Translational models of tumor angiogenesis: A nexus of in silico and in vitro models

Emerging evidence shows that endothelial cells are not only the building blocks of vascular networks that enable oxygen and nutrient delivery throughout a tissue but also serve as a rich resource of angiocrine factors. Endothelial cells play key roles in determining cancer progression and response to anti-cancer drugs. Furthermore, the endothelium-specific deposition of extracellular matrix is a key modulator of the availability of angiocrine factors to both stromal and cancer cells. Considering tumor vascular network as a decisive factor in cancer pathogenesis and treatment response, these networks need to be an inseparable component of cancer models. Both computational and in vitro experimental models have been extensively developed to model tumor-endothelium interactions. While informative, they have been developed in different communities and do not yet represent a comprehensive platform. In this review, we overview the necessity of incorporating vascular networks for both in vitro and in silico cancer models and discuss recent progresses and challenges of in vitro experimental microfluidic cancer vasculature-on-chip systems and their in silico counterparts. We further highlight how these two approaches can merge together with the aim of presenting a predictive combinatorial platform for studying cancer pathogenesis and testing the efficacy of single or multi-drug therapeutics for cancer treatment.     

Diet and cancer prevention: Dietary compounds,dietary MicroRNAs,and dietary exosomes

Cancer is one of main health public problems worldwide. Several factors are involved in beginning and development of cancer. Genetic and internal/external environmental factors can be as important agents that effect on emerging and development of several cancers. Diet and nutrition may be as one of important factors in prevention or treatment of various cancers. A large number studies indicated that suitable dietary patterns may help to cancer prevention or could inhibit development of tumor in cancer patients. Moreover, a large numbers studies indicated that a variety of dietary compounds such as curcumin, green tea, folat, selenium, and soy isoflavones show a wide range anti‐cancer properties. It has been showed that these compounds via targeting a sequence of cellular and molecular pathways could be used as suitable options for cancer chemoprevention and cancer therapy. Recently, dietary microRNAs and exosomes have been emerged as attractive players in cancer prevention and cancer therapy. These molecules could change behavior of cancer cells via targeting various cellular and molecular pathways involved in cancer pathogenesis. Hence, the utilization of dietary compounds which are associated with powerful molecules such as microRNAs and exosomes and put them in dietary patterns could contribute to prevention or treatment of various cancers. Here, we summarized various studies that assessed effect of dietary patterns on cancer prevention shortly. Moreover, we highlighted the utilization of dietary compounds, dietary microRNAs, and dietary exosomes and their cellular and molecular pathways in cancer chemoprevention.     

Design,synthesis, and biological evaluation of selective and potent Carbazole-based butyrylcholinesterase inhibitors

Alzheimer’s disease (AD) is the most common form of dementia. Inhibition of BChE might be a useful therapeutic target for AD. A new series of Carbazole-Benzyl Pyridine derivatives were designed synthesized and evaluated as butyrylcholinesterase (BChE) inhibitors. In vitro assay revealed that all of the derivatives had selective and potent anti- BChE activities. 3-((9H-Carbazol-9-yl)methyl)-1-(4-chlorobenzyl)pyridin-1-ium chloride (compound 8f) had the most potent anti-BChE activity (IC₅₀ value?=?0.073?μM), the highest BChE selectivity and mixed-type inhibition. Docking study revealed that 8f interacted with the peripheral site, the choline binding site, catalytic site and the acyl pocket of BChE. Physicochemical properties were accurate to Lipinski's rule. In addition, compound 8f demonstrated neuroprotective activity at 10?µM. This compound could also inhibit AChE-induced and self-induced Aβ peptide aggregation at concentration of 100?µM and 10?µM respectively. The in-vivo study showed that compound 8f in 10?mg/kg increased the time spent in target quadrant in the probe day and decreased mean training period scape latency in rats. All results suggest that new sets of potent selective inhibitors of BChE have a therapeutic potential for the treatment of AD.     

Effect of bisphenol A toxicity on growth performance,biochemical variables,and oxidative stress biomarkers of Nile tilapia,Oreochromis niloticus (L.)

Bisphenol A (BPA) is one of the industrial chemical compound which is used in the production of polycarbonate plastics and epoxy resins. BPA is used throughout the world and it could enter the aquatic ecosystems causing serious problems. To evaluate the potential effects of BPA toxicity on Nile tilapia, Oreochromis niloticus (L.) performance, its lethal concentration (LC₅₀) was determined and it was 13.13 µg/L. After that, fish (33.9 ± 0.55 g/fish) were exposed to 0.0, 1.64, or 3.28 µg/L of BPA for 6 weeks after which growth performance, biochemical variables, and oxidative defense system were assessed. The results showed that fish growth and feed intake were significantly reduced as BPA levels increased with no significant difference in fish survival. Total protein, albumin, globulin, and acetylcholine esterase decreased significantly; meanwhile, aspartate transferase, alanine transferase, alkaline phosphatase, uric acid, and creatinine increased significantly with exposure to BPA in a dose dependent manner. Furthermore, malondialdehyde value and the activities of superoxide dismutase and catalase increased significantly; while glutathione peroxidase and glutathione S‐transferase decreased significantly as BPA levels increased. In conclusion, BPA exposure in aquatic environment deteriorated fish performance and health causing liver and kidney dysfunction. Thus, fish exerted oxidative defense enzymes as a protection tool against BPA toxicity.     

Umbelliprenin shows antitumor,antiangiogenesis, antimetastatic,anti‐inflammatory,and immunostimulatory activities in 4T1 tumor‐bearing Balb/c mice

Umbelliprenin (UMB) has shown various pharmacological properties in vitro. We investigated the antineoplastic and immunostimulatory effects of UMB in 4T1 mammary‐tumor‐bearing mice. Two‐hundred microliter of UMB (12.5 mg/ml) was intraperitoneally administrated to healthy and tumor‐bearing female Balb/c mice for a period of 18 days. Data was analyzed using GraphPad Prism 5 software for Windows (version 5, La Jolla, CA). UMB caused a significant decrease in tumor size (P < 0.01). Serum interferon gamma (IFNγ) was augmented in both healthy and tumor‐bearing animals (P < 0.01), and IL‐4 declined in healthy animals (P < 0.01) treated with UMB. Expressions of Ki‐67, VEGF, CD31, MMP2, MMP9, VCAM1, and NF‐κB were significantly decreased in tumors from UMB‐treated animals (P < 0.001), whereas E‐Cadherin and TNFR1 expressions were markedly increased (P < 0.001). The rates of liver and lung metastases in UMB‐administrated animals were smaller compared to the control. UMB can potently inhibit tumor growth, angiogenesis, metastasis, and inflammation and potentiate an antitumor immune response in vivo. However, further investigations are required to evaluate the UMB mechanisms of action in cancerous cells.     

Possible molecular mechanisms of glucose-lowering activities of Momordica charantia (karela) in diabetes

Diabetes mellitus is a highly prevalent metabolic disorder which is characterized by impaired glucose tolerance, with a relative or absolute insulin deficiency and profound changes in the metabolism of macronutrients. Traditional and complementary medicine is therapeutic strategies that have both been applied to improving glycemic control. Momordica charantia is one of the plant-based, folk medicines that used for improving glycemic control. We aimed to review, the effects of M. charantia on blood glucose with a clarification of the molecular pathways involved. Of the compounds derived from the plants, the insulin-like peptide, charantin, and the alkaloid vicine, have been reported to have hypoglycemic effects. Different mechanisms contribute to the antidiabetic activities of M. charantia, these include increasing pancreatic insulin secretion, decreasing insulin resistance and increasing peripheral and skeletal muscle cell glucose utilization, inhibition of intestinal glucose absorption and suppressing of key enzymes in the gluconeogenic pathways.