Gemcitabine Integrated Nano-Prodrug Carrier System

Peptide nanomaterials have received a great deal of interest in drug-delivery applications due to their biodegradability, biocompatibility, suitability for large-scale synthesis, high drug-loading capacities, targeting ability, and ordered structural organization. The covalent conjugation of drugs to peptide backbones results in prolonged circulation time and improved stability of drugs. Therapeutic efficacy of gemcitabine, which is used for breast cancer treatment, is severely compromised due to its rapid plasma degradation. Its hydrophilic nature poses a challenge for both its efficient encapsulation into nanocarrier systems and its sustained release property. Here, we designed a new peptide prodrug molecule for the anticancer drug gemcitabine, which was covalently conjugated to the C-terminal of 9-fluorenylmethoxy carbonyl (Fmoc)-protected glycine. The prodrug was further integrated into peptide nanocarrier system through noncovalent interactions. A pair of oppositely charged amyloid-inspired peptides (Fmoc-AIPs) were exploited as components of the drug-carrier system and self-assembled into one-dimensional nanofibers at physiological conditions. The gemcitabine integrated nanoprodrug carrier system exhibited slow release and reduced the cellular viability of 4T1 breast cancer cell line in a time- and concentration-dependent manner. © 2017 American Chemical Society

Bioactive peptide functionalized aligned cyclodextrin nanofibers for neurite outgrowth

Guidance of neurite extension and establishment of neural connectivity hold great importance for neural tissue regeneration and neural conduit implants. Although bioactive-epitope functionalized synthetic or natural polymeric materials have been proposed for the induction of neural regeneration, chemical modifications of these materials for neural differentiation still remain a challenge due to the harsh conditions of chemical reactions, along with non-homogeneous surface modifications. In this study, a facile noncovalent functionalization method is proposed by exploiting host-guest interactions between an adamantane-conjugated laminin derived bioactive IKVAV epitope and electrospun cyclodextrin nanofibers (CDNFs) to fabricate implantable scaffolds for peripheral nerve regeneration. While electrospun CDNFs introduce a three-dimensional biocompatible microenvironment to promote cellular viability and adhesion, the bioactive epitopes presented on the surface of electrospun CDNFs guide the cellular differentiation of PC-12 cells. In addition to materials synthesis and smart functionalization, physical alignment of the electrospun nanofibers guides the cells for enhanced differentiation. Cells cultured on aligned and IKVAV functionalized electrospun CDNFs had significantly higher expression of neuron-specific βIII-tubulin and synaptophysin. The neurite extension is also higher on the bioactive aligned scaffolds compared to random and non-functionalized electrospun CDNFs. Both chemical and physical cues were utilized for an effective neuronal differentiation process. © The Royal Society of Chemistry

Local delivery of doxorubicin through supramolecular peptide amphiphile nanofiber gels

Peptide amphiphiles (PAs) self-assemble into supramolecular nanofiber gels that provide a suitable environment for encapsulation of both hydrophobic and hydrophilic molecules. The PA gels have significant advantages for controlled delivery applications due to their high capacity to retain water, biocompatibility, and biodegradability. In this study, we demonstrate injectable supramolecular PA nanofiber gels for drug delivery applications. Doxorubicin (Dox), as a widely used chemotherapeutic drug for breast cancer treatment, was encapsulated within the PA gels prepared at different concentrations. Physical and chemical properties of the gels were characterized, and slow release of the Dox molecules through the supramolecular PA nanofiber gels was studied. In addition, the diffusion constants of the drug molecules within the PA nanofiber gels were estimated using fluorescence recovery after the photobleaching (FRAP) method. The PA nanofiber gels did not show any cytotoxicity and the encapsulation strategy enhanced the activity of drug molecules on cellular viability through prolonged release compared to direct administration under in vitro conditions. Moreover, the local in vivo injection of the Dox encapsulated PA nanofiber gels (Dox/PA) to the tumor site demonstrated the lowest tumor growth rate compared to the direct Dox injection and increased the apoptotic cells within the tumor tissue for local drug release through the PA nanofiber gels under in vivo conditions. © The Royal Society of Chemistry 2017

Using the information embedded in the testing sample to break the limits caused by the small sample size in microarray-based classification

<p>Abstract</p> <p>Background</p> <p>Microarray-based tumor classification is characterized by a very large number of features (genes) and small number of samples. In such cases, statistical techniques cannot determine which genes are correlated to each tumor type. A popular solution is the use of a subset of pre-specified genes. However, molecular variations are generally correlated to a large number of genes. A gene that is not correlated to some disease may, by combination with other genes, express itself.</p> <p>Results</p> <p>In this paper, we propose a new classiification strategy that can reduce the effect of over-fitting without the need to pre-select a small subset of genes. Our solution works by taking advantage of the information embedded in the testing samples. We note that a well-defined classification algorithm works best when the data is properly labeled. Hence, our classification algorithm will discriminate all samples best when the testing sample is assumed to belong to the correct class. We compare our solution with several well-known alternatives for tumor classification on a variety of publicly available data-sets. Our approach consistently leads to better classification results.</p> <p>Conclusion</p> <p>Studies indicate that thousands of samples may be required to extract useful statistical information from microarray data. Herein, it is shown that this problem can be circumvented by using the information embedded in the testing samples.</p

The pulmonary radiologic findings of rheumatoid arthritis

The rheumatoid arthritis (RA) is can affect multiple organs and tissues including the lung. Several pleuropulmonary manifestations are associated with rheumatoid arthritis involving the lung parenchyma, pleura, airways, and vasculature. The various pulmonary radiological findings have been defined in patients with RA.In this study, we aimed to retrospectively evaluate of the pulmonary radiologic findings in the five patients with RA.In the present study, pleural effusion, hydropneumothorax, chylothorax, pulmonary micronodular, macronodular and necrobiotic nodular lesions, pleural plagues, ground glass opacity and interstitial lung diseases were defined according to chest radiographs and computed tomography. The most common pulmonary radiologic findings were pulmonary nodules in three of patients, necrobiotic nodule in two of patients, pleural plague in two of patients and pleural effusion in two patients. The one of them had hydropneumothorax. Interstitial lung diseases were defined in two of patients.In conclusion, the pulmonary changes may be accompanied as a systemic component of the RA. If these changes are well recognized, they can help in the diagnosis of the RA. © 2011

An unusual cause of dyspnea

PubMed: 20854029Background. Right-sided arcus aorta (RSAA) is a rare condition and usually asymptomatic. However, it may be symptomatic if it causes tracheal or esophageal compression. Methods. The authors evaluated clinical and radiological features of seven patients with RSAA who had the diagnosis between May 2006 and May 2009. Results. The authors found that the incidence of RSAA was 0.16 in patients who had applied to their clinic. The age of patients ranged from 17 to 55 years. The male to female ratio was 61. Four patients were symptomatic due to RSAA. Most common symptoms were dyspnea during exercise, which is similar to exercise-induced asthma and dysphagia. Two patients were misdiagnosed as asthma. The flow-volume curves on spirometry of the patients showed intrathoracic upper airway obstruction. Thorax magnetic resonance imaging (MRI) revealed marked narrowing of the tracheal air column due to external compression of RSAA in three patients. Conclusions. RSAA should be included in the differential diagnosis of asthma. Spirometry may help to suspect RSAA. Thorax computed tomography (CT) andor MRI are the best imaging methods for the diagnosis of RSAA. © 2010 Informa Healthcare USA, Inc