TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2019
·
IF 3.585
Wu Luo,Yiyi Jin,Gaojun Wu,Weiwei Zhu,Yuanyuan Qian,Yali Zhang,Jieli Li,Aisong Zhu,Guang Liang
Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes. A multitude of factors are involved in the pathogenesis of DCM including chronic inflammation and oxidative stress . We have recently shown that compound LF10 prevents inflammatory responses in an animal model of lung injury. In the present study, we explored the protective effects and mechanism of LF10 against DCM using a mouse model of streptozotocin-induced diabetes and high glucose (HG)-challenged cultured cardiomyocytes. We show that LF10 suppressed diabetes-induced cardiomyocyte hypertrophy and fibrosis , which was accompanied by preservation of cardiac function in mice. Mechanistically, LF10 prevented increases in the levels of pro-inflammatory molecules and oxidative stress under in vitro and in vivo diabetic conditions. Moreover, LF10 restored HG-downregulated sirtuin 1 (SIRT1) in cardiomyocytes and prevented HG-induced activation of MAPKs. Using specific small-molecule regulators, we found that SIRT1 was an upstream signal of MAPKs. In conclusion, LF10 inhibited ROS and MAPKs-mediated inflammation by restoring SIRT1, and prevented development of DCM. LF10 targeted both oxidative stress and inflammation, two tightly interconnected pathogenic pathways, which makes LF10 a highly advantageous therapeutic drug potential.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2019
·Vol. 63
·期 18
·1801255
·
IF 4.653
Peng Cao,Yu Zhang,Zi Huang,Mitchell A. Sullivan,Zihao He,Jinglin Wang,Zehong Chen,Huiping Hu,Kaiping Wang
Scope Autophagy plays an important role in alleviating alcoholic liver disease (ALD). In this study, it is discovered that a dimer procyanidin (DPC) significantly prevented ALD by promoting hepatic autophagy. Methods and results Both cell and animal disease models stimulated by excessive ethanol are employed to evaluate the protective actions of DPC. Specifically, in vitro, DPC significantly decreased intracellular lipid deposition, diminished reactive oxygen species (ROS) formation, and elevated the level of mitochondrial membrane potential. These beneficial effects can be remarkably blocked by 3-methyladenine, a potent autophagy inhibitor, suggesting the autophagy-dependent protective role of DPC. In vivo, DPC pretreatment can also significantly reduce lipid accumulation, ROS overproduction, and elevated GSH content in the liver. Similarly, these protective effects of DPC can be partially reversed by chloroquine, a lysosomal inhibitor used to block the late-stage autophagy flux. Moreover, the determinations of LC3 and p62 protein expressions, autophagic flux assessments, and transmission electron microscopy observation further demonstrate the pro-autophagic effect of DPC. Conclusions DPC may activate hepatic autophagy to eliminate lipid droplets and damaged mitochondria, thereby reducing hepatic lipid disposition and ROS overproduction. This study demonstrates that DPC is a protective reagent on ALD, providing a novel strategy of fighting ALD.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Longfa Kou,Rui Sun,Shuyi Xiao,Yawen Zheng,Zhiwei Chen,Aimin Cai,Hailun Zheng,Qing Yao,Vadivel Ganapathy,Ruijie Chen
An effective steady-state redox balance is maintained in cancer cells, allowing for protection against oxidative stress and thereby enhancing cell proliferation and tumor growth. Disruption of this redox balance would increase the cellular content of reactive oxygen species (ROS) and potentiate oxidative stress-induced cell death in tumor cells, thus representing an effective strategy for cancer treatment. Glutathione (GSH) is a major reducing agent, and its cellular levels are determined at least partly by the availability of cysteine via xCT (SLC7A11)-mediated entry of cystine into cells. We developed a nanoplatform using ZnO nanoparticles (NPs) as a carrier, loaded with salicylazosulfapyridine (SASP), and stabilized with DSPE-PEG, to form ultra-small NPs (SASP/ZnO NPs). The goal of this NP strategy is to disrupt the redox balance in cells by two mechanisms: increased generation of ROS and decreased synthesis of GSH. Such an approach would be effective in killing tumor cells. As expected, the SASP/ZnO NPs enhanced ROS production because of ZnO and impaired GSH synthesis because of SASP-induced inhibition of xCT (SLC7A11) transport function. As a consequence, treatment of tumor cells with SASP/ZnO NPs in vitro and in vivo resulted in a synergistic disruptive effect on redox balance in tumor cells and induced cell death and decreased tumor growth. This ambidextrous approach has potential in cancer therapy by combining two complementary pathways to disrupt the redox balance in tumor cells.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2018
·Vol. 14
·期 13
·1703736
·
IF 9.598
Jun-Ying Wang,Xiaoyu Mu,Yonghui Li,Fujuan Xu,Wei Long,Jiang Yang,Peixian Bian,Junchi Chen,Lufei Ouyang,Haile Liu,Yaqi Jing,Jingya Wang,Lingfang Liu,Haitao Dai,Yuanming Sun,Changlong Liu,Xiao-Dong Zhang
Catalytic nanomaterials can be used extrinsically to combat diseases associated with a surplus of reactive oxygen species (ROS). Rational design of surface morphologies and appropriate doping can substantially improve the catalytic performances. In this work, a class of hollow polyvinyl pyrrolidone-protected PtPdRh nanocubes with enhanced catalytic activities for in vivo free radical scavenging is proposed. Compared with Pt and PtPd counterparts, ternary PtPdRh nanocubes show remarkable catalytic properties of decomposing H 2 O 2 via enhanced oxygen reduction reactions. Density functional theory calculation indicates that the bond of superoxide anions breaks for the energetically favorable status of oxygen atoms on the surface of PtPdRh. Viability of cells and survival rate of animal models under exposure of high-energy γ radiation are considerably enhanced by 94% and 50% respectively after treatment of PtPdRh nanocubes. The mechanistic investigations on superoxide dismutase (SOD) activity, malondialdehyde amount, and DNA damage repair demonstrate that hollow PtPdRh nanocubes act as catalase, peroxidase, and SOD analogs to efficiently scavenge ROS.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Zhang Yuan,Bailong Tao,Ye He,Ju Liu,Chuanchuan Lin,Xinkun Shen,Yao Ding,Yonglin Yu,Caiyun Mu,Peng Liu,Kaiyong Cai
To inhibit bacterial infection in situ and improve osseointegration are essentially important for long-term survival of an orthopedic implant , in particular for infection-associating revision surgery. Herein, we fabricate a functional molybdenum disulfide (MoS 2 )/polydopamine (PDA)-arginine-glycine-aspartic acid (RGD) coating on titanium (Ti) implant to address above concerns simultaneously. The coating not only improved the osteogenesis of mesenchymal stem cells (MSCs), but also endowed Ti substrates with effective antibacterial ability when exposing to near-infrared (NIR) irradiation. It accelerated glutathione (GSH) oxidation via photothermal energy and induced intrinsic ROS-independent oxidative stress damage deriving from MoS 2 nanosheets . The results displayed that RGD-decorated MoS 2 nanosheets significantly increased the cellular osteogenic behaviors of MSCs via up-regulating osteogenesis-related genes (ALP, Runx2, Col I and OCN) in vitro. Moreover, the functionalized Ti substrates demonstrated great antibacterial efficiency of over 92.6% inhibition for S. aureus and E. coli under NIR-irradiation. Hyperthermia induced by photothermal effect accelerated the GSH consumption and ROS-independent oxidative stress destroyed the integrity of bacteria membranes , which synergistically led to protein leakage and ATP decrease. Furthermore, co-culture experiment showed that S. aureus contamination was efficiently cleaned from MoS 2 /PDA-RGD surface after NIR photothermal treatment, while MSCs adhered and proliferated on the MoS 2 /PDA-RGD surface. In an S. aureus infection model in vivo, MoS 2 /PDA-RGD modified Ti rods killed bacteria with an efficiency of 94.6% under NIR irradiation, without causing damage to normal tissue. More importantly, the MoS 2 /PDA-RGD modified Ti implants accelerated new bone formation in comparison with TNT implants in vivo .
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Environmental Chemical Engineering
·
2024
·
IF 7.4
Wenping Yang,Longjiao Zhu,Wentao Xu
Developing an efficient advanced oxidation technology is of great significance for water treatment and environmental protection. Here, inspired by the structure and feature of coenzyme B 12 in natural enzymes (cleavage of Co-C bond triggers the generation of radical), a Co based metal-organic framework (Co-MOF) with catalase-mimicking activity was synthesized and applied in the degradation of organic dyes. Firstly, Co-MOF nanozyme was fabricated via the coordination self-assembly strategy at room temperature. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive scanning (EDS), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR) were used to characterize the morphology and structure. The results showed that the obtained Co-MOF nanozyme was rhombic dodecahedral morphology with a size of ∼ 500 nm and excellent crystallinity. The enzymatic experiments proved that such nanozyme possessed a single catalase-like activity. Further research results demonstrated that Co-MOF-based degradation process of acid fuchsin (AF) or crystal violet (CV) had excellent pH adaptability (pH > 5.0). Unexpectedly, an ultra-high catalytic degradation rate (211.35 min −1 g −1 L) was successfully achieved in the catalytic degradation of AF, and it was approximately 5∼200 times of the previous optimal nanozyme or catalysts. In complex matrices and real wastewater, this catalytic process could still maintain degradation efficiency above 90% or even higher within 5 minutes, proving its excellent stability and adaptability. The results of radical and electron quenching experiments, electron paramagnetic resonance (EPR), and electrochemical analysis demonstrated that the excellent catalytic degradation performance was attributed to the generation of reactive oxygen species (ROS) (∙O 2 was the main contributor) and the existence of electron transfer. In summary, this new catalytic property endows Co-MOF nanozyme with considerable potential for dye degradation, extending the application scope of catalase mimics.
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Xiaotong Xu,Huimin Li,Binghua Tong,Weijie Zhang,Xiaofei Wang,Yue Wang,Geng Tian,Zhaowei Xu,Guilong Zhang
Herein, we designed a ccRCC targeting nanodrug to enhance chemodynamic therapy (CDT) as well as activate cuproptosis and tumor immunotherapy via ccRCC cell membrane modifying CuO@Gd 2 O 3 yolk-like particles (CGYL) loaded with lactate oxidase (LOx) (mCGYL-LOx). Benefiting from the homologous targeting effect of Renca cell membranes, the mCGYS-LOx could be effectively internalized by Renca cells, opened the “gate”, and then released LOx and copper ions. LOx could catalyze excessive lactate in Renca cells into H 2 O 2 , following that the produced H 2 O 2 was further converted by copper ions to the highly toxic ·OH, contributing to tumor CDT. Meanwhile, the excessive copper ions effectively triggered tumor cuproptosis. These synergistic effects induced the release of damage associated molecular patterns and activated immunogenic cell death, leading to DC maturation and infiltration of immune effector cells. Moreover, LOx-mediated lactate consumption downregulated the expression of PD-L1, crippling tumor immune escape. In addition, the mCGYL-LOx improved T 1 -weighted MRI signal, allowing for accurate diagnosis of ccRCC. This study demonstrated that the mCGYL-LOx had great potential for improving therapy of ccRCC via the synergistic actions of CDT and cuproptosis as well as immunotherapy. This article is protected by copyright. All rights reserved
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Tianyang Wang,Cheng Huang,Ziyuan Fang,Abudureheman Bahatibieke,Danping Fan,Xing Wang,Hongyan Zhao,Yajie Xie,Kun Qiao,Cheng Xiao,Yudong Zheng
High oxidative stress and inflammatory cell infiltration are major causes of the persistent bone erosion and difficult tissue regeneration in rheumatoid arthritis (RA). Triptolide (TPL) has become a highly anticipated anti-rheumatic drug due to its excellent immunomodulatory and anti-inflammatory effects. However, the sudden drug accumulation caused by the binding of “stimulus-response” and “drug release” in a general smart delivery system is difficult to meet the shortcoming of extreme toxicity and the demand for long-term administration of TPL. Herein, we developed a dual dynamically cross-linked hydrogel (SPT@TPL), which demonstrated sensitive RA microenvironment regulation and microenvironment modulation-independent TPL release for 30 days. The abundant borate ester/tea polyphenol units in SPT@TPL possessed the capability to respond and regulate high reactive oxygen species (ROS) levels on-demand. Meanwhile, based on its dense dual crosslinked structure as well as the spontaneous healing behavior of numerous intermolecular hydrogen bonds formed after the breakage of borate ester, TPL could remain stable and slowly release under high ROS environments of RA, which dramatically reduced the risk of TPL exerting toxicity while maximized its long-term efficacy. Through the dual effects of ROS regulation and TPL sustained-release, SPT@TPL alleviated oxidative stress and reprogrammed macrophages into M2 phenotype, showing marked inhibition of inflammation and optimal regeneration of articular cartilage in RA rat model. In conclusion, this hydrogel platform with both microenvironment initiative regulation and TPL long-term sustained release provides a potential scheme for rheumatoid arthritis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Haowen Qi,Bingqing Wang,Mingjuan Wang,Haifeng Xie,Chen Chen
Long-term inflammation, including those induced by bacterial infections, contributes to the superfluous accumulation of reactive oxygen species (ROS), further aggravating this condition, decreasing the local pH, and adversely affecting bone defect healing. Conventional drug delivery scaffold materials struggle to meet the demands of this complex and dynamic microenvironment. In this work, a smart gelatin methacryloyl (GelMA) hydrogel was synthesized for the dual delivery of proanthocyanidin and amikacin based on the unique pH and ROS responsiveness of boronate complexes. Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) demonstrated the co-crosslinking of two boronate complexes with GelMA. The addition of the boronate complexes improved the mechanical properties, swelling ratio, degradation kinetics and antioxidative properties of the hydrogel. The hydrogel exhibited pH and ROS responses and a synergistic control over the drug release. Proanthocyanidin was responsively released to protect mouse osteoblast precursor cells from oxidative stress and promote their osteogenic differentiation. The hydrogel responded to pH changes and released sufficient amikacin in a timely manner, thereby exerting an efficient antimicrobial effect. Overall, the hydrogel delivery system exhibited a promising strategy for solving infectious and inflammatory problems in bone defects and promoting early-stage bone healing.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Xiaokun Chen,Jihai Xu,Feng Qin,Ziyuan Yang,Xueyuan Li,Miao Yu,Ming Li,Yanhua Wang,Wang Xin
The repair and functional recovery of long-segment peripheral nerve injuries are crucial in clinical settings. Nerve conduits are seen as promising alternatives to autologous nerve grafts, but their effectiveness is limited by the controlled delivery of bioactive factors and meeting various functional requirements during different stages of repair. This research developed multifunctional nerve conduits using electrospinning and polydopamine (PDA) coating techniques to integrate bioactive substances. Chitosan-composite PLGA electrospun nerve conduits demonstrated exceptional mechanical properties and biocompatibility. Nanofibers with specific topological structures effectively promoted oriented cell growth. The PDA coating provided ROS scavenging and immune modulation functions. The bFGF growth factor attached to the PDA coating facilitated sustained release, enhancing Schwann cell functionality and stimulating neurite outgrowth. In a rat sciatic nerve defect model with a 10 mm gap, PLGA/CS-PDA-bFGF nerve conduits showed a positive impact on nerve regeneration and functional recovery. Consequently, nerve conduits with multiple functions modified with PDA-coated bioactive molecules are poised to be excellent materials for mending peripheral nerve injuries.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biofabrication
·
2024
·
IF 8.2
Pinli Lin,Xiaona Tang,Jintao Zhong,Fang Tang,Hanjiao Liu,Lu Peng,Biyu Wan,Mengya Wang,Yuling Ye,Rui Guo,Xusheng Liu,Lili Deng
Pressure ulcers have emerged as a substantial burden on individuals and society. The introduction of innovative dressings that facilitate the healing of pressure ulcer wounds represents a cost-effective alternative for treatment. In this study, we focus on the preparation of Carthamus tinctorius L. polysaccharide (CTLP) as hydrogel microspheres, which are then encapsulated within a hydrogel matrix crosslinked with phenylboronic acid gelatin (Gelatin-PBA) and ε-polylysine-grafted catechol (ε-PL-Cat) to enable sustained release for promoting pressure ulcer healing. The presented GPL/CTLP-MPs hydrogel demonstrated outstanding self-healing properties. In addition, in vitro experiments revealed that the hydrogel exhibited remarkable antibacterial activity, excellent biocompatibility. And it showed the capacity to promote vascular formation, effectively scavenge reactive oxygen species (ROS), and facilitate macrophage polarization from the M1 to M2 phenotype. In vivo wound healing of mice pressure ulcers indicated that the prepared GPL/CTLP-MPs hydrogel effectively accelerated the formation of granulation tissue and facilitated the healing of the wounds. In summary, in vivo and in vitro experiments consistently highlight the therapeutic potential of GPL/CTLP-MPs hydrogel in facilitating the healing process of pressure ulcers.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC MICROBIOLOGY
·
2016
·Vol. 16
·期 1
·1-11
·
IF 2.581
Wang Dan,Zhu Fengqiu,Wang Qian,Rensing Christopher,Yu Peng,Gong Jing,Wang Gejiao
Background Microbial antimonite [Sb(III)] oxidation converts toxic Sb(III) into less toxic antimonate [Sb(V)] and plays an important role in the biogeochemical Sb cycle. Currently, little is known about the mechanisms underlying bacterial Sb(III) resistance and oxidation. Results In this study, Tn5 transposon mutagenesis was conducted in the Sb(III)-oxidizing strain Pseudomonas stutzeri TS44 to isolate the genes responsible for Sb(III) resistance and oxidation. An insertion mutation into gshA, encoding a glutamate cysteine ligase involved in glutathione biosynthesis, generated a strain called P. stutzeri TS44-gshA 540 . This mutant strain was complemented with a plasmid carrying gshA to generate strain P. stutzeri TS44-gshA-C. The transcription of gshA , the two superoxide dismutase (SOD)-encoding genes sodB and sodC as well as the catalase-encoding gene katE was monitored because gshA -encoded glutamate cysteine ligase is responsible for the biosynthesis of glutathione (GSH) and involved in the cellular stress defense system as are superoxide dismutase and catalase responsible for the conversion of ROS. In addition, the cellular content of total ROS and in particular H 2 O 2 was analyzed. Compared to the wild type P. stutzeri TS44 and TS44-gshA-C, the mutant P. stutzeri TS44-gshA 540 had a lower GSH content and exhibited an increased content of total ROS and H 2 O 2 and increased the Sb(III) oxidation rate. Furthermore, the transcription of sodB , sodC and katE was induced by Sb(III). A positive linear correlation was found between the Sb(III) oxidation rate and the H 2 O 2 content ( R
2 = 0.97), indicating that the accumulated H 2 O 2 is correlated to the increased Sb(III) oxidation rate. Conclusions Based on the results, we propose that a disruption of the pathway involved in ROS-protection allowed H 2 O 2 to accumulate. In addition to the previously reported enzyme mediated Sb(III) oxidation, the mechanism of bacterial oxidation of Sb(III) to Sb(V) includes a non-enzymatic mediated step using H 2 O 2 as the oxidant.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）