Synthesis, structural characterization and in vivo anti-diabetic evaluation of some new sulfonylurea derivatives in normal and silicate coated nanoparticle forms as anti-hyperglycemic agents.

Series of new sulfonylurea derivatives (gliclazide analogues) was synthesized and characterized. Thus, p-tolylsulfonylisocyanate was left to react with different amino derivatives under mild conditions to afford the desired sulfonylurea derivatives 1-5. The molecular structure of the compound N-(2,6-Dichlorophenylcarbamoyl)-4-methylbenzenesulfonamide, 1c has been elucidated by single crystal X-ray diffraction. Anti-diabetic properties of the synthesized compounds relative to anti-diabetic drug (gliclazidem MR60) were carried out, where most of the tested compounds showed significant activity for reducing the blood glucose level. The results revealed that compounds 1c and 5 showed better anti-diabetic activities compared with gliclazide. Activity of the most potent derivatives of sulfonylurea compounds namely 1c and 5 were increased using coated nanostructure tetraethyl orthosilicate (TEOS) as a modified release (MR) agent. The effect of the prepared sulfonylurea compounds against the diabetic condition was investigated using specific selected biomarkers as of liver enzyme activities as transaminases (AST, ALT) and alkaline phosphatase (ALP), lipids profiles; total cholesterol (TC), triacylglycerols (TG) and total lipid (TL). The antioxidants, oxidative stress biomarkers and histological examination were also examined and discussed.

Crosslink among phosphatidylinositol-3 kinase/Akt, PTEN and STAT-5A signaling pathways post liposomal galactomannan hepatocellular carcinoma therapy.

Liposomal drug-delivery systems (LDDs) provide a promising opportunity to precisely target organs, improve drug bioavailability and reduce systemic toxicity. On the other hand, PI3K/Akt signaling pathways control various intracellular functions including apoptosis, invasion and cell growth. Hyper activation of PI3K and Akt is detected in some types of cancer that posses defect in PTEN. Tracking the crosstalk between PI3K/Akt, PTEN and STAT 5A signaling pathways, in cancer could result in identifying new therapeutic agents. The current study, identified an over view on PI3K/Akt, PTEN and STAT-5A networks, in addition to their biological roles in hepatocellular carcinoma (HCC). In the current study galactomannan was extracted from Caesalpinia gilliesii seeds then loaded in liposomes. Liposomes were prepared employing phosphatidyl choline and different concentrations of cholesterol. HCC was then induced in Wistar albino rats followed by liposomal galactomannan (700 ± 100 nm) treatment. Liver enzymes as well as antioxidants were assessed and PI3K/Akt, PTEN and STAT-5A gene expression were investigated. The prepared vesicles revealed entrapment efficiencies ranging from 23.55 to 69.17%, and negative zeta potential values. The optimum formulation revealed spherical morphology as well as diffusion controlled in vitro release pattern. Liposomal galactomannan elucidated a significant reduction in liver enzymes and MDA as well as PI3K/Akt, PTEN and STAT 5A gene expression. A significant elevation in GST and GSH were deduced. In conclusion, Liposomal galactomannan revealed a promising candidate for HCC therapy.

DNA damage and genetic aberration induced via different sized silver nanoparticles: Therapeutic approaches of Casimiroa edulis and Glycosmis pentaphylla leaves extracts.

Potential of Casimiroa edulis and Glycosmis pentaphylla leaves extracts were investigated against the effect of two different particle sizes of silver nanoparticles induced toxicity in mice. Mice received silver nanoparticles (AgNPs) (100 mg/kg) with 20 and 100 nm for four weeks followed by daily oral dose of extracts (500 mg/kg) for three weeks. C. edulis leaves identified fourteen phenolic compounds while, G. pentaphylla leaves identified, twelve phenolic compounds. Additionally, biochemical, genotoxicity, mutagenicity, and histopathological investigations were carried out, revealed that liver function activities, lipid profile, hydrogen peroxide, and C-reactive protein were significantly elevate post AgNPs exposure. While, superoxide dismutase, glutathione-S-transferases, and glutathione peroxidase significantly reduce. A marked amelioration in all detected biomarkers, improved histopathological changes and repair DNA damage after treated with C. edulis and G. pentaphylla leaves extracts. These extracts are used for the first time as promising candidate therapeutic agents against toxicity induced by AgNPs. PRACTICAL APPLICATIONS: The potential applications of AgNPs make it necessary to investigate the possible toxicity associated with release of free silver ions in the biological system. AgNPs of varying particle sizes had toxic effects as evidenced by alterations in some cellular biochemical parameters, genotoxicity, mutagenicity, and histopathological indices on mice. Casimiroa edulis and Glycosmis pentaphylla leaves extracts are used for the first time as promising candidate therapeutic, where they are able to ameliorate the toxicity induced via AgNPs and record vacillate percentage of improvement in the selected biomarkers, as a result of the bioactive secondary metabolites especially flavonoids and other polyphenolic compounds.

Identification of a genetic marker associated with the resistance to Schistosoma mansoni infection using random amplified polymorphic DNA analysis.

In schistosomiasis, the host/parasite interaction remains not completely understood. Many questions related to the susceptibility of snails to infection by respective trematode still remain unanswered. The control of schistosomiasis requires a good understanding of the host/parasite association. In this work, the susceptibility/resistance to Schistosoma mansoni infection within Biomphalaria alexandrina snails were studied starting one month post infection and continuing thereafter weekly up to 10 weeks after miracidia exposure. Genetic variations between susceptible and resistant strains to Schistosoma infection within B. alexandrina snails using random amplified polymorphic DNA analysis technique were also carried out. The results showed that 39.8% of the examined field snails were resistant, while 60.2% of these snails showed high infection rates.In the resistant genotype snails, OPA-02 primer produced a major low molecular weight marker 430 bp. Among the two snail strains there were interpopulational variations, while the individual specimens from the same snail strain, either susceptible or resistant, record semi-identical genetic bands. Also, the resistant character was ascendant in contrast to a decline in the susceptibility of snails from one generation to the next.

Identification of a genetic marker associated with the resistance to Schistosoma mansoni infection using random amplified polymorphic DNA analysis

In schistosomiasis, the host/parasite interaction remains not completely understood. Many questions related to the susceptibility of snails to infection by respective trematode still remain unanswered. The control of schistosomiasis requires a good understanding of the host/parasite association. In this work, the susceptibility/resistance to Schistosoma mansoni infection within Biomphalaria alexandrina snails were studied starting one month post infection and continuing thereafter weekly up to 10 weeks after miracidia exposure. Genetic variations between susceptible and resistant strains to Schistosoma infection within B. alexandrina snails using random amplified polymorphic DNA analysis technique were also carried out. The results showed that 39.8 percent of the examined field snails were resistant, while 60.2 percent of these snails showed high infection rates.In the resistant genotype snails, OPA-02 primer produced a major low molecular weight marker 430 bp. Among the two snail strains there were interpopulational variations, while the individual specimens from the same snail strain, either susceptible or resistant, record semi-identical genetic bands. Also, the resistant character was ascendant in contrast to a decline in the susceptibility of snails from one generation to the next.