RENAL FAILURE
·
2024
·
IF 3
Weike Hu
Sepsis represents an organ dysfunction resulting from the host’s maladjusted response to infection, and can give rise to acute kidney injury (AKI), which significantly increase the morbidity and mortality of septic patients. This study strived for identifying a novel therapeutic strategy for patients with sepsis-induced AKI (SI-AKI). Rat tubular epithelial NRK-52E cells were subjected to lipopolysaccharide (LPS) exposure for induction of in-vitro SI-AKI. The expressions of E1A binding protein p300 (EP300) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) in NRK-52E cells were assessed by western blot and qRT-PCR, and their interaction was explored by chromatin immunoprecipitation performed with antibody for H3K27 acetylation (H3K27ac). The effect of them on SI-AKI-associated mitochondrial dysfunction of tubular epithelial cells was investigated using transfection, MTT assay, TUNEL staining, 2′,7′-Dichlorodihydrofluorescein diacetate probe assay, Mitosox assay, and JC-1 staining. MTHFD2 and EP300 were upregulated by LPS exposure in NRK-52E cells. LPS increased the acetylation of H3 histone in the MTHFD2 promoter region, and EP300 suppressed the effect of LPS. EP300 ablation inhibited the expression of MTHFD2. MTHFD2 overexpression antagonized LPS-induced viability reduction, apoptosis promotion, reactive oxygen species overproduction, and mitochondrial membrane potential collapse of NRK-52E cells. By contrast, MTHFD2 knockdown and EP300 ablation brought about opposite consequences. Furthermore, MTHFD2 overexpress and EP300 ablation counteracted each other’s effect in LPS-exposed NRK-52E cells. EP300-mediated H3 acetylation elevates MTHFD2 expression to reduce mitochondrial dysfunction of tubular epithelial cells in SI-AKI.
研究领域:
分子生物学
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医学
·
病理学
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DOI
PubMed
高影响因子
MONATSHEFTE FUR CHEMIE
·
2022
·Vol. 153
·期 3
·257-266
·
IF 1.613
Zhang Dawei,Ren Lu,Liu Ailing,Li Wenyu,Liu Yuxin,Gu Qiang
An efficient synthesis of 1,3,5-trisubstituted 1 H -pyrazoles was developed. 1,3,5-Trisubstituted-1 H -pyrazoles were synthesized starting from α , β -unsaturated aldehydes/ketones and hydrazine using catalyst H 3 [PW 12 O 40 ]/SiO 2 under microwave irradiation and solvent-free conditions (74–90%) and were characterized by HR-MS, FT-IR, 1 H NMR, and 13 C NMR spectroscopy. It was found that silica had a good loading and dispersing effect on phosphotungstic acid and could effectively absorb microwave energy to promote the condensation reaction. The merits of the method included the environmental friendly reaction conditions, simple operation, extensive substrates, good yields, and reuse of the H 3 [PW 12 O 40 ]/SiO 2 . Moreover, the crystal structure of compound 1-(4-chlorophenyl)-5-(2-methoxyphenyl)-3-(4-nitrophenyl)-1 H -pyrazole in triclinic P-1 space group was presented. Graphical abstract
研究领域:
有机化学
·
绿色化学
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DOI
高影响因子
Cell Death & Disease
·
2021
·Vol. 12
·期 5
·1-17
·
IF 8.469
Wang Ruoqin,Sun Linqing,Xia Suhua,Wu Hongya,Ma Yanchao,Zhan Shenghua,Zhang Guangbo,Zhang Xueguang,Shi Tongguo,Chen Weichang
Emerging evidence suggests that cellular senescence induced by chemotherapy has been recognized as a new weapon for cancer therapy. This study aimed to research novel functions of B7-H3 in cellular senescence induced by a low dose of doxorubicin (DOX) in colorectal cancer (CRC). Here, our results demonstrated that B7-H3 knockdown promoted, while B7-H3 overexpression inhibited, DOX-induced cellular senescence. B7-H3 knockdown dramatically enhanced the growth arrest of CRC cells after low-dose DOX treatment, but B7-H3 overexpression had the opposite effect. By RNA-seq analysis and western blot, we showed that B7-H3 prevented cellular senescence and growth arrest through the AKT/TM4SF1/SIRT1 pathway. Blocking the AKT/TM4SF1/SIRT1 pathway dramatically reversed B7-H3-induced resistance to cellular senescence. More importantly, B7-H3 inhibited DOX-induced cellular senescence of CRC cells in vivo. Therefore, targeting B7-H3 or the B7-H3/AKT/TM4SF1/SIRT1 pathway might be a new strategy for promoting cellular senescence-like growth arrest during drug treatment in CRC.
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗
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DOI
PubMed
高影响因子
ChemistrySelect
·
2023
·Vol. 8
·期 43
·e202303563
·
IF 2.1
Chong Liang,Wei Zhao,Xutang Liu,Fei Wang,Zhijie Jiang
Graphical This attractive work examines the changes in CAs selectivity when lignite is oxidized by H 3+n [PMo 12-n V n O 40 ] (HPA-n, n=1-5) and discloses the catalytic mechanism of HPA. The catalytic process of HPA follows the electron transfer-oxygen transfer (ET-OT) mechanism, where it not only activates lignite through electron transfer, but also activates oxygen, leading to the generation of active substance ⋅OH in water. The ⋅OH promotes the breakage of lignite. Although the oxidation of lignite has been extensively studied, the factors affecting the selectivity of carboxylic acids (CAs) are unclear. This attractive work examines the changes in CAs selectivity when lignite is oxidized by H 3+n [PMo 12-n V n O 40 ] (HPA-n, n=1-5) and discloses the catalytic mechanism of HPA. The results show that the selectivity of benzene polycarboxylic acids and acetic acid (AA) increases with increasing vanadium content of HPA-n, such as mellitic acid and benzenepentacarboxylic acid from 0.8 % and 3.0 % to 5.4 % and 16.2 %, respectively. Consequently, the differences in the concentration of HPA or H 2 SO 4 used to obtain optimal formic acid and AA yields confirm that the intrinsic properties of CAs calculated by Gaussian 09 can also affect their selectivity. HPA can not only activate lignite through electron transfer, but also further activate oxygen, leading to the generation of active substance ⋅OH in water. Consequentially, ⋅OH as the key reactive substance can promote the breakage of bridge bonds, side chains and condensed aromatic rings during HPA-catalyzed oxidation of lignite. Thus, the oxidation pathway of lignite over HPA is proposed. This work constructs a relationship between oxidation capacity and CAs selectivity and discloses the lignite oxidation pathway at the molecular level, which is a significant progress in HPA-catalyzed conversion of lignite.
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Jingsheng Xu,Zhiyuan Wang,Runguo Zheng,Hongyu Sun,Yanguo Liu,Junhua You
Ni-rich cathodes especially with Ni content over 90 % are promising next-generation cathode materials for advanced high energy lithium − ion batteries. However, in comparison with Ni ≤ 80 % Ni-rich cathodes, these ultrahigh Ni-rich materials face more severe challenges in terms of harmful H2 − H3 phase transformations and structural degradation during cycling. Herein, we present a robust surface structure composted of defect-rich disordered structures and LiF/Li 2 SiO 3 coating for stabilizing the ultrahigh Ni-rich cathode LiNi 0.96 Co 0.03 Mn 0.01 O 2 (NCM96) by modification with (NH 4 ) 2 SiF 6 . The surface disordered structures including Li/TM mixing, spinel, and rock salt structure play a crucial role in inhibiting the irreversible H2-H3 phase transition and reducing lattice volume changes by lattice coherence effect. Moreover, the disordered surface in collaboration with the co-coating restrains the rapid growth of surface rock salt phase into the bulk, enhancing structural stability. The modified sample NSF-0.5 delivers a capacity of 238 mAh/g at 0.1C and maintains a capacity retention of 88.5 % at 0.5C after 100 cycles in half cell as well as 82.3 % at 1C after 300 cycles in full cell, significantly superior to the NCM96. The findings provide a simple and cost-effective surface modification strategy to enhance the structural stability and electrochemical performance of ultrahigh nickel cathodes for high-energy density LIBs.
研究领域:
材料科学
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电化学
·
能源存储
·
锂离子电池
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固态化学
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表面工程
·
电池材料
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DOI
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2021
·
IF 3.641
Yaping Cheng,Jingyuan Wu,Ying Han,Jingyao Xu,Yifan Da,Qian Zhao,Guoying Guo,Yani Zhou,Yimin Chen,Jinghong Liu,Huayao Chen,Xianxing Jiang,Xiaoqing Cai
Covalent target modulation with small molecules has been emerging as a promising strategy for drug discovery. However, covalent inhibitory antibody remains unexplored due to the lack of efficient strategies to engineer antibody with desired bioactivity. Herein, we developed an intracellular selection method to generate covalent inhibitory antibody against human rhinovirus 14 (HRV14) 3C protease through unnatural amino acid mutagenesis along the heavy chain complementarity-determining region 3 (CDR-H3). A library of antibody mutants was thus constructed and screened in vivo through co-expression with the target protease. Using this screening strategy, six covalent antibodies with proximity-enabled bioactivity were identified, which were shown to covalently target HRV14-3C protease with high inhibitory potency and exquisite selectivity . Compared to structure-based rational design, this library-based screening method provides a simple and efficient way for the discovery and engineering of covalent antibody for enzyme inhibition.
研究领域:
药物发现
·
蛋白质工程
·
病毒学
·
分子生物学
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2026
·
IF 6.3
Yang Liu,Yan Lu,Weilian Bao,Haiyan Zhu,Guoqi Yuan,Linfeng Guo,Hong Li,Jiyang Li,Tong Wu,Xunlong Shi,Daofeng Chen
Secondary bacterial infection is a major cause of severe progression and death in viral pneumonia. The excessive recruitment of neutrophils accompanied by the formation of neutrophil extracellular traps (NETs) plays an important role in excessive inflammation caused by viral-bacterial co-infection, but effective pharmacological interventions remain lacking. Our study revealed that quercitrin (QTN), a flavonoid commonly found in traditional Chinese medicine and daily diets, significantly reduced mortality, recruitment of neutrophils, the production of inflammatory cytokines, and viral and bacterial loads in H1N1 influenza and methicillin-resistant Staphylococcus aureus (MRSA) coinfection-induced pneumonia in mice. Mechanistically, QTN down-regulates the interaction between Histone H3 and myeloperoxidase (MPO), thereby mitigating excessive inflammation induced by NETs. Our study demonstrates that inhibiting NETosis with QTN is one of the effective strategies for co-infection treatment.
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DOI
PubMed
高影响因子
ONCOLOGY REPORTS
·
2026
·Vol. 56
·期 4
·1-12
·
IF 4.7
Jiawei Yu,Rui Pang,Bo Liu,Lili Chen,Jiewu Zhang
Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.
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产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Xue-Ting Xu,Jun-Kai Fan,Xi Chen,Si-Yi Que,Run-Xin Zhang,Yu-Yan Xie,Tian-Ci Zhou,Kunmei Ji,Zhen-Fu Zhao,Jia-Jie Chen
Background Mast cells (MCs) mediate high-affinity IgE Fc receptor (FcεRI)-mediated allergic reactions. Royal jelly acid (RJA), the major lipid constituent of royal jelly, has anti-inflammatory, anti-tumor, antibacterial, and immunomodulatory properties. Purpose This study aimed to investigate how RJA affects IgE-mediated MC activation and to elucidate mechanisms underlying anti-allergic effects. Methods Mouse bone marrow-derived mast cells (BMMCs) and rat basophilic leukemia cells-2H3 (RBLs) were stimulated with IgE-antigen (Ag). β-hexosaminidase (β-hex) and histamine (HA) release, inflammatory cytokines expression, and cellular morphology changes were examined in stimulated cells. Transcriptome changes associated with RJA-treated activated-MCs were analyzed. Network pharmacology, gene expression, and western blot analyses were employed to explore the relationship between H3 lactylation and anti-allergic effects of RJA on MC. In vivo studies were conducted in IgE-mediated passive cutaneous anaphylaxis (PCA), ovalbumin (OVA)-induced active systemic anaphylaxis (ASA), and HA-induced passive systemic anaphylaxis (PSA) mouse models. Results RJA inhibited IgE-dependent MC activation as evidenced by reduced β-hex and HA release. RJA inhibited MAPK and NF-κB signaling, down-regulated RELA and NFκB1 transcripts, and decreased NF-κB reporter activity. RJA inhibited cellular H3 lactylation and H3K9 lactylation (H3K9la), leading to reduced histone lactyllysine enrichment in RELA or NFκB1 promoter loci. RJA alleviated allergic symptoms in PCA and ASA mice by intraperitoneal injection or oral administration, but did not affect HA-induced hypothermia. Conclusion RJA inhibits IgE-dependent MC activation by reducing cellular H3K9la and suppressing NF-κB signaling via reduced histone lactyllysine enrichment in RELA or NFκB1 promoter sites. RJA may support MC inhibition in the prevention and treatment of allergic diseases.
研究领域:
免疫学
·
过敏与免疫疾病
·
分子生物学
·
表观遗传学
·
药理学
·
转化医学
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2021
·Vol. 12
·期 5
·1-15
·
IF 8.469
Xu Xing,Chen Jun,Li Yan,Yang Xiaojie,Wang Qing,Wen Yanjun,Yan Ming,Zhang Jianjun,Xu Qin,Wei Yan,Chen Wantao,Wang Xu
The histone methyltransferase EZH2 silences gene expression via H3 lysine 27 trimethylation and has been recognized as an important antitumour therapeutic target. However, the clinical application of existing EZH2 inhibitors is not satisfactory for the treatment of solid tumours. To discover novel strategies against head and neck squamous cell carcinoma (HNSCC), we performed genomics, metabolomics and RNA omics studies in HNSCC cells treated with EZH2 inhibitors. It was found that EZH2 inhibitors strongly induced the expression of genes in cholesterol synthesis. Through extensive drug screening we found that inhibition of squalene epoxidase (a key enzyme of endogenous cholesterol synthesis) synergistically increased the squalene content and enhanced the sensitivity of HNSCC cells to EZH2 inhibitors. Our findings provide an experimental and theoretical basis for the development of new combinations of EZH2 inhibitors to treat HNSCC.
研究领域:
肿瘤学
·
表观遗传学
·
药理学
·
代谢组学
·
基因组学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 45
·期 20
·9264-9273
·
IF 3.591
Chaowei Wang,Zhe Liu,Guangfa Hu,Ruimin Gao,Jianshe Zhao
In this study, the novel magnetic core–shell composites Fe3O4@UiO-66-HPA, consisting of magnetic Fe3O4@UiO-66 and vanadium-substituted Keggin-type heteropolyacid active species supported by Zr-MOF, were successfully prepared via a one-pot method and fully investigated using FT-IR, XRD, SEM, TEM, TEM-EDX, ICP, VSM and N2 adsorption–desorption isotherms. The synthetic composites were employed as catalysts in an ODS system of simulated fuel under oxygen. The catalyst Fe3O4@UiO-66-PW9V3 exhibits the supreme catalytic performance in this work, with sulfur removal of 99.85% and a TOF value of 31.16 h−1 under optimal reaction conditions (0.2 g catalyst mass, 60 °C reaction temperature, 500 rpm stirring speed, 1 L min−1 oxidant quantity and 180 min reaction time), and can also be recycled ten times without apparent loss of catalytic performance. Furthermore, the kinetic study shows that the ODS process accords with the pseudo-first-order model.
研究领域:
化学
·
材料科学
·
环境科学
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产品关联
DOI
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Rangrang Fan,Caili Chen,Junshan Hu,Min Mu,Di Chuan,Zhouyun Chen,Gang Guo,Jianguo Xu
Collateral damage to healthy tissue, uneven heat distribution, inflammatory diseases, and tumor metastasis induction hinder the translation of high-temperature photothermal therapy (PTT) from bench to practical clinical applications. In this report, a multifunctional gold nanorod (GNR)-based nanosystem was designed by attaching siRNA against B7-H3 (B7-H3si), glucose oxidase (GOx), and hyaluronic acid (HA) for efficient low-temperature PTT. Herein, GOx can not only exhaust glucose to induce starvation therapy but also reduce the heat shock protein (HSP), realizing the ablation of tumors without damage to healthy tissues. Evidence shows that B7-H3, a type I transmembrane glycoprotein molecule, plays essential roles in growth, metastasis, and drug resistance. By initiating the downregulation of B7-H3 by siRNA, siRNA-GOx/ [email protected] NPs may promote the effectiveness of treatment. By targeting cluster of differentiation 44 (CD44) and depleting B7-H3 and HSPs sequentially, siRNA-GOx/ [email protected] NPs showed 12.9-fold higher lung distribution than siRNA-GOx/GNR NPs. Furthermore, 50% of A549-bearing mice in the siRNA-GOx/GNR NPs group survived over 50 days. Overall, this low-temperature phototherapeutic nanosystem provides an appropriate strategy for eliminating cancer with high treatment effectiveness and minimal systemic toxicity. Statement of significance To realize efficient tumor ablation under mild low-temperature (42–45 ℃) and RNA interference simultaneously, here we developed a multifunctional gold nanorod (GNR)-based nanosystem (siRNA-GOx/ [email protected] NPs). This nanoplatform can significantly inhibit tumor cell proliferation and induce cell apoptosis by downregulation of HSP90α, HSP70, B7-H3, p-AKT, and p-ERK and upregulation of cleaved caspase-9 at mild low-temperature due to its superior tumor homing ability and the combined effect of photothermal effect, glucose deprivation-initiated tumor starvation, and B7-H3 gene silence effect. It is believed that this multifunctional low-temperature photothermal nanosystem with efficient and specific anticancer properties, shows a potential application in clinical tumor treatment.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
分子生物学
·
药学
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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）