PEG-400: An efficient and recyclable reaction medium for the synthesis of pyrazolo[1,5-a]pyrimidines

An efficient and convenient route is described for the synthesis of new pyrazolo [1,5-a] pyrimidine derivatives by the reaction of 4-(4’-chloro-phenylazo)-5-amino pyrazole with α,β-unsaturated carbonyl compounds (chalcones) using polyethylene glycol (PEG-400) as benign reaction medium. The advantage of this protocol includes the excellent yields, operational simplicity, short reaction times and avoidance of volatile organic solvents and expensive catalysts

Clinical- and cost-effectiveness of a technology-supported and solution-focused intervention (DIALOG plus ) in treatment of patients with chronic depression-study protocol for a multi-site, cluster randomised controlled trial [TACK]

Background Many with an acute depressive disorder go on to develop chronic depression, despite ongoing care. There are few specifically designed interventions to treat chronic depression. DIALOG+, a technology-assisted intervention based on the principles of solution-focused therapy, may be beneficial. It has been shown to be effective as a treatment for patients with psychotic disorders, especially in regards to increasing quality of life. DIALOG+ was designed to be flexibly applied and not diagnosis-specific, aiming to structure communication and generate a personally-tailored care plan. This cluster randomised controlled trial (RCT) is part of a programme of research to adapt and test DIALOG+ for patients with chronic depression. Methods Patients will be eligible for the trial, if they have exhibited symptoms of depression or non-psychotic low mood for at least 2 years, have regular contact with a clinician and have a low subjective quality of life and moderate depressive symptoms. Clinicians, who routinely see eligible patients, will be recruited from a number of sites across NHS England. Clusters will have between 1 and 6 patients per clinician and will be randomised in a 1:1 ratio to either the intervention (DIALOG+) or active control group (treatment as usual + DIALOG scale). Clinicians in the intervention group are trained and asked to deliver the intervention regularly for 12 months. Active control participants receive treatment as usual and are asked to rate their satisfaction with areas of life and treatment on the DIALOG scale at the end of the clinical session. Approximately 112 clinician clusters will be recruited to reach a total patient sample size of 376. Clinical and social outcomes including costs are assessed at baseline and 3, 6 and 12 months post randomisation. The primary outcome will be subjective quality of life at 12 months. Discussion This definitive multi-site, cluster RCT aims to evaluate the clinical- and cost-effectiveness of DIALOG+ for people with chronic depression. If shown to be effective for this patient population it could be used to improve outcomes of mental health care on a larger scale, ensuring that patients with complex and co-morbid diagnoses can benefit. Trial registration ISRCTN11301686. Registered on 13 Jun 2019

NaOH/PEG-400: An eloquent system for the synthesis of new thienyl benzo[b]1,4-diazepines

A simple and eloquent procedure for the synthesis of a new series of thienyl benzo[b]1,4-diazepines is reported. They were synthesized by the condensation of o-phenylenediamine (o-PDA) with distinct hetero chalcones using NaOH in polyethylene glycol (PEG-400) as green and alternative reaction solvent. The significances of this present method are shorter reaction time, easy work-up, high yields, and mild reaction conditions. Furthermore, this method is environment friendly and without use of an expensive catalyst. The all newly synthesized compounds are characterized by the spectroscopic methods

A novel and efficient approach for the synthesis of new halo substituted 2-arylpyrazolo[4,3-c] coumarin derivatives

A convenient protocol for the efficient synthesis of 2-arylpyrazolo[4,3-c]coumarins is described. The synthesis route involves molecular iodine catalyzed oxidative cyclization of 1-phenyl-3-(2'-hydroxyaryl)-4-formyl pyrazoles in dimethylsulfoxide. During the lactonisation of 4-formylpyrazoles, we found that iodine was incorporated into the unsubstituted O/P position of the 3-(2'-hydroxyaryl) group. Under similar conditions o-allyloxy derivative of pyrazoles gave same corresponding lactone derivatives by deallylation, lactonisation, and iodination in one step

Preventive Effect of Flavonol Derivatives Abundant Sanglan Tea on Long-Term High-Fat-Diet-Induced Obesity Complications in C57BL/6 Mice

Sanglan Tea (SLT) is a Chinese medicine-based formulation that is consumed as a health drink for the effective management of obesity-associated complications. However, its chemical components and mechanism of action in the prevention of hepatic steatosis and obesity-related impairments have been uncertain. In this study, we aimed to unveil the chemical profile of SLT and to explore its preventive mechanism in high-fat-diet-induced non-alcoholic fatty liver disease (NAFLD) and obesity-related consequences in C57BL/6 mice. Ultrahigh-performance liquid chromatography (UHPLC) coupled to a quadrupole-orbitrap high-resolution mass spectrometry (MS) analysis of SLT indicated that analogs of quercetin and kaempferol are major compounds of flavonoids in SLT. A dietary supplement of SLT efficiently managed the blood glucose elevation, retained the serum total cholesterol (TC), LDL-cholesterol (LDL-C), and triglyceride (TG) levels, as well as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity, and reduced the fat storage in the liver induced by a high-fat diet. The underlying mechanism of this preventive effect is hypothesized to be related to the inhibition of over-expression of lipogenesis and adipogenesis-related genes. Overall, this study suggests that SLT, being rich in quercetin and kaempferol analogs, could be a potential food supplement for the prevention of high-fat-diet-induced NAFLD and obesity-related complications

Dietary Supplement of Large Yellow Tea Ameliorates Metabolic Syndrome and Attenuates Hepatic Steatosis in db/db Mice

Yellow tea has been widely recognized for its health benefits. However, its effects and mechanism are largely unknown. The current study investigated the mechanism of dietary supplements of large yellow tea and its effects on metabolic syndrome and the hepatic steatosis in male db/db mice. Our data showed that dietary supplements of large yellow tea and water extract significantly reduced water intake and food consumption, lowered the serum total and low-density lipoprotein cholesterol and triglyceride levels, and significantly reduced blood glucose level and increased glucose tolerance in db/db mice when compared to untreated db/db mice. In addition, the dietary supplement of large yellow tea prevented the fatty liver formation and restored the normal hepatic structure of db/db mice. Furthermore, the dietary supplement of large yellow tea obviously reduced the lipid synthesis related to gene fatty acid synthase, the sterol regulatory element-binding transcription factor 1 and acetyl-CoA carboxylase α, as well as fatty acid synthase and sterol response element-binding protein 1 expression, while the lipid catabolic genes were not altered in the liver of db/db mice. This study substantiated that the dietary supplement of large yellow tea has potential as a food additive for ameliorating type 2 diabetes-associated symptoms

ATAD2 is a driver and a therapeutic target in ovarian cancer that functions by upregulating CENPE

Abstract Ovarian cancer is a complex disease associated with multiple genetic and epigenetic alterations. The emergence of treatment resistance in most patients causes ovarian cancer to become incurable, and novel therapies remain necessary. We identified epigenetic regulator ATPase family AAA domain-containing 2 (ATAD2) is overexpressed in ovarian cancer and is associated with increased incidences of metastasis and recurrence. Genetic knockdown of ATAD2 or its pharmacological inhibition via ATAD2 inhibitor BAY-850 suppressed ovarian cancer growth and metastasis in both in vitro and in vivo models. Transcriptome-wide mRNA expression profiling of ovarian cancer cells treated with BAY-850 revealed that ATAD2 inhibition predominantly alters the expression of centromere regulatory genes, particularly centromere protein E (CENPE). In ovarian cancer cells, changes in CENPE expression following ATAD2 inhibition resulted in cell-cycle arrest and apoptosis induction, which led to the suppression of ovarian cancer growth. Pharmacological CENPE inhibition phenotypically recapitulated the cellular changes induced by ATAD2 inhibition, and combined pharmacological inhibition of both ATAD2 and CENPE inhibited ovarian cancer cell growth more potently than inhibition of either alone. Thus, our study identified ATAD2 as regulators of ovarian cancer growth and metastasis that can be targeted either alone or in combination with CENPE inhibitors for effective ovarian cancer therapy

Utilization of De-oiled Jatropha Seed Cake for Renewable Gaseous Fuel Production and Digested Slurry for Growing Crops

Bio-methanation potential of de-oiled Jatropha seed cake was tested in a 1,200 l existing pilot plant digester in semi-continuous mode. The plant performance was monitored for 12 months at 15% (w/v) total solid concentration. Biogas production in the range of 229-370 l.kg-1 total solids was achieved in 40-days hydraulic retention time. The biogas produced from de-oiled Jatropha seed cake had higher calorific value as compared to the gas generated from cattle dung, as it had more methane content. The nutrient potential of the digested slurry and its toxicity on plants was studied by a series of pot culture experiments using maize (Zea mays L.) yields as the reference. The results indicated that the experimental digested slurry served as an excellent organic fertilizer, and was non-toxic to the plants