• Phelps Holland posted an update 6 months, 2 weeks ago

    To conclude, the activation of both the opioid and neurotensin receptors seems to be necessary to induce the full anti-inflammatory activity of the hybrid compound.This research presents the highly regioselective syntheses of 1,2-dicarboxylated cyclopentadienide salts 2 by reaction of a variety of organic cation methylcarbonate salts OCO2 Me (Cat=NR4 + , PR4 + , Im+ ) with cyclopentadiene (CpH) or by simply reacting organic cation cyclopentadienides Cat (Cat=NR4 + , PR4 + , Im+ ) with CO2 . One characteristic feature of these dianionic ligands is the acidic proton delocalized in an intramolecular hydrogen bridge (IHB) between the two carboxyl groups, as studied by 1 H NMR spectroscopy and XRD analyses. The reaction cannot be stopped after the first carboxylation. Therefore, we propose a Kolbe-Schmitt phenol-carboxylation related mechanism where the acidic proton of the monocarboxylic acid intermediate plays an ortho-directing and CO2 activating role for the second kinetically accelerated CO2 addition step exclusively in ortho position. The same and related thiocarboxylates 2 are obtained by reaction of COS with Cat (Cat=NR4 + , PR4 + , Im+ ). A preliminary study on 2 reveals, that its soft and hard coordination sites can selectively be addressed by soft Lewis acids (Mo0 , Ru2+ ) and hard Lewis acids (Al3+ , La3+ ).Calcium channels (CCs), a group of ubiquitously expressed membrane proteins, are involved in many pathophysiological processes of protozoan parasites. Our understanding of CCs in cell signaling, organelle function, cellular homeostasis, and cell cycle control has led to improved insights into their structure and functions. In this article, we discuss CCs characteristics of five major protozoan parasites Plasmodium, Leishmania, Toxoplasma, Trypanosoma, and Cryptosporidium. We provide a comprehensive review of current antiparasitic drugs and the potential of using CCs as new therapeutic targets. Interestingly, previous studies have demonstrated that human CC modulators can kill or sensitize parasites to antiparasitic drugs. Still, none of the parasite CCs, pumps, or transporters has been validated as drug targets. Information for this review draws from extensive data mining of genome sequences, chemical library screenings, and drug design studies. Parasitic resistance to currently approved therapeutics is a serious and emerging threat to both disease control and management efforts. In this article, we suggest that the disruption of calcium homeostasis may be an effective approach to develop new anti-parasite drug candidates and reduce parasite resistance.Effective drugs that can cure cognitive impairments remain elusive. Because synaptic dysfunction has been correlated with cognitive impairments, drug development to target synaptic dysfunction is important. Recently, natural compounds and crude drugs have emerged as potential therapeutic agents for cognitive disorders. However, their effects on synaptic function remain unclear, because of lack of evaluation system with high reproducibility. We have recently developed highly reproducible in vitro high-content imaging analysis system for evaluation of synaptic function using drebrin as a marker for synaptic states. Therefore, we aimed to examine the direct effects of well-known natural compounds and crude drugs on synaptic states using this system. Rat hippocampal neurons were treated using natural compounds (nobiletin, diosgenin and tenuifolin) and crude drugs (Uncaria Hook , Bezoar Bovis , Coptis Rhizome , Phellodendron Bark and Polygala Root ). Immunocytochemical analysis was performed, and dendrite lengths and drebrin cluster densities were automatically quantified. We found that diosgenin, tenuifolin, CR, PB and PR decreased drebrin cluster densities, and the effects of PB and PR were partially dependent on N-methyl-D-aspartic acid-type glutamate receptors (NMDARs). Nobiletin and UH did not show any effects, whereas low-dose BB treatment increased drebrin cluster densities. Our results showed that diosgenin, tenuifolin, BB, CR, PB and PR appeared to directly change synaptic states. Particularly, the NMDAR dependency of PB and PR appears to affect synaptic plasticity.Hydrogels with improved mechanical properties can expand to a greater range of applications. The fabrication of conventional toughened hydrogels typically requires precise modifications, multiple components, and complex steps. Here, a straightforward “one-step” polymerization method for the in situ preparation of hydrogels in aqueous solutions, is reported. Inspired by polymerization-induced self-assembly (PISA), water-miscible monomers are copolymerized during the hydrogel fabrication; the growing blocks eventually form physical bridges thus providing a mechanism for effective energy dissipation. The rheological and mechanical properties are evaluated and the results reveal that this strategy can be an effective approach to design mechanically enhanced hydrogels for a wide range of applications.Metabolic syndrome (MetS) is one of the most important health hazards. Curcumin is extracted from Curcuma longa (turmeric), which can affect the components of MetS. To increase the oral bioavailability of curcumin, nano-micelle curcumin is used instead of curcumin powder. In this randomized, double-blind, controlled clinical trial, 50 patients with MetS were randomly assigned to two groups to receive either 80 mg/day nano-curcumin (n = 25) or placebo (n = 25), for 12 weeks anthropometric measurements, blood pressure, and biochemical factors-including fasting blood sugar (FBS), Hemoglobin A1c (HbA1c), homeostatic model assessment (HOMA) for insulin resistance (HOMA-IR), pancreatic β cell function (HOMA-β) and lipid profile-were assessed at the baseline and the end of the study. find more Statistical analyses were done using SPSS software (Version 23). The analysis between the two groups has illustrated a significant reduction in the average change of triglyceride (TG) levels (-60.5 ± 121.7 vs. 13.1 ± 78.1 mg/dL; p  less then  .

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