INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Ruoyi Jia,Wen Chen,Yangyang Liu,Yonglu Li,Xiang Ye,Yong Jiang,Xiaodong Zheng
Ethyl Carbamate (EC), as a carcinogen widely found in fermented foods, was verified that its cytotoxicity was associated with oxidative stress. Polysaccharides from natural sources due to their antioxidative capacity have attracted great attention in the past time. In this study, purified polysaccharide from Tetrastigma hemsleyanum vines (TVP) with 64.89 kDA was extracted and conducted multiple analysis to identify its structural information. It could be discovered that TVP was composed of mannose, rhamnose, glucuronic acid, glucose, galactose, and arabinose. In vitro , TVP could inhibit cytotoxicity and genotoxicity, attenuate oxidative damage and mitochondrial dysfunction induced by EC in Caco-2 cells. Meanwhile, TVP could suppress apoptosis by mTOR and Bcl-2 signaling pathways, ameliorate oxidative via Sirt1-FoxO1 and Nrf2-Keap1 signaling pathways. In vivo , EC as well triggered the decline of survival and athletic ability in Caenorhabditis elegans ( C. elegans ) and TVP could reverse the decline. In the meantime, TVP could ameliorate oxidative damage in N2 and daf-2 (-) mutant but fail in daf-16 (-) mutant, which suggested that DAF-16 (FOXO) might affect the antioxidative protection of TVP in C. elegans . In brief, our results manifested that TVP could attenuate EC-induced cytotoxicity both in vitro and in vivo .
研究领域:
药理学
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毒理学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
BIOMETALS
·
2018
·Vol. 31
·期 6
·1051-1059
·
IF 2.478
Luo Junchong,Li Xiaowen,Li Xinran,He Yongming,Zhang Mengdan,Cao Changyu,Wang Kai
To investigate the effect of Selenium Rich Yeast ( SeY ) on hepatotoxicity of Aluminium (Al), SeY (0.1 mg/kg) was orally administrated to aluminium-exposed mice (10 mg/kg) for 28 days. The risk of oxidative stress was assessed by detecting the total antioxidant capacity (T-AOC), catalase activity, H 2 O 2 content, and mRNA levels of the Keap1/Nrf-2/HO-1 pathway. Inflammatory reactions were assessed by detecting the mRNA levels of inflammatory biomarkers. Our results showed that SeY protected against the liver histological changes induce by Al. The body weight gain of mice treated with SeY + Al restore to normal compare with mice exposed to Al alone. Al treatment significantly decreased the activities of antioxidant enzymes, reduced T-AOC levels, and up-regulated the mRNA level of Nrf2 and HO-1, thereby ultimately leading to peroxidation. SeY shown a significant protective effect against oxidative stress caused by Al. In addition, Al exposure induced inflammatory responses in rat liver by promoting the release of inflammatory cytokines (TNF-a, NF-kB, TNF-R1, IL-1, IL-6, and COX-2). SeY protected against changes in liver by regulating the mRNA expression levels of inflammatory factors. These results suggested that Se protected the liver from the Al-induced hepatotoxicity by regulating the mRNA level of Keap1/Nrf2/HO-1, and inhibited inflammatory responses by down-regulating the expression level of inflammatory cytokine.
研究领域:
毒理学
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药理学
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分子生物学
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营养科学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Bin Cheng,Jie Zhou,Xu Wang,Zihan He,Zhengyi Xu,Jian Wang,Junyu Chen,Zhou Zhu,Weifeng Zhao,Qianbing Wan,Xibo Pei
Diabetic wound healing poses a significant challenge in the biomedical domain. Inadequate angiogenesis and fibroblast dysfunction are two primary characteristics of diabetic microenvironment. Fibroblast dysfunction is characterized by excessive accumulation of reactive oxygen species (ROS) and fragmented mitochondria. Herein, we developed a microenvironment responsive zinc–gallic acid nanosheets (ZnGA NSs) for diabetic wound healing, which slowly release Zn 2+ and gallic acid (GA) in response to low pH and excessive ROS. The released Zn 2+ enhanced cell proliferation, migration, and endothelial tube formation. And the released GA activated antioxidant enzyme system via the KEAP1/NRF2 pathway and promoted mitochondrial fusion by upregulating MFN1/2 and OPA1, which ultimately reprograms dysfunctional fibroblast. The application of ZnGA NSs effectively facilitated wound healing in a rat diabetic model with full-thickness cutaneous defects. More importantly, skin wounds treated with ZnGA NSs exhibited enhanced angiogenesis, alleviated inflammation, and improved tissue regeneration. These findings highlight the potential of ZnGA NSs as a promising therapeutic modality for diabetic wound treatment.
研究领域:
生物医学工程
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材料科学
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药学
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伤口愈合
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糖尿病研究
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产品关联
DOI
高影响因子
Journal of Natural Medicines
·
2024
·
IF 2.5
Chen Ping,Zhang Xueer,Fang Qiaomiao,Zhao Zhongxiang,Lin Chaozhan,Zhou Yuan,Liu Fangle,Zhu Chenchen,Wu Aizhi
Betulinic acid (BA), a naturally occurring lupane-type triterpenoid, possesses a wide range of potential activities against different types of cancer. However, the molecular mechanisms involved in anti-cervical cancer about BA were rarely investigated. Herein, the role of BA in cervical cancer suppression by ROS-mediated endoplasmic reticulum stress (ERS) and autophagy was deeply discussed. The findings revealed that BA activated Keap1/Nrf2 pathway and triggered mitochondria-dependent apoptosis due to ROS production. Furthermore, BA increased the intracellular Ca 2+ levels, inhibited the expression of Beclin1 and promoted the expression of GRP78, LC3-II, and p62 associated with ERS and autophagy. Besides, BA initiated the formation of autophagosomes and inhibited autophagic flux by the co-administration of BA with 3-methyladenine (3-MA) and chloroquine (CQ), respectively. The in vivo experiment manifested that hydroxychloroquine (HCQ) enhanced the apoptosis induced by BA. For the first time, we demonstrated that BA could initiate early autophagy, inhibit autophagy flux, and induce protective autophagy in HeLa cells. Thus, BA could be a potential chemotherapy drug for cervical cancer, and inhibition of autophagy could enhance the anti-tumor effect of BA. However, the interactions of signaling factors between ERS-mediated and autophagy-mediated apoptosis deserve further attention. Graphical abstract
研究领域:
肿瘤学
·
细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Qin Chen,Fen-Sheng Qiu,Wei Xie,Wen-Ying Yu,Zhao-An Su,Guang-Ming Qin,You-Kun Kang,Song-Lin Jiang,Chen-Huan Yu
Diabetic retinopathy (DR) is one of the chronic microvascular complications of type 2 diabetes mellitus (T2DM), which will cause retinal detachment and blindness without ideal therapies. Gypenoside A (GPA) are the main bioactive compound from Gynostemma pentaphyllum , and have various pharmacological effects. However, it suffered from poor bioavailability and potential cardiotoxicity in the clinical application. To overcome those limitations, in this study, nearly spherical nanoparticles (GPA-NP) with a mean particle size of 140.6 ± 22.4 nm were prepared by encapsulating GPA into mPEG-PLGA. This encapsulation efficiency was 84.4 ± 6.9 %, and the drug load was 4.02 %±0.35 %. The results showed that GPA-NP displayed more prolonged GPA release and higher bioavailability in vitro than GPA. GPA-NP obviously reduced the levels of oxidative stress markers and inflammatory cytokines in both retinal tissues of DR mice and high glucose-exposed HRMEC better than GPA alone. Mechanismly, GPA blocked the Nrf2-Keap1 interaction by binding with Kelch domain of Keap1 via alkyl and hydrogen bonds. Therefore, GPA-NP exerted more potent protectivity effects against high glucose-induced retinal microvascular endothelial ferroptosis in vitro and in vivo by activating Nrf2/HO-1/GPX4 pathway. It could be a promising therapeutic agent for preventing DR.
研究领域:
药理学
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纳米技术
·
糖尿病
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眼科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2021
·
IF 4.451
Xiang-Rong Cheng,Piao-Han Tu,Wen-Le Dong,Bu-Tao Yu,Shu-Fang Xia,Mitchell N. Muskat,Bin Guan
Xiaoheiyao , the rhizomes of Inula nervosa Wall., is a culinary spice known to contain some electrophilic Nrf2 activators that could potentially intervene in nonalcoholic fatty liver disease (NAFLD). In this study, the electrophilic components from Xiaoheiyao were annotated by comprehensive cheminformatics analyses on UHPLC-MS/MS data after being knocked out with glutathione (GSH)-immobilized magnetic microspheres. Their intervention effects against hepatic steatosis were investigated in free fatty acid (FFA)-treated HepG2 cells. The electrophilic components in Xiaoheiyao were found to be the major bioactive components preventing hepatic steatosis in FFA-treated HepG2 cells. In particular, 10-isobutyryloxy-8,9-epoxythymol isobutyrate (XHY-1) improved hepatic lipid metabolism disorder, Krebs cycle activity, oxidative phosphorylation, and the cellular and mitochondrial redox status. Moreover, XHY-1 activates the Nrf2-ARE signaling pathway through the up-regulation of Nrf2 expression and promotion of Nrf2 nuclear translocation. Molecular docking further showed that XHY-1 could conjugate with Cys151 in the BTB domain of Keap1 through the epoxy group. In conclusion, the electrophilic components of Xiaoheiyao , especially XHY-1, attenuated hepatic steatosis in FFA-treated HepG2 cells through activation of the Nrf2-ARE signaling pathway.
研究领域:
药理学
·
细胞生物学
·
分子生物学
·
药物化学
✓ 已验证
产品关联
DOI
高影响因子
TOXICOLOGY
·
2021
·
IF 4.221
Peipei Qiao,Yingbing Zhang,Ying Yang,Ru Meng,Zhiming Xu,Xianlei Jiang,Yong Zhang,Chengtu Zhang,Jianmin Su
Isoniazid (INH), a synthetic first-line tuberculosis antibiotic, has been widely used in clinical treatment. It has been reported to cause toxic effects at multiple tissue sites and also increases the incidence of adverse pregnancy outcomes; but the mechanism of action of INH on the reproductive system of female mammals remains unclear. Here, we demonstrate that oral INH (40 mg/kg/day every other day for 28 days) severely affects oocyte maturation and fertilization, late blastocyst development and fertility. We found that INH could disrupt standard spindle assembly, chromosome arrangement, and actin filament dynamics, which compromised meiotic progression of mouse oocytes. INH treatment increased the level of reactive oxygen species (ROS) and activated the oxidative stress response pathway, Keap1-Nrf2. It also caused apoptosis of oocytes and mitochondrial dysfunction. Our findings demonstrate that oral INH reduces fertility and damages the mammalian reproductive system by altering cytoskeletal dynamics and Juno expression, inducing oxidative stress and apoptosis, and activating the Keap1-Nrf2 signaling pathway in mouse oocytes.
研究领域:
药理学
·
生殖生物学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Lei Xu,Jiahe Hu,Xiuwei Yan,Hongtao Zhao,Mo Geng,Jiheng Zhang,Chunxiao Zhou,Zhihui Liu,Bo Li,Shaoshan Hu
Photodynamic therapy (PDT) is an effective treatment for glioblastoma (GBM) that activates photosensitizers to produce reactive oxygen species (ROS) while minimizing harm to normal tissues. However, the therapeutic outcomes of PDT are often unsatisfactory. This limitation arises partly from the challenges posed by the blood–brain barrier (BBB) in transporting photosensitizers and partly from the excessive levels of glutathione (GSH) in the tumor microenvironment (TME), which can neutralize ROS. Hypericin (HYP) has emerged as a promising photosensitizer for PDT due to its excellent photosensitizing properties and antitumor activity. Dysregulated iron metabolism is a hallmark of numerous cancers, including GBM. In this study, biodegradable tetra-sulfide-bound dendritic mesoporous organosilicas nanocomposite (NCs) modified with bovine serum albumin (BSA) were synthesized. NCs penetrates the BBB and selectively targets GBM by binding to secreted acidic protein acidic and rich in cysteine (SPARC), an albumin-binding receptor that is prominently expressed in both the BBB and GBM. Upon degradation in response to high GSH concentrations in the TME, the NCs release their payload while concurrently depleting GSH. Under laser irradiation, the ROS-generating agent HYP, loaded within the NCs, is combined with the ferroptosis inducer erastin to achieve a synergistic anti-GBM effect via PDT/ferroptosis. Additionally, the NCs induces oxeiptosis by regulating KEAP1/PGAM5/AIFM1 pathway. Consequently, NC inhibits GBM growth by inducing ferroptosis and oxeiptosis through excessive ROS production. This study demonstrates the potential of NCs to enhance the effectiveness of PDT, offering a promising therapeutic strategy for GBM patients.
研究领域:
肿瘤学
·
纳米技术
·
治疗学
·
神经科学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Wanting Xue,Weihan Zheng,Huihui Zhang,Jiaxin Yang,Wenfeng Deng,Zhenning Dai,Ke Liu,Yunyun Chen,Xinyi Yun,Jiaying Li,Shiyu Li,Wenhua Huang
Reperfusion therapy for acute myocardial infarction is limited by myocardial ischemia-reperfusion injury (MIRI). MIRI is primarily mediated by oxidative stress in cardiomyocytes, exacerbated by M1 macrophages in the inflammatory microenvironment. Synergistic therapies targeting cardiomyocytes with antioxidants and M1 macrophages with anti-inflammatories have shown significant potential. Mitochondrial dysfunction is a unifying target for both cell types in MIRI; however, current nanoplatforms cannot simultaneously target them. Mito Q@MMNv is designed as a dual-targeting nanovesicle for cardiomyocytes and macrophages. It scavenges reactive oxygen species in cardiomyocytes while restoring oxidative phosphorylation in M1 macrophages through cell-selective metabolic reprogramming. In vivo, Mito Q@MMNv improves cardiac function and the inflammatory microenvironment: left ventricular ejection fraction increases by 62%, and the M1/M2 ratio shifts (delta cells increase 1.9-fold). Synergistic activation of Keap1 and inhibition of NF-κB attenuate inflammatory cascades while enhancing endogenous antioxidant defenses. Thus, this nano-engineered platform offers an immunomodulatory therapy for inflammation control and tissue repair in MIRI, providing new insights into cardiovascular nanomedicine.
研究领域:
心血管纳米医学
·
免疫调节治疗
·
代谢工程
·
活性氧清除
·
炎症调控
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Anwei Zhang,Zhiwei Liu,Ling Zou,Lu Yang,Yonghui Wu,Xinxing Wang,Daigui Cao,Junli Liu,Xiaochao Yang,Shengli Zhang
Osteoporosis induced by the long-term administration of glucocorticoids is a common clinical problem. Current anti-osteoporosis therapies mainly focus on bone resorption inhibition or bone formation promotion unilaterally. However, the imbalance between bone formation and resorption often leads to suboptimal therapeutic outcomes. This study confirms the pathways through which dexamethasone (DEX), a typical glucocorticoid, triggers GIO, and explores both the therapeutic potential and underlying mechanisms of ceria nanoparticles (CNPs) in mitigating GIO. Our results demonstrate that DEX-induced bone homeostasis imbalance is the primary mechanism underlying GIO development in mice. Specifically, DEX inhibits pre-osteoblast proliferation and differentiation by inducing apoptosis and ferroptosis. Concurrently, DEX promotes osteoclast precursor proliferation and differentiation, significantly accelerating bone resorption. Administration of CNPs significantly mitigates DEX-induced disruption of bone homeostasis by ameliorating intracellular reactive oxygen species (ROS) accumulation via regulation of the Keap1/Nrf2 signaling pathway. Regarding osteogenesis, CNPs are capable of alleviating DEX-induced pre-osteoblast apoptosis and ferroptosis through the regulation of GPX4/ACSL4 signaling pathway. In terms of bone resorption, CNPs inhibit the RANKL-dependent osteoclast formation pathway. These findings validate the potential application of inorganic nanoparticles in GIO prevention.
研究领域:
纳米医学
·
骨骼生物学
·
药理学
·
分子生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Qianxia Lin,Siyi Song,Jinfeng Pei,Leifang Zhang,Xiaoe Chen,Huoxi Jin
Cysteine (Cys) plays a significant role in the stability and antioxidant capacity of peptide. This study was to prepare Cys-rich collagen peptide and evaluate its preventive effect on microparticle (MPs)-induced HK-2 cell damage. The results showed that the Cys-rich peptides (AMP-C) were successfully prepared from collagen hydrolysate by plastein reaction in the presence of exogenous Cys. The scavenging activities of 2,2-Diphenyl-1-picrylhydrazyl and hydroxyl radical of AMP-C were significantly higher than those of original peptides without Cys. The fraction with molecular weight <3 kDa (AMP-CA) significantly improved MPs-induced damage and apoptosis of HK-2 cells. Compared with the same fractions lacking Cys (AMP-A), AMP-CA showed better performance in reducing reactive oxygen species and increasing the total superoxide dismutase and glutathione peroxidase levels, which may be related to its down-regulation of Kelch-like ECH-associated protein 1 (Keap1) expression. In addition, AMP-CA showed strong effects on inhibiting interleukin-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, kidney injury molecule-1, and nuclear factor kappa-B levels. Finally, 330 Cys-containing peptides were isolated from AMP-CA, among which Leucine-Glycine-Asparagine-Glycine-Cysteine-Proline (LGNGCP) showed the lowest binding energy with Keap1 protein. In conclusion, the Cys-rich collagen peptide with higher antioxidant activity was successfully prepared by plastein reaction, which alleviated the HK-2 cells damage induced by MPs through antioxidant and anti-inflammatory. Our findings suggested that Cys-rich collagen peptide might be used as a functional food to mitigate health hazards associated with MPs accumulation.
研究领域:
生物技术
·
毒理学
·
细胞生物学
·
药学
·
环境科学
✓ 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
危险品化学品经营许可证（带存储）