Testing the sensitivity and specificity of the fluorescence microscope (Cyscope®) for malaria diagnosis

Malaria pathogens are transmitted to humans by the bite of female Anopheles mosquitoes. The juvenile stages of these mosquitoes develop in a variety of water bodies and are key targets for vector control campaigns involving the application of larvicides. The effective operational implementation of these campaigns is difficult, time consuming, and expensive. New evidence however, suggests that adult mosquitoes can be co-opted into disseminating larvicides in a far more targeted and efficient manner than can be achieved using conventional methods.     

Dipeptides in nutrition and therapy: cyanophycin-derived dipeptides as natural alternatives and their biotechnological production

The numerous physiological functions of the nonessential amino acid L-aspartate, the semi-essential amino acid L-arginine, and the essential amino acid L-lysine, made them attractive for a wide range of nutritional and/or therapeutic applications. Furthermore, the administration of these amino acids as mixtures or as dipeptides for higher bioavailability is scientifically approved, and various commercial products of these forms are already available on the market. Although the industrial production of dipeptides is, with few exceptions, in an early stage, several strategies have been established and are compared in this review. Additionally, the recent developments in the technical production of aspartate–arginine and aspartate–lysine dipeptides from the biopolymer cyanophycin produced in microorganisms are discussed. Cyanophycin-derived dipeptides are produced exclusively by biotechnological procedures, probably possess higher bioavailability and may be used as better alternatives to the widely applied amino acid mixtures. Thus, the pivotal advantages and the potential applications of these dipeptides as well as of their constituting amino acids in nutrition and therapy are also discussed. Special emphasis is dedicated to arginine due to its numerous physiological roles in many cardiovascular, genitourinary, gastrointestinal, and immune disorders.     

Sustained Release Tablets Containing Soluble Polymethacrylates: Comparison with Tableted Polymethacrylate IPEC Polymers

The objective of this study was to compare a novel sustained release tablet formulation that has the potential to be used for drugs of different physicochemical properties using a binary mixture of polymethacrylate polymers in their salt forms with the polymethacrylate interpolyelectrolyte complex (IPEC) tablets in terms of drug release and compactness. Also, we aimed to compare this formulation with an IPEC tablet in terms of drug release. Tablets prepared using Eudragit E-Citrate and Eudragit L-Sodium were more convenient, easier to prepare, and showed better sustained release and compactness characteristics compared to IPEC tablets of similar concentrations and preparation methods.     

The role of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) gene expression in diagnosis and prognosis of acute myeloid leukemia

Molecular Biology Reports - Acute myeloid leukemia (AML) is still challenging in predicting the prognosis due to its high heterogeneity. Molecular aberrations and abnormalities play a significant...     

Comprehensive Profiling of Plasma Fatty Acid Concentrations in Young Healthy Canadian Adults

Circulating fatty acids (FA) are associated with a multitude of chronic diseases. However, a major gap in establishing such relationships is the lack of accepted fatty acid reference ranges representing healthy individuals. Data on validated FA reference ranges would provide a better understanding of study baseline measures and aid in the evaluation and interpretation of pharmaceutical or dietary interventions. Reference ranges for plasma FA levels have been reported in a few small studies and on a limited number of FA. Therefore, we determined the average and percentiles of a broad set of 61 FA (C14 - C24:1) from plasma total lipids from an ethnically diverse population of healthy young Canadian males and females (Total n = 826). Plasma concentrations of some of the major FA ranged from 0.3 to 4.1 mmol/L for palmitic acid, 0.1 to 1.0 mmol/L for stearic acid, 0.03 to 3.2 mmol/L for oleic acid, 0.2 to 5.0 mmol/L for linoleic acid (LA), 12.0 to 186.9 μmol/L for α-linolenic acid, and 7.2 to 237.5 μmol/L for docosahexaenoic acid (DHA). Males had significantly higher plasma concentrations of γ-linolenic acid (GLA) and n-3 docosapentaenoic acid and lower concentrations of palmitoleic acid, LA and DHA than females. Comparison of FA concentrations between Caucasians, East Asians and South Asians revealed that South Asians had significantly lower levels of palmitoleic acid (p < 0.01) and oleic acid (p = 0.01) while East Asians had lower levels of GLA (p = 0.02) and dihomo-γ-linolenic acid (p = 0.03). Overall, these data provide a comprehensive set of quantitative values that profiles a small cohort of Canadians which highlights the utility of establishing validated FA reference ranges that may be used to understand how deficient, suboptimal, or excess amounts of a given FA may be associated with chronic disease.     

Semisynthetic analogues of the marine cembranoid sarcophine as prostate and breast cancer migration inhibitors

Sarcophine (1) is a bioactive cembranoid diterpene isolated from the Red Sea soft coral Sarcophyton glaucum. Previous semisynthesis attempts resulted in decreased or complete loss of 1's anticancer activity. Sarcophine and analogues showed antimigratory activity against breast and prostate cancer cell lines. This encouraged further semisynthestic optimizations to improve its activity and establish a preliminary structure-activity relationship. Eight new and five known semisynthetic analogues were generated. These compounds were evaluated for their ability to inhibit growth, proliferation, and migration of the prostate and breast metastatic cancer cell lines PC-3 and MDA-MB-231, respectively. Most analogues exhibited enhanced antimigratory activity.     

Design, synthesis, and biological evaluation of substituted hydrazone and pyrazole derivatives as selective COX-2 inhibitors: Molecular docking study

New arylhydrazone derivatives and a series of 1,5-diphenyl pyrazoles were designed and synthesized from 1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione 1. The newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw oedema model. Moreover, they were tested for their inhibitory activity against ovine COX-1 and COX-2 using an in vitro cyclooxygenase (COX) inhibition assay. Some of the new compounds (2f, 6a and 6d) showed a reasonable in vitro COX-2 inhibitory activity, with IC?? value of 0.45 μM and selectivity index of 111.1. A virtual screening was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors. Docking study of the synthesized compounds 2f, 6a and 6d into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.     

Effect of spdC gene expression on virulence and antibiotic resistance in clinical Staphylococcus aureus isolates

International Microbiology - Surface protein display C (SpdC) protein was described as a novel virulence factor of Staphylococcus aureus that affects biofilm formation and pathogenesis and favors...     

Optimization of a Fluorescence-Based Assay for Large-Scale Drug Screening against Babesia and Theileria Parasites

A rapid and accurate assay for evaluating antibabesial drugs on a large scale is required for the discovery of novel chemotherapeutic agents against Babesia parasites. In the current study, we evaluated the usefulness of a fluorescence-based assay for determining the efficacies of antibabesial compounds against bovine and equine hemoparasites in in vitro cultures. Three different hematocrits (HCTs; 2.5%, 5%, and 10%) were used without daily replacement of the medium. The results of a high-throughput screening assay revealed that the best HCT was 2.5% for bovine Babesia parasites and 5% for equine Babesia and Theileria parasites. The IC₅₀ values of diminazene aceturate obtained by fluorescence and microscopy did not differ significantly. Likewise, the IC₅₀ values of luteolin, pyronaridine tetraphosphate, nimbolide, gedunin, and enoxacin did not differ between the two methods. In conclusion, our fluorescence-based assay uses low HCT and does not require daily replacement of culture medium, making it highly suitable for in vitro large-scale drug screening against Babesia and Theileria parasites that infect cattle and horses.