SKIN RESEARCH AND TECHNOLOGY
·
2023
·Vol. 29
·期 3
·e13303
·
IF 2.2
Chunxia Gan,Titi Liu,Xiaorong Jia,Xueqin Huang,Xiangdong Qin,Xuanjun Wang,Jun Sheng,Huanhuan Xu
Background Skin photoaging is the damage caused by excessive exposure to ultraviolet (UV) irradiation. We investigated the effect of adenosine triphosphate (ATP) supplementation on UVB-induced photoaging in HaCaT cells and its potential molecular mechanism. Materials and methods The toxicity of ATP on HaCaT cells was examined by the MTT assay. The effects of ATP supplementation on the viability and apoptosis of HaCaT cells were determined by crystal-violet staining and flow cytometry, respectively. Cellular and mitochondrial ROS were stained using fluorescent dyes. Expression of Bax, B-cell lymphoma (Bcl)-2, sirtuin (SIRT)3, and superoxide dismutase (SOD)2 was measured via western blotting. Results ATP (1, 2 mM) exerted no toxic effect on the normal growth of HaCaT cells. UVB irradiation caused the apoptosis of HaCaT cells, and ATP supplementation inhibited the apoptosis induced by UVB significantly, as verified by expression of Bax and Bcl-2. UVB exposure resulted in accumulation of cellular and mitochondrial reactive oxygen species (ROS), but ATP supplementation suppressed these increases. Expression of SIRT3 and SOD2 was decreased upon exposure to UVB irradiation but, under ATP supplementation, expression of SIRT3 and SOD2 was reversed, which was consistent with the reduction in ROS level observed in ATP-treated HaCaT cells after exposure to UVB irradiation. Conclusions ATP supplementation can suppress UVB irradiation-induced photoaging in HaCaT cells via upregulation of expression of SIRT3 and SOD2.
研究领域:
细胞生物学
·
分子生物学
·
皮肤科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2024
·Vol. 17
·期 10
·1288
·
IF 4.3
Chunhua Liu,Yu He,Mingjin Wang,Jia Sun,Jie Pan,Ting Liu,Yueting Li,Meng Zhou,Yong Huang,Yongjun Li,Yanmin Zhang,Yuan Lu
Background: Polygonum orientale L. (PO) has demonstrated notable efficacy in treating coronary heart disease. Previous research identified eight key active components in PO for cardiomyocyte protection, but the underlying mechanisms remained unclear; Methods: Network pharmacology and molecular docking were used to identify potential target proteins of PO’s active components. Experimental models assessed the cardioprotective effects and mechanisms; Results: Network analysis and molecular docking revealed that the active components exhibited the highest binding affinity with SOD2, indicating it as a key element in the cardiac protection of PO. In vivo, PO extract improved myocardial structure and function, and increased SOD2 protein levels. In vitro, the active components of PO (Mixture) mitigated oxidative stress and apoptosis, upregulating SIRT3 and decreasing acetylated SOD2, leading to increased SOD2 and reduced ROS levels. The observed effects were reversed by a SIRT3 inhibitor, indicating the involvement of the SIRT3/SOD2 signaling pathway; Conclusions: This comprehensive approach elucidated the critical mechanisms underlying the cardioprotective properties of PO’s bioactive constituents, highlighting the regulation of the SIRT3/SOD2 signaling pathway as a new mechanism for PO’s anti-cardiovascular disease effects, and suggesting the Mixture’s potential as a promising drug candidate.
研究领域:
药理学
·
心血管病学
·
网络药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2020
·Vol. 22
·期 1
·257-264
·
IF 2.1
Siqian Wang,Jingyuan Yang,Tingting Lin,Shengbing Huang,Jianfeng Ma,Xin Xu
The incidence of peri-implant bone loss is high, and is a difficult condition to treat. Previous studies have shown that titanium (Ti) ions released from implants can lead to osteoblast cell damage, but the specific mechanisms have not been elucidated. The present study established a Ti ion damage osteoblast cell model. The levels of mitochondrion‑derived reactive oxygen species (mROS) and autophagy, cell viability and the sirtuin 3 (SIRT3)/superoxide dismutase 2 (SOD2) pathway were examined in this model. It was found that Ti ions decreased osteoblast viability. Moreover, with increased Ti ion concentration, the expression levels of microtubule associated protein 1 light chain 3α (LC3) progressively increased, P62 decreased, autophagic flow increased and mROS levels increased. After the addition of an autophagy inhibitor Bafilomycin A1 and Mito‑TEMPO, a mitochondrial antioxidant, the production of mROS was inhibited, the level of autophagy was decreased and cell activity was improved. In addition, with increased Ti ion concentration, the activity of SOD2 decreased, the acetylation level of SOD2 increased, the SIRT3 mRNA and protein expression levels decreased, and the activity of SIRT3 was significantly decreased. Furthermore, it was demonstrated that SIRT3 overexpression reduced the acetylation of SOD2 and increased the activity of SOD2, as well as reducing the production of mROS and the expression level of LC3, thus increasing cell viability. Therefore, the present results suggested that excessive production of mROS induced by Ti ions led to autophagic cell death of osteoblasts, which is dependent on the SIRT3/SOD2 pathway.
研究领域:
生物材料
·
细胞生物学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2023
·
IF 5.3
Fei Li,Chunyu Ye,Xiuli Wang,Xinting Li,Xiaoxia Wang
Cigarette smoking can cause damage of airway epithelial cells and contribute to chronic obstructive pulmonary disease (COPD). Honokiol is originally isolated from Magnolia obovata with multiple biological activities. Here, we investigated the protective effects of honokiol on cigarette smoke extract (CSE)-induced injury of BEAS-2B cells. BEAS-2B cells were treated with 300 mg/L CSE to construct an in vitro cell injury model, and cells were further treated with 2, 5 and 10 μM honokiol, then cell viability and LDH leakage were analysed by CCK-8 and LDH assay kits, respectively. Apoptosis was detected by flow cytometry analysis. ELISA was used to measure the levels of tumour necrosis factor (TNF)-ɑ, IL-1β, IL-6, IL-8 and MCP-1. The results showed that honokiol (0.5–20 μM) showed non-toxic effects on BEAS-2B cells. Treatment with honokiol (2, 5 and 10 μM) reduced CSE (300 mg/L)-induced decrease in cell viability and apoptosis in BEAS-2B cells. Honokiol also decreased CSE-induced inflammation through inhibiting expression and secretion of inflammatory cytokines, such as TNF-ɑ, IL-1β, IL-6, IL-8 and MCP-1. Moreover, honokiol repressed CSE-induced reactive oxygen species (ROS) production, decrease of ATP content and mitochondrial biogenesis, as well as mitochondrial membrane potential. Mechanistically, honokiol promoted the expression of SIRT3 and its downstream target genes, which are critical regulators of mitochondrial function and oxidative stress. Silencing of SIRT3 reversed the protective effects of honokiol on CSE-induced damage and mitochondrial dysfunction in BEAS-2B cells. These results indicated that honokiol attenuated CSE-induced damage of airway epithelial cells through regulating SIRT3/SOD2 signalling pathway.
研究领域:
肺病学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOLOGY AND TOXICOLOGY
·
2022
·
IF 6.819
Gao Shuya,Yang Qingchen,Peng Yue,Kong Weixian,Liu Zekun,Li Zhe,Chen Jiawen,Bao Mengmeng,Li Xie,Zhang Yubin,Bian Xiaohong,Jin Liang,Zhang Hanwen,Zhang Yuexin,Sanchis Daniel,Yan Fangrong,Ye Junmei
The sirtuin 6 (SIRT6) participates in regulating glucose and lipid homeostasis. However, the function of SIRT6 in the process of cardiac pathogenesis caused by obesity-associated lipotoxicity remains to be unveiled. This study was designed to elucidate the role of SIRT6 in the pathogenesis of cardiac injury due to nutrition overload-induced obesity and explore the downstream signaling pathways affecting oxidative stress in the heart. In this study, we used Sirt6 cardiac-specific knockout murine models treated with a high-fat diet (HFD) feeding to explore the function and mechanism of SIRT6 in the heart tissue during HFD-induced obesity. We also took advantage of neonatal cardiomyocytes to study the role and downstream molecules of SIRT6 during HFD-induced injury in vitro, in which intracellular oxidative stress and mitochondrial content were assessed. We observed that during HFD-induced obesity, Sirt6 loss-of-function aggravated cardiac injury including left ventricular hypertrophy and lipid accumulation. Our results evidenced that upon increased fatty acid uptake, SIRT6 positively regulated the expression of endonuclease G (ENDOG), which is a mitochondrial-resident molecule that plays an important role in mitochondrial biogenesis and redox homeostasis. Our results also showed that SIRT6 positively regulated superoxide dismutase 2 (SOD2) expression post-transcriptionally via ENDOG. Our study gives a new sight into SIRT6 beneficial role in mitochondrial biogenesis of cardiomyocytes. Our data also show that SIRT6 is required to reduce intracellular oxidative stress in the heart triggered by high-fat diet-induced obesity, involving the control of ENDOG/SOD2.
研究领域:
心脏病学
·
分子生物学
·
肥胖研究
·
代谢
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Zekun Wang,Ruofei Zhang,Yanyu Hu,Qile Song,Xiaoyan Fu,Yifan Wang,Mei Chen,Kelong Fan,Cundong Fan,Dongdong Sun
Doxorubicin (DOX) treatment can lead to intracellular iron overload in cardiomyocytes, triggering excessive generation of reactive oxygen species (ROS) and resulting in cardiotoxicity. Superoxide dismutase (SOD) effectively scavenges ROS, and its catalytic activity depends on the binding of metal ions at its active site. Therefore, enhancing the activity of metal-dependent SOD represents a promising strategy to inhibit ferroptosis in cardiomyocytes and alleviate DOX-induced chronic heart failure. In this study, we constructed a biomimetic chiral MnO 2 nanozyme co-modified with macrophage and platelet membranes (D/L-MnO 2 @MM), enabling precise targeting of DOX-injured myocardial tissues. This nanozyme exhibited potent catalase-like and SOD-like activities, efficiently eliminating excessive local hydrogen peroxide (H 2 O 2 ) and superoxide anions (O 2 •− ). Notably, the D-enantiomeric nanozyme (D-MnO 2 @MM) significantly enhanced endogenous SOD2 activity via Mn 2+ ion release, thereby suppressing the accumulation of lipid peroxides. Furthermore, based on transcriptomic and proteomic analyses, we designed an siRNA targeting the Hmox1 gene (si Hmox1 ) and successfully loaded it onto the nanozyme platform (si Hmox1 @D/L-MnO 2 @MM). Both in vitro and in vivo experiments confirmed that the dual mechanism, SOD2 activation and Hmox1 silencing, effectively restored mitochondrial function, attenuated ferroptosis, and significantly improved cardiac function in a rat model of chronic heart failure. Collectively, this study proposes a novel ferroptosis-targeted therapeutic strategy based on a biomimetic chiral nanozyme, offering new insights and promising therapeutic potential for the treatment of DOX-induced cardiotoxicity.
研究领域:
心血管病学
·
纳米医学
·
分子生物学
·
药理学
·
氧化应激
·
基因治疗
·
转化医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2019
·Vol. 107
·期 11
·2414-2424
·
IF 3.221
Xiaopei Wu,Honglian Dai,Chao Xu,Langlang Liu,Shipu Li
Biomaterials can be used as carriers of antioxidant or drug to the oxidative injury site of tissue and decrease intracellular oxidative stress levels, however, low dosage delivery or unstable molecular structure of antioxidant or drug limited the long-term sustained release. A chemically stable antioxidant molecule is essential to serve as antioxidant structure components of biomaterials that may provide the relatively high antioxidant content and persisting local antioxidant release with the degradation of materials. In this study, we used citric acid modified polyvinyl alcohol (PVA-C) as a model biomaterial to investigate the role of citric acid on the material stimulated antioxidant and anti-inflammatory effects. In cellular-based assays, PVA-C extracts showed a protective effects on bone marrow mesenchymal stem cells (BMSCs) under oxidative stress. It could enhance the antiapoptotic ability of stem cells by inhibiting reactive oxygen species. Further studies revealed that PVA-C extracts upregulated the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) and superoxide dismutase [Mn] (SOD2). in vivo animal assays, PVA-C extracts showed significant inhibitory effects on the oxidative stress and inflammatory reaction which were induced by lipopolysaccharide (LPS). These findings suggest that the citric acid modified polymer can regulate the redox signaling of stem cells and tissues by the release of citric acid from materials, leading to enhanced oxidative stress-induced degenerative diseases and inflammatory diseases therapy.
研究领域:
材料科学
·
生物材料
·
细胞生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2026
·Vol. 12
·期 33
·
IF 13.9
Wenhao Zhao,Xudong Hu,Ruyi Wang,Han Zhang,Man Zhou,Hong Cao
Niemann-Pick type C (NPC) disease is a lysosomal storage disorder primarily caused by mutations in the NPC1 gene. Most patients present with early-life symptoms including hepatosplenomegaly and digestive system impairment, followed by progressive neurodegeneration. However, effective therapeutic approaches to improve survival in NPC disease remain limited. In this study, using an npc1 -knockout (NPC1-KO) zebrafish model established in our laboratory, our team suggests that npc1 deficiency appears to correlate with marked down-regulation of superoxide dismutase 2 (Sod2) expression, concurrent with excessive oxidative stress (OS), mitochondrial dysfunction, and defective mitophagy. Treatment with Mito-TEMPO, a mitochondria-targeted antioxidant acting on SOD, increased survival rates and ameliorated cholesterol accumulation and liver function impairment in early-stage NPC1-KO zebrafish. The underlying mechanism may involve attenuation of OS and promotion of PINK1/Parkin-dependent mitophagic flux through SOD2 enhancement. Our findings support Mito-TEMPO as a potential therapeutic agent and SOD2 as a possible target for NPC disease.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Weishan Zhuge,Jiayang Kuang,Keke Kuang,Meilin Rao,Dan Jian,Haizhen Lin,Zijun Li,Shaotang Li,Yihu Zheng,Namki Cho,Xiaokun Li,Ri Cui
Background Colorectal cancer (CRC) is among the most prevalent malignancies globally, with its incidence continuing to rise in recent years. Sorafenib, a multi-kinase inhibitor, has shown therapeutic effects in advanced CRC. Usenamine A (UD32-3), a natural compound, is isolated from lichens. However, anti-tumor activity of UD32-3 in CRC and its biological functions in anti-CRC activity of sorafenib remain unknown. Purpose This study aims to elucidate the mechanism underlying anti-CRC effects of UD32-3 and its potential to enhance the therapeutic efficacy of sorafenib. Study design and Methods Immunofluorescence assays were employed to investigate reactive oxygen species (ROS) and autophagy levels. Gene knockdown or overexpression was performed using Lipofectamine 3000 reagent, and relative gene and protein expression levels were evaluated by quantitative real-time PCR (qRT-PCR) and Western blot analyses. Molecular docking analysis was performed to investigate the interaction between UD32-3 and superoxide dismutase 2 (SOD2). Mouse xenograft models were employed to evaluate the effects of combination therapy with UD32-3 and sorafenib. Results UD32-3 exerts anti-CRC activity by inducing ROS-mediated autophagy and inhibiting YAP pathway through targeting SOD2. Knocking down SOD2 sufficiently induced ROS generation and autophagy, and inhibited the YAP pathway, thereby enhancing the anti-CRC activity of UD32-3. Conversely, overexpression of SOD2 yielded opposite results, attenuating these effects. Combined treatment with UD32-3 and sorafenib exerted synergistic anti-tumor activities by activating autophagy and inhibiting YAP signaling pathway. Additionally, YAP inhibitor strengthened anti-CRC activity of UD32-3 and sorafenib by inhibiting SOD2 expression, suggesting autophagy-mediated negative feedback loop between SOD2 and YAP. Conclusions UD32-3 has significant druggable potential, and combination treatment of UD32-3 and sorafenib may serve as an effective therapeutic strategy for patients with certain CRC.
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2026
·
IF 11
Xiaoling Liu,Run Huang,Ling Zou,Lu Yang,Yonghui Wu,Dandan Li,Jinbao Li,Jian He,Xiaochao Yang
Oxidative stress caused by the excessive accumulation of reactive oxygen species (ROS) plays a critical role in the development of acute respiratory distress syndrome (ARDS). Current antioxidant therapies using organic ROS scavengers fail in decreasing mortality due to the low ROS scavenging activity and fast metabolic rate. Inorganic ROS scavenging nanoparticles provide potential options for investigating ARDS antioxidant therapy. However, previous studies mainly focus on the ROS scavenging activity of these nanoparticles, while their capability to modulate the endogenous antioxidant system remains largely unexplored. Herein, mesoporous Ce–Mn–O bimetallic oxide nanoparticles (NP CeMn ) are designed and synthesized to activate the endogenous antioxidant system for ARDS therapy. Morphologically similar ceria nanoparticles (NP Ce ) and manganese oxide nanoparticles (NP Mn ) are used for comparison. In vivo and in vitro results demonstrate that NP Ce and NP Mn can promote the expression of SOD1 and SOD2, respectively, while NP CeMn can promote the expression of both SOD1 and SOD2. Mechanism studies establish a Keap1/Nrf2/SOD axis through which NP CeMn acts to activate the endogenous antioxidant system. Based on this property, NP CeMn can effectively alleviate oxidative stress and inflammation in the lung of the murine ARDS model. These findings suggest that activating the endogenous antioxidant system via inorganic nanoparticles is a promising ARDS therapeutic strategy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2019
·
IF 8.063
Hui-Min Lei,Ke-Ren Zhang,Cong Hui Wang,Yang Wang,Guang-Lei Zhuang,Li-Ming Lu,Jian Zhang,Ying Shen,Hong-Zhuan Chen,Liang Zhu
Background: Acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) such as erlotinib is a major challenge to achieve an overall clinical benefit of the targeted therapy. Recently, aldehyde dehydrogenase 1 (ALDH1) induction has been found to render lung adenocarcinomas resistant to EGFR-TKIs, and targeting ALDH1A1 becomes a novel strategy to overcome resistance. However, the molecular mechanism underlying such effect remains poorly understood. Methods: Comprehensive assays were performed in a panel of lung adenocarcinoma cell lines and xenografts that acquired resistance to erlotinib. Cancer phenotype was evaluated by cell viability, apoptosis, migration, and epithelial-mesenchymal transition analysis in vitro , tumorsphere formation analysis ex vivo , and tumor growth and dissemination analysis in vivo . Reactive oxygen species (ROS) and reactive carbonyl species (RCS) were detected based on fluorescent oxidation indicator and liquid chromatography coupled to mass spectrometry, respectively. Protein target was suppressed by RNA interference and pharmacological inhibition or ecto-overexpressed by lentivirus-based cloning. Gene promoter activity was measured by dual-luciferase reporting assay. Results: Knockdown or pharmacological inhibition of ALDH1A1 overcame erlotinib resistance in vitro and in vivo . ALDH1A1 overexpression was sufficient to induce erlotinib resistance. Metabolomic analysis demonstrated lower ROS-RCS levels in ALDH1A1-addicted, erlotinib-resistant cells; in line with this, key enzymes for metabolizing ROS and RCS, SOD2 and GPX4, respectively, were upregulated in these cells. Knockdown of SOD2 or GPX4 re-sensitized the resistant cells to erlotinib and the effect was abrogated by ROS-RCS scavenging and mimicked by ROS-RCS induction. The ALDH1A1 overexpressed cells, though resisted erlotinib, were more sensitive to SOD2 or GPX4 knockdown. The ALDH1A1 effect on erlotinib resistance was abrogated by ROS-RCS induction and mimicked by ROS-RCS scavenging. Detection of GPX4 and SOD2 expression and analysis of promoter activities of GPX4 and SOD2 under the condition of suppression or overexpression of ALDH1A1 demonstrated that the RCS-ROS-metabolic pathway was controlled by the ALDH1A1-GPX4-SOD2 axis. The ROS-RCS metabolic dependence mechanism in ALDH1A1-induced resistance was confirmed in vivo . Analysis of public databases showed that in patients undergoing chemotherapy, those with high co-expression of ALDH1A1, GPX4, and SOD2 had a lower probability of survival. Conclusions: ALDH1A1 confers erlotinib resistance by facilitating the ROS-RCS metabolic pathway. ALDH1A1-induced upregulation of SOD2 and GPX4, as well as ALDH1A1 itself, mitigated erlotinib-induced oxidative and carbonyl stress, and imparted the TKI resistance. The elucidation of previously unrecognized metabolic mechanism underlying erlotinib resistance provides new insight into the biology of molecular targeted therapies and help to design improved pharmacological strategies to overcome the drug resistance.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
·
2023
·Vol. 34
·期 1
·1-14
·
IF 3.7
Tao Zhou-Shan,Li Tian-Lin,Wei Shan
Magnesium (Mg) and Selenium (Se) are essential elements for bone health and have been studied extensively for its powerful osteogenesis and promoting bone regeneration. The purpose was to observe whether Co-modified 3D-printed β-tricalcium phosphate with Mg and Se could promote bone defect regeneration in an ovariectomized(OVX) rat model. The MC3T3-E1 cells were co-cultured with the leachate of β-TCP, Mg-TCP, and Mg/Se-TCP and induced to osteogenesis, and the cell viability, ROS, and osteogenic activity were observed by Cell Count Kit-8(CCK-8), fluorescent probe 2′, 7′-dichlorofluorescin diacetate, Alkaline phosphatase (ALP) staining, Alizarin Red(RES) staining, western blotting(WB), and immunofluorescence. Then the β-TCP, Mg-TCP, and Mg/Se-TCP were implanted into the femoral epiphysis bone defect model of OVX rats for 12 weeks. Micro-CT and histology analysis were used to observe the therapeutic effect. In vitro results show that the cell mineralization and osteogenic activity of the Mg/Se-TCP group is significantly higher than the β-TCP group and Mg-TCP group. Protein expressions such as FOxO1, SIRT1, SOD2, Runx-2, Cola1a, and OC of the Mg/Se-TCP group are significantly higher than the Con group and the β-TCP group. The results of intracellular ROS and SIRT1 and SOD2 immunofluorescence showed that Mg/Se-TCP can restore the oxidative stress balance of osteoblasts. Micro-CT and histology analysis showed that treatment with Mg/Se-TCP showed the largest amount of bone tissue in the defect area ( p < 0.05), and exhibited lower values of residual biological material ( p < 0.05), compared to that of the β-TCP group and Mg-TCP group. Our research results confirm that Mg/Se-TCP can improve the activity and function of osteoblasts and enhance bone regeneration mediated by reducing intracellular ROS in OVX rat models. Graphical Abstract
The release of Mg and Se during the degradation of Mg/Se-TCP can improve the local bone repair ability. At the same time, it can also inhibit cell ROS, and ultimately greatly promote local bone repair.
研究领域:
生物材料
·
骨再生
·
生物医学工程
·
细胞生物学
·
动物模型
✓ 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）