Synthesis of sulfadiazinyl acyl/aryl thiourea derivatives as calf intestinal alkaline phosphatase inhibitors,pharmacokinetic properties,lead optimization,Lineweaver-Burk plot evaluation and binding analysis

To seek the new medicinal potential of sulfadiazine drug, the free amino group of sulfadiazine was exploited to obtain acyl/aryl thioureas using simple and straightforward protocol. Acyl/aryl thioureas are well recognized bioactive pharmacophore containing moieties. A new series (4a–4j) of sulfadiazine derived acyl/aryl thioureas was synthesized and characterized through spectroscopic and elemental analysis. The synthesized derivatives 4a–4j were subjected to calf intestinal alkaline phosphatase (CIAP) activity. The derivative 4a–4j showed better inhibition potential compared to standard monopotassium phosphate (MKP). The compound 4c exhibited higher potential in the series with IC₅₀ 0.251?±?0.012?µM (standard KH₂PO₄ 4.317?±?0.201?µM). Lineweaver-Burk plots revealed that most potent derivative 4c inhibition CIAP via mixed type pathway. Pharmacological investigations showed that synthesized compounds 4a–4j obey Lipinsk’s rule. ADMET parameters evaluation predicted that these molecule show significant lead like properties with minimum possible toxicity and can serve as templates in drug designing. The synthetic compounds show none mutagenic and irritant behavior. Molecular docking analysis showed that compound 4c interacts with Asp273, His317 and Arg166 amino acid residues.     

<Emphasis Type="Italic">TaELF3-1DL</Emphasis>, a homolog of <Emphasis Type="Italic">ELF3</Emphasis>, is associated with heading date in bread wheat

Early flowering 3 (ELF3) is a regulator to modulate photoperiod flowering in Arabidopsis. The homologs of ELF3 in rice and barley also have been identified essential for regulation of flowering time. In the current study, TaELF3 genes, homologs of ELF3 in bread wheat (Triticum aestivum L.), were cloned by a comparative genomics approach and located on homologous group 1 chromosomes, designated as TaELF3-1AL, TaELF3-1BL, and TaELF3-1DL, respectively. A sequence-tagged site (STS) marker was developed based on sequence polymorphism at the TaELF3-1DL locus. A quantitative trait locus (QTL) for heading date (HD) co-segregating with TaELF3-1DL explained 7.7–20.6% of the phenotypic variance in a RIL mapping population derived from the Gaocheng 8901/Zhoumai 16 cross genotyped using the wheat 90K iSelect assay. The late HD allele of TaELF3-1DL was prevalently selected in China’s specific wheat-growing regions and other countries. This study produces novel information in better understanding HD and provides a reliable functional marker for molecular marker-assisted selection in wheat breeding.     

Length–weight relationships of four fish species from a coastal artisanal fishery,southern Bangladesh

This study presents the first report of length–weight relationships (LWRs) for Apocryptes bato (Hamilton, 1822), Salmophasia phulo (Hamilton, 1822), and Silonia silondia (Hamilton, 1822), excluding Anodontostoma chacunda (Hamilton, 1822), from fishermen's catches landed in a coastal artisanal fishery at Patuakhali, Southern Bangladesh. Specimens were sampled occasionally over a period of 1 year between August 2014 and September 2015. Fishes were collected from coastal fishermen using cast nets (mesh size <0.5 cm) for A. bato, set bag nets (mesh size 0.5 cm) for A. chacunda and S. silondia, and lift nets (mesh size <0.5 cm) for S. phulo. The LWRs obtained were W = 0.006L^2.99, (r²) = 0.976, W = 0.011L^3.04, (r²) = 0.971, W = 0.006L^3.00, (r²) = 0.945 and W = 0.007L^2.99, (r²) = 0.988 for A. bato, A. chacunda, S. phulo, and S. silondia, respectively.     

Oxytocin action: lipid metabolism in adipocytes from homozygous diabetes insipidus rats (Brattleboro strain)

Oxytocin, like insulin, stimulates glucose oxidation in normal rat adipocytes. Fat cells from homozygous Brattleboro rats that exhibit diabetes insipidus (HoDI animals) and that have a normal number of oxytocin receptors, however, are unable to respond to oxytocin in terms of glucose oxidation. We now report that in adipocytes from HoDI animals that are responsive to insulin, oxytocin was also unable to stimulate lipogenesis. In contrast, oxytocin like insulin was able to inhibit epinephrine-stimulated lipolysis in adipocytes from HoDI animals. Thus, in HoDI adipocytes, the results indicate that the receptor-effector system is only partially defective.     

Plant polyphenols mobilize endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: a putative mechanism for anticancer properties

Plant polyphenols are important components of human diet and a number of them are considered to possess chemopreventive and therapeutic properties against cancer. They are recognized as naturally occurring antioxidants but also act as prooxidants catalyzing DNA degradation in the presence of transition metal ions such as copper. Using human peripheral lymphocytes and Comet assay we have previously confirmed that resveratrol-Cu(II) is indeed capable of causing DNA degradation in cells. In this paper we show that the polyphenols alone (in the absence of added copper) are also capable of causing DNA breakage in cells. Incubation of lymphocytes with neocuproine inhibited the DNA degradation confirming that Cu(I) is an intermediate in the DNA cleavage reaction. Further, we have also shown that polyphenols generate oxidative stress in lymphocytes which is inhibited by scavengers of reactive oxygen species and neocuproine. These results are in further support of our hypothesis that anticancer mechanism of plant polyphenols involves mobilization of endogenous copper, possibly chromatin bound copper, and the consequent prooxidant action.     

Large-scale validation of a latex agglutination test for diagnosis of tuberculosis

Large-scale validation of a simple latex agglutination test for the diagnosis of tuberculosis is described. Soluble antigens extracted from a non-pathogenic saprophytic mycobacterium, Mycobacterium w, which shares antigenic determinants with Mycobacterium tuberculosis, were covalently linked to carboxylated polystyrene latex beads. Batch to batch reproducibility of coated latex was ensured. Latex reagents were standardized to overcome non-specific agglutination. Reagents of the test are stable for 1 year at 4 degrees C. A total of 1,058 serum samples of pulmonary and extrapulmonary tuberculosis patients or patients with other pulmonary diseases and healthy controls living in endemic areas were tested. Sensitivity of 94% for pulmonary tuberculosis and 87% for extrapulmonary tuberculosis was obtained. Specificity is 92.2% for healthy controls and patients with other respiratory diseases. We conclude that the latex agglutination test can be utilized for mass screening for both pulmonary and extrapulmonary tuberculosis where diagnosis by existing methods is much more difficult.     

Food environment and diabetes mellitus in South Asia: A geospatial analysis of health outcome data

BackgroundThe global epidemic of type 2 diabetes mellitus (T2DM) renders its prevention a major public health priority. A key risk factor of diabetes is obesity and poor diets. Food environments have been found to influence people’s diets and obesity, positing they may play a role in the prevalence of diabetes. Yet, there is scant evidence on the role they may play in the context of low- and middle-income countries (LMICs). We examined the associations of food environments on T2DM among adults and its heterogeneity by income and sex.Methods and findingsWe linked individual health outcome data of 12,167 individuals from a network of health surveillance sites (the South Asia Biobank) to the density and proximity of food outlets geolocated around their homes from environment mapping survey data collected between 2018 and 2020 in Bangladesh and Sri Lanka. Density was defined as share of food outlets within 300 m from study participant’s home, and proximity was defined as having at least 1 outlet within 100 m from home. The outcome variables include fasting blood glucose level, high blood glucose, and self-reported diagnosed diabetes. Control variables included demographics, socioeconomic status (SES), health status, healthcare utilization, and physical activities. Data were analyzed in ArcMap 10.3 and STATA 15.1. A higher share of fast-food restaurants (FFR) was associated with a 9.21 mg/dl blood glucose increase (95% CI: 0.17, 18.24; p < 0.05). Having at least 1 FFR in the proximity was associated with 2.14 mg/dl blood glucose increase (CI: 0.55, 3.72; p < 0.01). A 1% increase in the share of FFR near an individual’s home was associated with 8% increase in the probability of being clinically diagnosed as a diabetic (average marginal effects (AMEs): 0.08; CI: 0.02, 0.14; p < 0.05). Having at least 1 FFR near home was associated with 16% (odds ratio [OR]: 1.16; CI: 1.01, 1.33; p < 0.05) and 19% (OR: 1.19; CI: 1.03, 1.38; p < 0.05) increases in the odds of higher blood glucose levels and diagnosed diabetes, respectively. The positive association between FFR density and blood glucose level was stronger among women than men, but the association between FFR proximity and blood glucose level was stronger among men as well as among those with higher incomes. One of the study’s key limitations is that we measured exposure to food environments around residency geolocation; however, participants may source their meals elsewhere.ConclusionsOur results suggest that the exposure to fast-food outlets may have a detrimental impact on the risk of T2DM, especially among females and higher-income earners. Policies should target changes in the food environments to promote better diets and prevent T2DM.

Dian Kusuma and colleagues investigate the associations between exposure to the density and proximity of healthy and unhealthy food outlets and diabetes in Bangladesh and Sri Lanka.