Mechanical, corrosion and biological behavior of centrifugal casting processed Mg-2Zn-1Mn alloy reinforced with ß Tricalciumphosphate (ßTCP) for orthopaedic applications.

Zinc and manganese were selected to develop magnesium alloys along with the bioactive ceramic ß Tricalciumphosphate (ßTCP) for biomedical applications fabricated by centrifugal casting. Microstructure, mechanical properties, corrosion properties, and biocompatibility of the Mg-2Zn-1Mn-xßTCP (x = 0, 2.5, 5 wt%) alloys have been investigated by use of an optical microscope, field emission scanning electron microscopy (FESEM), energy dispersive X-ray (EDX) analysis, XRD analysis, mechanical testing, cell toxicity and blood hemolysis. A microstructure study has shown that the addition of ßTCP significantly reduces the size of the grain. The experimental results of mechanical testing and corrosion studies show that the Mg-2Zn-1Mn-2.5ßTCP alloy performs better among the three alloys developed, and the values in Vicker's microhardness, compressive strength, density, and porosity with 47.32HV, 238.22 MPa,1.75 g/cm3 and 2.28% respectively and the values of corrosion potential (Ecorr), corrosion current density (Icorr), linear polarization resistance (Rp) and corrosion rate (mm/year) of the Mg-2Zn-1Mn-2.5 ßTCP alloy in the outer and inner layers were found to be -1.46V, 2.71 ×10-5 A/cm2, 1677Ω, 0.62 mm/year and -1.41V, 3.92 ×10-6A/cm2, 4286Ω, 0.20 mm/year respectively. MTT Test and hemolysis experiments revealed that the magnesium alloy had no cell toxicity and good cytocompatibility, however, it produced hemolysis to the blood system. It was proposed that surface modification be used to improve the blood compatibility of the magnesium alloy for use in blood environments.

Recent Advances on the Biological Study of Pharmaceutical Cocrystals.

As a low-risk, low-cost, but high-reward route, cocrystallization of drugs with appropriate coformers is applied to improve the physiochemical and biopharmaceutical properties of drugs. Currently, most researchers concentrate their efforts on the preparation, characterization, and improvement of physicochemical properties of pharmaceutical cocrystals. On the contrary, the biological study of pharmaceutical cocrystals has not attracted wide attention of researchers. In this review, we have focused on recent advances reporting the biological studies of pharmaceutical cocrystals. The covered areas consist of the solubility and permeability, the pharmacokinetics study, metabolism and distribution, pharmacodynamics research, and the toxicological evaluation of pharmaceutical cocrystals. Besides, discussions have been made on the in vivo-in vitro correlations for pharmaceutical cocrystals, the enhancement of efficiency and reduction of toxicity for pharmaceutical cocrystals, and the interaction between APIs and coformers in pharmaceutical cocrystals and marketed pharmaceutical cocrystals as well as their biological studies. At the same time, some problems such as the amount of animal samples, the number and distribution of blood sampling points, investigation on the pharmacokinetics of physical mixtures containing APIs and coformers, and the consideration of species differences should be taken into account. Although pharmaceutical cocrystals face some challenges in clarifying the characteristics of metabolism and distribution, revealing potential pharmacological mechanism, and evaluating safety, cocrystal engineering is still considered a green and promising approach to developing valuable new drugs.

Design and synthesis of hetero-steroids via ring-closing metathesis: Biological studies towards in vitro anticancer activity.

Here, we report a synthetic approach to hetero-steroids and also studied their biological activities as anticancer agents. A novel class of oxacycles containing estrone moiety were synthesized in this report. Allyl ether derived from estrone underwent Claisen rearrangement (CR) and again O-allylation and subsequent ring-closure gave A-ring-furan and oxepine fused derivatives in high yields. We used double bond isomerization and ring-closing metathesis (RCM) as key steps to assemble hetero steroids containing a mixture of regio isomers like benzofurans and benzoxepine moieties. The novel benzofuran and benzoxepine-based hybrid steroid derivatives were subjected to in vitro cytotoxicity analysis and were found to exert cancer cell-specific activity.

A Biological Study of Composites Based on the Blends of Nanohydroxyapatite, Silk Fibroin and Chitosan.

In this work, the biological properties of three-dimensional scaffolds based on a blend of nanohydroxyapatite (nHA), silk fibroin (SF), and chitosan (CTS), were prepared using a lyophilization technique with various weight ratios: 10:45:45, 15:15:70, 15:70:15, 20:40:40, 40:30:30, and 70:15:15 nHA:SF:CTS, respectively. The basic 3D scaffolds were obtained from 5% (w/w) chitosan and 5% silk fibroin solutions and then nHA was added. The morphology and physicochemical properties of scaffolds were studied and compared. A biological test was performed to study the growth and osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs). It was found that the addition of chitosan increases the resistance properties and extends the degradation time of materials. In vitro studies with human mesenchymal stem cells found a high degree of biotolerance for the materials produced, especially for the 20:40:40 and 15:70:15 (nHa:SF:CTS) ratios. The presence of silk fibroin and the elongated shape of the pores positively influenced the differentiation of cells into osteogenic cells. By taking advantage of the differentiation/proliferation cues offered by individual components, the composites based on the nanohydroxyapatite, silk fibroin, and chitosan scaffold may be suitable for bone tissue engineering, and possibly offer an alternative to the widespread use of collagen materials.

Aflagellar Epimastigote of Trypanosoma caninum: Biological and Ultrastructural Study of this Atypical Evolutionary Form.

PURPOSE: Trypanosoma caninum exhibits atypical epimastigote forms under axenic conditions. This study aimed to analyze this evolutionary form under different cultivation conditions and provide more information about this evolutionary form. METHODS: We selected a T. caninum isolate with a high percentage of aflagellar epimastigote forms in axenic cultures. Two separate growth curves were generated for T. caninum cultured in Schneider axenic medium and co-cultured with the DH82 cell line, followed by analysis and quantification of evolutionary forms using bright field microscopy. In addition, ultrastructural analysis of T. caninum was performed under both cultivation conditions. RESULTS: The growth curves of T. caninum under axenic and co-cultivation conditions exhibited similar profiles. However, in the axenic culture, the number of parasites was three times higher at the peak of the exponential phase than in the co-culture. In contrast to that in the axenic culture, in which only the epimastigote forms were observed along the entire curve, during co-cultivation with the DH82 cell line, differentiation was observed for the trypomastigote and spheromastigote forms in low proportions. These results demonstrated that when cultured alone, the T. caninum isolate preserved the aflagellar epimastigote form, but in the presence of DH82 canine macrophages, they differentiated into evolutionary forms, particularly trypomastigote forms. Moreover, this study is the first to describe the presence of lipid bodies, structure described as the parasite's nutritional reserve, throughout the body of T. caninum. CONCLUSIONS: These findings describe biological and ultrastructural aspects of epimastigote aflagellar and suggest that this evolutionary form may be involved in the biological cycle of T. caninum, still unknown.

Quinazoline-4(3H)-one derivatives as novel and potent inhibitors of soluble epoxide hydrolase: Design, synthesis and biological evaluation.

Inhibition of soluble epoxide hydrolase (sEH) is considered as a promising target to reduce blood pressure, improve insulin sensitivity, and decrease inflammation. In this study, a series of some novel quinazoline-4(3H)-one derivatives (3a-t) with varying steric and electronic properties was designed, synthesized and evaluated as sEH Inhibitors. Most of the synthesized compounds had similar inhibitory activity to the commercial reference inhibitor, 12-(3-adamantan-1-ylureido)dodecanoic acid, and amongst them, 4-chloro-N-(4-(4-oxo-3,4-dihydroquinazoline-2-yl)phenyl)benzamide (3g) was identified as the most active sEH inhibitor (IC50 = 0.5 nM), about 2-fold more potent compared to the reference inhibitor. The results of molecular modeling followed by biological studies indicate that a quinazolinone ring serves as a suitable scaffold to develop novel small molecule candidates to inhibit sEH and the nature of substituent on the amide moiety has a moderate effect on the activity.

Discovery and optimization of 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one derivatives as mTORC1/mTORC2 dual inhibitors.

New potent mTORC1/mTORC2 dual inhibitors, 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one derivatives, were obtained by optimizing functional groups on our previously reported PI3Kα inhibitor. All the target compounds were synthesized and structural optimization on the structure of the lead compound based on cytotoxic activity. The results showed that some of the target compounds exhibited moderate to high cytotoxic activity against cell line U87MG and PC-3. The activities against mTOR kinase were investigated and the compound 12q showed excellent activity with an IC50 value of 54 nM in the same level of the positive control BEZ235 with IC50 value of 55 nM under the same test conditions. The western blot and cell cycle results demonstrate that compound 12q is a candidate as an mTORC1/mTORC2 dual-target inhibitor. The theoretical calculations were also performed to better understanding the binding modes of the compound 12q in the mTOR active site.

Discovery of 1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-ones based novel, potent and PI3Kδ selective inhibitors.

PI3Kδ is implicated in various inflammatory and autoimmune diseases. For the effective treatment of chronic immunological disorders such as rheumatoid arthritis, it is essential to develop isoform selective PI3Kδ inhibitors. Structure guided optimization of an imidazo-quinolinones based pan-PI3K/m-TOR inhibitor (Dactolisib) led to the discovery of a potent and orally bioavailable PI3Kδ isoform selective inhibitor (10h), with an improved efficacy in the animal models.

Electroorganic Synthesis and the Construction of Addressable Molecular Surfaces.

In this short review, an electroorganic synthesis approach to the construction of addressable, complex molecular surfaces is described along with the parameters that guided the development of that synthetic approach. The result of the work is a synthetic toolbox that will allow microelectrode arrays to be used for the "real-time" monitoring of small molecule interactions with biological targets.

Pyridoxal Based Fluorescent Chemosensor for Detection of Copper(II) in Solution With Moderate Selectivity and Live Cell Imaging.

A pyridoxal-based fluorescent probe HL was synthesized for the detection of Cu(2+) in methanol with moderate selectivity. Upon addition of Cu(2+), to the solution of the probe in methanol exhibited a remarkable change in emission at 500 nm. With the limit of detection of 10 µM, the probe could well meet the recommended (less than 32 µM in drinking water) of the World Health Organization (WHO). The intracellular Cu(2+) imaging behaviour of HL was carried out on HeLa cells.

Three new flavonol glycosides from Suaeda maritima.

Three new flavonol glycosides isolated from the 70% methanol extract of Suaeda maritima (Chenopodiaceae) were characterized based on spectroscopic and chemical methods as quercetin 3-O-α-l-rhamnopyranosyl(1″' â†’ 6″)-ß-d-galactopyranoside-7-O-ß-d-glucopyranosyl(1″″' â†’ 2″″)-glucopyranoside, kaempferol 3-O-α-l-rhamnopyranosyl(1″' â†’ 6″)-ß-d-galactopyranoside-7-O-ß-d-glucopyranosyl(1″″' â†’ 2″″)-glucopyranoside, and kaempferol 3-O-α-l-rhamnopyranosyl(1″' â†’ 6″)-ß-d-galactopyranoside-7-O-(2″″'-O-trans-feruloyl)-ß-d-glucopyranosyl-(1″″' â†’ 2″″)-ß-d-glucopyranoside. In addition, four known compounds, namely, quercetin and kaempferol, methyl cis, trans-ferulate, and methyl trans-ferulate were identified. The plant extract and these compounds showed cytotoxic activity against the human tumor cell lines MCF7, HCT116, and HEPG2.

Biological implications of the phenotypic plasticity in the Schistosoma mansoni - Nectomys squamipes model / Implicações biológicas da plasticidade fenotípica no modelo Schistosoma mansoni - Nectomys squamipes

The water-rat Nectomys squamipes is mostly important non-human host in schistosomiasis mansoni transmission in Brazil, due to its susceptibility, high abundance and water-contact pattern. During experimental infection of N. squamipes with Schistosoma mansoni, adult worms show phenotypic plasticity. This finding led us to investigate whether biological behavior is also affected. This was assessed comparing the biological characteristics of four S. mansoni strains: BE (State of Belém do Pará), CE (State of Pernambuco), CMO (State of Rio Grande do Norte) and SJ (State of São Paulo) using laboratory-bred N. squamipes. The infection was monitored by determination of the pre-patent period, fecal egg output, egg viability, intestinal egg count and, infectivity rate. No biological modification was observed in these parameters. Overall results highlight that N. squamipes was susceptible to several S. mansoni strains, suggesting that it might contribute to the maintenance of schistosomiasis mansoni in Brazil.

O rato d´água Nectomys squamipes é importante transmissor não-humano da esquistossomose. Durante a infecção experimental em N. squamipes, os vermes adultos apresentam plasticidade fenotípica. Esses achados levaram-nos a investigar se os aspectos biológicos também são afetados. Foram comparadas as características biológicas de quatro cepas de S. mansoni: BE (Estado de Belém do Pará), CM (Estado de Pernambuco), CMO (Estado do Rio Grande do Norte) e SJ (Estado de São Paulo), utilizando como modelo experimental N. squamipes criados e mantidos em laboratório. A infecção foi monitorada para a determinação do período pré-patente, eliminação de ovos nas fezes, viabilidade dos ovos, contagem de ovos retidos no intestino e infectividade. Nenhuma modificação biológica foi observada nesses parâmetros. Os resultados sugerem que o N. squamipes é susceptível a várias cepas de S. mansoni, contribuindo para a manutenção da esquistossomose no Brasil.