Design,synthesis and biological evaluation of novel anti-cytokine 1,2,4-triazine derivatives

A series of 16 novel 1,2,4-triazine derivatives bearing hydrazone moiety (7a–7p) have been designed, synthesized and evaluated for their activity to inhibit IL-1β and TNF-α production. All compounds are reported for the first time. The chemical structures of all compounds were confirmed by spectroscopic methods and elemental analyzes. Most of the synthesized compounds were proved to have potent anti-cytokine activity and low toxicity on PBMC and MCF-7 cell lines. Compounds 7f, 7k, 7l and 7j presented simultaneously good levels of inhibition of both cytokines. Moreover, compound 7l exhibited good anti-inflammatory effect in carrageenan-induced rat paw edema. The results of Western blotting demonstrated that the anti-cytokine potential of compound 7l is mainly mediated through the inhibition of p38 MAPK signaling pathway. Molecular docking was performed to position compound 7l into p38α binding site in order to explore the potential target. The information of this work might be helpful for the design and synthesis of novel scaffold toward the development of new therapeutic agent to fight against inflammatory diseases.     

Bag-of-words representation for biomedical time series classification

Automatic analysis of biomedical time series such as electroencephalogram (EEG) and electrocardiographic (ECG) signals has attracted great interest in the community of biomedical engineering due to its important applications in medicine. In this work, a simple yet effective bag-of-words representation that is originally developed for text document analysis is extended for biomedical time series representation. In particular, similar to the bag-of-words model used in text document domain, the proposed method treats a time series as a text document and extracts local segments from the time series as words. The biomedical time series is then represented as a histogram of codewords, each entry of which is the count of a codeword appeared in the time series. Although the temporal order of the local segments is ignored, the bag-of-words representation is able to capture high-level structural information because both local and global structural information are well utilized. The performance of the bag-of-words model is validated on three datasets extracted from real EEG and ECG signals. The experimental results demonstrate that the proposed method is not only insensitive to parameters of the bag-of-words model such as local segment length and codebook size, but also robust to noise.     

Upregulation of SATB1 Is Associated with Prostate Cancer Aggressiveness and Disease Progression

Disease aggressiveness remains a critical factor to the progression of prostate cancer. Transformation of epithelial cells to mesenchymal lineage, associated with the loss of E-cadherin, offers significant invasive potential and migration capability. Recently, Special AT-rich binding protein (SATB1) has been linked to tumor progression. SATB1 is a cell-type restricted nuclear protein, which functions as a tissue-specific organizer of DNA sequences during cellular differentiation. Our results demonstrate that SATB1 plays significant role in prostate tumor invasion and migration and its nuclear localization correlates with disease aggressiveness. Clinical specimen analysis showed that SATB1 was predominantly expressed in the nucleus of high-grade tumors compared to low-grade tumor and benign tissue. A progressive increase in the nuclear levels of SATB1 was observed in cancer tissues compared to benign specimens. Similarly, SATB1 protein levels were higher in a number of prostate cancer cells viz. HPV-CA-10, DU145, DUPro, PC-3, PC-3M, LNCaP and C4-2B, compared to non-tumorigenic PZ-HPV-7 cells. Nuclear expression of SATB1 was higher in biologically aggressive subclones of prostate cancer cells with their respective parental cell lines. Furthermore, ectopic SATB1 transfection conferred increased cell motility and invasiveness in immortalized human prostate epithelial PZ-HPV-7 cells which correlated with the loss of E-cadherin expression. Consequently, knockdown of SATB1 in highly aggressive human prostate cancer PC-3M cells inhibited invasiveness and tumor growth in vivo along with increase in E-cadherin protein expression. Our findings demonstrate that SATB1 has ability to promote prostate cancer aggressiveness through epithelial-mesenchymal transition.     

Ultra-Compact High-Speed Electro-Optical Modulator with Extremely Low Energy Consumption Based on Polymer-Filled Hybrid Plasmonic Waveguide

Plasmonics - In this paper, we propose an ultra-compact high-speed electro-optical modulator with extremely low energy consumption based on silicon-polymer-metal hybrid plasmonic waveguide. Spatial...     

Hypercapnia slows down proliferation and apoptosis of human bone marrow promyeloblasts

Stem cells are being applied in increasingly diverse fields of research and therapy; as such, growing and culturing them in scalable quantities would be a huge advantage for all concerned. Gas mixtures containing 5 % CO₂ are a typical concentration for the in vitro culturing of cells. The effect of varying the CO₂ concentration on promyeloblast KG-1a cells was investigated in this paper. KG-1a cells are characterized by high expression of CD34 surface antigen, which is an important clinical surface marker for human hematopoietic stem cells (HSCs) transplantation. KG-1a cells were cultured in three CO₂ concentrations (1, 5 and 15 %). Cells were batch-cultured and analyzed daily for viability, size, morphology, proliferation, and apoptosis using flow cytometry. No considerable differences were noted in KG-1a cell morphological properties at all three CO₂ levels as they retained their myeloblast appearance. Calculated population doubling time increased with an increase in CO₂ concentration. Enhanced cell proliferation was seen in cells cultured in hypercapnic conditions, in contrast to significantly decreased proliferation in hypocapnic populations. Flow cytometry analysis revealed that apoptosis was significantly (p = 0.0032) delayed in hypercapnic cultures, in parallel to accelerated apoptosis in hypocapnic ones. These results, which to the best of our knowledge are novel, suggest that elevated levels of CO₂ are favored for the enhanced proliferation of bone marrow (BM) progenitor cells such as HSCs.     

Salt Intake and Health Risk in Climate Change Vulnerable Coastal Bangladesh: What Role Do Beliefs and Practices Play?

BackgroundHigh salt consumption is an important risk factor of elevated blood pressure. In Bangladesh about 20 million people are at high risk of hypertension due to climate change induced saline intrusion in water. The objective of this study is to assess beliefs, perceptions, and practices associated with salt consumption in coastal Bangladesh.MethodsThe study was conducted in Chakaria, Bangladesh between April-June 2011. It was a cross sectional mixed method study. For the qualitative study 6 focus group discussions, 8 key informant interviews, 60 free listing exercises, 20 ranking exercises and 10 observations were conducted. 400 adults were randomly selected for quantitative survey. For analysis we used SPSS for quantitative data, and Anthropac and Nvivo for qualitative data.ResultsSalt was described as an essential component of food with strong cultural and religious roots. People described both health benefits and risks related to salt intake. The overall risk perception regarding excessive salt consumption was low and respondents believed that the cooking process can render the salt harmless. Respondents were aware that salt is added in many foods even if they do not taste salty but did not recognize that salt can occur naturally in both foods and water.ConclusionsIn the study community people had low awareness of the risks associated with excess salt consumption and salt reduction strategies were not high in their agenda. The easy access to and low cost of salt as well as unrecognised presence of salt in drinking water has created an environment conducive to excess salt consumption. It is important to design general messages related to salt reduction and test tailored strategies especially for those at high risk of hypertension.     

Isolation and Characterization of Bacteria from Coal Mines of Dara Adam Khel,Pakistan

The coal fields of Pakistan and their microbiology have not been fully explored. Therefore, a study was conducted on the coal mines of Dara Adam Khel located in the Federally Administered Tribal Areas of Pakistan. For this purpose, sampling was done from nine different mines with varying depths. A total of 32 bacterial strains were isolated and their colony size, form, texture, color, margin, elevation and opacity were noted. The majority of the strains (75%) were found Gram negative. The bacterial strains were then characterized in detail by different biochemical tests including catalase, citrate, oxidase, indole, triple sugar iron, motility, methyl red-Vogues Proskeur, nitrate reduction and phenylalanine deaminase, and an enormous physiological diversity was observed. The Gram positive strains were further characterized on molecular level using 16S rRNA gene amplification and sequence analysis. Based on molecular analysis, seven strains were identified as Bacillus tequilensis, B. cereus, Janibacter melonis, Kocuria atrinae, B. anthracis, K. rosea and B. simplex. The other two strains (strains 6 and 41) had molecular similarity of only 98% and 97% with Brachybacterium spp. and Arthrobacter spp. respectively. The phylogenetic analysis further suggested that the strains 6 and 41 may be potential candidates for novel species; however, further work is needed for confirmation.