Biolmpacts
Volume:4 Issue: 2, Jun 2014

The genesis of cancer appears to be a complex matter, which is not simply based upon few genetic abnormalities/alteration. In fact, irregular microvasculature and aberrant interstitium of solid tumors impose significant pathophysiologic barrier functions against cancer treatment modalities, hence novel strategies should holistically target bioelements of tumor microenvironment (TME). In this study, we provide some overview and insights on TME and important strategies used to control the impacts of such pathophysiologic barriers. We reviewed all relevant literature for the impacts of tumor interstitium and microvasculature within the TME as well as the significance of the implemented strategies. While tumorigenesis initiation seems to be in close relation with an emergence of hypoxia and alterations in epigenetic/genetic materials, large panoplies of molecular events emerge as intricate networks during oncogenesis to form unique lenient TME in favor of tumor progression. Within such irregular interstitium, immune system displays defective surveillance functionalities against malignant cells. Solid tumors show multifacial traits with coadaptation and self-regulation potentials, which bestow profound resistance against the currently used conventional chemotherapy and immunotherapy agents that target solely one face of the disease. The cancerous cells attain unique abilities to form its permissive microenvironment, wherein (a) extracellular pH is dysregulated towards acidification, (b) extracellular matrix (ECM) is deformed, (c) stromal cells are cooperative with cancer cells, (d) immune system mechanisms are defective, (e) non-integrated irregular microvasculature with pores (120-1200 nm) are formed, and (h) interstitial fluid pressure is high. All these phenomena are against cancer treatment modalities. As a result, to control such abnormal pathophysiologic traits, novel cancer therapy strategies need to be devised using multifunctional nanomedicines and theranostics.

In vitro antioxidant and antibacterial activity and volatile compositions of two Heracleum species (Apiaceae) including Heracleum transcaucasicum and Heracleum anisactis roots Essential Oil (EO) were investigated. The volatile compositions of EOs were analyzed by GC/Mass spectroscopy. To detect the antioxidant activity of essential oils TLC-bioautography and DPPH radical scavenging assay by spectrophotometry was performed. Additionally, the antibacterial activity of two essential oils were studied and compared against four pathogenic bacteria by agar disc diffusion method and MIC values of the EOs were determined using the broth dilution method. Myristicin was the dominant component in both EOs. It was identified as 96.87% and 95.15% of the essential oil composition of H. transcaucasicum and H. anisactis roots, respectively. The TLC-bioautography showed antioxidant spots in both EOs and IC50 of H. anisactis and H. transcaucasicum EO was found to be 54 μg × ml (-1) and 77 μg × ml (-1), respectively. Regarding the antimicrobial assay, H. anisactis EO exhibited weak to moderate antibacterial activity against gram-positive bacteria and also Escherichia coli, whereas the essential oil from H. transcaucasicum was inactive. Based on the results from this study, both tested EOs mainly consist of myristicin. Despite the presence of myristicin with known antibacterial property, the EO from H. transcacausicum showed no antibacterial activity. Thus it is supposed that the biological activity of plants is remarkably linked to the extracts’ chemical profile and intercomponents’ synergistic or antagonistic effect could play a crucial role in bioactivity of EOs and other plant extracts.

In previous studies, the relaxant and antihistaminic effects of thymoquinone, the main constituents of Nigella sativa, have been demonstrated on guinea pig tracheal chains. In the present study, the prophylactic effect of (IP) single dose of thymoquinone on tracheal responsiveness and lung inflammation of guinea pig model of asthma was examined. Thirty guinea pigs were randomly divided to 3 groups; control (C), sensitized (S) and pretreated group with (TQ); 3 mg/kg, IP (S+TQ). Tracheal responsiveness to methacholine and ovalbumin (OA), total and differential cell count in bronchoalveolar lavage, lung pathological changes and blood Interleukin 4(IL-4) and Interferon gamma (IFNγ) level in three groups were measured. Increased tracheal responsiveness to methacholine and OA, lung lavage fluid white blood cell (WBC) and eosinophil count, IL-4 and IFN-γ levels and pathological changes were seen in sensitized group in comparison to control group (p<0.001 to p<0.05). Decreased tracheal responsiveness to methacholine and OA, pathological changes and bronchoalveolar lavage eosinophil were observed in S+TQ group compared to S group (p<0.001 to p<0.05). However, tracheal responsiveness to methacholine and OA, contractility, bronchoalveolar lavage WBC and eosinophil and most of pathological changes in S+TQ group were significantly higher than those in controls (p<0.01 to p<0.05). These results showed the preventive effect of single dose of thymoquinone on guinea pig model of asthma.

The role of inflammatory cytokines in diabetes and its complications has been shown in some studies. The purpose of this study was to compare the effect of probiotic and conventional yogurt on inflammatory markers in patients with type 2 diabetes. Forty-four patients with type 2 diabetes were participated in this randomized, doubleblind controlled clinical trial and assigned to two intervention and control groups. The subjects in the intervention group consumed 300 g/d probiotic yogurt and subjects in the control group consumed 300 g/d conventional yogurt for 8 weeks. Anthropometric indices, dietary intakes, and serum levels of glucose, HbA1c, IL-6, TNF-α and hs-CRP were evaluated at the beginning and end of the intervention. For anthropometric indices and dietary intakes, no significant differences were seen within and between groups post intervention (p> 0.05). The consumption of probiotic yogurt caused significant decrease in HbA1c and TNF-α levels (p= 0.032 and p= 0.040, respectively) in the intervention group. It is suggested that probiotic yogurt may be used as an alternative prevention approach and treatment method to control diabetic complications.

This paper represents the numerical simulation of blood flow in the circle of Willis (CoW). Circle of Willis is responsible for the oxygenated blood distribution into the cerebral mass. To investigate the blood behavior, two Newtonian and non-Newtonian viscosity models were considered and the results were compared under steady state conditions. Methodologically, the arterial geometry was obtained using 3D magnetic resonance angiography (MRA) data. The blood flow through the cerebral vasculature was considered to be steady and laminar, and the Galerkin’s finite element method was applied to solve the systems of non-linear Navier-Stokes equations. Flow patterns including flow rates and shear rates were obtained through the simulation. The minimal magnitude of shear rates was much greater than 100 s-1 through the larger arteries; thus, the non-Newtonian blood viscosity tended to approach the constant limit of infinite shear viscosity through the CoW. So, in larger arteries the non-Newtonian nature of blood was less dominant and it would be treated as a Newtonian fluid. The only exception was the anterior communicating artery (ACoA) in which the blood flow showed different behavior for the Newtonian and non-Newtonian cases. By comparing the results it was concluded that the Newtonian viscosity assumption of blood flow through the healthy, complete circle of Willis under the normal and steady conditions would be acceptably accurate.

Decline in circulating estrogen levels causes lessening of bone mass accompanied with musculoskeletal pain, which is the primary cause of treatment discontinuation in patients taking aromatase inhibitors. Evidence from recent genome-wide association studies (GWAS) suggests that the genetic variability underlying TCL1A gene increases the risk of aromatase inhibitors (AIs) - induced musculoskeletal toxicity. Currently, no data is available on the frequency distribution of TCL1A gene polymorphisms in Indians. In this pilot study, we used TaqMan fluorescent probes to assess the genotypes of four TCL1A gene polymorphisms associated with musculoskeletal toxicity in 247 healthy homogenous South Indian subjects on real time thermocycler. Haplotype estimation and pairwise linkage disequilibrium (LD) analysis were executed by Haploview. The incidence of polymorphic variant allele (G) frequencies of rs7158782, rs7159713, rs2369049 and rs11849538 were 22.1%, 23.5%, 18.2% and 22.9% in the study population, respectively. The polymorphisms were found to be in complete LD with each other. Four different haplotypes, each of which having a frequency of above 1% were inferred in South Indians using an expectation-maximization algorithm. Notably, three haplotypes were found to be population specific viz H4 A-A-A-G (1.2%) for South India, H5 G-G-A-C (1.3%) for JPT and H6 G-G-G-C (40.4%) for YRI. Further, H3 G-G-A-G (2.3-16.3%) haplotype occurs primarily in Asians and is virtually absent in Africans. Overall, the genetic variability and haplotype profile of South Indian population revealed significant inter-racial variability compared with HapMap data. This documentation contributes for further investigations on the pharmacogenetics of AIs in South Indians.

Free radicals are implicated in several metabolic diseases and the medicinal properties of plants have been explored for their potent antioxidant activities to counteract metabolic disorders. This research highlights the chemical composition and antioxidant potential of leaf gall extracts (aqueous and methanol) of Syzygium cumini (S. cumini), which have been extensively used in traditional medications to treat various metabolic diseases. The antioxidant activities of leaf gall extracts were examined using diphenylpicrylhydrazyl (DPPH), nitric oxide scavenging, hydroxyl scavenging and ferric reducing power (FRAP) methods. In all the methods, the methanolic extract showed higher antioxidant potential than the standard ascorbic acid. The presence of phenolics, flavonoids, phytosterols, terpenoids, and reducing sugars was identified in both the extracts. When compared, the methanol extract had the highest total phenolic and flavonoid contents at 474±2.2 mg of GAE/g d.w and 668±1.4 mg of QUE/g d.w, respectively. The significant high antioxidant activity can be positively correlated to the high content of total polyphenols/flavonoids of the methanol extract. The present study confirms the folklore use of S. cumini leaves gall extracts as a natural antioxidant and justifies its ethnobotanical use. Further, the result of antioxidant properties encourages the use of S. cumini leaf gall extracts for medicinal health, functional food and nutraceuticals applications.