BIOORGANIC CHEMISTRY
·
2023
·
IF 5.1
Rui Li,Weiheng Zhao,Chen Jin,Huihua Xiong
Platinum(II)–based drugs play an important role in many chemotherapeutic protocols, but their further clinical applications are hindered by the development of drug resistance and serious side effects. Therefore, to reverse cisplatin (CDDP) resistance in tandem with reduced side effects, nine novel platinum(IV) complexes modified with key pharmacophore of Olaparib were synthesized and evaluated for biological activities. Among them, the optimal complex 8–2 showed good inhibitory activity against PARP–1 and superior anticancer effects over CDDP on parental (MDA–MB–231, IC 50 = 1.13 μM) and CDDP –resistant triple–negative breast cancer (TNBC) cell line (MDA–MB–231/CDDP, IC 50 = 1.72 μM). Detailed mechanisms revealed that compared with Olaparib and CDDP, the enhanced intracellular accumulation of 8–2 could efficiently reverse CDDP resistance in MDA–MB–231/CDDP cells via inhibiting DNA repair–associated mechanisms, enhancing DNA damage, and activating mitochondrion–dependent apoptosis pathway. Furthermore, 8–2 obtained higher tumor growth inhibition rate (64.1 %) than CDDP (26.5 %) in MDA–MB–231/CDDP xenografts, but it did not induce significant toxicity in vivo and in intro , making it a potential drug candidate for the treatment of TNBC.
研究领域:
肿瘤学
·
药理学
·
化疗
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DOI
PubMed
高影响因子
Neural Regeneration Research
·
2022
·Vol. 18
·期 8
·1809
·
IF 6.058
Xu Ai-Hua,Yang Yang,Shao Yang,Jiang Man-Yu,Sun Yong-Xin
Poly(ADP-ribose)polymerase family member 14 ( PARP14 ), which is an intracellular mono(ADP-ribosyl) transferase, has been reported to promote post-stroke functional recovery, but its role in spinal cord injury (SCI) remains unclear. To investigate this, a T10 spinal cord contusion model was established in C57BL/6 mice, and immediately after the injury PARP14 shRNA-carrying lentivirus was injected 1 mm from the injury site to silence PARP14 expression. We found that PARP14 was up-regulated in the injured spinal cord and that lentivirus-mediated downregulation of PARP14 aggravated functional impairment after injury, accompanied by obvious neuronal apoptosis , severe neuroinflammation , and slight bone loss. Furthermore, PARP14 levels were elevated in microglia after SCI, PARP14 knockdown activated microglia in the spinal cord and promoted a shift from M2-polarized microglia (anti-inflammatory phenotype) to M1-polarized microglia (pro-inflammatory phenotype) that may have been mediated by the signal transducers and activators of transcription (STAT) 1/6 pathway. Next, microglia M1 and M2 polarization were induced in vitro using lipopolysaccharide/interferon-γ and interleukin-4, respectively. The results showed that PARP14 knockdown promoted microglia M1 polarization , accompanied by activation of the STAT1 pathway . In addition, PARP14 overexpression made microglia more prone to M2 polarization and further activated the STAT6 pathway . In conclusion, these findings suggest that PARP14 may improve functional recovery after SCI by regulating the phenotypic transformation of microglia via the STAT1/6 pathway.
研究领域:
神经科学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ARCHIV DER PHARMAZIE
·
2019
·Vol. 353
·期 2
·1900231
·
IF 2.145
Xiujie Liu,Xin Chen,Kai Qiu,Zhihao Zhang
A series of 4-methoxy-3-arylamido- N -(substitutedphenyl)benzamides 6a – u were designed according to the splicing principle of structural design in the medicinal chemistry theory and were synthesized in five steps: nitration, acylation, ammoniation, reduction, and secondary ammoniation. The structures of the target compounds were characterized and verified by infrared, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and electron spray ionization spectroscopy. Their in vitro antiplatelet aggregation activities induced by adenosine diphosphate (ADP) or arachidonic acid (AA) were assessed by Born's method. The biological evaluation revealed that all compounds exhibited certain levels of activities in both of the antiplatelet aggregation assays; compounds 6c (IC 50 = 3.84 μM) and 6f (IC 50 = 3.12 μM) displayed the strongest antiplatelet aggregation activities in the ADP-induced and AA-induced assay, separately. Moreover, compounds that had stronger activities were chosen for cell toxicity testing via the cell counting kit-8 assay. The results indicated that none of the compounds had obvious cell toxicity against L929 cells at the doses of 10 and 20 μM. It is worth pointing out that compound 6c showed the highest antiplatelet activity and the lowest cell toxicity. In general, 4-methoxy-3-arylamido- N -(substitutedphenyl)benzamides have the potential to become a kind of safer and more effective antiplatelet agents.
研究领域:
药物化学
·
药理学
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DOI
PubMed
高影响因子
Food & Function
·
2017
·Vol. 8
·期 9
·3259-3270
·
IF 3.247
Xiaozhou Zhou,Shiguo Chen,Xingqian Ye
The anti-obesity effects of different proanthocyanidin extracts (PE) from Chinese bayberry (Myrica rubra Sieb.et Zucc.) leaves were evaluated in a high-fat (HF) diet-induced obese rat model. The leaves of Chinese bayberry (LCB), a non-desaccharified proanthocyanidin extract (NDPE), and a desaccharified proanthocyanidin extract (DPE) were compared with orlistat, a conventional anti-obesity drug used as a positive control. The rats from all of the PE-treated groups showed obvious weight loss, with the greatest weight loss in the DPE group (P < 0.05). Compared to the HF group, almost all of the PE-treated groups showed significantly reduced levels of serum TC, TG, AST, ALT, ALP, LDL-C, ADP and a LEP/ADP ratio, and increased levels of HDL-C and LEP. Furthermore, the expression levels of SIRT1, PPAR-γ, C/EBP-α, BMP4 and UCP1 were investigated in the liver, kidney, epididymis and abdominal adipose tissue. Compared to the HF group, PPAR-γ and C/EBP-α levels were significantly reduced and SIRT1, BMP4 and UCP1 levels were significantly upregulated in the DPE-treated group. Our results suggested that PE exerted its anti-obesity effects by upregulating the expression of SIRT1, thus inducing the deacetylation of PPAR-γ and downregulating the expression of C/EBP-α, and also upregulating the expression of BMP4 to boost the levels of brown fat.
研究领域:
药理学
·
营养学
·
分子生物学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Liyi Wei,Cuiping Qi,Tingting Wang,Xiuping Jin,Xinli Zhou,Mingcui Luo,Mengxi Lu,Huijun Chen,Juanjuan Guo,Hui Wang,Dan Xu
Amoxicillin is a widely used antibiotic globally, and its pervasive environmental presence poses significant risks to human health and ecosystems. Notably, prenatal amoxicillin exposure (PAmE) may have long-term neurodevelopmental toxicity for offspring. In this study, we investigated the lasting effects of PAmE on depressive-like behaviors in offspring rats, emphasizing the biological mechanisms mediated by changes in gut microbiota and its metabolite, myristic acid. Our results showed that PAmE significantly disrupted the gut microbiota composition in offspring, particularly through the reduction of Lachnospiraceae , leading to decreased levels of myristic acid. This disruption hindered the N-myristoylation of ADP-ribosylation factor 1 (ARF1), impaired the normal degradation of the stimulator of interferon genes protein, inhibited autophagic processes, and promoted M1 polarization of microglia, ultimately leading to depressive-like behaviors in the offspring. Remarkably, supplementation with Lachnospira or myristic acid effectively reversed the PAmE-induced neurodevelopmental and behavioral abnormalities, alleviating depressive-like symptoms. This study reveals how PAmE affects offspring neurodevelopment and behavior through gut microbiota and myristic acid, highlighting the crucial role of the gut-brain axis in the modulation of depressive symptoms. Supplementing Lachnospira or myristic acid could represent a novel strategy to mitigate PAmE-induced fetal-originated depression, providing new biological evidence and potential therapeutic avenues.
研究领域:
药理学
·
神经科学
·
微生物学
·
行为科学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2014
·Vol. 42
·期 2
·146-153
·
IF 2.405
Xiao-Yun Hu,Ji-Yun Liang,Xue-Jun Guo,Li Liu,Ya-Bing Guo
Summary The development of chemoresistance may reduce the efficacy of chemotherapeutic drugs for treating hepatocellular carcinoma (HCC). In the present study, the effects of apigenin on intensifying the chemosensitivity of HCC cells and an HCC xenograft model in response to 5-fluorouracil (5-FU) were investigated. Sub-toxic concentrations of apigenin (4 μ mol/L) significantly enhanced the cytotoxicity of 5-FU (100 μ g/mL) in HCC cells. In vivo , combined treatment with apigenin (20 mg/kg, five times/week for 3 weeks) and 5-FU (20 mg/kg for 5 consecutive days) significantly inhibited the growth of HCC xenograft tumours. Annexin V–propidium iodide dual staining assays, terminal deoxyribonucleotidyl transferase-mediated dUTP–digoxigenin nick end-labelling assays and western blotting analysis were used to confirm the synergistic effects of apigenin and 5-FU on HCC apoptosis. Coincubation of HCC cells with apigenin and 5-FU increased levels of reactive oxygen species (ROS), which was followed by a decrease in the mitochondrial membrane potential (ΔΨm). In addition, combined triggered the mitochondrial apoptotic pathway, as indicated by decreased Bcl-2 expression and loss of ΔΨm, with significant activation of caspase 3 and poly(ADP-ribose) polymerase. The present study is the first to demonstrate that apigenin may potentiate the cytotoxicity of 5-FU in HCC via inhibition of ROS-mediated drug resistance and concurrent activation of the mitochondrial pathways of apoptosis.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2023
·Vol. 8
·期 3
·e10507
·
IF 7.4
Jingyan Yi,Xin Luo,Jinshan Xing,Aharon Gedanken,Xiukun Lin,Chunxiang Zhang,Gan Qiao
Micelle Encapsulation Zinc-doped copper oxide nanocomposites (MEnZn-CuO NPs) is a novel doped metal nanomaterial prepared by our group based on Zinc doped copper oxide nanocomposites (Zn-CuO NPs) using non-micellar beam. Compared with Zn-CuO NPs, MEnZn-CuO NPs have uniform nanoproperties and high stability. In this study, we explored the anticancer effects of MEnZn-CuO NPs on human ovarian cancer cells. In addition to affecting cell proliferation, migration, apoptosis and autophagy, MEnZn-CuO NPs have a greater potential for clinical application by inducing HR repair defects in ovarian cancer cells in combination with poly (ADP-ribose) polymerase inhibitors for lethal effects.
研究领域:
纳米技术
·
癌症研究
·
药理学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Jing Gao,Liangyuan Qi,Liang Chen,Wenyue Guo,Bicheng Lin,Zefan Feng,Suhong Li,Yuan Hu,Fukai Chu,Weiyi Xing
The development of zero-power radiative cooling technology in buildings is of great significance for coping with global warming. However, the absorption of thermal radiation from the surrounding environment cannot be effectively avoided by conventional broadband emitters, resulting in cooling performance degradation. Furthermore, the fire safety standards established for architectural coatings are generally not met by conventional radiative cooling coatings. Here, the phosphorus flame retardants aluminum diethylphosphonate (ADP) was introduced into PVDF-HFP coating through a non-solvent-induced phase separation (NIPS) to enhance both the cooling performance and fire safety. The composite coating demonstrates excellent solar reflectance (97.4 %) and mid-infrared emissivity (95.7 %), owing to its unique hierarchical porous structure and the vibrational properties of C C, F-C-F, P O, and P O bonds. Therefore, compared to the absence of coatings, the porous coating significantly enhances the cooling effect, resulting in a temperature reduction of 6.6 °C in an outdoor cooling test. With the introduction of the flame retardant ADP, the temperature of composite coating decrease is further extended to 8.1 °C, accompanied by a remarkable cooling efficiency of 129.4 W/m 2 . Concurrently, the addition of ADP not only reduces the peak heat release rate during combustion (58.3 %) but also significantly inhibits the release of the total smoke product, thus greatly improving fire safety performance. The simplicity of this manufacturing process, coupled with its exceptional fire resistance and optical properties facilitates the practical implementation of radiative cooling materials in airports, buildings, grain silos, and other applications.
研究领域:
材料科学
·
建筑节能
·
环境科学
·
消防安全工程
·
纳米技术
·
光学工程
·
高分子科学
·
气候变化缓解
✓ 已验证
产品关联
DOI
高影响因子
Analytical Methods
·
2019
·Vol. 11
·期 42
·5398-5404
·
IF 2.378
Shengting Zhang,Mingrui Li,Dongbo Liu,Kunhao Qin,Yingying Xiang,Xiuling Ji,Congwen Li,Yunlin Wei
The human purinergic P2Y1 receptor (P2Y1R) belongs to the family of G-protein coupled receptors (GPCRs). Two stable cell lines, hP2Y1R-tGFP/U2OS and hP2Y1R-β-AR2-tGFP/U2OS, were generated with steady expression of fluorescent tGFP tagged P2Y1R or tGFP tagged β-arrestin2. The High Content Screening (HCS) technique was used to investigate P2Y1R mediated signal transduction processes based on the distribution of fluorescent receptors or the β-arrestin2/receptor complex. All procedures including aggregation, endolysis and resensitization that were involved in the interaction between the P2Y1 receptor and its ligand can be visualized using the tGFP labeled receptor combined with HCS technology in this study. ADP activated P2Y1R to induce a distinguished pattern of fluorescent vesicle formation inside both cell types. These two cell lines produced different peak fluorescence signals when activated by ADP at 100 μM, and the time to form the maximal vesicles was detected as 15 and 20 min respectively. The EC50 values of the concentration–response curves of ADP induced formation of fluorescent vesicles were 35.7 nM and 71.8 nM respectively. The ADP effects could be blocked by a P2Y1R specific antagonist MRS2179. The P2Y1R are coupled to Gq protein to activate PLC first, PLC cleave PIP2 into IP3 and DAG. And then DAG and Ca2+ activate PKC pathway, and finally the phospholipase D initiates β-arrestin2 mediated signal pathway. It took 30 and 45 min to complete P2Y1R re-sensitization in these two constructs respectively. Our results demonstrated that P2Y1R triggered downstream responses not only via heterotrimeric Gq proteins but also through β-arrestin2.
研究领域:
细胞生物学
·
药理学
·
分子生物学
·
信号转导
✓ 已验证
产品关联
DOI
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
·
2014
·Vol. 71
·期 3
·1349-1356
·
IF 2.38
Jin Di,Cao Ming,Mu Xin,Yang Guoliang,Xue Wei,Huang Yiran,Chen Haige
Catalpol is an iridoid glucoside extracted from the traditional Chinese medicinal plant called Rehmannia glutinosa , and it is reported to possess a variety of pharmacological activities. The goal of this research was to explore the effect of catalpol on the human bladder cancer cells T24. The cells were treated for different durations with various concentrations of catalpol. Then the viability, mobility, and invasiveness of the cells were determined by MTT assay and flow cytometry, respectively. Catalpol was found to significantly suppress the proliferation, migration, and invasiveness of T24 bladder cancer cells in a dose- and time-dependent manner. The results also revealed that catalpol promoted apoptosis and caused the cell-cycle arrest at G2/M phase. Furthermore, the catalpol-mediated apoptosis was found to involve the modulation of PI3K/Akt pathway and inhibit the expression of anti-apoptotic B cell lymphoma-2 (Bcl-2) family proteins. Also, the expressions of Bcl-2 proapoptotic effectors, Bcl-2-associated X protein, and Bcl-2 associated death promoter were up-regulated in the cells treated with catalpol. The enzymes involved in the ultimate process of apoptosis, active caspase-3 and poly ADP ribose polymerase were elevated, and the latter was observed to be cleaved, indicating that catalpol-accelerated cell apoptosis involved a caspase-dependent pathway. These results suggest that catalpol might serve to be a promising therapeutic agent for the treatment of human bladder cancer.
研究领域:
肿瘤学
·
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
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Xiaoyang Liang,Ping Liu,Wen Li,Long Binh Vong,Tingting Wang,Lujing Geng,Yue Zhou,Siyu Wang,Qiang Lu,Fengping Tan,Xinxing Wang,Nan Li
Reactive oxygen species (ROS)-mediated cell cycle arrest mechanism shows distinguished potential for the inhibiting of cancer cells. However, poly ADP-ribose polymerase (PARP), an enzyme which can contribute to the repair of single-strand DNA nicks, largely limited the efficiency in cell cycle arrest. Here, polydopamine (PDA)/hyaluronic acid (HA) decorated and protein translation inhibitor homoharringtonine (HHT) loaded tellurium (Te)-prussian blue (PB) nanorods ( [email protected] @PDA-HA/HHT NRs) were synthesized for boosted G2 cell cycle arrest to realize tumor ablation. Under NIR-II irradiation, Te and Fe elements can collectively generate ROS and deplete GSH due to the fenton-like reaction and metal-reducing reaction under tumor microenvironment (TME), thus disturbing the DNA structure to induce cell cycle arrest. More importantly, HHT suppresses PARP production to induce DNA repair dysfunction, thereby boosting DNA oxidative damage. Remarkably, this nanoplatform degrades into ionic form under acid condition, illustrating inherently TME-responsive biodegradability. The anti-tumor evaluation illustrated that [email protected] @PDA-HA/HHT NRs could notably destroy tumor cells in both cellular experiments and mouse models. This study made a successful attempt in boosted cell cycle arrest and encouraged more biological explorations on biodegradation nanomaterials, especially in combating cancers.
研究领域:
癌症生物学
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Weibin Jia,Liling Liu,Min Li,Yuanmeng Zhou,Hang Zhou,Hongjuan Weng,Guofeng Gu,Min Xiao,Zonggang Chen
The current use of synthetic grafts often yields low patency in the reconstruction of small-diameter blood vessels owing to the deposition of thrombi and imperfect coverage of the endothelium on the graft lumen. Therefore, the design of vascular scaffolds with antithrombotic performance and endothelialization is greatly required. Herein, we developed an enzyme-laden scaffold based on hyaluronic acid oligosaccharides-modified collagen nanofibers (labeled HA-COL) to improve the anti-platelet capacity and endothelialization of vascular grafts. In this study, HA-COL nanofibers not only encouraged the endothelialization of vascular scaffolds, but acted as an antiplatelet enzyme-laden platform. Apyrase (Apy) and 5’-nucleotidase (5’-NT) were covalently grafted onto the nanofibers, which in turn converted the platelet-sensitive substance: adenosine diphosphate (ADP) into adenosine monophosphate (AMP) and adenosine, thereby, improving the antithrombotic performance of the scaffolds. Notably, the catalytic end-product: adenosine would work in coordination with HA-COL to synergistically enhance the endothelialization of the vascular scaffolds. The results demonstrated that the enzyme-laden scaffolds maintained catalytic performance, reduced platelet adhesion and aggregation, and guaranteed higher patency after 1-month in situ transplantation. Moreover, these scaffolds showed optimal cytocompatibility, tissue compatibility , scaffold biodegradability and tissue regenerative capability during in vivo implantation. Overall, these engineered vascular scaffolds demonstrated their capacity for endothelialization and antithrombotic performance, suggesting their potential for small-diameter vascular tissue engineering applications. Statement of significance Considering the critical problems in small-diameter vascular reconstruction, the enzyme-laden vascular scaffolds were prepared for improving in-situ endothelialization and antithrombotic performances of artificial blood vessels . The electrospun HA-COL nanofibers were used as the main matrix materials, which provided favorable structural templates for the regeneration of vasculature and functioned as a platform for the loading of enzymes. The enzyme-laden scaffolds with the biomimetic cascading reaction would convert ADP into adenosine, thereby, decreasing the sensitivity of platelets and improving the antithrombotic performance of tissue-engineered blood vessels (TEBVs). The nanofibrous scaffolds exhibited optimal cytocompatibility, tissue compatibility and regenerative capability, working together with catalytic products of dual-enzyme reaction that would synergistically contribute to TEBVs endothelialization. This study provides a new method for the improvement of in-situ endothelialization of small-diameter TEBVs while qualified with antithrombotic performance.
研究领域:
组织工程
·
生物医学工程
·
血管生物学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）