Bioengineered
·
2022
·
IF 6.832
Zhipeng Jiang,Zehui Hou,Wei Liu,Zhuomin Yu,Zhiqiang Liang,Shuang Chen
The dysregulated circular RNAs (circRNAs) are linked to progression and chemoresistance in colorectal cancer (CRC). However, the role of circRNA protein tyrosine kinase 2 (circPTK2) in CRC progression and chemoresistance is uncertain. The circPTK2, microRNA (miR)-136-5p, m6A ‘reader’ protein YTH domain family protein 1 (YTHDF1), β-catenin and cyclin D1 abundances were examined via quantitative reverse transcription PCR or Western blotting. The progression was investigated by cell counting kit-8 (CCK-8), colony formation, transwell and xenograft analysis. The resistance to 5-fluorouracil (5-FU) and oxaliplatin was analyzed via detecting cell viability and apoptosis using CCK-8 analysis and flow cytometry. The binding relationship was examined through dual-luciferase reporter, RNA immunoprecipitation and pull-down analysis. In our study, circPTK2 abundance was enhanced in CRC and associated with liver metastasis, clinical stage and chemoresistance. CircPTK2 knockdown constrained cell proliferation, migration, invasion, resistance to 5-FU and oxaliplatin, and the Wnt/β-catenin signaling. MiR-136-5p was bound with circPTK2 and downregulated in CRC. MiR-136-5p knockdown attenuated the influence of circPTK2 silence on CRC progression and chemoresistance. YTHDF1 was targeted via miR-136-5p and upregulated in CRC samples and cells. MiR-136-5p targeted YTHDF1 to restrain CRC progression and chemoresistance. In addition, we confirmed that circPTK2 silence reduced xenograft tumor growth. In conclusion, circPTK2 interference suppressed CRC proliferation, migration, invasion and chemoresistance via regulating miR-136-5p and YTHDF1.Abbreviations: circRNAs: circular RNAs; CRC: colorectal cancer; circPTK2: circRNA protein tyrosine kinase 2; miR: microRNA; YTHDF1: YTH domain family protein 1; CCK-8: cell counting kit-8; 5-FU: 5-fluorouracil; RIP: RNA immunoprecipitation.
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SCRIPTA MATERIALIA
·
2021
·
IF 5.611
Lei Meng,Chu Xin Peng,Chen He,Fei Yen
The polarity of the magnetic susceptibility χ( T ) of ammonium alum NH 4 Al(SO 4 ) 2 •12H 2 O single crystals below its ferroelectric Curie temperature T C is identified to depend only on the cooling rate. To explain this, we consider reorienting distorted NH 4 + to carry weak magnetic and electric dipole moments that are linearly coupled. Slow cooling allows the dipole moments to align which enhances χ( T ) to become positive. However, due to energy degeneracy of rotational motion and geometric frustration of the NH 4 + , faster cooling rates render the system to become an orientational glass state causing χ( T ) to remain negative. Specific heat measurements also show the presence of excess entropy below a negative anomaly near 53 K. Our findings identify a possible new class of non-equilibrium system with potential applications in non-volatile memory devices.
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TOXICON
·
2021
·
IF 3.033
Xiong Zhang,Chen Feng,Yimao Li,Chenlin Su,Shuxin Zhao,Shengdi Su,Feng Yu,Ji LI
Aristolactam I (AL-I) is the main active ingredient in the Aristolochia plant species, which have been associated with severe nephrotoxicity. In order to investigate the mechanism of AL-I induced renal epithelial-mesenchymal transition (EMT), we established an AL-I induced EMT model in human proximal tubular epithelial cells (HK-2 cells). Biochemical analysis experiment including Morphological examination, 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay, and Western blot analysis were performed. The results showed that AL-I accumulates in the cytosol causing cytotoxicity and inhibition of proliferation in a concentration- and time-dependent manner. Morphological examination showed that with the increasing concentration of AL-I, the tendency of HK-2 cells transform form epithelial cell to fibroblast cells was stronger. In the Western blot analysis, the expression of α-Smooth muscle actin (α-SMA) and Transforming Growth Factor β1 (TGF-β1) were significantly up-regulated, the expression of E-cadherin was significantly down-regulated after administrating. The ratio of the expression of P-Smad2/3 and Smad2/3 was significantly up-regulated, suggested that TGF-β/Smad-dependent signaling pathway was activated in this process. With presence of TGF-β receptor inhibitor (LY364947), we found that the expressions of three EMT related proteins (E-cadherin, α-SMA and TGF-β1) were obviously reversed. In conclusion, we acknowledge that AL-I can induce renal EMT process in HK-2 cell, which is triggered by the activation of TGF-β/Smad-dependent signaling pathway.
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Molecular Catalysis
·
2021
·
IF 5.062
Wei Luo,Jiagui Hu,Jiapeng Lu,Huili Zhang,Xiaoping Wang,Yuantao Liu,Liqing Dong,Xiaobin Yu
ω-transaminase can mediate the asymmetric synthesis of chiral amines from aldehydes and ketones , which has important value in the synthesis of pharmaceutical intermediates. A novel ω-transaminase derived from Paracoccus pantotrophus ( Pp TA) was obtained and cloned in E. coli BL21(DE3) for expression. The enzyme has high activity for 2-ketobutyric acid and benzylamine , as well as for aromatic compounds with side chains longer than ethyl aliphatic hydrocarbons . Molecular simulation showed that the S-pocket in the active center is larger than those of other ω-transaminases. Thereafter, a whole-cell catalytic system was designed to prepare l -2-aminobutyric acid by cascading Pp TA and other enzymes. By using several strategies (regulation of RBS intensity, by-product decomposition and cofactor self-sufficiency), whole-cell cascade biocatalysis showed a high ee value (> 99%) and high yield (71%) in one pot reaction . This study therefore proposes an efficient biocatalyst for the synthesis of unnatural amino acids with the participation of ω-transaminase.
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CHEMICAL ENGINEERING SCIENCE
·
2021
·
IF 4.311
Gaobo Lin,Wenwen Lin,Jianghua Wu,You Zhan,Francis Okejiri,Mingwei Weng,Jie Fu
Biomass-derived 2,5-furandicarboxylic acid (FDCA) is considered a viable alternative to petroleum-derived terephthalic acid as a monomer in the production of bioplastic. FDCA is currently mainly produced via a two-step process involving the conversion of fructose to 5-hydroxymethylfurfural (HMF) and the subsequent oxidation of HMF to FDCA. However, the storage stability HMF is far below the industrial expectations, further inhibiting the HMF-mediated route. Herein, we report efficient oxidation of 5-methoxymethylfurfural (MMF) to FDCA over a homemade Ru/hydroxyapatite (Ru/HAP) catalyst. A complete conversion of MMF and > 65% molar yield of FDCA could be realized under mild reaction conditions of 130 °C and 1 MPa O 2 pressure. The effects of process parameters, including MMF/catalyst ratios, reaction temperature/time, and O 2 pressure, were systematically studied and optimized on MMF oxidation. A plausible reaction pathway was also proposed. This study and our previously reported fructose-to-MMF work may provide a feasible MMF-intermediated route for large-scale industrial FDCA production.
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PHYTOMEDICINE
·
2021
·
IF 5.34
Yang Zhang,Shan Liu,Jiu-Long Ma,Chen Chen,Peng Huang,Jia-Hua Ji,Di Wu,Li-Qun Ren
Background Doxorubicin (DOX) is a broad-spectrum anti-tumor drug that has been associated with cardiotoxicity. Plant extracts have been shown to confer protection against DOX-induced cardiotoxicity. Apocynum venetum L . belongs to the Apocynaceae family. Flavonoid extracted from Apocynum venetum L . possess various biological effects, such as lowering blood pressure levels, sedation, diuresis, anti-aging, and improving immunity. Purpose This study investigated the mechanism by which dry leaf extract of Apocynum venetum L. (AVLE) alleviates DOX-induced cardiomyocyte apoptosis. Methods HPLC-MS/MS and HPLC methods were used to analyze the components of AVLE. The effects of DOX and AVLE on apoptosis of H9c2 and HMC cells were assessed using the MTT assay. Calcein AM/PI, TUNEL, and flow cytometry were carried out to determine the effects of AVLE on DOX-induced apoptosis. The effect of AVLE on DOX-induced oxidative stress in cardiomyocytes was investigated using ELISA test. Mito-Tracker Red CMXRos, JC-1, and RT-qPCR assays were performed to evaluate the impact of AVLE on DOX-induced cardiomyocyte mitochondrial activity and membrane permeability. Western blot assay was carried out to determine the activation of multiple signaling molecules, including phosphorylated-protein kinase B (p-AKT), Cytochrome c, Bcl-2 family, and caspase family in the apoptosis pathway. The AKT inhibitor was used to block AKT/Bcl-2 signaling pathway to investigate the role of AKT in the protection conferred by AVLE against DOX-induced cardiotoxicity. Results A total of 8 compounds, including rutin, hyperoside, isoquercetin, unidentified compounds, myricetin, quercetin, quercetin-3-O-glucuronide and kaempferol, were detected in AVLE. Of note, DOX suppressed lactate dehydrogenase (LDH) levels, aggravated oxidative stress, and promoted cardiomyocyte apoptosis. It also upregulated the mRNA expression levels of voltage-dependent anion channel 1 (VDAC1), adenosine nucleotide transporter 1 (ANT1), and cyclophilin D (CYPD), while suppressing mitochondrial activity and mitochondrial membrane permeability. Treatment with DOX altered the expression levels of apoptosis-associated proteins, Bcl-2 and Bax. However, AVLE treatment alleviated DOX-induced effects on cardiomyocytes. In addition, application of AKT inhibitors promoted DOX-induced apoptosis and reversed the inhibitory effects of AVLE on DOX-induced apoptosis. Conclusions AVLE confer cardio protection by suppressing oxidative stress and apoptosis of cardiomyocytes via AKT/Bcl-2 signaling pathway.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2021
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IF 6.953
Xiang Xiao,Yurong Zhou,Cui Tan,Juan Bai,Ying Zhu,Jiayan Zhang,Xinghua Zhou,Yansheng Zhao
β-glucan is an important functional active component with relatively high content in barley. It is reported to possess various biological activities, including anti-oxidative stress, but its mechanism of action remains obscure. In the current study, C. elegans was used as an in vivo animal model to explore its anti-oxidative stress mechanism. We found that both RBG (raw barley β-glucan) and FBG (fermented barley β-glucan) could significantly reduce the ROS level in C. elegans under oxidative emergency conditions. In addition, both FBG and RBG had positive effects on SOD and CAT enzyme activity, and FBG treatment obviously reduced the MDA content in nematodes under oxidative stress. Moreover, FBG and RBG pretreatment could extend the median lifespan of C. elegans under oxidative stress. The CB1370 and CF1038 mutants further confirmed that daf-2 and daf-16 were necessary for FBG or RBG to participate in anti-oxidative stress, and the RT-PCR results also evidenced that β-glucans resist oxidative stress in C. elegans partially through the daf-2 / daf-16 pathway. In summary, barley β-glucan has high potential to defense oxidative stress as a natural polysaccharide.
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NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 45
·期 36
·16705-16713
·
IF 3.591
Xue Meng,Li Yan,Maobin Wei,Tao Wang,Ting Xu,Yongsheng Yan,Shihan Cheng
The developed peroxydisulfate (PDS) activation for removing pollutants is a significant technology. Here, a Co(OH)2/Cu2O composite was synthesized and used to activate PDS for tetracycline (TC) degradation. Covering the surface of Cu2O with Co(OH)2 could improve the stability of the material, reactive active sites, and electron transfer efficiency of the catalyst. Thus, Co(OH)2/Cu2O composite exhibited excellent performance in terms of degrading the TC pollutant, and in the Co(OH)2/Cu2O/PDS system, the removal rate of TC could reach 98% within 30 min. Moreover, the effect of pH value, PDS dosage, and TC concentration on the degradation efficiency of TC was systematically studied. According to free radical quenching experiments, the possible mechanism of TC degradation over the Co(OH)2/Cu2O/PDS system was proposed. This work provided a research basis for the use of metal oxides for PDS activation in environmental treatment.
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Acta Pharmaceutica Sinica B
·
2021
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IF 11.614
Ziru Yu,Dewen Kong,Yu Liang,Xiaoyue Zhao,Guanhua Du
Nicotinic α 4 β 2 receptor antagonists have drawn increasing attention in the development of new antidepressants. In this study, we aimed to investigate the protective effect of VMY-2-95, the new selective antagonist of α 4 β 2 nicotinic acetylcholine receptor (nAChR) on corticosterone (CORT) injured mice and cellular models. Fluoxetine was applied as a positive control, and the effects of VMY-2-95 were investigated with three different doses or concentrations (1, 3, 10 mg/kg in mice, and 0.003, 0.03, 0.1 μmol/L in cells). As a result, VMY-2-95 showed significant antidepressant-like effects in the CORT injured mice by improving neuromorphic function, promoting hippocampal nerve proliferation, and regulating the contents of monoamine transmitters. Meanwhile, VMY-2-95 exhibited protective effects on cell viability, cell oxidant, cell apoptosis, and mitochondrial energy metabolism on corticosterone-impaired SH-SY5Y cells. Also, the PKA–CREB–BDNF signaling pathway was up-regulated by VMY-2-95 both in vitro and in vivo , and pathway blockers were also combined with VMY-2-95 to verify the effects furtherly. Therefore, we preliminarily proved that VMY-2-95 had protective effects in depressed mice and SH-SY5Y cells against injuries induced by corticosterone. This work indicated that the application of VMY-2-95 is a potential pharmacological solution for depression. This study also supported the development of α 4 β 2 nAChR antagonists towards neuropsychiatric dysfunctions.
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CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Xuerui Bai,Maiqian Nie,Zhenjun Diwu,Lei Wang,Hongyun Nie,Yan Wang,Qiuyue Yin,Bo Zhang
2-Hydroxymuconic semialdehyde (2-HMS) is a useful intermediate in organic synthesis, but there are few reports for its preparation. 2-HMS accumulates in phenol-containing wastewater treated with Pseudomonas stutzeri N2. This work has studied the extraction of 2-HMS so that the phenolic wastes of high concentration may be used to produce 2-HMS. When 4.25 mmol/L phenol was degraded by Pseudomonas stutzeri N2, the accumulated 2-HMS can reach 3.79 ± 0.08 mmol/L within 30 h. A saturated solution of NaHSO 3 was added into the 2-HMS culture, and white rod-like precipitates formed gradually. Through SEM, XRD and FT-IR, the precipitates were identified as monoclinic hexagonal crystals of α-hydroxy sulfonate sodium with high purity. In the presence of NaOH, α-hydroxy sulfonate sodium could be reduced to the desired 2-HMS product. The optimized conditions were characterized to be 3 mol/L NaOH solution, 5 min and 50 °C. The conversion rate of α-hydroxy sulfonate sodium was up to 87.3 ± 0.2%, and 0.42 ± 0.02 mmol/L 2-HMS were obtained.
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Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Rongzhen Fang,Yan Liu,Lei Ma,Xiang Yu,Yiguang Jin
Drug solid dispersions improve the dissolution of drugs in aqueous media for enhancement of oral bioavailability. The current preparation methods of drug solid dispersions mainly involve the evaporation of solvents or the melting of drugs and matrix. Here, we create a new and simple method for the preparation of drug solid dispersions by dissolving drugs in N -vinyl-2-pyrrolidone (NVP) and then NVP photopolymerization. A variety of drugs were explored to find whether they were suitable for this method and only some of them were soluble in NVP and formed transparent and hard solid dispersions, including fluconazole, ketoconazole, bifonazole, miconazole nitrate, sulfamethoxazole, aspirin, ibuprofen and artesunate. The formation of photocuring solid dispersions was highly related to the free radical scavenging function of drugs. Those drugs with strong free radical scavenging capability, including curcumin, resveratrol, quercetin, genistein, puerarin, nicergoline, olanzapine, indomethacin, did not form solid dispersions. They scavenged 2,2-diphenyl-1-picrylhydrazyl free radicals, which was demonstrated by ultraviolet spectrometry and electron spin resonance. The scavenging of free radicals stopped the chain polymerization of NVP. The Fourier transform infrared spectra, X-ray diffraction and differential scanning calorimetry of ibuprofen solid dispersions and artesunate solid dispersions showed the molecularly miscible state of the drugs and the hydrogen bonding between the drugs and polyvinyl pyrrolidone. The NVP-based solid dispersions of the two drugs had faster and more complete dissolution than their traditional solid dispersions. The NVP photopolymerization-based solid dispersion method provides a new choice for the production of solid dispersions in the research and industrial fields.
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CHEMOSPHERE
·
2021
·
IF 7.086
Fang Zhu,Siyi Zhou,Mengying Sun,Jianfeng Ma,Wei Zhang,Kunjie Li,Hao Cheng,Sridhar Komarneni
Mg doped Ni(OH) 2 was synthesized and investigated as an efficient material to activate persulfate (PS) for phenol degradation. The property of the Ni(OH) 2 material was enhanced by Mg doping as the removal efficiency of phenol was increased from 74.82 % in Ni(OH) 2 /PS system to 89.53 % in Mg-doped Ni(OH) 2 /PS system within 20 min. Such a high removal efficiency revealed that doping Mg into Ni(OH) 2 brings about more defects (oxygen vacancies), which facilitated the formation of more active species in the degradation process. The removal efficiencies of phenol increased with the increase of the initial pH from 3 to 11. The influences of Cl − , NO 3 − and HCO 3 − on the stability of the system were also studied and the results showed that removal rates of all systems in the presence of these different inorganic anions could reached about 90 % within 20 min. Based on the electron spin resonance (ESR) experiments, 1 O 2 , O 2 ·- , ·OH and SO 4 •− were identified as the active species in Mg-doped Ni(OH) 2 /PS system for phenol degradation and a degradation mechanism was proposed for this system. In addition, the as-prepared material retained its activation performance even after 3 repeated cycles.
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