查找使用阿拉丁产品的科研文献

Hernandezine, a natural herbal alkaloid, ameliorates type 2 diabetes by activating AMPK in two mouse models

Jing Bai,Shuai Zhang,Jinjing Cao,Hongbin Sun,Zhiguo Mang,Wei L. Shen,Hao Li

Background AMP-activated protein kinase (AMPK) is an effective target for treating diabetes. However, successful drug development is delayed due to issues including toxicity. Plant-derived natural product AMPK activators have emerged as a new way to treat diabetes due to its potential low safety risks. Here, we studied the effect of hernandezine (HER), a natural product derived from Thalictrum , in activating AMPK and treating T2D in mouse models. Method We tested HER in various cells and tissues, including primary hepatocytes, skeletal myotubes cell lines, as well as major metabolic tissues from diabetic (db/db) and diet-induced obesity (DIO) model mice. The effect of HER on glucose uptake via AMPK in vitro and in vivo was confirmed utilizing cell transfection and adenovirus interference analysis. Tissue staining assessed the effect of HER on adipogenesis. Real-time quantitative polymerase chain reaction (real-time PCR) was applied to verify the effect of HER on transcription factors. Western blot analysis was used to determine the activation of phosphorylated AMPK and ACC pathways. Results Biochemically, we found that HER prevented pAMPK from dephosphorylation to prolong its activity, disproving previous direct activation model and providing a new model to explain HER-mediated AMPK activation. HER could be orally delivered to animals and has a 3-fold long half-life in vivo as compared to metformin. Importantly, long-term oral HER treatment potently reduced body weight and blood glucose in both type 2 diabetes mullitus (T2DM) mouse models by increasing glucose disposal and reducing lipogenesis, and appeared not to induce cardiac hypertrophy. Conclusion Natural product HER indirectly activates AMPK by suppressing its dephosphorylation. Oral HER effectively alleviated hyperglycemia and reduced body weight in T2D mouse models, appeared to have a low risk of causing cardiac hypertrophy, and might be a potential therapeutic option for T2DM.

Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab

Pengkai Ma,Xuemei Zhang,Ling Ni,Jinming Li,Fengpu Zhang,Zheng Wang,Shengnan Lian,Kaoxiang Sun

Production and purification of 2‐phenylethanol by Saccharomyces cerevisiae using tobacco waste extract as a substrate

Ye J.,Tian S.,Lv L.,Ding Y.,Xu J.,Zhang J.,Li L.

2‐phenylethanol (2‐PE), which is extracted naturally from plant or biotechnology processing, is widely used in the food and cosmetics industries. Due to the high cost of 2‐PE production, the valorization of waste carbon to produce 2‐PE has gained increasing attention. Here, 2‐PE was produced by Saccharomyces cerevisiae using tobacco waste extract (TWE) as the substrate. Considering the toxicity of nicotine and its inhibition of 2‐PE, the tolerance of S. cerevisiae was first evaluated. The results suggested that the production of 2‐PE by S. cerevisiae in TWEs could be carried out at 2·0 mg ml−1 nicotine concentrations and may be inhibited by 1·0 mg ml−1 2‐PE. Thus, the compounds in the TWEs prepared at different temperatures were detected, and the results revealed that the TWEs prepared at 140°C contained 2·18 mg ml−1 of nicotine, had total sugar concentrations of 26·8 mg ml−1 and were suitable for 2‐PE production. Due to feedback regulation, the 2‐PE production was only 1·11 mg ml−1, and the remaining glucose concentration remained at 13·78 mg ml−1, which indicated insufficient glucose utilization. Then, in situ product recovery was further implemented to remove this inhibition; the glucose utilization (the remaining concentration decreased to 3·64 mg ml−1) increased, and the 2‐PE production increased to 1·65 mg ml−1. The 2‐PE produced in the fermentation broth was first isolated by elution from the resin with 75% ethanol and then by removing the impurities with 2·5% activated charcoal, and pure 2‐PE was identified by gas chromatography mass spectrometry. The results of this study suggest that TWE could be an alternative carbon source for 2‐PE production. This could provide an outlet tobacco waste as well as reducing the price of natural 2‐PE, although more strategies need to be explored to improve the production yield of 2‐PE by using TWE.

Intervention effect of Potentilla discolor-Euonymus alatus on intestinal flora of type 2 diabetes mellitus rats

S.-Y. He,X.-M. Qiu,Y.-Q. Wang,Z.-Q. Su,B.-Y. Zhang,Z. Wen,Y.-F. Yang,B.-F. Xing,M. Hong,R. Liao

OBJECTIVE: With this study, we aimed at exploring the regulation mechanism of Potentilla discolor-Euonymus alatus on intestinal flora of T2DM (Type 2 Diabetes Mellitus) rats induced by high-fat diet combined with streptozotocin.MATERIALS AND METHODS: T2DM rats were induced by high-fat diet combined with streptozotocin. There were normal control group, model group, metformin group, high-dose Chinese medicine group and low-dose Chinese medicine group. Each group included 10 rats. Normal control group: normal feeding, no modeling, ordinary feed, and gavage of 0.9% normal saline. Model group: T2DM rats, high-fat diet, and gavage of 0.9% normal saline. Metformin group: T2DM rats, high-fat diet and fed with metformin solution. High-dose Chinese medicine group: T2DM rats, high-fat diet, and gavage of concentrated Chinese medicine at a dose of 6 times the clinical dose. Low-dose Chinese medicine group: T2DM rats, high-fat diet, and gavage of concentrated Chinese medicine at a dose twice the clinical dose. The general situation of T2DM rats was observed, and the changes of intestinal flora were observed with 16SrDNA sequencing.RESULTS: The T2DM rats induced by high-fat diet combined with streptozotocin were molded. After intervention, at the class level, the ratio of γ-proteobacteria was 22.30% in the model group, 11.97% in the metformin group, 3.24% in the high-dose Chinese herbs group and 1.72% in the low-dose Chinese herbs group; the ratio of Erysipelothrix insidiosa was 4.73% in the model group, 4.68% in the metformin group, 3.93% in the high-dose Chinese herbsgroup and 2.92% in the low dose group; the ratio of Lactinobacillus was 2.30% in the model group, 0.01% in the metformin group, 0.00% in the high-dose Chinese herbs group, and 0.00% low-dose Chinese herbs group; at the portal level, the Firmicutes/Bacteroides was 0.88 in the normal control group, 3.40 in the model group, 1.71 in the metformin group, 2.74 in high-dose Chinese medicine group, and 1.34 in low-dose Chinese medicine group; at the genus level, the relative abundance of Lactobacillus in the model group was 3.28%, that of Akkermansia was 1.99%, that of Shigella coli was 22.08%, and that of Vibrio phaseus was 7.67%. All of them were improved after the intervention of metformin and traditional Chinese medicine.CONCLUSIONS: Potentilla discolor-Euonymus Alatus could improve the composition and structure of intestinal flora in T2DM rats and regulate the diversity of intestinal flora. The ratio of Firmicutes/Bacteroidetes was adjusted, mainly to increase the number of Bacteroides; the flora related to intestinal barrier was adjusted, mainly to increase the number of Lactobacillus and Akkermansia bacteria.

Surface-modified polylactic acid nanospheres with chitosan for antibacterial activity of 1, 2-benzisothiazolin-3-one

Junwei Yao,Jingxia Liu,Heng Zhi,Hongbing Tao,Xiaobao Xie,Qingshan Shi

The primary purpose of this study was to develop an innovative chitosan (CS) modified polylactic acid (PLA) nanospheres for enhancing the bioavailability of 1, 2-benzisothiazolin-3-one (BIT). The cellular uptake efficiency was corresponded positively to the quantity of CS coated on BIT-PLA nanospheres against E. coli and S. aureus . The membrane potentials of E.coli and S. aureus treated with BIT-PLA, BIT-PLA-0.1%CS and BIT-PLA-0.5%CS were reduced with the extension of incubation time and the ratio of coated CS. The enhancement of CS modified on BIT-PLA nanospheres was reduced antioxidase activities and generated excessive reactive oxygen species . The lowest EC 50 value of the modified BIT-PLA-0.5%CS suggested that its toxicity index was around 2.95-fold and 2.11-fold that of non-modified BIT-PLA against E. coli and S. aureus , respectively. These results revealed that the CS modified BIT-PLA nanospheres had a bright prospect in antibacterial formulation delivery system and improving the bioavailability.

Ebsulfur and Ebselen as highly potent scaffolds for the development of potential SARS-CoV-2 antivirals

Le-Yun Sun,Cheng Chen,Jianpeng Su,Jia-Qi Li,Zhihui Jiang,Han Gao,Jia-Zhu Chigan,Huan-Huan Ding,Le Zhai,Ke-Wu Yang

The emerging COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised a global catastrophe. To date, there is no specific antiviral drug available to combat this virus, except the vaccine. In this study, the main protease (M pro ) required for SARS-CoV-2 viral replication was expressed and purified. Thirty-six compounds were tested as inhibitors of SARS-CoV-2 M pro by fluorescence resonance energy transfer (FRET) technique. The half-maximal inhibitory concentration (IC 50 ) values of Ebselen and Ebsulfur analogs were obtained to be in the range of 0.074–0.91 μM. Notably, the molecules containing furane substituent displayed higher inhibition against M pro , followed by Ebselen 1i (IC 50  = 0.074 μM) and Ebsulfur 2k (IC 50  = 0.11 μM). The action mechanism of 1i and 2k were characterized by enzyme kinetics, pre-incubation and jump dilution assays, as well as fluorescent labeling experiments, which suggested that both compounds covalently and irreversibly bind to M pro , while molecular docking suggested that 2k formed an S S bond with the Cys145 at the enzymatic active site. This study provides two very potent scaffolds Ebsulfur and Ebselen for the development of covalent inhibitors of M pro to combat COVID-19.

Dually pH-responsive polyelectrolyte complex hydrogel composed of polyacrylic acid and poly (2-(dimthylamino) ethyl methacrylate)

Gang Li,Guoping Zhang,Rong Sun,Ching-Ping Wong

Via the radical polymerization of 2-(dimthylamino) ethyl methacrylate in the polyacrylic acid solution, we obtain the dually pH-reponsive polyelectrolytes complex hydrogel, which could be triggered to be swollen either in acid and basic environments. The results show that the responsive behavior of these PEC hydrogels is insensitive to monomer concentration in the prepolymerization, but can be tuned by changing the charge ratio or introducing chemical crosslinker. Moreover, other amazing propertise of the prepared PEC hydrogel are presented, which are including the ionic strength-responsiveness, the modest mechanical property (a tensile stress of 0.2 MPa and a tensile strain of 1500%) and the self-healing ability (a self-healing efficiency of ca. 70%). In brief, we report a multi-functional hydrogel which might serve as a new platform for responsive materials.

La2B3O4(OH)3(SO4)2: A new rare-earth borate-sulfate with second-harmonic generation response

Hui Yang,Ziyu Wang,Cuixia Xu,Yuan Lin,Guoliang Liu

The first example of lanthanide borate-sulfate compound, namely, La 2 B 3 O 4 (OH) 3 (SO 4 ) 2 has been obtained through hydrothermal synthesis , which belongs to polar space group Pna 2(1) (No. 33). Its structure possesses double lanthanum sulfate layers in the ab plane in which the lanthanide ions are bridged by SO 4 tetrahedra. These layers are further cross-linked by borate chains into the final 3D framework. It is noteworthy that this compound is the first lanthanide borate-sulfate which crystalizes in polar space group and it displays second-harmonic generation (SHG) signal of about 0.1 times that of KH 2 PO 4 . The SHG coefficient of the compound is ascribed to the synergistic effect of SO 4 units and borate units. Meanwhile, distorted LaO x polyhedra also play an important role in the contribution to SHG response.

Thermoresponsive block copolymer supported Pt nanocatalysts for base-free aerobic oxidation of 5-hydroxymethyl-2-furfural

Qu Huaxin,Deng Jie,Wang Bei,Ouyang Lezi,Tang Yong,Yu Kai,Lou Lan-Lan,Liu Shuangxi

A base-free catalytic system for the aerobic oxidation of 5-hydroxymethyl-2-furfural was exploited by using Pt nanoparticles immobilized onto a thermoresponsive poly(acrylamide- co -acrylonitrile)- b -poly( N -vinylimidazole) block copolymer, with an upper critical solution temperature of about 45 °C. The Pt nanocatalysts were well-dispersed and highly active for the base-free oxidation of 5-hydroxymethyl-2-furfural by molecular oxygen in water, affording high yields of 2,5-furandicarboxylic acid (up to >99.9%). The imidazole groups in the block copolymer were conducive to the improvement of catalytic performance. Moreover, the catalysts could be easily separated and recovered based on their thermosensitivity by cooling the reaction system below the upper critical solution temperature. Good stability and reusability were observed over these copolymer-immobilized catalysts with no obvious decrease in catalytic activity in the five consecutive cycles.

Synthesis of membrane adsorbers via surface initiated ATRP of 2-dimethylaminoethyl methacrylate from microporous PVDF membranes

Sun Tian,Zhang Yu-feng,Chen Chun-lin,Gong Xiang-zhuang,Meng Jian-qiang

Surface-initiated atom transfer radical polymerization (SI-ATRP) was used to tether poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) onto microporous PVDF membranes in order to synthesize membrane adsorbers for protein adsorption. The alkaline treatment and bromine addition reaction were used to anchor ATRP initiators on membrane surface. Then PDMAEMA was grafted from the membrane surface via SI-ATRP. Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) revealed the chemical composition and surface topography of the PVDF- g -PDMAEMA membrane surfaces. These results showed that PDMAEMA was grafted from the membrane surface successfully and a grafting yield as high as 1500 μg/cm 2 was achieved. The effects of the grafting time and the density of initiators on the static and dynamic binding capacity of bovine serum albumin (BSA) were systematically investigated. Both the static and dynamic binding capacities increase with the bromination and polymerization time. However, the benefits of the initiator density on binding capacities are limited by the graft density of PDMAEMA chains.

A Serum Metabolite Classifier for the Early Detection of Type 2 Diabetes Mellitus-Positive Hepatocellular Cancer

Lin-Lin Cao,Yi Han,Lin Pei,Zhi-Hong Yue,Bo-Yu Liu,Jing-Wen Cui,Mei Jia,Hui Wang

Type 2 diabetes mellitus (T2DM) has been identified as an independent risk factor for hepatocellular cancer (HCC). However, there are no ideal biomarkers for the surveillance and early detection of HCC in the T2DM population at present. In this study, we aimed to explore novel metabolite biomarkers for T2DM-positive [T2DM(+)] HCC by metabolomic analysis. At first, many serum metabolites were found dysregulated in T2DM(+) HCC patients in untargeted metabolomic analyses. Targeted metabolite analyses confirmed that serum benzoic acid and citrulline were increased, and creatine was decreased in T2DM(+) HCC compared to the T2DM group. A metabolite classifier including benzoic acid, creatine, and citrulline was identified as a novel biomarker for the diagnosis of T2DM(+) HCC, with an area under the ROC curve (AUC) of 0.93 for discriminating T2DM(+) HCC patients from T2DM patients. In addition, the metabolite classifier detected small-size (AUC = 0.94), early-stage (AUC = 0.94), and AFP-negative (AUC = 0.96) tumors with high sensitivity and specificity. The combination of this metabolite classifier and AFP might be useful in the surveillance and early detection of HCC in the T2DM population. In conclusion, this study establishes a novel diagnostic tool for T2DM(+) HCC.Keywords:hepatocellular cancer;type 2 diabetes mellitus;metabolomics;metabolite classifier;benzoic acid;creatine;citrulline

BF3·OEt2-Promoted Tandem O-Arylation/Hydroxylation: Efficient Synthesis of 2-Hydroxyflavanones from Triazenylaryl-Substituted Diketones

Zhengkai Chen,Weijun Yang,Lijun Xu,Lili Zhang,Maozhong Miao,Hongjun Ren

Graphical Highly substituted 2-hydroxyflavanones can be obtained through a tandem O -arylation/hydroxylation process from triazenylaryl-substituted diketones in the presence of a Lewis acid. A transition-metal-free tandem O -arylation/hydroxylation approach has been developed for the efficient synthesis of highly substituted 2-hydroxyflavanones from triazenylaryl-substituted diketones. The intermediate benzopyrylium cation may be involved in these reactions.