APPLIED CATALYSIS B-ENVIRONMENTAL
·
2023
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IF 22.1
Xuedong He,Xiang Han,Xueyan Zhou,Jiadong Chen,Juan Wang,Yan Chen,Lianghao Yu,Nan Zhang,Jun Li,Shun Wang,Huile Jin
Achieving large current density is crucial to the practical application of large-scale hydrogen production by water splitting, but it is hindered by sluggish and unstable catalysts. Herein, a Pt-induced NiFe layered double hydroxide (Pt-NiFe LDH) nanosheet is synthesized for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). It affords 10 mA cm –2 at overpotentials of only 198 mV and 36 mV for OER and HER, respectively. Impressively, an alkali-electrolyzer (Pt-NiFe LDH || Pt-NiFe LDH) exhibits a stable cell voltage of 1.887 V to deliver a current density of 1000 mA cm –2 over 3000 h. The introduction of Pt modulates the electronic structure on the surface of NiFe LDH by charging redistribution at the interface and decreasing the Gibbs free energy change (ΔG) for the potential determining step (from *O to *OOH) during OER. This work provides a facile strategy for developing catalysts for large current density water splitting.
研究领域:
材料科学
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电化学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Wenxin Zhang,Hongbo Teng,Tianyi Zhao,Roberts I. Eglitis,Xv Wang,Zhengxuan Yu,Shurong Qu,Haijing Wang,Yaru Zhao,Bowen Fan,Shuangli Liu,Yan Zhao
Introduction: Cisplatin is extensively employed in the treatment of multiple solid malignant tumors. Nevertheless, side effects such as cisplatin-induced ototoxicity (CIO) pose obstacles to tumor therapy.The important natural product chiisanoside from Acanthopanax sessiliflorus has abundant activity against CIO.Methods: In this study, 26 chiisanoside derivatives were screened, and compound 19 demonstrated significant protective activity against CIO damage. A cisplatin—induced HEI—OC1 cell injury model and a mouse ototoxicity model were established. The regulatory effects were revealed through transcriptome sequencing, and the protein expression levels were analyzed by molecular docking, ELISA, Western blotting, and immunofluorescence.Results: It was found that compound 19 inhibited cell apoptosis, alleviated abnormal hearing and spiral ganglion damage. Transcriptome sequencing revealed its regulatory effects. Compound 19 treatment increased autophagy levels, thereby alleviating mitochondrial dysfunction and reducing the accumulation of reactive oxygen species (ROS).In-depth studies have found that the autophagy inhibitor 3-methyladenine (3-MA) weakens the regulatory effect of compound 19 on autophagy and inhibits the clearance of damaged cells, resulting in oxidative stress damage, apoptosis and necrosis. By knocking down LRP6, it was found that the protective effect of compound 19 was eliminated, the autophagy level was significantly reduced, oxidative stress and ROS production were induced, and apoptosis after cisplatin exposure was promoted. Finally, the inhibitor LiCl was used to suppress the expression of GSK3β. It was found that inhibiting GSK3β could protect cells from cisplatin-induced damage by activating autophagy.Discussion: These findings suggest that compound 19 is capable of preventing ototoxicity by activating autophagy via the LRP6/GSK3β axis and consequently inhibiting oxidative stress, offering a new approach for treating CIO and sensorineural hearing loss.
研究领域:
药理学
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肿瘤学
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分子生物学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2025
·
IF 3.3
Yu-jiao Hua,Ying Zhang,Rui-Rong Wu,Juan Lv,Yan Zhang,Yan-yan Chen,Yong-juan Ding,Jing-hua Chen
Background Oxaliplatin-induced peripheral neuropathy (OIPN) poses a significant challenge for patients with colorectal tumor, often resulting in treatment interruption or discontinuation and subsequent treatment failure. Herein, a longitudinal untargeted metabolomic study to reveal the metabolomic profiles and biomarkers associated with the progression of OIPN. Methods A prospective cohort of 129 colorectal cancer patients receiving oxaliplatin-based chemotherapy was stratified into four OIPN severity grades (Level 0-3). Serum samples underwent untargeted LC-MS/MS metabolomic analysis, detecting 521 metabolites. Multivariate statistical models and SHAP-guided random forest algorithms were employed to prioritize biomarkers. Machine learning validation included six classifiers assessed via ROC-AUC. Results The cumulative dose of Oxaliplatin chemotherapy plays an important role in OIPN. At the same time, our findings implied that the occurrence of OIPN may be associated with the progression of the disease and the patients’ tumor markers (CEA, CA19-9, CA72-4), as well as immune response and inflammation (ANC, PLT), and metabolic and liver function abnormalities (GGT and UA) (P<0.05).Multivariate statistical analysis combined with SHAP-guided machine learning identified six biomarkers, including thiabendazole, 1-methylxanthine, imidazol-5-yl-pyruvate, 5-hydroxypentanoic acid, spermidine, and 4’-oxolividamine that consistently distinguished OIPN patients (Level 1-3) from non-OIPN controls (Level 0). Machine learning models, validated across six classifiers, demonstrated near-perfect discrimination for early-stage OIPN (AUC nearly 1). However, differentiation between intermediate OIPN grades (Level 1 vs 2, Level 1 vs 3, Level 2 vs 3) yielded lower predictive accuracy (AUC: 0.549–0.843), likely due to cohort size limitations and reliance on subjective sensory-based grading. Pathway enrichment analysis highlighted dysregulation in ABC transporters, central carbon metabolism in cancer, amino acid metabolism, and linoleic acid metabolism, suggesting potential roles in OIPN pathogenesis. Conclusions These findings suggest that the selected biomarkers could serve as a foundation for the prediction and management of OIPN in colorectal cancer patients.
研究领域:
肿瘤学
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神经毒理学
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转化医学
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药物代谢
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代谢组学
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精准医学
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临床药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2021
·
IF 6.543
Xiao-lu Wang,Liang Wang,Fo-lan Lin,Si-si Li,Ting-xuan Lin,Ren-wang Jiang
Copper/zinc superoxide dismutase (SOD1) can clear cisplatin- (CP-) induced excessive reactive oxygen species (ROS), but exogenous SOD1 cannot enter cells because of its low biomembrane permeability. Cell-penetrating peptides (CPPs) can rapidly cross plasma membranes. This study is aimed at identifying an efficient and stable CPP-SOD1 and investigating its effects on CP-induced nephrotoxicity. We recombined SOD1 with 14 different CPPs and purified them using an NTA-Ni2+ column. In in vitro experiments, CPPs-SOD1 cell membrane penetration ability and JNK/p38 MAPK signaling pathway were evaluated using Western blotting. ROS production, mitochondrial membrane potential (MMP), and cell apoptosis were determined using flow cytometry and immunofluorescence staining in VERO and HK-2 cells. For in vivo experiments, mice were administered PSF-SOD1 for 2 h before cotreatment with a single CP injection for an additional 4 days. Blood and kidney samples were collected for renal function assessment (creatinine, urea nitrogen, histopathology, TUNEL assay, and JNK/p38 MAPK signaling pathway). Compared with TAT-SOD1, we found that PSF-SOD1 is more efficient at crossing the cell membrane and is stable after transduction into cells. Pretreatment with PSF-SOD1 inhibited CP-induced apoptosis, ROS generation, and JNK/p38 MAPK activation and restored CP-induced MMP loss in VERO and HK-2 kidney cells. Treatment of mice with PSF-SOD1 inhibited CP-induced serum creatinine, blood urea nitrogen elevation, and JNK/p38 MAPK activation. H&E staining and TUNEL assay indicated that kidney tissue damage was alleviated following PSF-SOD1 pretreatment. Overall, PSF-SOD1 ameliorated CP-induced renal damage by partially reducing oxidative stress and cell apoptosis by regulating JNK/p38 MAPK signaling pathway and might be a better cytoprotective agent than TAT-SOD1.
研究领域:
药理学
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肾病学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
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IF 6.7
Changjun Zhang,Yi Lu,Jingqi Zhang,Anjie Zang,Jinhui Ren,Zhiyuan Zheng,Miaoliang Fan,Yuanyuan Xie
Recent advances in understanding the role of iron and ROS in cell death suggest new therapeutic avenues to treat organ damage including acute kidney injury (AKI). Inhibiting ferroptosis was expected to have great potential for the treatment of this disease. Ferroptosis is characterized by iron-dependent lipid peroxidation and currently, a majority of reported ferroptosis inhibitors belong to either radical-trapping antioxidants or iron chelators . However, clinically used iron chelators such as deferoxamine and deferiprone have limited efficacy against ferroptosis (generally with EC 50 > 100 μM), despite their proven safety. Herein, we present the rational design of novel ferroptosis inhibitors by incorporating the naturally occurring cinnamic acid scaffold and the 3-hydroxypyridin-4(1 H )-one iron-chelating pharmacophore . Through ABTS ˙ + radical-scavenging assay, oxygen radical absorbance capacity (ORAC) measurement, Fe 3+ affinity evaluation, and anti-erastin-induced HT22 cell ferroptosis assays, we identified compound 9c as the most prospective ferroptosis inhibitor (ABTS ˙ + , IC 50 = 4.35 ± 0.05 μM; ORCA = 23.79 ± 0.56 TE; pFe 3+ = 18.59; EC 50 = 14.89 ± 0.08 μM, respectively). Notably, 9c dose-dependently alleviated cell death in cisplatin-induced AKI model. Our results provide insight into the development of new ferroptosis inhibitors through rational incorporation of pharmacophores from existing ferroptosis inhibitors, and compound 9c could be a promising lead compound worth further investigation.
研究领域:
药理学
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医学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Shuai Liu,Xintao Gao,Yulan Yin,Jing Wang,Kehong Dong,Dayong Shi,Xiaochen Wu,Chuanlong Guo
Silk fibroin (SF) has excellent biocompatibility and biodegradability as a biomaterial. The purity and molecular weight distribution of silk fibroin peptide (SFP) make it more suitable for medical application. In this study, SFP nanofibers (molecular weight ∼30kD) were prepared through CaCl 2 /H 2 O/C 2 H 5 OH solution decomposition and dialysis, and adsorbed naringenin (NGN) to obtain SFP/NGN NFs. In vitro results showed that SFP/NGN NFs increased the antioxidant activity of NGN and protected HK-2 cells from cisplatin-induced damage. In vivo results also showed that SFP/NGN NFs protected mice from cisplatin-induced acute kidney injury (AKI). The mechanism results showed that cisplatin induced mitochondrial damage, as well as increased mitophagy and mtDNA release, which activated the cGAS-STING pathway and induced the expression of inflammatory factors such as IL-6 and TNF-α. Interestingly, SFP/NGN NFs further activated mitophagy and inhibited mtDNA release and cGAS-STING pathway. Demonstrated that mitophagy-mtDNA-cGAS-STING signal axis was involved in the kidney protection mechanism of SFP/NGN NFs. In conclusion, our study confirmed that SFP/NGN NFs are candidates for protection of cisplatin-induced AKI, which is worthy of further study.
研究领域:
生物材料
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药理学
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肾病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2023
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IF 3.5
Jinping Shao,Wenli Yu,Wei Wei,Suifeng Wang,Zhenli Zheng,Lei Li,Yanyan Sun,Jingjing Zhang,Zhihua Li,Xiuhua Ren,Weidong Zang,Jing Cao
The voltage-gated sodium channel subtype Nav1.6 is involved in the electrophysiological changes of primary sensory neurons that occur in oxaliplatin-induced neuropathic pain , but its regulatory mechanism remains unclear. In this study, Western blot , RT-qPCR, immunofluorescence staining, chromatin immunoprecipitation were used to prove the mechanism of MAPK-ERK-CREB signaling pathway participating in oxaliplatin-induced neuropathic pain by regulating Nav1.6. The results showed that p-Raf1 and p-ERK, key molecules in MAPK/ERK pathway, and Nav1.6 were significantly increased in DRGs of oxaliplatin-induced neuropathic pain rats. Inhibition of p-Raf1 and p-ERK respectively not only reduced the expression of Nav1.6 protein in DRGs of OXA rats, but also caused a decrease in Nav1.6 mRNA, which led us to further explore the transcription factor CREB regulated by MAPK/ERK pathway. Results showed that CREB was co-distributed with Nav1.6. Inhibition of CREB resulted in decreased mRNA and protein expression of Nav1.6, and alleviated oxaliplatin-induced neuropathic pain. A chromatin immunoprecipitation experiment proved that OXA caused p-CREB to directly bind to the promoter region of Scn8A, which is the encoding gene for Nav1.6, and promote the transcription of Scn8A. In summary, in this study, we found that oxaliplatin can activate the MAPK/ERK pathway, which promotes the expression and activation of CREB and leads to an increase in Scn8A transcription, and then leads to an increase in Nav1.6 protein expression to enhance neuronal excitability and cause pain. This study provides an experimental basis for the molecular mechanism of sodium channel regulation in oxaliplatin-induced neuropathic pain.
研究领域:
神经科学
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药理学
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分子生物学
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疼痛研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2021
·
IF 5.275
Hongbo Wang,Jiawei Zuo,Liang Zha,Xia Jiang,Caixia Wu,Yong-An Yang,Wenjian Tang,Tianlu Shi
To develop new anti-inflammatory drugs for the prevention and treatment of acute kidney injury, a series of novel glycyrrhetic ureas were designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells. Compounds 5r-5u (2.04, 2.50, 3.25 and 2.48 μM, respectively) with acidic or neutral amino acid showed potent anti-inflammatory activity (IC 50 = 2–3 μM for NO inhibition), amongst them, compound 5r also inhibited tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in a dose-dependent manner. In cisplatin-induced AKI mice model, compound 5r significantly reduced the level of pro-inflammatory factors, ameliorated the pathological damage of kidney tissue, and maintained the normal metabolic capacity.
研究领域:
药理学
·
药物化学
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炎症研究
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肾病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Redox Biology
·
2024
·
IF 10.7
Bi-Xin Xu,Tian-Yu Hu,Jin-Biao Du,Tao Xie,Ya-Wen Xu,Xin Jin,Si-Tao Xu,Hao-Wen Jin,Guangji Wang,Jiankun Wang,Le Zhen
Redox-responsive hydropersulfide prodrugs are designed to enable a more controllable and efficient hydropersulfide (RSSH) supply and to thoroughly explore their biological and therapeutic applications in oxidative damage. To obtain novel activation patterns triggered by redox signaling, we focused on NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1), a canonical antioxidant enzyme, and designed NQO1-activated RSSH prodrugs. We also performed a head-to-head comparison of two mainstream structural scaffolds with solid quantitative analysis of prodrugs, RSSH, and metabolic by-products by LC-MS/MS, confirming that the perthiocarbamate scaffold was more effective in intracellular prodrug uptake and RSSH production. The prodrug was highly potent in oxidative stress management against cisplatin-induced nephrotoxicity. Strikingly, this prodrug possessed potential feedback activation properties by which the delivered RSSH can further escalate the prodrug activation via NQO1 upregulation. Our strategy pushed RSSH prodrugs one step further in the pursuit of efficient release in biological matrices and improved druggability against oxidative stress.
研究领域:
药学
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生物化学
·
分子生物学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2020
·
IF 4.831
Jiawei Zuo,Shi-Meng Wang,Xia Jiang,Mengxin Cao,Ziwen Zhang,Tianlu Shi,Hua-Li Qin,Wenjian Tang
Acute kidney injury (AKI) is associated with a strong inflammatory response, and inhibiting the response effectively prevents or ameliorates AKI. A series of novel arylpropionic esters were designed, synthesized and evaluated their biological activity in LPS-stimulated RAW264.7 cells. Novel arylpropionic esters bearing multi-functional groups showed significant anti-inflammatory activity, in which, compound 13b exhibited the most potent activity through dose-dependent inhibiting the production of nitric oxide (NO, IC 50 = 3.52 μM), TNF-α and IL-6 (84.1% and 33.6%, respectively), as well as suppressing the expression of iNOS, COX-2 and TLR4 proteins. In C57BL/6 mice with cisplatin-induced AKI, compound 13b improved kidney function, inhibited inflammatory development, and reduced pathological damage of kidney tissues. In brief, this arylpropionic ester scaffold may be developed as anti-inflammatory agents.
研究领域:
药理学
·
药物化学
·
炎症研究
·
肾脏生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Hanchun Yao,Zhihui Zhu,Mengyu Liu,Fangfang Sun,Mengyu Du,Yilin Sun,Bin Du
Acute kidney injury (AKI) is a critical medical condition characterized by high morbidity and mortality rates. The pathogenesis of AKI potentially involves bursts of reactive oxygen species (ROS) bursts and elevated levels of inflammatory mediators. Developing nanoparticles (NPs) that downregulate ROS and inflammatory mediators is a promising approach to treat AKI. However, such NPs would be affected by the glomerular filtration barrier (GFB). Typically, NPs are too large to penetrate the glomerular system and reach the renal tubules─the primary site of AKI injury. Herein, we report the development of ultrasmall carbon dots-gallic acid (CDs-GA) NPs (∼5 nm). These NPs exhibited outstanding biocompatibility and were shown not only to efficiently eliminate ROS and alleviate oxidative stress but also to suppress the activation of the NF-κB signaling pathway, leading to a reduction in the release of inflammatory factors. Importantly, CDs-GA NPs were shown to be able to rapidly accumulate rapidly in the renal tissues without the need for intricate targeting strategies. In vivo studies demonstrated that CDs-GA NPs significantly reduced the incidence of cisplatin (CDDP)-induced AKI in mice, surpassing the efficacy of the small molecular drug, N-acetylcysteine. This research provides an innovative strategy for the treatment of AKI.
研究领域:
纳米技术
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药学
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肾脏生理学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2017
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IF 6.32
Hong Cheng,Shi-Ying Li,Hao-Ran Zheng,Chu-Xin Li,Bo-Ru Xie,Ke-Wei Chen,Bin Li,Xian-Zheng Zhang
A novel single-molecular fluorescent probe was developed for spatiotemporal matrix metalloproteinase-2 (MMP-2) and caspase-3 imaging with distinct fluorescence signals. Due to the multi-Förster resonance energy transfer (FRET) processes, the probe could respond to MMP-2 and caspase-3 independently with high signal-to-noise ratio. Moreover, the overexpression of MMP-2 in cancer cell lines and the cisplatin induced cell apoptosis were spatiotemporal imaged with distinct fluorescence emissions. Because of the independent process of the probe for MMP-2 and caspase-3 imaging, the probe could meet the demands for precise disease diagnosis and cancer theranostic applications, which could extensively simplify the processes for precise cancer diagnosis and imaging.
研究领域:
生物医学工程
·
分子生物学
·
癌症研究
·
成像科学
✓ 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）