Synthesis and Evaluation of Antioxidant Activity of Some New Heterocyclic Compounds Bearing the Benzo[B]Furan Moiety

New compounds were synthesized by the reaction of 3-acetyl-5- methoxy-2-methylbenzofuran (1) with cyanoacetylhydrazine which afforded the hydrazide hydrazone derivative 2. Compound 2 underwent a series of heterocyclization reactions to give the new pyrazole, isoxazole, cyclopentanothiophene, thiazole, triazole, 2H-chromene and pyridone derivatives (3-13). The elemental and spectral data (IR, 1H NMR and MS) characterized their structures. Screening for some selected compounds was carried for their potential antioxidant activities using ABTS. Among the tested samples compounds 9, 11, 5 and 10 exhibited promising activity

Windbreak-Grown Casuarina and Eucalyptus Trees for Unbleached Kraft Pulp

A laboratory-scale evaluation was conducted of juvenile windbreak-grown Casuarina and Eucalyptus trees for kraft pulp production. Test results of unscreened pulp yields, pulp chemical analyses, and handsheet physical properties indicated that windbreak-grown materials are suitable for unbleached kraft pulp. Casuarina gave the best pulp yield and had higher tear strength than Eucalyptus, but both species were superior to kraft pulps from agricultural raw materials such as rice straw and Thymelia, which are currently used in Egypt. For both species, the best kraft pulping schedule tested was a 4:1 liquor-to-wood ratio with 20% active alkali with additional conditions constant. Scanning electron micrographs of handsheets helped explain the observed differences in physical properties between the two species. Mixing of Casuarina and Eucalyptus raw material prior to pulping shows promise for unbleached kraft pulp production

In vivo evaluation the efficiency of nitazoxanide with cationic Gemini surfactant on Cryptosporidiosis

تُعرض الإصابة بداء خفيات الأبواغ حياة العديد من الأشخاص للخطر وخصوصا المصابين بنقص المناعة، تحديدا مرضى فيروس نقص المناعة البشرية.  يُعد النيتازوكسانيد أحد الأدوية العلاجية الرئيسية المستخدمة في علاج داء الكريبتوسبوريديوسس. ومع ذلك، فهو ضعيف الذوبان في الماء ، مما يحد من فائدته وفعاليته في المرضى الذين يعانون من نقص المناعة. يحتوي الفاعل بالسطح على طابع برمائي وهذا يشير إلى قدرتها على تحسين قابلية الذوبان في الماء للعقار المضاد للماء. يتعلق بحثنا بتركيب مواد خافضة للتوتر السطحي من الجوزاء الموجبة الجديدة والتي لديها القدرة على تحسين قابلية ذوبان عقار نانازوكسيد. لذلك قمنا بتوليف مواد خافضة للتوتر السطحي توأمية موجبة.  N1,N1,N3,N3-tetramethyl-N1,N3-bis(2-octadecanamidoethyl)propane-1,3-diaminium bromide (CGSPS18) و  2,2‘-(ethane-1,2-diylbis(oxy))bis(N-(2-octadecanamidoethyl)-N,N-dimethyl-2-oxoethane-1-aminium) dichloride (CGSES18)   وتأكيد تركيبها الكيميائي بالطرق الطيفية المختلفة وكذلك دراسة خصائص السطح والسمية لها. بالإضافة إلى ذلك، تمت دراسة فعالية نيتازوكسانيد في الفئران المصابة بإضافة ثلاث جرعات مختلفة من المواد الخافضة للتوتر السطحي. لمعرفة تأثير النيتازوكسانيد والمواد الخافضة للتوتر السطحي معا، تم حساب العدوى بالطفيليات قبل العلاج وبعده ، كما تم فحص الأنسجة المعوية والكبدية والرئوية. في هذه الدراسة وجد أن الجمع بين عقار نيتازوكسانيد مع المواد الخافضة للتوتر السطحي وخاصة المركب (CGSPS18) بتركيز 25٪ زاد من الفعالية وأدى إلى انخفاض بنسبة 90.8٪. أظهر فحص الأنسجة المرضية أن المجموعة التي عولجت بعقار نيتازوكسانيد مع CGSPS18 أظهرت أفضل النتائج التي أظهرت نمطًا زغبيًا طبيعيًا تقريبًا. أظهرت هذه الدراسة زيادة في فعالية النيتازوكسانيد عند دمجه مع المواد الخافضة للتوتر السطحي ، وهذا يشير إلى مستقبل واعد لاستخدام المواد الخافضة للتوتر السطحي كعامل مساعد لتعزيز فعالية النيتازوكسانيد في علاج داء خفيات الأبواغ في المرضى الذين يعانون من نقص المناعة ، وخاصة مرضى فيروس نقص المناعة البشرية.Infection with cryptosporidiosis endangers the lives of many people with immunodeficiency, especially HIV patients. Nitazoxanide is one of the main therapeutic drugs used to treat cryptosporidiosis. However, it is poorly soluble in water, which restricts its usefulness and efficacy in immunocompromised patients. Surfactants have an amphiphilic character which indicates their ability to improve the water solubility of the hydrophobic drugs. Our research concerns the synthesis of new cationic Gemini surfactants that have the ability to improve the solubility of the drug Nanazoxide. So, we synthesized cationic Gemini surfactants. N1,N1,N3,N3-tetramethyl-N1,N3-bis(2-octadecanamidoethyl)propane-1,3-diaminium bromide (CGSPS18) and 2,2‘-(ethane-1,2-diylbis(oxy))bis(N-(2-octadecanamidoethyl)-N,N-dimethyl-2-oxoethane-1-aminium) dichloride (CGSES18) and the detection of their chemical composition by spectroscopic methods, as well as studying the properties of their surfaces and their toxicity. Furthermore, the efficacy of nitazoxanide in infected mice was studied in conjunction with three different doses of surfactants. To assess the effect of nitazoxanide and surfactants, the infection was parasitologically counted before and after treatment, and the intestinal, liver, and lung tissues were also examined histopathologically. In this study, it was found that the combination of the drug nitazoxanide with surfactants, especially the compound (CGSPS18) at a concentration of 25% increased the efficacy and resulted in a percentage reduction of 90.8%. Histopathological examination revealed that the group treated with the drug nitazoxanide in combination with CGSPS18 showed the best results exhibiting an almost normal villous pattern. This study demonstrated an increase in the effectiveness of nitazoxanide when combined with surfactants, and this suggests a promising future for the use of surfactants as an adjunct to enhance the effectiveness of nitazoxanide for the treatment of cryptosporidiosis in immunocompromised patients, particularly HIV patients

Mathematical Description of the Change in Properties of Casuarina Wood Upon Exposure to Gamma Radiation. 1. Changes in the Compressive and Tensile Strength

Casuarina cunninghamiana specimens were exposed to gamma-radiation doses ranging from 104 to 108 rad and tested in compression and tension parallel to grain. The percentage values of the irradiated specimens relative to that of the matched control (Y) were determined. The relationship between (Y) and log gamma radiation dose (X) was represented mathematically by the equation: Y = aXbcx. This equation described the change in compressive and tensile strength very well as was detected from the high correlation coefficients. Generally these properties increased slightly at low levels of radiation, reached a maximum, then decreased gradually thereafter. The reduction in tensile strength was more pronounced than in compressive strength.The threshold dose, i.e., the dose beyond which the properties began to decrease, was calculated. This dose ranged from 3.69 x 106 to 3.76 x 106 rad for compressive strength properties and from 1.51 x 106 to 1.70 x 106 rad for tensile strength properties. This indicated that irradiated casuarina wood had a greater resistance to compression than to tension

Synthesis of some nucleosides derivatives from L- rhamnose with expected biological activity

Practical procedures for production of variously blocked compounds from L-rhamnose have been developed. These compounds are highly useful as indirect β-L-rhamnosyl donors. This approach represents a new method for the synthesis of aromatic nucleoside analogues and the synthesis of (3S, 4S, 5S, 6R) 3, 4, 5-triacetoxy-2-methyl-7,9-diaza-1-oxa-spiro [4,5]decane-10-one-8-thione (7)

Insulin Gene Expression Is Regulated by DNA Methylation

BACKGROUND:Insulin is a critical component of metabolic control, and as such, insulin gene expression has been the focus of extensive study. DNA sequences that regulate transcription of the insulin gene and the majority of regulatory factors have already been identified. However, only recently have other components of insulin gene expression been investigated, and in this study we examine the role of DNA methylation in the regulation of mouse and human insulin gene expression. METHODOLOGY/PRINCIPAL FINDINGS:Genomic DNA samples from several tissues were bisulfite-treated and sequenced which revealed that cytosine-guanosine dinucleotide (CpG) sites in both the mouse Ins2 and human INS promoters are uniquely demethylated in insulin-producing pancreatic beta cells. Methylation of these CpG sites suppressed insulin promoter-driven reporter gene activity by almost 90% and specific methylation of the CpG site in the cAMP responsive element (CRE) in the promoter alone suppressed insulin promoter activity by 50%. Methylation did not directly inhibit factor binding to the CRE in vitro, but inhibited ATF2 and CREB binding in vivo and conversely increased the binding of methyl CpG binding protein 2 (MeCP2). Examination of the Ins2 gene in mouse embryonic stem cell cultures revealed that it is fully methylated and becomes demethylated as the cells differentiate into insulin-expressing cells in vitro. CONCLUSIONS/SIGNIFICANCE:Our findings suggest that insulin promoter CpG demethylation may play a crucial role in beta cell maturation and tissue-specific insulin gene expression

Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits — The Hispanic/Latino Anthropometry Consortium

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta‐analysis of individual participant data from 20 634 hospitalised patients with laboratory‐confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64–1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44–1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71–1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55–0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54–0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support