ANALYST
·
2018
·Vol. 143
·期 11
·2501-2507
·
IF 3.864
Yong Liu,Xiaolin Xu,Haitang Yang,Ensheng Xu,Shuangshuang Wu,Wei Wei,Jin Chen
Poly(ADP-ribose) polymerase-1 (PARP-1) is a highly conserved nuclear enzyme, which binds tightly to damaged DNA and plays a key role in DNA repair, recombination, proliferation, and genomic stability. However, due to the poor electrochemical and optical activity of PARP-1 and its product PAR, only a few studies on its activity detection method have been reported. Herein, we report a simple and sensitive colorimetric strategy to monitor PARP-1 activity based on enzyme-initiated auto-PARylation-controlled aggregation of hemin-graphene nanocomposites (H-GNs). PARP, activated by dsDNA, catalyzed its substrate nicotinamide adenine dinucleotide (NAD+) to polymerize as a poly(ADP-ribose) polymer (PAR). PAR possesses several negative charges, and its charge density is twice that of a single-stranded DNA, which greatly impacts the dispersibility of H-GNs; due to their peroxidase-like catalytic activities, H-GNs can catalyze the chromogenic reaction of TMB and H2O2. As a result, in the presence of different PARP-1 activities, the supernatant of the corresponding solution contained different amounts of dispersed H-GNs and showed different colors after the chromogenic reaction that could be discerned easily by the absorbance or the color changes of the solution. The method was simple, sensitive, and reliable. The proposed method displays a linear range from 0.05 to 1 U with a detection limit of 0.03 U. In addition, this new method has been successfully applied to detect PARP-1 activity in human serum and different cancer cells and evaluate PARP-1 inhibitors.
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JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 7.3
Bei Zhang,Yi-Yi Yang,Zheng-Jiong Zhao,Run-Duo Liu,Ling-Ling Feng,Mei-Yan Jiang,Yijun Yuan,Shuheng Huang,Zhe Li,Quan Wang,Hai-Bin Luo,Yinuo Wu
Phosphodiesterase 1 (PDE1) is a subfamily of PDE super enzyme families that can hydrolyze cyclic adenosine monophosphate and cyclic guanosine monophosphate simultaneously. Currently, the number of PDE1 inhibitors is relatively few, significantly limiting their application. Herein, a novel series of quinolin-2(1H)-ones were designed rationally, leading to compound 10c with an IC50 of 15 nM against PDE1C, high selectivity across other PDEs, and remarkable safety properties. Furthermore, we used the lead compound 10c as a chemical tool to explore whether PDE1 could work as a novel potential target for the treatment of inflammatory bowel disease (IBD), a disease which is a chronic, relapsing disorder of the gastrointestinal tract inflammation lacking effective treatment. Our results showed that administration of 10c exerted significant anti-IBD effects in the dextran sodium sulfate-induced mice model and alleviated the inflammatory response, indicating that PDE1 could work as a potent target for IBD.
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Molecular Catalysis
·
2022
·
IF 5.089
Ying Zhang,Zhi-Wen Duan,Han-Yu Liu,Feng Qian,Pu Wang
Microbial whole-cell catalysis has been a popular method for chiral alcohols preparation. In this study, Cyberlindnera saturnus ZJPH1807 was successfully employed as a biocatalyst to reduce 2-chloro-1-(2,4-dichlorophenyl)ethanone (CPE) to ( R )-2-chloro-1-(2,4-dichlorophenyl)ethanol (( R )-CPEO), a key chiral intermediate of antifungal drug miconazole. In order to further improve the bioprocess yield, natural deep eutectic solvent and cyclodextrin were introduced into the reaction system as additives. It was found that carnitine/trehalose (C/Tre, 1:1 mol/mol) could increase the permeability of cell membrane appropriately and improve the mass transfer rate. And the addition of methyl-β-cyclodextrin (MCD) could improve the solubility of CPE in buffer solution, simultaneously promoting cofactor recycling. Furthermore, MCD and C/Tre exerted a synergistic effect on the acceleration of CPE bioreduction, producing 91.0% yield in 1.5 h at 35.8 mM CPE in a C/Tre-MCD-containing system, with a 12.4-fold increase in productivity compared to neat buffer solution only. When the substrate loading was increased to 67.1 mM, the yield could also achieve 84.2%. The established bioreduction process was also feasible at 100 mL preparation scale with a 88.5% ( R )-CPEO yield. The integration of C/Tre and MCD can significantly improve catalytic efficiency for hydrophobic substrates and be applied in biocatalysis.
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Experimental and Therapeutic Medicine
·
2019
·Vol. 18
·期 4
·2924-2932
·
IF 1.448
Jingjing Wang,Yongzhong Ning,Shu Li,Yun Wang,Jinhua Liang,Chunming Jin,Hairun Yan,Yongcun Huang
Acinetobacter baumannii is an important cause of hospital‑acquired, multidrug‑resistant (MDR) infections occurring worldwide. Anti‑microbial combination regimens may be the only feasible treatment option for affected patients. In the present study, the efficacy of the combined therapy of meropenem with colistin, ampicillin‑sulbactam, tazobactam and vancomycin against clinical strains of MDR A. baumannii was determined. Anti‑microbial susceptibility testing was performed and resistance genes were characterized by a multiplex polymerase chain reaction (PCR)‑reverse line blot assay. The genetic background of New Delhi metallo‑β‑lactamase 1 (NDM‑1) was analysed by primer walking. The presence of NDM‑1 was detected using the modified Hodge test and the EDTA‑combined disk test. To screen for synergistic drug effects, the fractional inhibitory concentration index was calculated using a checkerboard assay. The results of the PCR as well as the sequence analyses suggested that NDM‑1 was located downstream of the ISAba125 element. In addition, a synergistic effect was determined for meropenem + vancomycin, meropenem + tazobactam and meropenem + ampicillin + sulbactam in two strains each, and in four strains for meropenem + colistin. A total of five A. baumannii strains with resistance to numerous antibiotics and carrying numerous resistance genes were identified. In the strains of A. baumannii, the NDM‑1 gene was integrated in a transposon structure with a copy of the ISAba125 insertion sequence. However, the genetic background was not identical among the different species and strains. The genetic variability of NDM‑1 may facilitate the rapid dissemination of this gene. In conclusion, meropenem may enhance the efficacy of antibiotics in A. baumannii strains with NDM‑1‑associated MDR.
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XENOBIOTICA
·
2021
·
IF 1.908
Weibin Xiao,Zhirong Deng,Chongfa Lai,Haoyang Lu,Mutu Huang,Yuguan Wen,Lei Shi
l-tetrahydropalmatine (l-THP) is mainly metabolised by CYP450 enzymes.This study was to investigate the possible effect of co-administered CYP inhibitors on the pharmacokinetics of l-THP and its metabolites in rats.An established LC-MS/MS method has been applied for the evaluation of drug-drug interaction between l-THP and CYP inhibitors. Following the administration of CYP inhibitors, a single dose of l-THP (9 mg/kg) was orally administrated.With regard to l-THP, the AUC0–48 were significantly increased by 4.3, 3.79, and 11.39 folds, and Cmax were increased by 4.74, 3.64, and 2.76 folds in the ketoconazole group (KET), quinidine group (QD), and 1-aminobenzotriazole group (ABT), respectively. KET and QD both significantly increased the AUC0–48 of 2-DM and 2-DM-Glu by 1.38 ∼ 2.43 times, while Cmax was significantly decreased by 41.3 and 78.0% in the ABT group, respectively. The Cmax of 3-DM was reduced by 51.38, 48.02, and 63.31% after pre-treatment with KET, QD, and ABT, respectively, and Cmax of 3-DM-Glu decreased correspondingly by 29.6, 22.1, and 58.0%.Results indicated that CYP inhibitors could markedly influence the systemic level of l-THP and its metabolites. To guarantee the safe use of l-THP, attention should be paid when l-THP was co-administered with CYP inhibitors, particularly with CYP3A4 and 2D6 inhibitors.
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Theranostics
·
2019
·
IF 8.063
Xu-Qi Kang,Gao-Feng Shu,Sai-Ping Jiang,Xiao-Lin Xu,Jing Qi,Fei-Yang Jin,Di Liu,Yong-Hong Xiao,Xiao-Yang Lu,Yong-Zhong Du
The prevalence of antibiotic resistance and lack of alternative drugs have posed an increasing threat to public health. Here, we prepared β-Ga 2 O 3 :Cr 3+ nanoparticles modified with ICAM1-antibody-conjugated TPGS (I-TPGS/Ga 2 O 3 ) as a novel antibiotic carrier for the treatment of drug-resistant infections. Methods : I-TPGS/Ga 2 O 3 were firstly characterized by measuring particle size, morphology, crystal structure, drug loading capacity, and in vitro drug release behaviors. The in vitro antibacterial activities of I-TPGS/Ga 2 O 3 /TIG were evaluated using standard and drug-resistant bacteria. The internalization of I-TPGS/Ga 2 O 3 was observed by fluorescence confocal imaging, and the expression levels of the efflux pump genes of TRKP were analyzed by real-time RT-PCR. In vitro cellular uptake and in vivo biodistribution study were performed to investigate the targeting specificity of I-TPGS/Ga 2 O 3 using HUEVC and acute pneumonia mice, respectively. The in vivo anti-infective efficacy and biosafety of I-TPGS/Ga 2 O 3 /TIG were finally evaluated using acute pneumonia mice. Results : It was found that TPGS could down-regulate the over-expression of the efflux pump genes, thus decreasing the efflux pump activity of bacteria. I-TPGS/Ga 2 O 3 with small particle size and uniform distribution facilitated their internalization in bacteria, and the TPGS modification resulted in a significant reduction in the efflux of loaded antibiotics. These properties rendered the encapsulated tigecycline to exert a stronger antibacterial activity both in vitro and in vivo . Additionally, targeted delivery of I-TPGS/Ga 2 O 3 mediated by ICAM1 antibodies contributed to a safe and effective therapy. Conclusion : It is of great value to apply I-TPGS/Ga 2 O 3 as a novel and effective antibiotic delivery system for the treatment of drug-resistant infections.
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PLANT PHYSIOLOGY AND BIOCHEMISTRY
·
2023
·
IF 6.5
Yunshuai Huang,Jiawei Song,Qixian Hao,Changling Mou,Hongming Wu,Fulin Zhang,Ziyan Zhu,Ping Wang,Tengfei Ma,Kai Fu,Yaping Chen,Thanhliem Nguyen,Shijia Liu,Ling Jiang,Jianmin Wan
Seed dormancy is a critical trait that enhances plant survival by preventing seed germination at the wrong time or under unsuitable conditions. Lack of seed dormancy in rice can lead to pre-harvest sprouting on mother plants leading to reduced yield and seed quality. Although some genes have been identified, knowledge of regulation of seed dormancy is limited. Here, we characterized a weak seed dormancy mutant named weak seed dormancy 1 ( wsd1 ) that showed a higher seed germination percentage than the wild-type following the harvest ripeness. We cloned the WSD1 encoding an aminotransferase protein using a MutMap approach. WSD1 was stably expressed after imbibition and its protein was localized in the endoplasm reticulum. A widely targeted metabolomics assay and amino acid analysis showed that WSD1 had a role in regulating homeostasis of amino acids. PAC treatment and RNA-seq analysis showed that WSD1 regulates seed dormancy by involvement in the GA biosynthesis pathway. GA 1 content and expression of GA biosynthesis-related genes were increased in the wsd1 mutant compared with the wild-type. The wsd1 mutant had reduced sensitivity to ABA. Our overall results indicated that WSD1 regulates seed dormancy by balancing the ABA and GA pathways.
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ANALYTICA CHIMICA ACTA
·
2019
·
IF 5.256
Jun Feng,Yajuan Xu,Wenyi Huang,Hongxing Kong,Yanqing Li,Hao Cheng,Lijun Li
Hepatocellular carcinoma (HCC) is a common and lethal cancer. New serum markers for detecting HCC are urgently needed. Human carboxylesterase 1 (hCE1) is an important member of the serine hydrolase superfamily and is closely related to the occurrence of HCC. It can be used as a good serum marker for early diagnosis of HCC. Here, we developed a surface enhanced Raman scattering (SERS)- based magnetic immunosensor that specifically recognizes and detects trace amounts of hCE1 in human serum via a sandwich structure consisting of a SERS tags, magnetic supporting substrates, and target antigen (hCE1). The SERS tags are 4-mercaptobenzoic acid (4-MBA)-labeled AgNPs, and the SERS supporting substrates are composed of a raspberry-like morphology of Fe 3 O 4 @SiO 2 @AgNPs magnetic nanocomposites surface-functionalized with a hCE1 antibody. The prepared SERS magnetic immunosensor exhibits excellent selectivity and extremely high sensitivity for hCE1 detection. The SERS signal and logarithm of hCE1 concentration presented a wide linear response range of 0.1 ng mL −1 to 1.0 mg mL −1 , and the detection limit of hCE1 was 0.1 ng mL −1 . The results indicate that the immunosensor can be used for the rapid determination of hCE1 in human serum without a complicated sample pre-treatment. Furthermore, the immunosensor has good reproducibility and stability, and has a promising prospect for the quantitative detection of other tumor markers in early clinical diagnosis.
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BIOMATERIALS
·
2016
·
IF 8.387
WenTing Li,JinRong Peng,LiWei Tan,Jing Wu,Kun Shi,Ying Qu,XiaWei Wei,ZhiYong Qian
Patients suffering from cancer have benefited from combination therapy. Nanocarriers are the ideal candidates for combination therapy. In this study, we constructed docetaxel (DTX) loaded micellar nanomedicines co-loaded with near infrared (NIR) dye-IR820 for photothermal therapy (PTT)/photodynamic therapy (PDT)/chemotherapy of breast cancer. Lyp-1, a tumor homing peptide, was introduced into the nanosystems to construct the active targeting nanomedicine. In order to deliver IR820 to the tumor site and overcome its short lifetime in vivo , a PEI derivative—PCL-g-PEI was introduced. IR820 with negative charge was formed stable static interaction with the amine groups, meanwhile, the absorption of IR820 in the NIR region was weakened. It indicated that the nanosystem constructed in this study may provide an alternative candidate for mild PTT. By the evaluation of the photothermal conversion in vivo , we can confirm that IR820 has been successfully delivered and effectively accumulated in the tumor site. Furthermore, the tumor cells targeting and anticancer performances of this nanosystem have been studied in vitro and in vivo . The results demonstrated Lyp-1 modification has enhanced the tumor targeting delivery of DTX and IR820. By combining PTT and PDT, DTX nanomedicine efficiently inhibited the growth and metastasis of breast cancer in mice. This nanosystem is a promising candidate for combination therapy of breast cancer.
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CATALYSIS LETTERS
·
2022
·Vol. 153
·期 2
·348-363
·
IF 2.936
Chu Jidong,Ge Zhijin,Peng Jiahui,Hu Hui,Guo Shujuan,Chen Xiaohui
The efficient and economic heteroatom-implanting method for MWW-type zeolite has been the focus of attention and needs further exploration. Ti incorporated MWW zeolite was synthesized by sequential treatment of boron-containing zeolite precursor. The catalysts were applied to the epoxidation of 1-hexene. The implanting titanium process was conducted under a mild condition with Ti(SO 4 ) 2 /NH 4 HF 2 /HNO 3 solution, and the product Ti-MWW precursors have framework titanium alone, the novel method is named as refluxing and implanting titanium method which integrates acid treatment and titanium incorporation into one step and reduces the consumption of time of this process into 1 h. A density functional theory was conducted to explain the formation mechanism of interlayer-expanded structure of Ti-MWW zeolite. Subsequently, Ti-MWW precursors were treated in modified reagent solution to obtain larger pore structure, which increase the conversion of 1-hexene from 20.45 to 62.96%. The catalytic performance of Ti-MWW zeolite in this work are superior to Ti-MWW zeolite synthesized by traditional dry-gel conversion method the conversion of 1-hexene of which was 4.2%. This novel method is a promising approach for the synthesis of high catalytic performance heteroatomic zeolite. Graphical abstract
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JOURNAL OF CELLULAR PHYSIOLOGY
·
2018
·Vol. 234
·期 5
·6136-6146
·
IF 3.923
Yucang He,Xiaofang Yu,Zhuojie Chen,Liqun Li
Autologous fat transplantation is increasingly applied in plastic and reconstructive surgery. Stromal vascular fraction cells (SVFs) combined with angiogenic factors, such as VEGF (vascular endothelial growth factor A) and Ang-1 (angiogenin-1), can improve angiogenesis, which is a critical factor for graft survival. However, direct transplant with such a mixture is insufficient owing to the short half-life of angiogenic factors. In this study, we evaluated whether a double sustained release system of VEGF/ANG-1-PLGA (poly (lactic-co-glycolic acid)) microspheres plus SVFs can improve angiogenesis and graft survival after autologous fat transplantation. VEGF/ANG-1-PLGA-sustained release microspheres were fabricated by a modified double emulsion–solvent evaporation technique. Human aspirated fat was mixed with SVF suspension plus VEGF/ANG-1 sustained release microspheres (Group C), SVF suspension (Group B) alone, or Dulbecco’s modified Eagle’s medium as the control (Group A). Eighteen immunocompromised nude mice were injected with these three mixtures subcutaneously at random positions. After 8 weeks, the mean volume of grafts was greater in the SVFs plus VEGF/ANG-1-PLGA group than in the control and SVFs groups (1.08 ± 0.069 ml vs. 0.62 ± 0.036 ml, and 0.83 ± 0.059 ml, respectively). Histological assessments showed that lower fibrosis, but greater microvascular density in the SVFs plus VEGF/ANG-1-PLGA group than in the other groups, though the SVFs group also had an appropriate capillary density and reduced fibrosis. Our findings indicate that SVFs plus VEGF/ANG-1-PLGA-sustained release microspheres can improve angiogenesis and graft survival after autologous fat transplantation.
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JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2018
·Vol. 18
·期 4
·2914-2920
·
IF 1.354
Li Jie,Zhang Jia,Chen Lianxi,Wang Yu,Liu Zhenhui
A new effective surface poly(1-vinyl-2-pyrrolidone) (PVP) grafted layer protected selective etching strategy has been used for preparing vinyl functionalized porous silica nanospheres (V-PSNSs). The main reaction mechanism was relied on the vinyl groups distributed on the surface of
outer vinyl silica nanospheres (V-SiO2) which can be polymerized with another vinyl monomer, such as 1-vinyl-2-pyrrolidone (VP), in the presence of initiator. It was observed from the research results that only grafting PVP on the surface of outer vinyl silica nanospheres (V-SiO2)
can V-PSNSs be obtained, because grafting PVP was able to protect outer V-SiO2 from being etched prior to inner pure silica (sSiO2). In addition, effect of the amounts of sSiO2@V-SiO2 as another monomer substrate on the formation of PVP grafted sSiO2@V-SiO2
(sSiO2@V-SiO2/PVP) was discussed. The results showed that the less of the sSiO2@V-SiO2 amounts, the thinner of the PVP grafted layer on the surface of sSiO2@V-SiO2, the poorer protection ability of the surface. In the present
study, V-PSNSs with 29 m2g−1 of BET surface areas and 0.1 cm3g−1 pore volumes were successfully synthesized by grafting 0.3 g of VP on the surface of 0.3 g of sSiO2@V-SiO2 and subsequent etching.
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