Fabrication and characterization of the Fe3O4@SiO2-rGO nanocomposite: a catalyst for multi-component reactions.

A novel nanocomposite is synthesized by covalently modifying reduced graphene oxide (rGO) with Fe3O4@SiO2 nanoparticles. Fe3O4 was synthesized using a co-precipitation method, and SiO2 was then coated onto the Fe3O4via a sol-gel method. Graphene oxide was synthesized using the Hummers' method. Furthermore, a hydrothermal method was applied to create the Fe3O4@SiO2-GO composite, and a simple reduction was used to obtain three-dimensional (3D) Fe3O4@SiO2-rGO core-shell spheres. XRD, FTIR, FE-SEM, VSM, BET, TGA, and Raman analyses were used to characterize the prepared nanocomposites. X-Ray diffraction (XRD) and Raman spectra reveal that the nanostructures consist of highly crystallized cubic Fe3O4, amorphous SiO2, and rGO sheets stacked in a disordered fashion. Field emission scanning electron microscopy (FE-SEM) characterization indicates that the form of the Fe3O4@SiO2 core-shell structures is spherical, with an average size of about 25 nm. Magnetic hysteresis loops reveal the super-paramagnetic behavior of the samples at room temperature. All of the results obtained confirm the synthesis of high-quality nanocomposites, which can be a good candidate for use as a catalyst in multi-component reactions.

Comparison of Intraperitoneal Normal Saline Infusion with Pulmonary Recruitment Maneuver in Reducing Shoulder and Upper Abdomen Pain Following Gynecologic Laparoscopic Procedures: A Randomized, Controlled, Triple-Blind Trial.

OBJECTIVES: The current study aimed at evaluating the effect of intraperitoneal infusion of normal saline (NS) and pulmonary recruitment maneuver (PRM) on the reduction of pain in shoulder, upper abdomen, and incision site after elective laparoscopic gynecologic surgery. METHODS: Totally, 280 patients (mean age: 30.5 years) that underwent laparoscopic gynecologic surgery from October 2013 to August 2015 were randomly and equally allocated into four groups. Group A received intraperitoneal infusion of NS 1.5 - 2 mL/kg of body weight; group B received PRM with five manual pulmonary inflations at a maximum pressure of 60 cm H2O; group C simultaneously received two former interventions; and finally the control group D received routine method of gentle abdominal pressure. All patients were assessed in the first 24 hours after surgery. RESULTS: There was an unsteady pattern for pain in shoulder, upper abdomen, and incision site at different time points across the studied groups over the trial. Patients in group B showed significantly lower shoulder pain 24 hours after laparoscopic gynecologic surgery (P = 0.01), while patients in group D had significantly lower incision site pain (P < 0.001). CONCLUSIONS: PRM was superior to intraperitoneal infusion of NS for reducing pain in the first 24 hours after laparoscopic gynecologic surgery.

Distribution of CYP2D6 polymorphism in the Middle Eastern region.

Cytochrome P450 2D6 (CYP2D6) is an important drug-metabolizing enzyme involved in the pharmacokinetic metabolism of drugs. CYP2D6 gene is highly polymorphic, and the combination of its different alleles yields different phenotypes including extensive metabolizer (EM), intermediate metabolizer (IM), poor metabolizer (PM), and ultrarapid metabolizer (UM). Genotyping of the important alleles for this gene in different ethnicities is of particular importance for assessing the efficacy of various drugs. In this study, we reviewed the CYP2D6 allele and phenotype frequencies predicted from the genotypes of CYP2D6 in the Middle East area. Regardless of different ethnicities, the CYP2D6*41 allele frequency was shown to be higher than that of other reduced functional alleles. In addition, CYP2D6*4 was the most frequent nonfunctional allele in all studied populations in the Middle East. Taken together, our findings illustrated that the frequencies of PM or IM alleles and different genotypes harboring these alleles are relatively high in the Middle Eastern countries. Therefore, the study of CYP2D6 alleles for each patient to detect those that are at risk is of great importance to prevent adverse drug reactions through individualization therapy.

Clinical Trial: CYP2D6 Related Dose Escalation of Tamoxifen in Breast Cancer Patients With Iranian Ethnic Background Resulted in Increased Concentrations of Tamoxifen and Its Metabolites.

Introduction: The polymorphic enzyme cytochrome P450 2D6 (CYP2D6) catalyzes a major step in the bioactivation of tamoxifen. Genotyping of clinically relevant CYP2D6 alleles and subsequent dose adjustment is a promising approach to individualize breast cancer therapy. The aim of this study was to investigate the relationship between the plasma levels of tamoxifen and its metabolites and different CYP2D6 genotypes under standard (20 mg/day) and dose-adjusted therapy (Registration ID in Iranian Registry of Clinical Trials: IRCT2015082323734N1). Materials and Methods: Using TaqMan® assays common alleles of CYP2D6 (∗1, ∗2, ∗4, ∗5, ∗6, ∗10, ∗17, and ∗41) and gene duplication were identified in 134 breast cancer patients. Based on CYP2D6 genotypes patients with an activity score 1 (n = 15) and 0-0.5 (n = 2) were treated with tamoxifen adjusted dosage of 30 and 40 mg/day, respectively. The concentration of tamoxifen and its metabolites before and after 4 and 8 months of dose adjustment were measured using LC-MS/MS technology. Results: At baseline, (Z)-endoxifen plasma concentrations (33 ± 15.5, 28.1 ± 14, 26.6 ± 23.4, 14.3 ± 8.6, and 10.7 ± 5.5 nmol/l for EM/EM, EM/IM, EM/PM, IM/IM and PM/PM, respectively) and the metabolic ratio (Z)-Endoxifen/N-desmethyltamoxifen (0.0558 ± 0.02, 0.0396 ± 0.0111, 0.0332 ± 0.0222, 0.0149 ± 0.0026, and 0.0169 ± 0.0177 for EM/EM, EM/IM, EM/PM, IM/IM, and PM/PM, respectively) correlated with CYP2D6 genotype (Kruskal-Wallis p = 0.013 and p < 0.0001, respectively). Dose escalation to 30 and 40 mg/day in patients with a CYP2D6 activity score of 1 (n = 15) and 0-0.5 (n = 2) resulted in a significant increase in (Z)-endoxifen plasma levels (22.17 ± 24.42, 34.43 ± 26.54, and 35.77 ± 28.89 nmol/l at baseline, after 4 and 8 months, respectively, Friedman p = 0.0388) along with the plasma concentrations of tamoxifen and its other metabolites. No severe side effects were recorded during dose escalation. Conclusion: For the first time, we show the feasibility of dose escalation of tamoxifen in breast cancer patients with compromised CYP2D6 activity and Iranian ethnic background to increase the plasma concentrations of (Z)-endoxifen.

Aberrant expression of PlncRNA-1 and TUG1: potential biomarkers for gastric cancer diagnosis and clinically monitoring cancer progression.

AIM: To evaluate PlncRNA-1, TUG1 and FAM83H-AS1 gene expression and their possible role as a biomarker in gastric cancer (GC) progression. PATIENTS & METHODS: Long noncoding RNA expressions and clinicopathological characteristics were assessed in 70 paired GC tissues. Furthermore, corresponding data from 318 GC patients were downloaded from The Cancer Genome Atlas database. RESULTS: Expression of PlncRNA-1 and TUG1 were significantly upregulated in GC tumoral tissues, and significantly correlated with clinicopathological characters. However, FAM83H-AS1 showed no consistently differential expression. The expression of these three long noncoding RNAs was significantly higher in The Cancer Genome Atlas tumoral tissues. CONCLUSION: In conclusion, PlncRNA-1 and TUG1 genes may play a critical role in GC progression and may serve as potential diagnostic biomarkers in GC patients.

Laminin matrix promotes hepatogenic terminal differentiation of human bone marrow mesenchymal stem cells.

OBJECTIVES: The application of stem cells holds great promises in cell transplants. Considering the lack of optimal in vitro model for hepatogenic differentiation, this study was designed to examine the effects of laminin matrix on the improvement of in vitro differentiation of human bone marrow mesenchymal stem cells (hBM-MSC) into the more functional hepatocyte-like cells. MATERIALS AND METHODS: Characterization of the hBM-MSCs was performed by immunophenotyping and their differentiation into the mesenchymal-derived lineage. Then, cells were seeded on the laminin-coated or tissue culture polystyrene (TCPS). The differentiation was carried out during two steps. Afterward, the expression of hepatocyte markers such as AFP, ALB, CK-18, and CK-19 as well as the expression of C-MET, the secretion of urea, and the activity of CYP3A4 enzyme were determined. Moreover, the cytoplasmic glycogen storage was examined by periodic acid-Schiff (PAS) staining. RESULTS: The results demonstrated that the culture of hBM-MSC on laminin considerably improved hepatogenic differentiation compared to TCP group. A significant elevated level of urea biosynthesis and CYP3A4 enzyme activity was observed in the media of the laminin-coated differentiated cells (P<0.05). Furthermore higher expressions of both AFP and ALB were determined in cells differentiated on laminin matrix. Glycogen accumulation was not detected in the undifferentiated hBM-MSCs, however, both differentiated cells in laminin and TCPS groups demonstrated the intracellular glycogen accumulation on day 21 of hepatogenic differentiation. CONCLUSION: Taken together, these findings may indicate that laminin matrix can improve terminal differentiation of hepatocyte-like cells from hBM-MSCs. Thus, laminin might be considered as a suitable coating in hepatic tissue engineering designs.

Brain tumors: Special characters for research and banking.

A brain tumor is an intracranial neoplasm within the brain or in the central spinal canal. Primary malignant brain tumors affect about 200,000 people worldwide every year. Brain cells have special characters. Due to the specific properties of brain tumors, including epidemiology, growth, and division, investigation of brain tumors and the interpretation of results is not simple. Research to identify the genetic alterations of human tumors improves our knowledge of tumor biology, genetic interactions, progression, and preclinical therapeutic assessment. Obtaining data for prevention, diagnosis, and therapy requires sufficient samples, and brain tumors have a wide range. As a result, establishing the bank of brain tumors is very important and essential.

Human Bone Marrow Mesenchymal Stem Cell Behaviors on PCL/Gelatin Nanofibrous Scaffolds Modified with A Collagen IV-Derived RGD-Containing Peptide.

OBJECTIVE: We introduce an RGD (Arg-Gly-Asp)-containing peptide of collagen IV origin that possesses potent cell adhesion and proliferation properties. MATERIALS AND METHODS: In this experimental study, the peptide was immobilized on an electrospun nanofibrous polycaprolactone/gelatin (PCL/Gel) hybrid scaffold by a chemical bonding approach to improve cell adhesion properties of the scaffold. An iodine-modified phenylalanine was introduced in the peptide to track the immobilization process. Native and modified scaffolds were characterized with scanning electronmicroscopy (SEM) and fourier transform infrared spectroscopy (FTIR). We studied the osteogenic and adipogenic differentiation potential of human bone marrow-derived mesenchymal stem cells (hBMSCs). In addition, cell adhesion and proliferation behaviors of hBMSCs on native and peptide modified scaffolds were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 4',6-diamidino-2-phenylindole (DAPI) staining, and the results compared with tissue culture plate, as the control. RESULTS: FTIR results showed that the peptide successfully immobilized on the scaffold.MTT assay and DAPI staining results indicated that peptide immobilization had a dramatic effect on cell adhesion and proliferation. CONCLUSION: This peptide modified nanofibrous scaffold can be a promising biomaterial for tissue engineering and regenerative medicine with the use of hBMSCs.

Functionalized mesoporous silicon for targeted-drug-delivery.

The present work concerns a preliminary step in the production of anticancer drug loaded porous silicon (PSi) for targeted-drug-delivery applications. A successful procedure for the covalent attachment of folic acid, polyethylene glycol (PEG) and doxorubicin to hydrophilic mesoporous silicon layers is presented. A systematic approach has been followed to obtain the optimal composition of the N,N'-dicyclohexylcarbodiimide (DCC)/N-hydroxysuccimide (NHS) in dimethylsulfoxide (DMSO) solution for the surface activation process of the undecylenic acid (UD) grafted molecules to take place with minimal undesired byproduct formation. The effect of reactant concentration and kind of solvent (aqueous or DMSO) on the attachment of folic acid to the activated PSi layer has been investigated. The covalent attachment of the doxorubicin molecules to the PSi layer functionalized with folic acid and PEG is discussed. The drug release kinetics as a function of pH has been studied. The functionalized PSi particles show a high cytotoxicity compared to the equivalent amount of free drug. Cell toxicity tests show clearly that the incorporation of folate molecules increases substantially the toxicity of the loaded PSi particles. Accordingly this new functionalized PSi may be considered a proper candidate for targeted drug delivery.

Deposition of DLC Film on Stainless Steel Substrates Coated by Nickel Using PECVD Method.

Research on diamond-like carbon (DLC) films has been devoted to find both optimized conditions and characteristics of the deposited films on various substrates. In the present work, we investigate the quality of the DLC films grown on stainless steel substrates using different thickness of the nickel nanoparticle layers on the surface. Nickel nanoparticles were sputtered on the stainless steel substrates at 200 °C by a DC-sputtering system to make a good adherence between DLC coating and steel substrates. Atomic Force Microscopy was used to characterize the surface roughness and distribution function of the nickel nanoparticles on the substrate surface. Diamond like carbon films were deposited on stainless steel substrates coated by nickel using pure acetylene and C2H2/H2 with 15% flow ratio by DC-Plasma Enhanced Chemical Vapor Deposition (PECVD) systems. Microstructural analysis by Raman spectroscopy showed a low intensity ratio ID/IG for DLC films by increasing the Ni layer thickness on the stainless steel substrates. Fourier Transforms Infrared spectroscopy (FTIR) evidenced the peaks attributed to C-H bending and stretching vibration modes in the range of 1300-1700 cm-1 and 2700-3100 cm-1, respectively, in good agreement with the Raman spectroscopy and confirmed the DLC growth in all samples.