Ablation of Breast Cancer Cells Using Trastuzumab‐Functionalized Multi‐Walled Carbon Nanotubes and Trastuzumab‐Diphtheria Toxin Conjugate

Trastuzumab (Herceptin^®) is a monoclonal antibody (mAb) for specific ablation of HER2‐overexpressing malignant breast cancer cells. Intensification of antiproliferative activity of trastuzumab through construction of immunotoxins and nano‐immunoconjugates is a promising approach for treatment of cancer. In this study, trastuzumab was directly conjugated to diphtheria toxin (DT). Also, conjugates of trastuzumab and multiwalled carbon nanotubes (MWCNT) were constructed by covalent immobilization of trastuzumab onto MWCNTs. Then, antiproliferative activity of the fusion constructs against HER2‐overexpressing SK‐BR‐3 and also HER2‐negative MCF‐7 cancer cell lines were examined. Cells treated with trastuzumab‐MWCNT conjugates were irradiated with near‐infrared (NIR) light. Efficient absorption of NIR radiation and its conversion to heat by MWCNTs can be resulted to thermal ablation of cancerous cells. Our results strongly showed that both trastuzumab‐MWCNT and trastuzumab‐DT conjugates were significantly efficient in the specific killing of SK‐BR‐3 cells. Targeting of MWCNTs to cancerous cells using trastuzumab followed by exposure of cells to NIR radiation was more efficient in repression of cell proliferation than treatment for cancer cells with trastuzumab‐DT. Our results also showed that conjugation linkers can significantly affect the cytotoxicity of MWCNT‐immunoconjugates. In conclusion, our data demonstrated that trastuzumab‐MWCNT is a promising nano‐immunoconjugate for killing of HER2‐overexpressing cancerous cells.     

Antibacterial,antibiofilm, and antiquorum sensing activities of phytosynthesized silver nanoparticles fabricated from Mespilus germanica extract against multidrug resistance of Klebsiella pneumoniae clinical strains

The aim of the present work was to investigate the antibacterial, antibiofilm, and antiquorum sensing activities of phytosynthesized silver nanoparticles (AgNPs) fabricated from Mespilus germanica extract against multidrug-resistant (MDR) Klebsiella pneumoniae strains. Fifty strains of K. pneumoniae were isolated from various clinical specimens. Biofilm-forming strains were identified using Congo red agar and polymerase chain reaction (PCR) techniques. Subsequently, the antibacterial activity of phytosynthesized AgNPs on MDR K. pneumoniae strains was investigated by broth microdilution assay and agar well-diffusion method. Finally (in the last step), the antibiofilm activity of phytosynthesized AgNPs was determined using microtiter plate assay and real-time PCR (RT-PCR) methods for the analysis of type 3 fimbriae (mrkA) and quorum-sensing system (luxS) gene expression. The results of this study showed that the phytosynthesized AgNPs had a spherical nanostructure with the mean size of 17.60 nm. The AgNPs exhibited dose-dependent antibacterial activity. The results of the microtiter plate and RT-PCR methods show that AgNPs inhibited the biofilm formation in MDR K. pneumoniae strains, and the expressions of mrkA and luxS genes were downregulated significantly in MDR strains after treatment with a subminimum inhibitory concentration of AgNPs. In conclusion, AgNPs effectively prevent the formation of biofilms and kill bacteria in established biofilms, which suggests that AgNPs might be a promising candidate for the prevention and treatment of biofilm-related infections caused by MDR K. pneumoniae strains.     

Undiagnosed inferior vena cava type of sinus venosus atrial septal defect in a middle-aged woman: A rare case report

Sinus venosus atrial septal defect (ASD) accounts for 5% to 10% of ASDs. In contrast with the more common superior vena cava (SVC) type, the inferior vena cava (IVC) type of sinus venosus ASD with overriding IVC is extremely rare. The sinus venosus defect occur posterior to the fossa ovalis and is not regarded as true ASD. Transesophageal echocardiography (TEE) is a diagnostic procedure of choice due to close proximity of atrial septum to TEE transducer. However; it may not constantly yield detailed anatomical and functional characterization, and other imaging modalities such as cardiac magnetic resonance imaging (MRI) may be needed. We report the case of a 45-year-old woman with an undiagnosed hemodynamically significant IVC-type ASD without any anomalous drainage of pulmonary veins, who presented with progressive dyspnea.     

The development of an artificial neural network – genetic algorithm model (ANN-GA) for the adsorption and photocatalysis of methylene blue on a novel sulfur–nitrogen co-doped Fe2O3 nanostructure surface

In this study, a new sulfur–nitrogen co-doped Fe₂O₃ nanostructure was synthesized via a simple and efficient method and characterized via UV-Vis spectrophotometry, X-ray diffraction, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Brunauer–Emmett–Teller surface area analysis. The as-synthesized nanoparticles showed high efficiency for the removal of methylene blue. The experimental conditions including the dose of the nanoparticle, the concentration of the dye, pH and the light dose were studied and optimized. The removal percentage was approximately 95% in a short time (5 min). A three-layer artificial neural network (ANN) model was proposed for predicting the efficiency of the dye removal. The network was trained using the obtained experimental data at optimum values. Some training functions were tested and their ability to predict different numbers of neurons was evaluated. The coefficient of determination (R-squared) and the mean squared error (MSE) were measured for comparison. In order to improve the accuracy of the prediction and to remove its dependency on the number of neurons, the ANN parameters were optimized using the genetic algorithm (GA). The final model results showed an acceptable agreement with experimental data. Furthermore, the relative importance of the dose of the nanoparticle, the concentration of the dye, and pH on the efficiency were obtained as 39%, 46%, and 15%, respectively. Moreover, interestingly, the obtained results showed that this newly synthesized nanoparticle has some photocatalytic properties with a band gap of 1.65 eV and therefore, it can be proposed as a low-cost visible light-driven photocatalyst for engineering applications.

In this research an S-N doped Fe₂O₃ nanostructure is synthesized and its adsorption ability and photocatalytic activity were evaluated. The optimum experimental conditions were obtained and an ANN-GA model was proposed for predicting experimental values.     

Do Subjective Norms Predict the Screening of Cancer Patients’ First-Degree Relatives? A Systematic Review and Meta-Analysis

Background: Early detection and preventive measures can reduce the risk of cancer among first degree relatives (FDRs) of cancer patients.Several studies investigated the effect of subjective norm in relation to FDRs’ tendency to conduct preventive behaviors. Therefore, the purpose of this study was to systematically evaluate the effect of subjective norms on cancer patients’ FDRs as well as their willingness for screening. Methods: PubMed and Scopus were studied to investigate the effect of subjective norms on preventive measures such as breast cancer self-examination, colonoscopy, PSA testing, skin examination, and genetic testing. Odds Ratio (OR), correlation was and confidence intervals were extracted for meta-analysis. After reviewing the studies, only 16 studies met the criteria to be included in this systematic review. Results: The meta- analysis and OR showed that Physician Recommendation (OR=6.98, 95% CI; 2.55–19.09, P<0.001), Health Care Provider (HCP) (OR=2.79, 95% CI; 1.26-6.16; P=0.011), family and friends (OR=1.82, 95% CI; 1.33–2.50, P <0.001) significantly enhanced the likelihood of referring for screening and preventive measures. Conclusions: The results of the current study indicated that subjective norms can significantly increase willingness to screening.     

EEG synchronization measures are early outcome predictors in comatose patients after cardiac arrest

Objective

Outcome prognostication in comatose patients after cardiac arrest (CA) remains a major challenge. Here we investigated the prognostic value of combinations of linear and non-linear bivariate EEG synchronization measures.

Central noradrenergic blockade prevents autotomy in rat: implication for pharmacological prevention of postdenervation pain syndrome

Following transection of peripheral nerve, rats exhibit autotomy, which is considered to be the animal model of postdenervation pain syndrome. It has been suggested that phantom limb pain is a result of peripheral denervation leading to reorganization of somatosensory pathways, particularly in the cerebral cortex, which is shown to depend upon central noradrenergic activity. In this study, sciatic and saphenous nerves were sectioned in the left hindpaw of 30 adult rats resulting in complete loss of pain sensation in the hindpaw. A group of rats received normal saline, compared to another group which received N-(2-) Chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) injection 24 h prior to transection. The latter group was also compared to a third group whose central noradrenergic system were also blocked by bilateral injection of 6-OHDA into the ascending noradrenergic bundle 1 week prior to transection. A fourth group received contralateral cortical ablation in addition to peripheral nerve transection and was compared to the first group whose cortex remained intact. The animals were observed daily for 60 days and autotomy was scored in accordance to the system of Wall et al. After 1 week, control animals began to exhibit autotomy. In contrast, autotomy was absent in rats treated with DSP4, similar to rats which received 6-OHDA. Rats which had contralateral cortical ablation showed a considerably delayed onset of autotomy and a reduction in final autotomy scores. We conclude that autotomy, as a model of postdenervation pain syndrome, can be prevented by blockade of noradrenergically mediated cortical reorganization. The clinical implications of this finding are discussed.