiently vascularised and innervated bone tissue through a sustained-release scaffold with excellent injectability and body temperature sensitivity represents a promising tactic towards bone defect repair.
研究领域:
组织工程
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生物材料
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再生医学
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生物医学工程
✓ 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）