Peristaltic motion of Jeffrey fluid with nonlinear mixed convection.

Since previous few decays the consideration of non-Newtonian liquids motion due to its immense usages in medicine, biology, industrial procedures, chemistry of catalysts and in environment. Various studies examine the significance of bio-materials flow in physiological procedures to explore the cure of diagnosed symptoms of disease appearing during movement in a human physiological system. To illustrate the characteristics of physiological liquids various non-Newtonian models have been proposed, but yet no such single liquid model is exploited which describes all the properties of nonlinear behaving liquids. Among these several non-Newtonian models, Jeffery liquid model should be reduced to its base fluid case (i.e. viscous liquid) by choosing λ1 = λ2 = 0. Various physiological materials which represents both linear and nonlinear characteristics respectively blood is one of these. Jeffery fluid and peristaltic motion have some common properties such as radii, relaxation time and retardation time. Moreover heat and mass transfer is also an important phenomenon which is suitable for various physiological processes such as hemodialysis and oxygenation etc. Thus due to such motivating facts this research is conducted to investigate the peristaltic motion of electrically conducting Jeffery liquid. The peristaltic propagating channel walls are asymmetric and inclined. Joule heating and magnetic field effects are considered by applying magnetic field in transverse direction to the flow. Further conservation laws modelled the flow situation via considering quadric mix convection, thermos diffusion and diffusion-thermos, heat generation and absorption, chemical reaction with activation energy features. Moreover, creeping flow and long wavelength assumptions are used to simplify the mathematical modelling. The reduced system of equation is solved numerically through built-in technique in Mathematica software. This built-in technique is working through ND Solve command and shooting and RK-Felburg numerical schemes are behind this technique. These numerical results are used to discuss the flow quantities i.e., velocity, temperature and concentration against the sundry dimensionless quantities. Examining the results it comes to know that both thermal and concentration nonlinear mix convection have oppositely affecting the axial velocity. Both heat and mass transfer are escalating function of thermo-diffusion/diffusion-thermo aspects.

Targeting the monocarboxylate transporter MCT2 and lactate dehydrogenase A LDHA in cancer cells with FX-11 and AR-C155858 inhibitors.

OBJECTIVE: In 1930, Otto Warburg reported that "aerobic glycolysis" is the intrinsic property of all tumor cells' fermentation of glucose to L-Lactate by lactate dehydrogenase A (LDHA) activity. This only produces per mole of glucose two moles of adenosine triphosphate (ATP), compared with 32 moles of ATP in a normal cell. Thus, tumor cells have to uptake 30 folds more glucose, the resulting accumulated lactate are then transported by a monocarboxylate transporter (MCT) with the participation of a CD147 molecule. Inhibition of MCT1 by RNA interference (RNAi) disrupted the unique metabolism of the tumor and caused tumor cell death. However, the effectiveness of the strategies depends on the targeted delivery of the therapeutics. MATERIALS AND METHODS: In this study, a synergistic approach was used to target LDHA and MCT1 with small molecule inhibitors FX11 and AR-C155858, respectively. Cell cytotoxicity assays (AlamarBlue assay), and Mitochondria Membrane Potential (JC-1) dye assays were performed on human breast cancer cells MCF-7 and colorectal cancer cells HCT116. To achieve this aim, the following objectives were proposed: the effect of metabolic inhibitors on tumor glycolytic metabolite environment, and the efficacy of metabolite inhibitors on human breast and colorectal cancer cells in vitro. Then, gene expression analysis was performed using Qiagen RT2 Profiler PCR array for apoptosis. All these assays were performed on human breast cancer cells MCF-7 and colorectal cancer cells HCT116. Normal human fibroblasts were used as control cells under normal and hypoxic culture conditions. RESULTS: In this study, the use of FX-11 inhibitors under normoxia or hypoxia in two or more cancer and normal cell lines has a direct effect on LDHA, whereby it inhibits its production, and this reduces the growth and cell proliferation of tumors. One of the more significant findings to emerge from this study is that using AR-C155858 inhibitor alone has increased the cell proliferation and showed no significant changes compared with the control. The other major finding was that combination of the two inhibitors, FX-11 and AR-C155858, under normoxia or hypoxia in two different cell lines MCF-7 and HCT-116 measured a decrease in the cells proliferative and red/green ratio. CONCLUSIONS: We successfully demonstrated that a combination of MCT1 inhibitor and LDHA inhibitor led to better outcomes. Indeed, this makes LDHA an ideal metabolic therapeutic target.

The correlation between copy number variation in Chromosome 14 and DNA methylation in Saudi autistic children.

OBJECTIVE: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that represents a range of aberrant behaviour symptoms such as repetitive behaviours and defects in social communication. The prevalence of ASD has been increasing worldwide and many studies have reported that both genetic and epigenetic factors play an important role in the etiology of this disorder. The aim of this study was to investigate the implementation of DNA methylation and Copy number variation (CNV) in the diagnosis of ASD. PATIENTS AND METHODS: This study was carried out on 14 Saudi autistic children and four of their healthy siblings. Comparative genomic hybridization array was used to identify CNV in chromosome 14 and MethyLight qPCR was used to estimate levels of DNA methylation. RESULTS: The results identified CNVs in six cytobands in chromosome 14 for 13 out of 14 autistic samples: 14q11.1-q11.2, 14q11.2, 14q12, 14q21.1, 14q32.2, and 14q32.33. However, some of these cytobands were also found in normal samples with different sizes. Interestingly, chromosomal abnormalities in 14q11.1-q11.2 was only found in ASD samples. The result also showed an increase in methylation ratio of ASD samples in those CNV regions compared with their siblings. CONCLUSIONS: The findings suggest that CNV in 14q11.1-q11.2 might be a potential target in ASD diagnosis and further work is required to detect which biological pathways are affected.