Synergistic Effect of Garcinol and Curcumin on Antiproliferative and Apoptotic Activity in Pancreatic Cancer Cells

Pancreatic cancer (PaCa) is a major health concern due to its aggressiveness and early metastasis. Current treatments for PaCa are limited by development of resistance against therapy. As an alternative strategy, we assessed the combinatorial effect of dietary compounds, garcinol and curcumin, on human PaCa cells (BxPC-3 and Panc-1). A significant (P < 0.05) dose-dependent reduction in cell viability and increase in apoptosis were observed in both cell lines as compared to untreated controls. A combination index (CI) value < 1, for a two-way comparison of curcumin and garcinol, suggests synergism. The potency (Dm) of the combination of garcinol and curcumin was 2 to 10 fold that of the individual agents. This indicates that curcumin and garcinol in combination exhibit a high level of synergism, with enhanced bioactivity, thereby reducing the required effective dose required for each individually. This combinatorial strategy may hold promise in future development of therapies against PaCa

Natural genetic variation in Calligonum Tunisian genus analyzed by RAPD markers

The Calligonum genus is one of the most economically important resources of the Tunisian desert, playing an important role in the lives of desert local population. A great range of genetic diversity could be seen in diverse populations of this genus which are spread all over Tunisian areas. DNA-based molecular markers are playing increasingly important role in the analysis of genetic diversity in wide range of plants. This study is an attempt to collect, compile and collate information on the existing natural genetic diversity, at intra-specific and inter-populational levels in Calligonum genus (C.azel, C.arich and C.comosum). This study deals with 16 genotypes of Calligonum (Polygonaceae) collected from different regions of Tunisian desert using random amplified polymorphic DNA (RAPD) marker. In total, 46 polymorphic bands amplified by 4 random primers, with the polymorphic rate of 89.06% were recorded. The commercial software package SPSS 16 was used to develop similar matrices based on the Dice coefficient which is defined as 2a/2a+u, where “a” is the number of positive matches and “u” is the number of non-matches. From the analysis, it is imperative that predominantly obligate out breeding behavior of Calligonum genus, helps these diverse accessions to spread and occupy specific geographical niches in the Tunisian arid regions.Key words: Calligonum, genetic diversity, Inter-specific variation, RAPD marker, Tunisian desert

Thermal stability of the essential oils isolated from Tunisian Thymus capitatus Hoff. et Link.: Effect on the chemical composition and the antioxidant and antibacterial activities

The chemical composition, the antioxidant and the antibacterial activities of essential oils, isolated from the aerial parts of Tunisian Thymus capitatus during the flowering phase, and stored in the dark during 37 days in the oven, at 60 degrees C were evaluated. Samples taken periodically were used to evaluate the chemical composition, the antioxidant and the antibacterial activities. With some fluctuations, carvacrol (68-74%) was the major component of the oil independent of the storage period. alpha-Terpinene and gamma-terpinene decreased over time, whereas p-cymene increased in the same period. Despite the thirty-seven days of storage at 60 degrees C, T. capitatus essential oil still showed high antioxidant and stable antimicrobial activity

Hybrid case‑base maintenance approach for modeling large scale case‑based reasoning systems

YesCase-based reasoning (CBR) is a nature inspired paradigm of machine learning capable to continuously learn from the past experience. Each newly solved problem and its corresponding solution is retained in its central knowledge repository called case-base. Withρ the regular use of the CBR system, the case-base cardinality keeps on growing. It results into performance bottleneck as the number of comparisons of each new problem with the existing problems also increases with the case-base growth. To address this performance bottleneck, different case-base maintenance (CBM) strategies are used so that the growth of the case-base is controlled without compromising on the utility of knowledge maintained in the case-base. This research work presents a hybrid case-base maintenance approach which equally utilizes the benefits of case addition as well as case deletion strategies to maintain the case-base in online and offline modes respectively. The proposed maintenance method has been evaluated using a simulated model of autonomic forest fire application and its performance has been compared with the existing approaches on a large case-base of the simulated case study.Authors acknowledge the internal funding support received from Namal College Mianwali to complete the research work

Pathophysiological role of microRNA-29 in pancreatic cancer stroma

poster abstractBackground: Dense fibrotic stroma associated with pancreatic ductal adenocarcinoma (PDAC) has been a major obstacle for drug delivery to the tumor bed and may impede attempts to slow down PDAC progression and metastasis. However, current antistromal drugs have not improved tumor response to chemotherapy or patient survival. Thus, a better understanding of the molecular mechanisms associated with tumorstromal interactions is desperately needed to develop novel anti-stromal therapeutic approaches. MicroRNAs (miRNAs) are an abundant class of highly conserved, small non-coding RNAs that function as key regulators of eukaryotic gene expression and cellular homeostasis. miR-29 is known to play a paramount role in the fibrotic process of several organs by providing crucial functions downstream of pro-fibrotic signaling pathways such as TGF-β1 and regulates the expression of extracellular matrix (ECM) proteins, a major component in the PDAC stroma. Upregulation of TGF-β1 is associated with PDAC pathogenesis and is known to activate stromal cells. Furthermore, vascular endothelial growth factor (VEGF) that stimulates tumor angiogenesis is a predicted target of miR-29. We hypothesize that miR-29 may be misregulated in TGF-β1 activated PDAC stromal cells and lead to excessive accumulation of ECM proteins and VEGF. Kwon et al. 2015 Annual AACR Meeting Restored expression of miR-29 could be therapeutically beneficial to modulate tumorstromal interactions. Methods: Northern blot or qPCR techniques were used to assess miR-29 levels in vitro stromal cells, murine PDAC model, and PDAC patient biopsies, and stromal deposition/fibrosis was determined by Sirius red staining. In murine and human PDAC samples, stromal specific miR-29 expression was determined via in situ hybridization by co-staining pancreatic tissues with glial fibrillary acidic protein a marker for stromal cells and miR-29. miR-29 functional studies were conducted by transfection of stroma cells with synthetic miR-29 mimics and locked nucleic acid, a miR-29 inhibitor, and ECM protein/VEGF expression was analyzed by western blot analysis. The effect of miR-29 overexpression in stromal cells on cancer colony growth was evaluated by direct coculture of stromal cells ectopically expressing miR-29 with pancreatic cancer cells, and subsequently, cancer colony number and stromal accumulation was determined by crystal violet and sirius red stains respectively. Results: In both in vitro and in vivo models as well as PDAC patient biopsies, we observed loss of miR-29 is a common phenomenon of activated stromal cells, and is associated with a significant increase in ECM and VEGF accumulation. Restored expression of miR-29 in stromal cells reduced the deposition of matrix proteins, VEGF expression, and cancer colony formation in direct co-culture. Conclusion: These results provide insight into the mechanistic role of miR-29 in PDAC stroma and its potential use as an anti-stromal/angiogenic therapeutic agent

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

The influence of C and O in the grain boundary on the brittle-ductile transition temperature of tungsten bi-cristals.

International audienc

La fragilité intrinsèque des joints de grains du tungstène étudiée à l'aide de bicristaux orientés.

National audienc