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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2019 · IF 2.606

Internalization and subcellular transport mechanisms of different curcumin loaded nanocarriers across Caco-2 cell model

Xia Yan,Shuqing Cao,Ying Li,Pei Xiao,Zipeng Huang,Haiyan Li,Yan Ma

Curcumin (Cur) and its nanomedicine were researched in Caco-2 cells to investigate the internalization and subcellular transport across Caco-2 cell monolayer membrane. Cur loaded polymer micelle (PM), nanoemulsion (NE) and liposome (Lipo) were prepared to explore the transport process incorporating endocytosis, intracellular trafficking and transcytosis in Caco-2 cells. Firstly, nanocarriers could contribute to the cellular uptake and improve the stability of Cur within the Caco-2 cells. The co-mediation of clathrin , lipid raft/caveolae and/or macropinocytosis were involved in the internalization of Cur nanopreparations, indicating the diversity and partial energy-dependency of the endocytosis. Secondly, the endocytosed nanocarriers with Cur successively transported from apical early endosome to late endosome with the extension of incubation time . Furthermore, the intracellular location of Cur nanomedicines in lysosome and endoplasmic reticulum (ER) were detected and illustrated the actual transport of Cur nanomedicine to lysosome and ER. Finally, nanocarriers could enhance the transcytosis of Cur, involving the energy-dependent patterns. Especially, Cur-PM exhibited more advantages in regulating and coordinating the entry and the exit of Cur. The study indicated that the coexistence of multiple transport pathways had the potency to promote nanocarriers transcytosis and provided a rational dosage design for oral Cur.

CAS / MDL: 7440-50-8 59-02-9
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2019 · IF 3.571

Synthesis of 2-Monochloropanol Fatty Acid Esters and Their Acute Oral Toxicities in Swiss Mice

Zhongfei Zhang,Puyu Yang,Boyan Gao,Guoren Huang,Man Liu,Liangli Lucy Yu

A novel synthetic route was designed, developed, and utilized to synthesize six high-purity 2-monochloropropanediol fatty acid esters (2-MCPD esters), a group of potential processing-induced food contaminants. A chlorine atom was introduced to C-2 of a diethyl malonate molecule, which was reduced by NaBH4 and followed by esterification using fatty acids. The reaction products were isolated and purified using silica gel columns to obtain three 2-MCPD monoesters and three diesters at about 50–54% and 56–59% yields, respectively. In addition, 2-MCPD monopalmitate and dipalmitate were examined for their acute oral toxicities in Swiss mice. The LD50 values of 2-MCPD mono- and dipalmitate were greater than 5000 mg/kg body weight (BW), along with detectable nephrotoxicity and testicular toxicity. The results of this study may promote future investigation of MCPD ester toxicology and detection.

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Frontiers in Pharmacology · 2019 · IF 3.845

The Role of Prostaglandin-Endoperoxide Synthase-2 in Chemoresistance of Non-Small Cell Lung Cancer

Lin Xiao-mian,Luo Wu,Wang Heng,Li Rong-zhen,Huang Yi-shan,Chen Lian-kuai,Wu Xiao-ping

The prostaglandin-endoperoxide synthase-2 (PTGS2) plays essential roles in diverse pathological process. Although recent studies implied that PTGS2 was closely related with chemoresistance, the precise roles and the underlying mechanisms of PTGS2 in the developing process of chemoresistance in non-small cell lung cancer (NSCLC) remained elusive. In the present study, we revealed a novel molecular mechanism of PTGS2 implicated in the chemoresistance of NSCLC and proposed a model for the positive feedback regulation of PTGS2 in the process of developing resistance phenotype in NSCLC cells. Our results demonstrated that cisplatin induced PTGS2 expression through the ROS-ERK1/2-NF-κB signaling axis. The prostaglandin E2 (PGE2) derived from PTGS2 catalyzation further strengthened PTGS2 expression via the PGE2-EPs-ERK1/2 positive feedback loop, which induced multidrug resistance of NSCLC cells through up-regulation of BCL2 expression and the subsequent attenuation of cell apoptosis. Consistently, high levels of both PTGS2 and BCL2 were closely associated with poor survival in NSCLC patients. Inhibition of PTGS2 significantly reversed the chemoresistance in the resistant NSCLC in vitro and in vivo. Our results suggested that PTGS2 might be employed as an adjunctive therapeutic target for improving the response to the therapeutic agents in a subset of resistant NSCLC.

CAS / MDL: 95058-81-4
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JOURNAL OF CHEMICAL AND ENGINEERING DATA · 2019 · IF 2.298

Analysis of Surface Thermodynamics for Amino Acid Ionic Liquid–1-Dimethylamino-2-propanol Aqueous Blends

Lemeng Wang,Xiangfeng Tian,Chi Fang,Hao Huang,Dong Fu,Yuheng Quan

In this work, the surface tensions (γ) of the aqueous blends of 1-dimethylamino-2-propanol (DMA2P) + amino acid ionic liquids (AAILs) were studied using the Wilhelmy plate method at temperatures from 303.2 to 323.2 K and atmospheric pressure. The AAILs include tetramethylammoniumglycinate ([N1111][Gly]), 1-butyl-3-methylimidazolium glycinate ([Bmim][Gly]), and 1-butyl-3-methylimidazolium-l-lysinate ([Bmim][Lys]). The concentrations of DMA2P and AAILs were varied between 0.300 and 0.500 wt % and 0.025 and 0.075 wt %, respectively. A thermodynamic correlation approach with respect to the mass fraction and temperature was employed to correlate the surface tension of DMA2P–AAILs aqueous solutions. The surface entropy (SS) and surface enthalpy (HS) were calculated from the analytical formulation, and their variation with mass fraction and temperature was demonstrated. The effects of the types of AAILs on the surface properties were also analyzed and compared.

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ACS Omega · 2019 · IF 2.584

Effects of Impurities on CaSO4 Crystallization in the Ca(H2PO4)2–H2SO4–H3PO4–H2O System

Xinru Mu,Ganyu Zhu,Xu Li,Shaopeng Li,Xiaokang Gong,Huiquan Li,Guoxin Sun

Wet-process phosphoric acid is a fundamental process in the fertilizer industry. The influence of impurities on crystallization kinetics of CaSO4 was investigated in the Ca(H2PO4)2–H2SO4–H3PO4–H2O system using a mixed suspension mixed product removal crystallizer. Effects of Si, Al, Fe, Mg, K, and Na on crystal morphology and structure were examined in the highly acidic system through scanning electron microscopy and high-resolution transmission electron microscopy. Results show that the increase of Mg, K, and Na content facilitates crystal growth. Si, Al, and Fe are beneficial to CaSO4 crystal growth at a certain concentration range. Impurities also affect the crystal morphology, and the addition of Si, Fe, and Na promotes the formation of needle-like crystals compared with other impurities. X-ray diffraction results show that the preferred crystal growth direction is (020), and the interplanar spacing of the crystals is affected by the element radius of the impurities.

CAS / MDL: 10031-30-8
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MICROCHIMICA ACTA · 2019 ·Vol. 186 ·期 7 ·1-9 · IF 5.479

A silica nanoparticle based 2-color immunochromatographic assay for simultaneous determination of clenbuterol and ractopamine

Yu Qiongqiong,Liu Jing,Zhao Guangying,Dou Wenchao

An immunochromatographic assay (ICA) is presented that can be applied to simultaneous detection of clenbuterol (CLE) and ractopamine (RAC). It is making use of two red and blue silica nanoparticles (SiNPs) that act as labels for encoding the antibodies. This design permits multiplexed analysis in a single test line and does not require an external source for photoexcitation. Anti-CLE was labeled with red SiNPs, and anti-RAC with blue SiNPs. The capture antigens CLE-BSA and RAC-BSA were placed onto the conjugate pad and the test line of the test strip, respectively. Under bare eye examination, no cross-colored lines or nonspecific bioconjugate adsorption were observed, and the visible limit of detections for CLE (red) and RAC (blue) are 3 and 2 ng‧mL −1 , respectively. This design allows for multiplexed detection with reduced device dimensions and costs, and with easy integration and manufacturing. Conceivably, the method may be extended to simultaneous determination of numerous other analytes. The principle of qualitative detection strategy of multiplex immunochromatographic assay for clenbuterol (CLE) and ractopamine (RAC) is schematically illustrated. Depending on the type and ratio of organic dyes, the color of colored silica nanoparticle can be tuned from red to purple and even to black (lower right corner).

CAS / MDL: 4432-31-9 78-10-4
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Microbial Cell Factories · 2019 ·Vol. 18 ·期 1 ·1-10 · IF 4.402

Fermentative production of the unnatural amino acid l-2-aminobutyric acid based on metabolic engineering

Xu Jian-Miao,Li Jian-Qiang,Zhang Bo,Liu Zhi-Qiang,Zheng Yu-Guo

Background l -2-aminobutyric acid ( l -ABA) is an unnatural amino acid that is a key intermediate for the synthesis of several important pharmaceuticals. To make the biosynthesis of l -ABA environmental friendly and more suitable for the industrial-scale production. We expand the nature metabolic network of Escherichia coli using metabolic engineering approach for the production of l -ABA. Results In this study, Escherichia coli THR strain with a modified pathway for threonine-hyperproduction was engineered via deletion of the rhtA gene from the chromosome. To redirect carbon flux from 2-ketobutyrate (2-KB) to l -ABA, the ilvIH gene was deleted to block the l -isoleucine pathway. Furthermore, the ilvA gene from Escherichia coli W3110 and the leuDH gene from Thermoactinomyces intermedius were amplified and co-overexpressed. The promoter was altered to regulate the expression strength of ilvA* and leuDH . The final engineered strain E. coli THR Δ rhtA Δ ilvIH /Gap- ilvA *-Pbs- leuDH was able to produce 9.33 g/L of l -ABA with a yield of 0.19 g/L/h by fed-batch fermentation in a 5 L bioreactor. Conclusions This novel metabolically tailored strain offers a promising approach to fulfill industrial requirements for production of l -ABA.

CAS / MDL: 8063-07-8
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES · 2018 · IF 2.441

The metabolism of a natural product mogroside V, in healthy and type 2 diabetic rats

Guisheng Zhou,Yulong Zhang,Yang Li,Mengyue Wang,Xiaobo Li

Mogroside V, a natural compound isolated from the fruits of Siraitia grosvenorii (Swingle), is a promising candidate for anti-diabetic activity. The present study aims to develop a simple and practical strategy for comparing the in vivo metabolite profiling of mogroside V in healthy and type 2 diabetic (T2D) model rats. In this paper, a highly sensitive and rapid ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) with MetaboLynx™ software combined with mass defect filtering (MDF) method was established and successfully applied to detect and identify the metabolites in plasma, urine, bile and feces samples of healthy and model rats administrated with mogroside V. The distribution of metabolites in plasma, bile, urine and feces of healthy and model rats had obvious differences. A total of 23 metabolites were observed in healthy rats while 26 metabolites were detected in model rats. The results indicated that dehydrogenation , deoxidation , oxidation and isomerization were the major metabolic transformations of mogroside V. Additionally, it was noticed that the peak areas of metabolites in T2D rat plasma samples were much larger than those of metabolites in healthy rat plasma sample, whereas in T2D rat urine samples they were remarkably smaller compared with healthy rat urine sample. These high blood concentrations of metabolites might be beneficial for the treatment of T2D. The results of this study are valuable and important in understanding the metabolic process and therapeutic mechanism of mogroside V.

CAS / MDL: 18883-66-4
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APPLIED SURFACE SCIENCE · 2018 · IF 4.439

Electrodeposition of Ni(OH)2 reinforced polyaniline coating for corrosion protection of 304 stainless steel

Li Jiang,Junaid Ali Syed,Yangzhi Gao,Hongbin Lu,Xiangkang Meng

In the present paper, polyaniline (PANI) coating was electropolymerized in the presence of phosphoric acid with subsequent deposition of Ni(OH) 2 particles. The Ni(OH) 2 reinforced PANI coating significantly enhances the corrosion resistance of 304 stainless steel (304SS) in comparison with the pristine PANI coating. The galvanostatically deposited Ni(OH) 2 particles fill the pores of the pristine PANI coating and improves the coatings hydrophobicity which decreases the diffusion of aggressive media. Importantly, the R p values of Ni(OH) 2 reinforced PANI coating is much higher than that of pristine PANI coating and the Ni(OH) 2 reinforced PANI coating presents a long-term anti-corrosive ability (360 h) in 3.5 wt% NaCl solution. The prolonged corrosion protection of Ni(OH) 2 reinforced PANI coating is attributed to the improved physical barrier as well as the facile formation of passive oxide film that sustain the anodic protection of the coating.

CAS / MDL: 62-53-3 7664-38-2
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ELECTROCHIMICA ACTA · 2018 · IF 5.116

Synthesis of self-assembly 3D porous Ni(OH)2 with high capacitance for hybrid supercapacitors

Fangyan Liu,Xiang Chu,Haitao Zhang,Binbin Zhang,Hai Su,Long Jin,Zixing Wang,Haichao Huang,Weiqing Yang

Nickel hydroxide has shown extraordinary promise for hybrid supercapacitors because of the high theoretical capacity and low cost, but is usually limited by its low power density and complex synthetic process. Here, we report the design of a self-assembly three-dimensional (3D) porous Ni(OH) 2 for high-performance energy storage through a simple, cost-effective, and environmentally friendly solvothermal-precipitation method. The 3D structure with interconnected network provides superior electron transportation properties, and the hierarchical porous architecture facilitates quick ion diffusion. The Ni(OH) 2 obtained at 250 °C delivers a high capacitance of 2110 F g −1  at 1.0 A g −1 and a moderate cycling stability with 53% of the maximum specific capacitance over 2000 cycles at 5.0 A g −1 . Additionally, on integration of the prepared Ni(OH) 2 with hierarchically porous carbons as negative electrode material , the hybrid supercapacitor device delivers a high capacitance of 115 F g −1 and a high energy density of 40.9 W h kg −1 at a power density of 405 W kg −1 . This study not only provides a simply controllable growth method of the unique self-assembly 3D porous Ni(OH) 2 with high performance but also opens up a new approach to prepare various metallic oxides/hydroxides with excellent performance for highly promising practical energy-storage systems.

CAS / MDL: 6018-89-9
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ASIAN JOURNAL OF ANDROLOGY · 2018 · IF 3.259

Pancreatic kininogenase improves erectile function in streptozotocin-induced type 2 diabetic rats with erectile dysfunction

Guo-Tao Chen,Bai-Bing Yang,Jian-Huai Chen,Zheng Zhang,Lei-Lei Zhu,He-Song Jiang,Wen Yu,Yun Chen,Yu-Tian Dai

Erectile dysfunction (ED) associated with type 2 diabetes is a severe problem that requires effective treatment. Pancreatic kininogenase (PK) has the potential to improve the erectile function of ED patients. This study aims to investigate the effect of PK on erectile function in streptozotocin-induced type 2 diabetic ED rats. To achieve this goal, we divided male Sprague–Dawley rats into five groups. One group was not treated, and the other four groups were treated with saline, sildenafil, PK or sildenafil, and PK, respectively, for 4 weeks after the induction of type 2 diabetic ED. Then, intracavernous pressure under cavernous nerve stimulation was measured, and penile tissue was collected for further study. Endothelial nitric oxide synthase levels, smooth muscle content, endothelium content, cyclic guanosine monophosphate (cGMP) levels in the corpus cavernosum, and neuronal nitric oxide synthase levels in the dorsal penile nerve were measured. Improved erectile function and endothelium and smooth muscle content in the corpus cavernosum were observed in diabetic ED rats. When treating diabetic ED rats with PK and sildenafil at the same time, a better therapeutic effect was achieved. These data demonstrate that intraperitoneal injection of PK can improve erectile function in a rat model of type 2 diabetic ED. With further research on specific mechanisms of erectile function improvement, PK may become a novel treatment for diabetic ED.

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BIOCHEMICAL PHARMACOLOGY · 2018 · IF 4.235

E4bp4 regulates carboxylesterase 2 enzymes through repression of the nuclear receptor Rev-erbα in mice

Mengjing Zhao,Tianpeng Zhang,Fangjun Yu,Lianxia Guo,Baojian Wu

Carboxylesterases (CES) are a family of phase I enzymes that play an important role in xenobiotic clearance and lipid metabolism. Here, we investigate a potential role of E4 promoter-binding protein 4 (E4bp4) in regulation of Ces and CPT-11 (irinotecan, a first-line drug for treating colorectal cancer) pharmacokinetics in mice. Mouse hepatoma Hepa-1c1c7 cells were transfected with Rev-erbα expression plasmid or siRNA targeting E4bp4. The relative mRNA and protein levels of Ces enzymes in the cells or the livers of wild-type and E4bp4-deficient (E4bp4 −/− ) mice were determined by qPCR and Western blotting , respectively. Transcriptional regulation of Ces by E4bp4/Rev-erbα were investigated using luciferase reporter, mobility shift, and co-immunoprecipitation (Co-IP) assays. Pharmacokinetic studies were performed with wild-type and E4bp4 −/− mice after intraperitoneal injection of CPT-11. E4bp4 ablation down-regulated an array of hepatic Ces genes in mice. E4bp4 −/− mice also showed reduced Ces-mediated metabolism and elevated systemic exposure of CPT-11, a well-known Ces substrate. Consistently, E4bp4 knockdown reduced the expression of Ces genes ( Ces2b , Ces2e and Ces2f ) in Hepa-1c1c7 cells. Furthermore, Rev-erbα repressed the transcription of Ces2b, whereas E4bp4 antagonized this repressive action. Co-IP experiment confirmed a direct interaction between E4bp4 and Rev-erbα. Through a combination of promoter analysis and mobility shift assays, we demonstrated that Rev-erbα trans-repressed Ces (Ces2b) through its specific binding to the -767 to-754 bp promoter region. In conclusion, E4bp4 regulates Ces enzymes through inhibition of the transrepression activity of Rev-erbα, thereby impacting the metabolism and pharmacokinetics of Ces substrates.

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