Structural Modification in Hepatitis C Virus Envelope Protein; Potential Viral Strategy Against Interferon Therapy

International Journal of Peptide Research and Therapeutics - Interferons (IFNs) are the main part of the immune system as a defensive response to viral infection. The phosphorylation domain of...     

Assessment of Fatty Acid and Amino Acid Composition of Macroalgae from the Persian Gulf to Characterize their Suitability for Nutritional Supplements

Biology Bulletin - Macroalgae, commonly known as seaweed, can be found worldwide. Seaweeds offer a novel dietary ingredient because of their excellent biochemical composition and health protective...     

Extracellular Alkaline pH Leads to Increased Metastatic Potential of Estrogen Receptor Silenced Endocrine Resistant Breast Cancer Cells

Introduction

Endocrine resistance in breast cancer is associated with enhanced metastatic potential and poor clinical outcome, presenting a significant therapeutic challenge. We have established several endocrine insensitive breast cancer lines by shRNA induced depletion of estrogen receptor (ER) by transfection of MCF-7 cells which all exhibit enhanced expression profile of mesenchymal markers with reduction of epithelial markers, indicating an epithelial to mesenchymal transition. In this study we describe their behaviour in response to change in extracellular pH, an important factor controlling cell motility and metastasis.

Methods

Morphological changes associated with cell exposure to extracellular alkaline pH were assessed by live cell microscopy and the effect of various ion pumps on this behavior was investigated by pretreatment with chemical inhibitors. The activity and expression profile of key signaling molecules was assessed by western blotting. Cell motility and invasion were examined by scratch and under-agarose assays respectively. Total matrix metalloproteinase (MMP) activity and specifically of MMP2/9 was assessed in conditioned medium in response to brief alkaline pH exposure.

Results

Exposure of ER –ve but not ER +ve breast cancer cells to extracellular alkaline pH resulted in cell shrinkage and spherical appearance (termed contractolation); this was reversed by returning the pH back to 7.4. Contractolation was blocked by targeting the Na⁺/K⁺ and Na⁺/H⁺ pumps with specific chemical inhibitors. The activity and expression profile of key signaling molecules critical for cell adhesion were modulated by the exposure to alkaline pH. Brief exposure to alkaline pH enhanced MMP2/9 activity and the invasive potential of ER –ve cells in response to serum components and epithelial growth factor stimulation without affecting unhindered motility.

Conclusions

Endocrine resistant breast cancer cells behave very differently to estrogen responsive cells in alkaline pH, with enhanced invasive potential; these studies emphasise the crucial influence of extracellular pH and caution against indiscriminate application of alkalinising drug therapy.     

Bimodal electricity generation and aromatic compounds removal from purified terephthalic acid plant wastewater in a microbial fuel cell

Wastewater of purified terephthalic acid (PTA) from a petrochemical plant was examined in a membrane-less single chamber microbial fuel cell for the first time. Time course of voltage during the cell operation cycle had two steady phases, which refers to the fact that metabolism of microorganisms was shifted from highly to less biodegradable carbon sources. The produced power density was 31.8 mW m^?2 (normalized per cathode area) and the calculated coulombic efficiency was 2.05 % for a COD removal of 74 % during 21 days. The total removal rate of different pollutants in the PTA wastewater was observed in the following order: (acetic acid) > (benzoic acid) > (phthalic acid) > (terephthalic acid) > (p-toluic acid). The cyclic voltammetry results revealed that the electron transfer mechanism was dominated by mediators which were produced by bacteria.     

Comparison of Diagnostic Methods in the Evaluation of Onychomycosis

Onychomycosis is a common nail problem, accounting for up to half of all nail diseases. Several nail disorders may mimic the onychomycosis clinically. Therefore, a sensitive, quick, and inexpensive test is essential for screening nail specimens for the administration of the proper drug. The aim of this study was to compare 4 different diagnostic methods in the evaluation of onychomycosis and to determine their sensitivity, specificity, positive predictive value, and negative predictive value. In a cross-sectional study, nail specimens were collected from 101 patients suspected to have onychomycosis during a 14-month period. The nail specimens were examined using potassium hydroxide (KOH) 20 %, KOH-treated nail clipping stained with periodic acid-Schiff (KONCPA), and calcofluor white (CFW) stain, and grew a fungal culture. The culture was chosen as the gold standard for statistical analysis using the McNemar and chi-square tests. Out of 101 patients, 100 (99 %) patients had at least 1 of the 4 diagnostic methods positive for the presence of organisms. The positive rates for the fungal culture, KOH preparation, CFW, and KONCPA were 74.2, 85.1, 91.09, and 99.01 %, respectively. The sensitivity and negative predictive value of KONCPA was 100 %. KONCPA was the most sensitive among the tests and was also superior to other methods in its negative predictive value. KONCPA was easy to perform, rapid, and gave significantly higher rates of detection of onychomycosis compared to the standard methods of KOH preparation and fungal culture. Therefore, KONCPA should be the single method of choice for the evaluation of onychomycosis.     

Prevalence of HBV genotypes among Egyptian hepatitis patients

Phylogenetic analysis has led to the classification of hepatitis B virus into eight genotypes, designated A to H. The genotypes have differences in biological properties and show heterogeneity in their global distribution. These attributes of the genotypes may account not only for differences in the prevalence of hepatitis B virus mutants in various geographic regions, but also makes them responsible for differences in the clinical outcome and response to antiviral treatment in different population groups. Africa is one of the highly endemic regions of HBV with five genotypes (A–E) identified. Almost all patients in the Mediterranean area are infected with genotype D. However, there is little information of genotype distribution in Egypt. A total of 140 Egyptian patients with hepatitis B surface antigen (HBsAg) positive were enrolled in this study. Of the 140 patients, only 100 patients were HBV DNA positive and only these were included in the study. They were classified into 20 patients with acute hepatitis (AH), 75 patients with chronic active hepatitis (CAH) and 5 patients with hepatocellular carcinoma (HCC). HBV genotypes were determined using INNO-LiPA methodology which is based on the reversed hybridization principle. This study showed that genotype D constituted 87% of the total infections (75 CAH cases, 7 AH cases and 5 HCC cases). The other 13% showed mixed infections of D/F. These findings show that the most prevalent genotype in Egypt is genotype D especially in CAH and HCC patients while the mixed type D/F is only encountered in AH.     

microRNA-214 contributes to melanoma tumour progression through suppression of TFAP2C

Malignant melanoma is fatal in its metastatic stage. It is therefore essential to unravel the molecular mechanisms that govern disease progression to metastasis. MicroRNAs (miRs) are endogenous non-coding RNAs involved in tumourigenesis. Using a melanoma progression model, we identified a novel pathway controlled by miR-214 that coordinates metastatic capability. Pathway components include TFAP2C, homologue of a well-established melanoma tumour suppressor, the adhesion receptor ITGA3 and multiple surface molecules. Modulation of miR-214 influences in vitro tumour cell movement and survival to anoikis as well as extravasation from blood vessels and lung metastasis formation in vivo. Considering that miR-214 is known to be highly expressed in human melanomas, our data suggest a critical role for this miRNA in disease progression and the establishment of distant metastases.     

Pretreatment CT and PET radiomics predicting rectal cancer patients in response to neoadjuvant chemoradiotherapy

BackgroundThe purpose of this study was to characterize pre-treatment non-contrast computed tomography (CT) and ¹⁸F-fluorodeoxyglucose positron emission tomography (PET) based radiomics signatures predictive of pathological response and clinical outcomes in rectal cancer patients treated with neoadjuvant chemoradiotherapy (NACR T).Materials and methodsAn exploratory analysis was performed using pre-treatment non-contrast CT and PET imaging dataset. The association of tumor regression grade (TRG) and neoadjuvant rectal (NAR) score with pre-treatment CT and PET features was assessed using machine learning algorithms. Three separate predictive models were built for composite features from CT + PET.ResultsThe patterns of pathological response were TRG 0 (n = 13; 19.7%), 1 (n = 34; 51.5%), 2 (n = 16; 24.2%), and 3 (n = 3; 4.5%). There were 20 (30.3%) patients with low, 22 (33.3%) with intermediate and 24 (36.4%) with high NAR scores. Three separate predictive models were built for composite features from CT + PET and analyzed separately for clinical endpoints. Composite features with α = 0.2 resulted in the best predictive power using logistic regression. For pathological response prediction, the signature resulted in 88.1% accuracy in predicting TRG 0 vs. TRG 1–3; 91% accuracy in predicting TRG 0–1 vs. TRG 2–3. For the surrogate of DFS and OS, it resulted in 67.7% accuracy in predicting low vs. intermediate vs. high NAR scores.ConclusionThe pre-treatment composite radiomics signatures were highly predictive of pathological response in rectal cancer treated with NACR T. A larger cohort is warranted for further validation.     

The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line

Chinese hamster ovary (CHO)-derived cell lines are the preferred host cells for the production of therapeutic proteins. Here we present a draft genomic sequence of the CHO-K1 ancestral cell line. The assembly comprises 2.45 Gb of genomic sequence, with 24,383 predicted genes. We associate most of the assembled scaffolds with 21 chromosomes isolated by microfluidics to identify chromosomal locations of genes. Furthermore, we investigate genes involved in glycosylation, which affect therapeutic protein quality, and viral susceptibility genes, which are relevant to cell engineering and regulatory concerns. Homologs of most human glycosylation-associated genes are present in the CHO-K1 genome, although 141 of these homologs are not expressed under exponential growth conditions. Many important viral entry genes are also present in the genome but not expressed, which may explain the unusual viral resistance property of CHO cell lines. We discuss how the availability of this genome sequence may facilitate genome-scale science for the optimization of biopharmaceutical protein production.