Chemical Composition and Cytotoxic Activity of Eucalyptus torquata Luehm. and Eucalyptus salmonophloia F. Muell. Trunk Bark Essential Oils against Human SW620 and MDA-MB-231 Cancer Cell Lines

In recent years, there has been a growing interest in the screening of natural active ingredients from Eucalyptus essential oils because of their evident importance in practical utility and their undeniable therapeutic properties. Based on this, the aim of the present study was to investigate the chemical profile of the essential oils of the trunk bark of Eucalyptus torquata Luehm. (ETEO), and E. salmonophloia F. Muell. (ESEO), growing in Tunisia. The in vitro cytotoxic properties of the extracted EOs were also evaluated against two human cancer cell lines: breast carcinoma cell lines MDA-MB-231 and colorectal cancer cell lines SW620. The analysis by gas chromatography coupled with mass spectrometry (GC/MS) led to the identification of 32 compounds from the ETEO, with the dominant constituents being the monoterpenes trans-myrtanol (73.4 %) and myrtenol (4.7 %), and the apocarotene (E)-β-ionone (3.9 %). In the case of ESEO, 29 compounds were identified with trans-myrtanol (25.0 %), decanoic acid (22.1 %), nonanoic acid (9.8 %), γ-elemene (6.5 %), γ-maaliene (5.5 %), and α-terpineol (5.3 %) as the main components. The cytotoxicity of EOs against the two chosen cell lines was tested using Crystal Violet Staining (CVS) assay and 5-fluorouracil as a reference drug. The two EOs exhibited a significant dose-dependent inhibition against the viability of the used cell lines. Their inhibitory effects were particularly observed towards SW620 colon carcinoma cells with IC₅₀ values of 26.71±1.22 and 22.21±0.85 μg/mL, respectively, indicating that both oils were more cytotoxic for SW620 cells compared to MDA-MB-231 one.     

Ameliorated Effects of (−)-Epigallocatechin Gallate Against Toxicity Induced by Vanadium in the Kidneys of Wistar Rats

Obesity is a chronic disease characterized by excessive accumulation of body fat and the presence of metabolic disorders such as insulin resistance. In this sense, zinc is an important nutrient that stimulates insulin secretion and increases sensitivity to insulin. The aim of this study was to investigate the effect of zinc supplementation on insulin resistance in obese subjects through a systematic review of the available clinical trials. The search for articles was conducted using the PubMed, SciVerse Scopus, SciVerse ScienceDirect, and Cochrane databases, on May 25, 2016, by two authors independently. The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed in the conduct of this review. The Cochrane Collaboration tool was used to assess the risk of bias of the trials included in this review. After screening of the articles, six clinical trials were included in this systematic review. The scientific evidence presented in this systematic review shows that zinc supplementation improves insulin resistance in obese individuals of both sexes.     

Detection of biomarkers for Hepatocellular Carcinoma using a hybrid univariate gene selection methods

ABSTRACT: BACKGROUND: Discovering new biomarkers has a great role in improving early diagnosis of Hepatocellular carcinoma (HCC). The experimental determination of biomarkers needs a lot of time and money. This motivates this work to use in-silico prediction of biomarkers to reduce the number of experiments required for detecting new ones. This is achieved by extracting the most representative genes in microarrays of HCC. RESULTS: In this work, we provide a method for extracting the differential expressed genes, up regulated ones, that can be considered candidate biomarkers in high throughput microarrays of HCC. We examine the power of several gene selection methods (such as Pearson's correlation coefficient, Cosine coefficient, Euclidean distance, Mutual information and Entropy with different estimators) in selecting informative genes. A biological interpretation of the highly ranked genes is done using KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, ENTREZ and DAVID (Database for Annotation, Visualization, and Integrated Discovery) databases. The top ten genes selected using Pearson's correlation coefficient and Cosine coefficient contained six genes that have been implicated in cancer (often multiple cancers) genesis in previous studies. A fewer number of genes were obtained by the other methods (4 genes using Mutual information, 3genes using Euclidean distance and only one gene using Entropy). A better result was obtained by the utilization of a hybrid approach based on intersecting the highly ranked genes in the output of all investigated methods. This hybrid combination yielded seven genes (2 genes for HCC and 5 genes in different types of cancer) in the top ten genes of the list of intersected genes. CONCLUSIONS: To strengthen the effectiveness of the univariate selection methods, we propose a hybrid approach by intersecting several of these methods in a cascaded manner. This approach surpasses all of univariate selection methods when used individually according to biological interpretation and the examination of gene expression signal profiles.     

Ultrastructural and histochemical study of previtellogenic oogenesis in the desert lizard Scincus mitranus (Squamata,Sauropsida)

The structure of the granulosa in reptilian sauropsids varies between groups. We investigated the follicle development in the desert lizard Scincus mitranus. In the germinal bed, oogonia, and primary oocytes were identified and found to be interspersed between the epithelial cells. Previtellogenesis was divided into three stages: early, transitional, and late previtellogenic stages. During the early previtellogenic stage (diplotene), the oocyte is invested by small epithelia cells that formed a complete single layer, which may be considered as a young follicle. The transitional previtellogenic stage was marked by proliferation and differentiation of the granulosa layer from a homogenous layer consisting of only small cells to a heterogeneous layer containing three cell types: small, intermediate, and large cells. The late previtellogenic stage was marked by high-synthetic activity of large cells and the initiation of cytoplasmic bridges between large granulosa cells and the oocyte. Small cells were the only type of granulosa cells that underwent division. Thus, these cells may be stem cells for the granulosa cell population and may develop into intermediate and subsequently large cells. The intermediate cells may be precursors of large cells, as suggested by their ultrastructure. The ultrastructure of the large granulosa was indicative of their high synthetic activity. Histochemical analysis indicated the presence of cholesterol and phospholipids in the cytoplasm of large cells, the zona pellucida, among the microvilli, in the bridges region, and in the cortical region of the oocyte cytoplasm. These materials may be transferred from large cells into the oocyte through cytoplasmic bridges and provide nutritive function to large cells rather than functioning in steroidogenesis or vitellogenesis.     

Formulation development of self-nanoemulsifying drug delivery system of celecoxib for the management of oral cavity inflammation

The oral administration of celecoxib (CLX) is a real problem because of its low aqueous solubility that results in high variability in absorption and its severe adverse effect such as cardiotoxic effects and gastrointestinal toxicity. Self-nanoemulsifying drug delivery systems (SNEDDS) can enhance the poor dissolution and erratic absorption of poorly water-soluble drugs such as CLX. This study was conducted to investigate the potential of SNEDDS to enhance the efficacy of CLX on inflamed mucous tissue and reduce systemic adverse effects by increasing its poor dissolution properties. A pseudo-ternary phase diagram was derived from the results of CLX solubility experiments in various excipients. These studies revealed the use of Labrafil M 2515 CS as oil, tween 80 as a surfactant, and polyethylene glycol 400 as a co-surfactant for the optimization of SNEDDS formulations. Eight formulations were formulated and characterized by their particle size, polydispersity index, viscosity, globular shape, drug solubility, self-emulsification efficiency, in vitro drug release, and permeation. The anti-inflammatory effect of CLX-SNEDDS was evaluated by carrageenan-induced cheek oedema in rats. The cheeks were treated with CLX-SNEDDS before oedema induction and then noticed for narrow periods (2?h) followed by histopathological studies to determine the efficacy of treatment. The selected formulations (F3 and F5) showed spherical morphologies under transmission electron microscopy, mean droplet sizes of 116.9?±?1.78 and 124?±?1.87?nm, respectively, complete in vitro drug release, and high cumulative amounts of drug permeation in 8?h. They also showed significant remarkable cheek oedema inhibition in comparison with the control groups (p?<?0.05). CLX-SNEDDS was found to achieve effective local therapeutic concentration and intended to reduce cheek oedema, congestive capillary, inflammatory cells, and side effects due to lower dose size.     

Edge activators and a polycationic polymer enhance the formulation of porous voriconazole nanoagglomerate for the use as a dry powder inhaler

Purpose: Voriconazole has both low aqueous solubility and stability. We hypothesize that designing voriconazole in the form of a nano powder inhaler at a geometric diameter within 1–5?μm will enhance its stability and solubility. Therefore, we prepared nanoagglomerates of voriconazole which will collapse in the lungs to reform the nanoparticles.

Method: The nanoparticles were formulated using both stearic acid and sodium deoxycholate as edge activators. Osmogenic polycation polyethyleneimine (PEI) was used to form agglomerates of controllable size.

Results: Voriconazole nanoparticles and agglomerates showed a significant higher cumulative drug release than the pure powder (p?R^2?=^?0.95. Small-sized particles were formed (353?nm), while their zeta potential was ?30.7?mV. The agglomerates were 2.7?μm in size and their zeta potential was ?20.9?mV. The formation of porous agglomerates was confirmed using a transmission electron microscope. Cascade impactor was used to evaluate the aerodynamic properties of the nanoparticles and the agglomerates. The aerodynamic characterization of the nanoparticles and the agglomerates resulted in a significant smaller mass median aerodynamic diameter (MMAD) (p?p?p?p?Conclusion: The results suggest that using the combination of edge activators and diluted polycationic polymer solution provides porous voriconazole nanoagglomerates in a respirable range, which is proved successful in enhancing both the deposition and the dissolution of water insoluble-drugs in the lung.     

Gene transfer into insect brain and cell-specific expression of bombyxin gene

 A transgene reporter consisting of the bombyxin gene promoter and the green fluorescent protein coding region was introduced into intact brains of the silkworm Bombyx mori by in vitro electroporation. After in vitro culture of the brains, the fluorescence derived from the introduced reporter gene was observed in all cases in eight neurosecretory cells that had previously been identified as bombyxin-producing cells (BPCs). Although the fluorescence was not always observed in all cells, it was specific to BPCs, indicating that the reporter was under the control of the bombyxin gene promoter in a BPC-specific manner. Electroporatical introduction of a reporter gene was therefore found to be a suitable method for analyzing cell-specific expression in intact tissues and to be substitute for germ-line transmission of reporters in the transgenic system. Application of this technique enables us to analyze the cell-specific expression of transgene reporters within a few days and treat more than several dozens of the reporters within 1 month, which is difficult to do with the transgenic system. Received: 8 December 1998 / Accepted: 8 March 1999     

Partial characterization of IR-alpha-MSH peptides found in melanoma tumors.

Our previous work indicated that IR-alpha-MSH (immunoreactive alpha-melanocyte-stimulating hormone) plasma levels are three times as high in melanoma patients with progressing disease than in disease-free patients, and that the melanoma tumor itself may be the source of IR-alpha-MSH. Further identification of the material in tumor extracts has been carried out in this study, and the results presented here show that the immunoreactivity is associated with a major fraction of about 16 kDa and another of 5-9 kDa. Significant amounts of the immunoreactive material were also found in human melanoma cells but not in culture supernatants. The presence of this material may be related to the melanogenic status of the tumor cells. We have estimated the intracellular IR-alpha-MSH to be within a 0.4 to 2.3 nM range in melanoma tumor cells. We have investigated the melanogenic effect of the IR-alpha-MSH material and its relationship to alpha-MSH. Purified extracts both from metastases and cultured cells were found to promote frog skin darkening as well as tyrosinase activity in Cloudman S91 melanoma cells. The IR material could also displace labeled alpha-MSH from its binding sites in human melanoma cells. Our data clearly indicate that melanoma cells engage in an autocrine production of alpha-MSH-like bioactive peptides by melanoma cells, of larger mol.wt., which are able to bind to MSH receptors. These peptides may be involved in the regulation of melanogenesis and possibly in the growth and proliferation of melanoma cells by an autocrine/paracrine mechanism.