Molecular Mechanism of Fucoidan Nanoparticles as Protector on Endothelial Cell Dysfunction in Diabetic Rats' Aortas.

Antioxidants have an important role in protecting against diabetes complications such as vascular endothelial cell damage. Fucoidan has strong antioxidant properties, therefore the aim of this study was to investigate the protective mechanism of fucoidan nanoparticles through the pathway of antioxidant activity against streptozotocin-induced diabetic aortic endothelial cell dysfunction in rats. Fucoidan nanoparticles are made utilizing high-energy ball milling. This research consists of five groups, namely: control rats, rats were administered aquadest; diabetic rats, rats were administered streptozotocin (STZ); fucoidan nanoparticle rats, rats were administered STZ and fucoidan nanoparticles. Aortic tissue was collected for the evaluation of ROS (reactive oxygen species), Malondialdehyde (MDA), superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), Nuclear factor erythroid-2-related factor 2 (Nrf2), Nitric Oxide (NO), cyclic Guanosine Monophosphate (cGMP), relaxation response of acetylcholine (Ach), and the diameter of the aorta. The size distribution of the fucoidan nanoparticles was 267.2 ± 42.8 nm. Administration of fucoidan nanoparticles decreased the levels of ROS and MDA, and increased the levels of SOD, levels of GPx, Nrf2 expression, NO levels, cGMP expression, the relaxation response of Ach, and lumen diameter of the aorta, which are significantly different when compared with diabetic rats, p < 0.05. In this study, we concluded that the mechanism pathway of fucoidan nanoparticles prevents aortic endothelial cell dysfunction in diabetic rats through antioxidant activity by reducing ROS and MDA and incrementing SOD levels, GPx levels, and Nrf2 expression. All of these can lead to an elevated relaxation response effect of Ach and an increase in the lumen diameter of the aorta, which indicates a protective effect of fucoidan nanoparticles on aortic endothelial cells.

Anti-Ulcerogenic and Cytoprotective Effects of Saharian (Sidr) Honey from Algeria.

AIM AND OBJECTIVE: This study aimed at investigating the gastro-protective effects of Algerian Sahara (Sidr) honey from Apis mellifera intermissa against HCl/Ethanol-induced gastric ulcers in rats. MATERIALS AND METHODS: Total phenolic content, antioxidant activity and phenolic compounds were determined. Then, three groups of rats (control, HCl/ Ethanol-induced ulcer, and orally administered honey) were used for the determination of gastro-protective effect of Sidr honey. RESULTS: Total phenolic content, total flavonoid content, and DPPH activity of the honey sample were determined as 47.35±3.35 mg GAE/ 100 g, 2.13±0.17 mg QE/ 100 g, and 229.24±0.02 mg/mL, respectively. Oral pretreatment of rats with honey (1.2 g/Kg body weight orally at an interval of 2 days) protected gastric mucosa against HCl/Ethanol-induced damage by decreasing ulcer score, the volume and acidity of gastric juice and increasing pH. CONCLUSION: These results were confirmed by the histological assessment, which demonstrated a significant gastro-protective activity of Saharian (Sidr) honey against HCl/Ethanol-induced stomach ulcer. Plasma tumor necrosis factor-α, IL-6 and PGE2 were also measured. Sahara honey significantly decreased the plasma TNF-α, PGE2, and IL-6 concentrations.

Lifestyle interventions for non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a multi-factorial disease and the most common of chronic liver diseases worldwide. The four clinical-pathological entities which are usually followed by NAFLD course include non-alcoholic steatosis, non-alcoholic steatohepatitis, advanced fibrosis/cirrhosis, and hepatocellular carcinoma. The cornerstones of NAFLD management and treatment, however, are healthy lifestyles such as dietary modifications, regular physical activity, and gradual weight loss. At present, no drugs or pharmacological agents have been approved for long-term treatment of NAFLD. Therefore, lifestyle modification is considered the main clinical recommendation and an initial step for the management of NAFLD.

Seasonal adaptations of the hypothalamo-neurohypophyseal system of the dromedary camel.

The "ship" of the Arabian and North African deserts, the one-humped dromedary camel (Camelus dromedarius) has a remarkable capacity to survive in conditions of extreme heat without needing to drink water. One of the ways that this is achieved is through the actions of the antidiuretic hormone arginine vasopressin (AVP), which is made in a specialised part of the brain called the hypothalamo-neurohypophyseal system (HNS), but exerts its effects at the level of the kidney to provoke water conservation. Interestingly, our electron microscopy studies have shown that the ultrastructure of the dromedary HNS changes according to season, suggesting that in the arid conditions of summer the HNS is in an activated state, in preparation for the likely prospect of water deprivation. Based on our dromedary genome sequence, we have carried out an RNAseq analysis of the dromedary HNS in summer and winter. Amongst the 171 transcripts found to be significantly differentially regulated (>2 fold change, p value <0.05) there is a significant over-representation of neuropeptide encoding genes, including that encoding AVP, the expression of which appeared to increase in summer. Identification of neuropeptides in the HNS and analysis of neuropeptide profiles in extracts from individual camels using mass spectrometry indicates that overall AVP peptide levels decreased in the HNS during summer compared to winter, perhaps due to increased release during periods of dehydration in the dry season.

Cancer prevention and therapy through the modulation of transcription factors by bioactive natural compounds.

The association between chronic inflammation and cancer development has been well documented. One of the major obstacles in cancer treatment is the persistent autocrine and paracrine activation of pro-inflammatory transcription factors such as nuclear factor-κB, signal transducer and activator of transcription 3, activator protein 1, fork head box protein M1, and hypoxia-inducible factor 1α in a wide variety of tumor cell lines and patient specimens. This, in turn, leads to an accelerated production of cellular adhesion molecules, inflammatory cytokines, chemokines, anti-apoptotic molecules, and inducible nitric oxide synthase. Numerous medicinal plant-derived compounds have made a tremendous impact in drug discovery research endeavors, and have been reported to modulate the activation of diverse oncogenic transcription factors in various tumor models. Moreover, novel therapeutic combinations of standard chemotherapeutic drugs with these agents have significantly improved patient survival by making cancer cells more susceptible to chemotherapy and radiotherapy. In this review, we critically analyze the existing literature on the modulation of diverse transcription factors by various natural compounds and provide views on new directions for accelerating the discovery of novel drug candidates derived from Mother Nature.

Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: wild type and mutant (L1196M) active compounds with unique binding mode.

We have identified a novel 7-azaindole series of anaplastic lymphoma kinase (ALK) inhibitors. Compounds 7b, 7 m and 7 n demonstrate excellent potencies in biochemical and cellular assays. X-ray crystal structure of one of the compounds (7 k) revealed a unique binding mode with the benzyl group occupying the back pocket, explaining its potency towards ALK and selectivity over tested kinases particularly Aurora-A. This binding mode is in contrast to that of known ALK inhibitors such as Crizotinib and NVP-TAE684 which occupy the ribose binding pocket, close to DFG motif.