In vitro and in vivo studies of cancer cell behavior under nutrient deprivation

Cancer cells are confronted with nutrient deprivation because of high proliferation rate, especially at the early stage of their development. There is a frequent assumption that nutrient deprivation decreases the basal activity of cancer cells. Contrarily, there are recent evidence suggesting that cancer cells are able to modulate signaling pathways to adapt with new condition and continue their survival. This property of cancer cells is believed to be one of the prerequisites for cancer progression and chemoresistance. Moreover, recent experiments show that serum starvation in vitro as a mimic situation of nutrient deprivation in vivo triggers different signaling pathways leading to changes in cancer cell behavior, which may interfere with experimental results. Considering these facts, a better understanding of the effect of nutrient deprivation on cancer cell behavior will help us to give more accurate conclusions regarding results of in vitro studies and also to develop new strategies to treat different cancers in vivo.     

The effects of microRNAs in activating neovascularization pathways in diabetic retinopathy

Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus that causes diabetic macular edema and visual loss. DR is categorized, based on the presence of vascular lesions and neovascularization, into non-proliferative and proliferative DR. Vascular changes in DR correlate with the cellular damage and pathological changes in the capillaries of blood-retinal barrier. Several cytokines have been involved in inducing neovascularization. These cytokines activate different signaling pathways which are mainly responsible for the complications of DR. Recently; microRNAs (miRNAs) have been introduced as the key factors in the regulation of the cytokine expression which plays a critical role in neovascularization of retinal cells. Some studies have demonstrated that changing levels of miRNAs have essential role in the pathophysiology of vascular changes in patients with DR. The aim of this study is to identify the effects of miRNAs in the pathogenesis of DR via activating neovascularization pathways.     

Proinflammatory cytokine gene polymorphisms in Behçet's disease

Beh?et's disease (BD) is a chronic, systemic disease, characterized by oral and genital lesions, and ocular inflammation. There is evidence indicating altered levels of proinflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) in patients with BD. This study involved 150 patients with BD and 140 healthy controls, and investigated the role of proinflammatory cytokine gene polymorphisms in the disease. The frequency of the TNF-α (-238) G/G genotype was significantly higher in the patient group, compared to the controls (p < 0.001), whilst the G/A genotype was significantly lower in the patients with BD (p < 0.001). Patients with BD showed a significant increase in the TNF-α (- 308, - 238) GG haplotype (p < 0.001), whilst there was a significant decrease in the GA haplotype (p < 0.001). The heterozygous, IL-6 (- 174) C/G genotype (p = 0.005), and the IL-6 (- 174, nt565) haplotype CG (p < 0.001), were significantly decreased in the patient group. The increased production of proinflammatory cytokines in BD could be a consequence of specific, cytokine gene polymorphisms. Particular genotypes and haplotypes in TNF-α were over-represented in BD, which may, in turn, predispose individuals to this disease.     

Alginate as an antiglycating agent for human serum albumin

Hyperglycemia and the accumulation of advanced glycation endproducts (AGEs) in tissues and serum have important roles in diabetic complications. Therefore, the identification of anti-glycation compounds is attracting considerable interest. In this study, the interaction of human serum albumin (HSA) with fructose, in the absence and presence of alginate, was studied by circular dichroism, absorbance and fluorescence techniques. The characterization study of AGEs was performed using autofluorescence, fibrillar formation, the increase in absorbance and the quantification of free lysine side chains. The results indicate that alginate inhibits the fructation of HSA as observed by a reduction in the formation of fluorescent AGEs and fibrils. Furthermore, alginate reduces the amount of modified lysine side chains, signified by the lack of increase in absorbance, and increases the helicity of this protein.     

Structural Basis of the Regulation of the CbpA Co-chaperone by its Specific Modulator CbpM

CbpA, one of the Escherichia coli DnaJ homologues, acts as a co-chaperone in the DnaK chaperone system. Despite its extensive similarity in domain structure and function to DnaJ, CbpA has a unique and specific regulatory mechanism mediated through the small protein CbpM. Both CbpA and CbpM are highly conserved in bacteria. Earlier studies showed that CbpM interacts with the N-terminal J-domain of CbpA inhibiting its co-chaperone activity but the structural basis of this interaction is not known. Here, we have combined NMR spectroscopy, site-directed mutagenesis and surface plasmon resonance to characterize the CbpA/CbpM interaction at the molecular level. We have determined the solution structure of the CbpA J-domain and mapped the residues that are perturbed upon CbpM binding. The NMR data defined a broad region on helices α2 and α3 as involved in the interactions. Site-directed mutagenesis has been used to further delineate the CbpA J-domain/CbpM interface. We show that the binding sites of CbpM and DnaK on CbpA J-domain overlap, which suggests a competition between DnaK and CbpM for binding to CbpA as a mechanism for CbpA regulation. This study also provides the explanation for the specificity of CbpM for CbpA versus DnaJ, by identifying the key residues for differential binding.     

Emulsifying Activity, Particle Uniformity and Rheological Properties of a Natural Polysaccharide-Protein Biopolymer from Durian Seed

Polysaccharide-protein gums are complex polymers with many applications in emulsion and emulsion-based products. It is crucial to enclose a concept on understanding of functional properties of polysaccharide-protein biopolymer in order to select the appropriate one based on the application scope. The main objective of the current study was to investigate the effect of three extraction variables on the surface activity, particle uniformity, apparent viscosity, and protein content of a natural polysaccharide-protein biopolymer from durian fruit seed. Three extraction variables namely water: seed (W/S) ratio (20:1?C60:1), temperature (25.0?C85.0?°C) and pH (4.0?C10.0) were considered as independent variables. The results indicated that durian seed gum induced very low viscosity (0.93?C4.98?mPa.s) with pseudoplastic rheological behavior in the aqueous system. The current study revealed that the extraction variables had the most significant (p?<?0.05) effect on the emulsifying surface activity of the natural biopolymer from durian fruit seed. This might be due to the significant (p?<?0.05) effect of the proteineous constituent present in the chemical structure of the biopolymer from durian fruit seed. The aqueous extraction variables showed the most and least significant (p?<?0.05) effect on the specific surface area and protein content, respectively. Among all extraction variables, W/S ratio and pH exhibited the highest and lowest significant (p?<?0.05) effect on the physicochemical and functional properties of the natural biopolymer from durian fruit seed.     

Solid-phase microextraction for determining twelve orange flavour compounds in a model beverage emulsion

Solid-phase microextraction (SPME) coupled to gas chromatography has been applied for the headspace analysis (HS) of 12 target flavour compounds in a model orange beverage emulsion. The main volatile flavour compounds studied were: acetaldehyde, ethyl acetate, alpha-pinene, ethyl butyrate, beta-pinene, myrcene, limonene, gamma-terpinene, octanal, decanal, linalool and citral (neral plus geranial). After screening the fibre type, the effect of other HS-SPME variables such as adsorption temperature (25-55 degrees C), extraction time (10-40 min), sample concentration (1-100% w/w), sample amount (5-10 g) and salt amount (0-30% w/w) were determined using a two-level fractional factorial design (2(5-2)) that was expanded further to a central composite design. It was found that an extraction process using a carboxen-polydimethylsiloxane fibre coating at 15 masculineC for 50 min with 5 g of diluted emulsion 1% (w/w) and 30% (w/w) of sodium chloride under stirring mode resulted in the highest HS extraction efficiency. For all volatile flavour compounds, the linearity values were accurate in the concentration ranges studied (r(2) > 0.97). Average recoveries that ranged from 90.3 to 124.8% showed a good accuracy for the optimised method. The relative standard deviation for six replicates of all volatile flavour compounds was found to be less than 15%. For all volatile flavour compounds, the limit of detection ranged from 0.20 to 1.69 mg/L.     

Qualities and Inequalities in Online Social Networks through the Lens of the Generalized Friendship Paradox

The friendship paradox is the phenomenon that in social networks, people on average have fewer friends than their friends do. The generalized friendship paradox is an extension to attributes other than the number of friends. The friendship paradox and its generalized version have gathered recent attention due to the information they provide about network structure and local inequalities. In this paper, we propose several measures of nodal qualities which capture different aspects of their activities and influence in online social networks. Using these measures we analyse the prevalence of the generalized friendship paradox over Twitter and we report high levels of prevalence (up to over 90% of nodes). We contend that this prevalence of the friendship paradox and its generalized version arise because of the hierarchical nature of the connections in the network. This hierarchy is nested as opposed to being star-like. We conclude that these paradoxes are collective phenomena not created merely by a minority of well-connected or high-attribute nodes. Moreover, our results show that a large fraction of individuals can experience the generalized friendship paradox even in the absence of a significant correlation between degrees and attributes.