Synthesis,molecular docking,acetylcholinesterase and butyrylcholinesterase inhibitory potential of thiazole analogs as new inhibitors for Alzheimer disease

A series of thirty (30) thiazole analogs were prepared, characterized by ¹H NMR, ¹³C NMR and EI-MS and evaluated for Acetylcholinesterase and butyrylcholinesterase inhibitory potential. All analogs exhibited varied butyrylcholinesterase inhibitory activity with IC₅₀ value ranging between 1.59 ± 0.01 and 389.25 ± 1.75 μM when compared with the standard eserine (IC₅₀, 0.85 ± 0.0001 μM). Analogs 15, 7, 12, 9, 14, 1, 30 with IC₅₀ values 1.59 ± 0.01, 1.77 ± 0.01, 6.21 ± 0.01, 7.56 ± 0.01, 8.46 ± 0.01, 14.81 ± 0.32 and 16.54 ± 0.21 μM respectively showed excellent inhibitory potential. Seven analogs 15, 20, 19, 24, 28, 30 and 25 exhibited good acetylcholinesterase inhibitory potential with IC50 values 21.3 ± 0.50, 35.3 ± 0.64, 36.6 ± 0.70, 44.81 ± 0.81, 46.36 ± 0.84, 48.2 ± 0.06 and 48.72 ± 0.91 μM respectively. All other analogs also exhibited well to moderate enzyme inhibition. The binding mode of these compounds was confirmed through molecular docking.     

分泌型磷脂酶PLA2G5的生物学功能及其抑制剂研究进展

分泌型磷脂酶PLA2G5属于磷脂酶A2超家族的一员,在免疫细胞和非免疫细胞中均有表达.研究表明,PLA2G5参与生物学事件的发生发展,在特定的病理条件下具有诱导作用.本文简要阐述了PLA2G5的来源、结构特征、生物学功能和在疾病中的作用,以及现有或潜在的PLA2G5抑制剂,以期探索基于PLA2G5的治疗新靶标.     

Essential role of MESP1-RING1A complex in cardiac differentiation

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Deciduous enamel defects and caries susceptibility in a prehistoric Ohio population

Clinical studies of the relationship between developmental enamel defects and caries susceptibility have often produced conflicting results. This has been due in part to a failure to distinguish between different types of defects. Studies of this association in prehistoric populations have been rare. The complete deciduous dentitions of 57 subadults from the Libben site, a large Late Woodland cemetery in Ottawa County, Ohio, were selected for analysis. Defects were classified as either hypoplasias (deficiencies in matrix apposition) or hypocalcifications (deficiencies in mineralization) and were graded for severity. The presence or absence of carious lesions was recorded for each tooth. Results indicate a strong positive relationship between hypocalcifications and caries susceptibility. The elevated caries susceptibility of hypocalcified teeth may be related to high levels of magnesium or altered enamel microcrystallite orientation within these teeth. Variations in the frequency of hypocalcifications may partially explain differences in caries rates that have been observed in different prehistoric populations.     

Biomechanical rationale of coronary artery bypass grafting of multivessel disease

The biomechanical model of human coronary arteries was modified for improving the quality of diagnosis and surgical treatment for coronary heart disease. The problem of hemodynamics in the left coronary artery with multivessel bed disease – 45% stenosis of the anterior descending branch and 75% stenosis of the circumflex branch – was particularly considered. Numerical simulation of the coronary arterial bypass of the main trunk was carried out to estimate the functional condition of the coronary arteries after restoring myocardial blood supply by surgery.     

Distribution of Fusarium wilt of Bambara nut (Vigna subterranea (L.) Verdc.) in farmers’ fields’ of Busia County in Western Kenya and its management using farmyard manure

A study was carried out to determine Fusarium wilt distribution in Bambara nut farmers’ fields and its management using farm yard manure (FYM). Four villages in Busia County were purposively sampled for the study. The data generated were subjected to analysis of variance and treatment means separated by least significant difference test. Fusarium wilt incidence in the fields ranged from 14.63 to 43.56%. In the greenhouse, FYM reduced the disease incidence by 10.2% and severity by 9.5% on the black landrace and 1.9 and 12.8%, respectively, on the red landrace. In the field, FYM reduced disease incidence by 9.1% and severity by 6.9% on the black landrace and 10.4 and 10.4%, respectively, on the red landrace. Farm yard manure had the lowest area under disease progress curve irrespective of the landrace. The study confirmed the presence of the pathogen in the fields and the ability to manage the disease using FYM.     

Uric acid modulates vascular endothelial function through the down regulation of nitric oxide production

Abstract

Endothelial dysfunction characterized by decreased nitric oxide (NO) bioavailability is the first stage of coronary artery disease. It is known that one of the factors associated with an increased risk of coronary artery disease is a high plasma level of uric acid. However, causative associations between hyperuricaemia and cardiovascular risk have not been definitely proved. In this work, we tested the effect of uric acid on endothelial NO bioavailability. Electrochemical measurement of NO production in acetylcholine-stimulated human umbilical endothelial cells (HUVECs) revealed that uric acid markedly decreases NO release. This finding was confirmed by organ bath experiments on mouse aortic segments. Uric acid dose-dependently reduced endothelium-dependent vasorelaxation. To reveal the mechanism of decreasing NO bioavailability we tested the effect of uric acid on reactive oxygen species production by HUVECs, on arginase activity, and on acetylcholine-induced endothelial NO synthase phosphorylation. It was found that uric acid increases arginase activity and reduces endothelial NO synthase phosphorylation. Interestingly, uric acid significantly increased intracellular superoxide formation. In conclusion, uric acid decreases NO bioavailability by means of multiple mechanisms. This finding supports the idea of a causal association between hyperuricaemia and cardiovascular risk.     

Possible Phytoplasma Disease in Papaya (Carica papaya L.) from Baja California Sur: Diagnosis by Scanning Electron Microscopy

The symptoms of possible phytoplasma infection in introduced and local varieties of papaya were first noted in the Mexican state of Baja California Sur (BCS) during field surveys in 2002–2003. Phytoplasma structures were observed using scanning electron microscopy (SEM) in phloem sieve elements in diseased papaya plants, but not in healthy plants. They were rounded structures 400–1600 nm in diameter. This is the first report of the possible association of phytoplasmas with diseased papaya plants in BCS. The use of SEM for the primary detection of disease aetiology is discussed.     

Detection of a natural point mutation in Potato virus A that overcomes resistance to vascular movement in Nicandra physaloides., and studies on seed-transmissibility of the mutant virus

Isolate M of Potato virus A (PVA‐M; genus Potyvirus) is avirulent in Nicandra physaloides L. (family Solanaceae). The inoculated leaves are infected but no systemic infection is observed. Forty plants of ‘Black Pod’ (BP) and ‘Black Pod Alba’ (BPA), two variants of N. physaloides described in this study, were inoculated with PVA‐M. Two plants of BP and one plant of BPA were systemically infected. Mosaic, blistering and dark green islands developed on the systemically infected leaves, and flowers showed colour‐break symptoms. PVAprogeny were sequence‐characterised for the 6K2 protein and viral genome‐linked protein (VPg) encoding regions known to control the long distance movement of PVA in N. physaloides. All virus progeny (designated as PVA‐Mm) in the systemically infected leaves of the plants inoculated with PVA‐M contained only a single amino acid substitution (Vail 16Met) in the central part of VPg due to a nucleotide substitution G6033A, as compared to PVA‐M. Other PVA isolates that infected N. physaloides systemically also contained Metll6 in VPg. In a previous study using chimeric viruses, Metl16 in VPg was shown to be a major determinant for vascular movement of PVA in N. physaloides, and this study reveals that the mutation for Metl16 can occur in vivo during replication of the avirulent PVA‐M in infected plants. Immunolocalisation studies on BP and BPA plants showed that the pods (berries) and seed coat contained PVA‐Mm in the developing seeds, but no virus was detected in embryons. Up to 27% of the mature seeds contained PVA‐Mm but no transmission to seedlings was observed in a total of 450 seeds tested, and no test plants were infected following mechanical inoculation with extracts prepared from the seeds.