An experiment was conducted on the polyphenol content, flavonoid content, anthocyanin content, and antioxidant capacity of Furong plum ( Lindl. cv. "furong") at different maturity stages to determine the most suitable maturity stage.
View Article and Find Full Text PDFHerein, a series of novel 1-((4-methoxy-3-(piperazin-1-yl)phenyl)sulfonyl)- 1H-indole derivatives were designed and synthesized via hybridization strategy of idalopirdine and SB-271046. The optimal compound C14 (K = 0.085 nM), with difluoromethyl on C3 position on indole scaffold, increased the affinity for the 5-HTR up to 10-folds than idalopirdine (K = 0.
View Article and Find Full Text PDFBackground: The association of insomnia treatment with medical costs is not well characterized in Japan, despite the high economic burden of insomnia.
Objective: The aim of this study was to investigate the impact of suvorexant, the first dual orexin receptor antagonist, on direct medical costs in insomnia patients.
Patients And Methods: This retrospective cohort study, conducted using a large-scale claims database, included Japanese patients with diagnosed insomnia receiving suvorexant who were treatment naïve or treatment switchers (pre-treated with a different hypnotic and switched to suvorexant).
Background: Brown adipose tissue (BAT) is an important tissue for thermogenesis, making it a potential target to decrease the risks of obesity, type 2 diabetes, and cardiovascular disease, and recent studies have also identified BAT as an endocrine organ. Although BAT has been implicated to be protective in cardiovascular disease, to this point there are no studies that identify a direct role for BAT to mediate cardiac function.
Methods: To determine the role of BAT on cardiac function, we utilized a model of BAT transplantation.
β-Glucosidase (BGL) is a rate-limiting enzyme of lignocellulose hydrolysis for second-generation bioethanol production, but its inhibition by lignocellulose pretreatment products, ethanol, and salt is apparent. Here, the recombinant Penicillium oxalicum 16 BGL 1 (rPO16BGL1) from Pichia pastoris GS115 kept complete activity at 0.2-1.
View Article and Find Full Text PDFβ-Glucuronidase plays a vital role in the metabolism of drugs and endogenous substance. Herein, we assayed the inhibitory effects of thirty-six flavonoids (1-36) toward β-glucuronidase (Escherichia coli) using the probe reaction of DDAO-glu hydrolysis. The results showed that kushenol X (6), (2S)-farrerol (10), 5,7,2'-trihydroxy-8,6'-dimethoxy flavone (20), demethylbellidifolin (31), and gentisin (32) exhibited potent inhibitory activities toward β-glucuronidase with the IC values of 2.
View Article and Find Full Text PDFDevelopment of pharmacological tools for the ionotropic glutamate receptors (iGluRs) is imperative for the study and understanding of the role and function of these receptors in the central nervous system. We report the synthesis of 18 analogues of (2 S,3 R)-2-carboxy-3-pyrrolidine acetic acid (3a), which explores the effect of introducing a substituent on the ε-carbon (3c-q). A new synthetic method was developed for the efficient synthesis of racemic 3a and applied to give expedited access to 13 racemic analogues of 3a.
View Article and Find Full Text PDFIn order to understand the accumulation of heavy metals of agricultural land in Chongqing and make clear priority control elements, the soil heavy metal baseline values need to be determined. Based on geochemical baselines, a total of 214 surface soil samples of six soil types were collected according to stratified sampling. Under strict quality control, the As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn content in each sample was measured.
View Article and Find Full Text PDFJ Trauma Acute Care Surg
July 2017
Background: Earlier use of in-hospital plasma, platelets, and red blood cells (RBCs) has improved survival in trauma patients with severe hemorrhage. Retrospective studies have associated improved early survival with prehospital blood product transfusion (PHT). We hypothesized that PHT of plasma and/or RBCs would result in improved survival after injury in patients transported by helicopter.
View Article and Find Full Text PDFFront Neurosci
November 2016
Spike frequency adaptation (SFA) exists in many types of neurons, which has been demonstrated to improve their abilities to process incoming information by synapses. The major carrier used by a neuron to convey synaptic signals is the sequences of action potentials (APs), which have to consume substantial metabolic energies to initiate and propagate. Here we use conductance-based models to investigate how SFA modulates the AP-related energy of neurons.
View Article and Find Full Text PDFOsteoclast cells (OCs) are differentiated from bone marrow-derived macrophages (BMMs) by activation of receptor activator of nuclear factor κB (NF-κB) ligand (RANKL). Activation of NADPH oxidase (Nox) isozymes is involved in RANKL-dependent OC differentiation, implicating Nox isozymes as therapeutic targets for treatment of osteoporosis. Here, we show that a novel pyrazole derivative, Ewha-18278 has high inhibitory potency on Nox isozymes.
View Article and Find Full Text PDFThe authors studied the effects of ketoconazole and rifampicin on the pharmacokinetics of a single dose of fimasartan (BR-A-657), a newly developed angiotensin II receptor antagonist for the treatment of hypertension, in 22 healthy participants. Ketoconazole increased the maximumplasma concentration (Cmax) and area under the plasma concentration vs time curve to infinity (AUC∞ of fimasartan by 2.47-fold (90% confidence interval [CI], 1.
View Article and Find Full Text PDFJ Environ Sci Health A Tox Hazard Subst Environ Eng
March 2012
A new petroleum hydrocarbon-degrading fungus, isolated from an oil contaminant soil, was identified as Neosartorya (teleomorph of Aspergillus) sp. This isolate was able to degrade total petroleum hydrocarbons (TPHs) without a lag phase, but degradation rates decreased with increasing initial TPH concentrations (5,000-20,000 mg L(-1)). The TPH degradation by the isolate showed a substrate inhibition behavior with an inhibition constant (K(i)) of 1,860 mg L(-1).
View Article and Find Full Text PDFWe report the discovery and characterization of SM-406 (compound 2), a potent and orally bioavailable Smac mimetic and an antagonist of the inhibitor of apoptosis proteins (IAPs). This compound binds to XIAP, cIAP1, and cIAP2 proteins with K(i) of 66.4, 1.
View Article and Find Full Text PDFA series of compounds were designed and synthesized as antagonists of cIAP-1/2 and XIAP based upon our previously identified lead compound SM-122 (1). The most potent of these (7) binds to XIAP, cIAP-1, and cIAP-2 proteins with K(i) values of 36, <1, and <1.9 nM, respectively.
View Article and Find Full Text PDFWe report herein the structure-based design of a class of conformationally constrained, potent, cell-permeable small-molecule inhibitors to target the SH2 domain in STAT3. Compound 11 (CJ-1383) binds to STAT3 with a K(i) value of 0.95 µM, dose-dependently inhibits cellular STAT3 signaling and cancer cell growth, and induces apoptosis in the MDA-MB-468 cancer cell line with constitutively activated STAT3.
View Article and Find Full Text PDFLeptin is a peptide hormone produced primarily by adipose tissue that acts as a major regulator of food intake and energy homeostasis. Impaired transport of leptin across the blood-brain barrier (BBB) contributes to leptin resistance, which is a cause of obesity. Leptin as a candidate for the treatment of this obesity is limited because of the short half-life in circulation and the decreased BBB transport that arises in obesity.
View Article and Find Full Text PDFA series of novel 4-hydroxybenzaldehyde derivatives were synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were investigated. Most of target compounds had more potent inhibitory activities than the parent compound 4-hydroxybenzaldehyde (IC(50)=1.22 mM).
View Article and Find Full Text PDFThe STAT3 oncogene is a promising molecular target for the design of a new class of anticancer drugs. In this letter, we describe the design, synthesis, and evaluation of peptidomimetics containing Freidinger lactams as novel STAT3 inhibitors. Compound 3 binds to STAT3 with a K(i) value of 190nM and is a promising lead compound for further design and optimization.
View Article and Find Full Text PDFMacromolecular assemblies play critical roles in regulating cellular functions. The cysteine synthase complex (CSC), which is formed by association of serine O-acetyltransferase (SAT) and O-acetylserine sulfhydrylase (OASS), acts as a sensor and modulator of thiol metabolism by responding to changes in nutrient conditions. Here we examine the oligomerization and energetics of formation of the soybean CSC.
View Article and Find Full Text PDFA series of small-molecule Smac mimetics containing a diazabicyclic core structure have been designed, synthesized, and evaluated. The most potent compound (6) binds to XIAP, cIAP-1, and cIAP-2 with K(i) values of 8.4, 1.
View Article and Find Full Text PDFThe inhibitory effects of four carbamate insecticides, methomyl, thiodicarb, carbofuran and carbosulfan, on acetylcholinesterase of male and female Carassius auratus were investigated in the laboratory. Kinetic constants, biomolecular rate constant (k(i)), carbamylation rate constant (k2) and decarbamylation rate constant (k3) were determined in vitro. The ratios of bimolecular rate constant (female/male) for AChE reacting with methomyl, thiodicarb, carbofuran and carbosulfan were 1.
View Article and Find Full Text PDFPropargylamine derivatives, rasagiline and (-)deprenyl, are anti-Parkinson agents and protect neurons from cell death as shown by in vivo and in vitro experiments. The studies on the chemical structure-activity relationship proved that the propargyl moiety is essentially required for the neuroprotective function. In this paper, neuroprotective activity of free N-propargylamine was studied using SH-SY5Y cells expressing only type A monoamine oxidase (MAO) against apoptosis induced by an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol.
View Article and Find Full Text PDFMassive, multiple fire ant, Solenopsis invicta, stings are often treated aggressively, particularly in the elderly, despite limited evidence of systemic toxicity due to the venom. Over 95% of the S. invicta venom is composed of piperidine alkaloid components, whose toxicity, if any, is unknown.
View Article and Find Full Text PDFPeptide deformylase catalyzes the removal of the N-terminal formyl group from newly synthesized polypeptides in eubacteria. Its essential character in bacterial cells makes it an attractive target for antibacterial drug design. In this work, we have rationally designed and synthesized a series of peptide thiols that act as potent, reversible inhibitors of purified recombinant peptide deformylase from Escherichia coli and Bacillus subtilis.
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