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991.
Tae Jung Oh Ji Yon Shin Gyeong Hoon Kang Kyong Soo Park Young Min Cho 《Experimental & molecular medicine》2013,45(7):e30
Metformin has been reported to increase the expression of the glucagon-like peptide-1 (GLP-1) receptor in pancreatic beta cells in a peroxisome proliferator-activated receptor (PPAR)-α-dependent manner. We investigated whether a PPARα agonist, fenofibrate, exhibits an additive or synergistic effect on glucose metabolism, independent of its lipid-lowering effect, when added to metformin. Non-obese diabetic Goto-Kakizaki (GK) rats were divided into four groups and treated for 28 days with metformin, fenofibrate, metformin plus fenofibrate or vehicle. The random blood glucose levels, body weights, food intake and serum lipid profiles were not significantly different among the groups. After 4 weeks, metformin, but not fenofibrate, markedly reduced the blood glucose levels during oral glucose tolerance tests, and this effect was attenuated by adding fenofibrate. Metformin increased the expression of the GLP-1 receptor in pancreatic islets, whereas fenofibrate did not. During the intraperitoneal glucose tolerance tests with the injection of a GLP-1 analog, metformin and/or fenofibrate did not alter the insulin secretory responses. In conclusion, fenofibrate did not confer any beneficial effect on glucose homeostasis but reduced metformin''s glucose-lowering activity in GK rats, thus discouraging the addition of fenofibrate to metformin to improve glycemic control. 相似文献
992.
Sylvie‐Mireille Bambi‐Nyanguile Peter Mangwala Kimpende Bernard Pirotte Luc Van Meervelt 《Acta Crystallographica. Section C, Structural Chemistry》2013,69(8):901-903
The title compound, C19H21N3O4S, crystallizes in the space group P2/c with two molecules in the asymmetric unit. The conformation of both molecules is very similar and is mainly determined by an intramolecular N—H...O hydrogen bond between a urea N atom and a sulfonyl O atom. The O and second N atom of the urea groups are involved in dimer formation via N—H...O hydrogen bonds. The intramolecular hydrogen‐bonding motif and conformation of the C—SO2—NH(C=O)—NH—C fragment are explored and compared using the Cambridge Structural Database and theoretical calculations. The crystal packing is characterized by π–π stacking between the 5‐cyanobenzene rings. 相似文献
993.
Somatic embryogenesis receptor kinases (SERKs) play a significant role in morphogenesis, stress/defense and signal transduction. In the present study, we have identified two SERK and 11 SERK-like (SERL) genes in Phalaenopsis equestris, two SERK and 11 SERL genes in Dendrobium catenatum, and one SERK and eight SERL genes in Apostasia shenzhenica genome. Characterization of the SERK proteins revealed the presence of a signal peptide, a leucine zipper, five leucine-rich repeats (LRRs), a serine proline proline (SPP) motif, a transmembrane region, a kinase domain, and a C-terminus. Most of the SERK/SERL proteins were characterized with similar physicochemical properties. The presence of transmembrane region predicted their membranous localization. Tertiary structure prediction of all the five identified SERK proteins had sequence identity with BAK1 protein of Arabidopsis thaliana. Generally, all the SERK/SERL genes shared similar gene architecture and intron phasing. Gene ontology analysis indicated the role of SERKs in receptor and ATP binding, signal transduction, and protein phosphorylation. Phylogenetic analysis revealed the clustering of SERKs and SERLs in distinct clades. Expression of SERKs in reproductive tissues like floral bud, floral stalk, whole flower and pollen was reported to be higher than their expression in vegetative tissues with an exception of PeSERK1 and DcSERK1 which showed higher expression in leaves and roots, respectively. Likewise, a higher expression of AsSERK1 was observed in tubers. However, lower expression of SERLs was observed in majority of tissues studied irrespective of their vegetative or reproductive origin. This work paves way for future studies involving functional characterization of SERK/SERLs and their potential role in embryogenesis/organogenesis as an aid to regeneration and multiplication of endangered orchids. 相似文献
994.
995.
Nayelli Guadalupe Teran-Saavedra Jose Andrei Sarabia-Sainz Enrique Fernando Velzquez-Contreras Gabriela Ramos-Clamont Montfort Martín Pedroza-Montero Luz Vazquez-Moreno 《Molecules (Basel, Switzerland)》2020,25(22)
Doxorubicin (Dox) is the most widely used chemotherapeutic agent and is considered a highly powerful and broad-spectrum for cancer treatment. However, its application is compromised by the cumulative side effect of dose-dependent cardiotoxicity. Because of this, targeted drug delivery systems (DDS) are currently being explored in an attempt to reduce Dox systemic side-effects. In this study, DDS targeting hepatocellular carcinoma (HCC) has been designed, specifically to the asialoglycoprotein receptor (ASGPR). Dox-loaded albumin-albumin/lactosylated (core-shell) nanoparticles (tBSA/BSALac NPs) with low (LC) and high (HC) crosslink using glutaraldehyde were synthesized. Nanoparticles presented spherical shapes with a size distribution of 257 ± 14 nm and 254 ± 14 nm, as well as an estimated surface charge of −28.0 ± 0.1 mV and −26.0 ± 0.2 mV, respectively. The encapsulation efficiency of Dox for the two types of nanoparticles was higher than 80%. The in vitro drug release results showed a sustained and controlled release profile. Additionally, the nanoparticles were revealed to be biocompatible with red blood cells (RBCs) and human liver cancer cells (HepG2 cells). In cytotoxicity assays, Dox-loaded nanoparticles decrease cell viability more efficiently than free Dox. Specific biorecognition assays confirmed the interaction between nanoparticles and HepG2 cells, especially with ASGPRs. Both types of nanoparticles may be possible DDS specifically targeting HCC, thus reducing side effects, mainly cardiotoxicity. Therefore, improving the quality of life from patients during chemotherapy. 相似文献
996.
Chieh-Yu Shen Cheng-Hsun Lu Cheng-Han Wu Ko-Jen Li Yu-Min Kuo Song-Chou Hsieh Chia-Li Yu 《Molecules (Basel, Switzerland)》2020,25(23)
Advanced glycation end products (AGEs) are generated by nonenzymatic modifications of macromolecules (proteins, lipids, and nucleic acids) by saccharides (glucose, fructose, and pentose) via Maillard reaction. The formed AGE molecules can be catabolized and cleared by glyoxalase I and II in renal proximal tubular cells. AGE-related diseases include physiological aging, neurodegenerative/neuroinflammatory diseases, diabetes mellitus (DM) and its complications, autoimmune/rheumatic inflammatory diseases, bone-degenerative diseases, and chronic renal diseases. AGEs, by binding to receptors for AGE (RAGEs), alter innate and adaptive immune responses to induce inflammation and immunosuppression via the generation of proinflammatory cytokines, reactive oxygen species (ROS), and reactive nitrogen intermediates (RNI). These pathological molecules cause vascular endothelial/smooth muscular/connective tissue-cell and renal mesangial/endothelial/podocytic-cell damage in AGE-related diseases. In the present review, we first focus on the cellular and molecular bases of AGE–RAGE axis signaling pathways in AGE-related diseases. Then, we discuss in detail the modes of action of newly discovered novel biomolecules and phytochemical compounds, such as Maillard reaction and AGE–RAGE signaling inhibitors. These molecules are expected to become the new therapeutic strategies for patients with AGE-related diseases in addition to the traditional hypoglycemic and anti-hypertensive agents. We particularly emphasize the importance of “metabolic memory”, the “French paradox”, and the pharmacokinetics and therapeutic dosing of the effective natural compounds associated with pharmacogenetics in the treatment of AGE-related diseases. Lastly, we propose prospective investigations for solving the enigmas in AGE-mediated pathological effects. 相似文献
997.
Christian Gentzsch Kerstin Seier Antonios Drakopoulos Marie‐Lise Jobin Yann Lanoisele Zsombor Koszegi Damien Maurel Rmy Sounier Harald Hübner Peter Gmeiner Sbastien Granier Davide Calebiro Michael Decker 《Angewandte Chemie (International ed. in English)》2020,59(15):5958-5964
μ‐Opioid receptors (μ‐ORs) play a critical role in the modulation of pain and mediate the effects of the most powerful analgesic drugs. Despite extensive efforts, it remains insufficiently understood how μ‐ORs produce specific effects in living cells. We developed new fluorescent ligands based on the μ‐OR antagonist E‐p‐nitrocinnamoylamino‐dihydrocodeinone (CACO), that display high affinity, long residence time and pronounced selectivity. Using these ligands, we achieved single‐molecule imaging of μ‐ORs on the surface of living cells at physiological expression levels. Our results reveal a high heterogeneity in the diffusion of μ‐ORs, with a relevant immobile fraction. Using a pair of fluorescent ligands of different color, we provide evidence that μ‐ORs interact with each other to form short‐lived homodimers on the plasma membrane. This approach provides a new strategy to investigate μ‐OR pharmacology at single‐molecule level. 相似文献
998.
Ion segregation is critically important for achieving high ion conductivity for anion exchange membranes(AEMs).Herein,a new bisphenol monomer bearing ten electron-rich phenyl groups was designed and polymerized with various amounts of electron-deficient 4,4′-dihydroxydiphenylsulfone and 4,4′-difluorobenzophenone to yield dense and selective reaction sites for chloromethylation and quaternization.As the most challenging step,chloromethylation was optimized by tuning the reaction temperature,reaction time,and reactant ratios.Ion exchange capacity,water uptake,anion conductivity,mechanical stability,and alkaline stability of the resulting AEMs were characterized in detail.It is found that chloromethylation reaction needed to be carried out at low equivalent of chloromethylation agents to avoid undesirable crosslinking.The QA-PAEKS-20 sample with an IEC of 1.19 mmol·g^-1 exhibited a Cl^–conductivity of 11.2 mS·cm^-1 and a water uptake of 30.2%at80°C,which are promising for AEM applications. 相似文献
999.
Peptide-functionalized Au-Fe2O3 nanoparticles(termed as anti-CXCR4-Au-Fe2O3NPs) have been constructed through conjugation of dumbbell-like Au-Fe2O3NPs with C-X-C motif chemokine receptor 4(CXCR4) binding cyclic peptide. One dumbbell-like Au-Fe2O3NP composes an Au NP[(3.3±0.3) nm in diameter] for conjuga-ting CXCR4 binding cyclic peptide through Au-S covalent bond and a Fe2O3NP[(8.7±0.8) nm in diameter] for using as T2-weighted magnetic resonance imaging(MRI) contrast agent. The anti-CXCR4-Au-Fe2O3NPs have reasonable biocompatibility and integration of T2-weighted MRI contrast and tumor-targeting functionalities. The anti-CXCR4-Au-Fe2O3NPs exhibit strong interactions with two kinds of breast tumor cells, MCF-7 cells and MDA-MB-231 cells, and high negative contrast in MRI of MDA-MB-231 tumor bearing mouse with 62% decreasing of MRI signal, indicating that the anti-CXCR4-Au-Fe2O3NPs can recognize tumor with high efficacy and specificity. 相似文献
1000.
A kind of strong anion exchanger (SAX) was prepared with chloromethylstyrene encapsulated silica. This strong anion silica column has superior ability for the separation of anions, organic acids and also the mixture of them. Using this strong anion exchanger, the sulfonic acids can be separated. With gradient elution, the separation of petroleum mono- and di- sulfonates in Yumen sample can be also well obtained. This anion exchanger’s stability has been studied. After continuous use for three months the carbon and nitrogen contents and the chromatographic behavior of the exchanger were unchanged. 相似文献