Biolmpacts
Volume:9 Issue: 3, Jun 2019

Despite rapid advances in diagnostic and treatment approaches, the overall survival rate of cancer has not been improved. Colorectal cancer (CRC) is recognized as the third leading cause of neoplasm-related deaths worldwide, in large part due to its considerable metastasis and drug resistance. For developing new anticancer strategies, rapid progression of multimodal nanomedicines and nanoconjugates has provided promising treatment modalities for effective therapy of cancer. The limitations of cancer chemotherapy might be overcome through the use of such nanosized therapeutics, including nanoconjugates of monoclonal antibodies (mAbs) along with drugs and organic/inorganic nanoparticles. CRC cells express various molecular markers against which mAbs can be designed and used as targeting/therapeutic agents. This editorial highlights the importance of such targeted nanosystems against CRC.

Bullying in academic science is a growing concern. It may vary in severity from insults, snubs, or invasions of privacy to violations of intellectual property and unfair crediting of authors. In extreme cases it may even include coercing lab workers to sign away rights to authorship or even intellectual property. Cumbersome institutional protocols and fears of reprisal may discourage targets of bullying from reporting such incidents; lab workers in the US on visas may feel especially vulnerable. Possible strategies to combat bullying include detailed examination of relevant documentation for signs of coercion or inaccuracy and specific training on reporting for those at risk of abuse.

Hydatid disease is a ubiquitous parasitic zoonotic disease, which causes different medical, economic and serious public health problems in some parts of the world. The causal organism is a multi-stage parasite named Echinococcus granulosus whose life cycle is dependent on two types of mammalian hosts viz definitive and intermediate hosts. In this study, enolase, as a key functional enzyme in the metabolism of E. granulosus (EgEnolase), was targeted through a comprehensive in silico modeling analysis and designing a host-specific multi-epitope vaccine. Three-dimensional (3D) structure of enolase was modeled using MODELLER v9.18 software. The B-cell epitopes (BEs) were predicted based on the multi-method approach and via some authentic online predictors. ClusPro v2.0 server was used for docking-based T-helper epitope prediction. The 3D structure of the vaccine was modeled using the RaptorX server. The designed vaccine was evaluated for its immunogenicity, physicochemical properties, and allergenicity. The codon optimization of the vaccine sequence was performed based on the codon usage table of E. coli K12. Finally, the energy minimization and molecular docking were implemented for simulating the vaccine binding affinity to the TLR-2 and TLR-4 and the complex stability. The designed multi-epitope vaccine was found to induce anti-EgEnolase immunity which may have the potential to prevent the survival and proliferation of E. granulosus into the definitive host. Based on the results, this step-by-step immunoinformatics approach could be considered as a rational platform for designing vaccines against such multi-stage parasites. Furthermore, it is proposed that this multi-epitope vaccine is served as a promising preventive anti-echinococcosis agent.

Testis-specific gene antigen 10 (TSGA10) is a less-known gene, which is involved in the vague biological paths of different cancers. Here, we investigated the TSGA10 expression using different concentrations of glucose under hypoxia and also its interaction with the hypoxia-inducible factor 1 (HIF-1). The breast cancer MDA-MB-231 and MCF-7 cells were cultured with different concentrations of glucose (5.5, 11.0 and 25.0 mM) under normoxia/hypoxia for 24, 48, and 72 hours and examined for the HIF-1α expression and cell migration by Western blotting and scratch assays. The qPCR was employed to analyze the expression of TSGA10. Three-dimensional (3D) structure and the energy minimization of the interacting domain of TSGA10 were performed by MODELLER v9.17 and Swiss-PDB viewer v4.1.0/UCSF Chimera v1.11. The UCSF Chimera v1.13.1 and Hex 6.0 were used for the molecular docking simulation. The Cytoscape v3.7.1 and STRING v11.0 were used for protein-protein interaction (PPI) network analysis. The HIF-1a related hypoxia pathways were obtained from BioModels database and reconstructed in CellDesigner v4.4.2. The increased expression of TSGA10 was found to be significantly associated with the reduced metastasis in the MDA-MB-231 cells, while an inverse relationship was seen between the TSGA10 mRNA level and cellular migration but not in the MCF-7 cells. The C-terminal domain of TSGA10 interacted with HIF-1α with high affinity, resulting in PPI network with 10 key nodes (HIF-1α, VEGFA, HSP90AA1, AKT1, ARNT, TP53, TSGA10, VHL, JUN, and EGFR). Collectively, TSGA10 functional expression alters under the hyper-/hypo-glycemia and hypoxia, which indicates its importance as a candidate bio-target for the cancer therapy.

Mesenchymal stromal/stem cells (MSCs) derived from fat tissue are an encouraging tool for regenerative medicine. They share properties similar to the bone marrow-derived MSCs, but the amount of MSCs per gram of fat tissue is 500x higher. The fat tissue can easily be digested by collagenase, releasing a heterogeneous cell fraction called stromal vascular fraction (SVF) which contains a variable amount of stromal/stem cells. In Europe, cell products like the SVF derived from fat tissue are considered advanced therapy medicinal product (ATMPs). As a consequence, the manufacturing process has to be approved via GMP-compliant process validation. The problem of the process validation for SVF is the heterogeneity of this fraction. Here, we modified existing purification strategies by adding an additional plastic adherence incubation of maximal 20 hours after SVF isolation. The resulting cell fraction was characterized and compared to SVF as well as cultivated adipose-derived stromal/stem cells (ASCs) with respect to viability and cell yield, the expression of surface markers, differentiation potential and cytokine expression. Short-term incubation significantly reduced the heterogeneity of the resulting cell fraction compared to SVF. The cells were able to differentiate into adipocytes, chondrocytes, and osteoblasts. More importantly, they expressed trophic proteins which have been previously associated with the beneficial effects of MSCs. Furthermore, GMP compliance of the production process described herein was acknowledged by the national regulatory agencies (DE_BB_01_GMP_2017_1018). Addition of a short purification-step after the SVF isolation is a cheap and fast strategy to isolate a homogeneous uncultivated GMP-compliant cell fraction of ASCs.

Many studies confirm that diabetes mellitus is associated with higher risks of bone fracture. The beneficial effects of Nigella sativa (NS) and clinoptilolite in preventing/reducing some diabetes-related disorders have been shown. This study was conducted to examine the effects of separate and concurrent supplementation of natural nano-sized clinoptilolite (NCLN) and NS on serum bone markers in rats with type 2 diabetes. A total of 42 (case=36 and control=6) adult male Wistar rats were divided into 2 groups: diabetic and non-diabetic. An oral glucose tolerance test and a homeostatic model assessment of insulin resistance (HOMA-IR) test were conducted to confirm diabetes. Then, the diabetic group was divided into 4 subgroups: [1] control (n=9), [2] NS 1%/food (n=9), [3] NCLN 2%/food (n=9), [4] NS 1%/food + NCLN 2%/food (n=9). After 7 weeks, serum levels of bone markers were determined using ELISA kits. Analysis showed that serum levels of alkaline phosphatase (ALP) in the NCLN group (1318.6 ± 217.5 U/L) was significantly (P<0.05) higher than other intervented groups. On the other hand, serum levels of calcium in NCLN+NS group (10.8 ± 2.6 mg/dL) were higher (P=0.027) compared to all other study groups. However, rats in the NS group had higher (535.8 ± 49.3 pg/mL) PTH (P<0.0001) compared to other supplementation groups. There were no significant differences in vitamin D and osteoprotegerin. The results of the current study suggest that bone mineralization may be affected by concurrent use of NS and NCLN through influencing calcium circulation. Moreover, dietary NS administration is strongly related to an augmented level of PTH.

Modafinil (MDF) is used orally for the treatment of attention-deficit/hyperactivity disorder and narcolepsy. It holds low solubility and high permeability; therefore, improving its dissolution properties by preparing nanoformulations can be a promising approach to enhance its oral absorption. Our aims were to prepare and characterize MDF-Eudragit® RS100 (MDF-ERS) nanoparticles by electrospray technique. Electrosprayed nanoparticles were fabricated by varying MDF to ERS ratios and concentrations. The formulations were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FTIR). Release studies were performed on nanoparticles, physical mixtures, and raw MDF. The release data were fitted to different models to understand the mechanism of the drug release. Electrospraying of MDF and ERS solution resulted in the preparation of nonobeads or nanofibers, and the particulate characteristics of the obtained products were largely controlled by the polymer amount in the solution. PXRD and thermal analyses showed that MDF was an amorphous phase in the structures of nanoparticles. Using FTIR, no interaction was observed between MDF and ERS in nanoparticles. Nanoparticles showed biphasic release profiles and the order of dissolution rates was: nanofibers>MDF>nanobeads. The well-fitted model was Weibull model, indicating a Fickian diffusion as the main mechanism of release. The results suggest that by optimization of variables such as solution concentration of MDF-ERS nanofibers and nanobeads with higher dissolution rates can be made by electrospray. Electrospray deposition as a simple, continuous, and surfactant free method is an excellent choice for preparation of drug loaded polymeric nanoparticles.

Humans manifest a behavioral inclination towards more utility of one side of the body, in relation with the dominant hemisphere of the brain. The current investigation assessed handedness together with chewing preference which have not been evaluated in various food textures before. Nineteen young and healthy volunteers chewed hard (walnut) and soft (cake) foods, during surface electromyography recording from masseter muscles. The side of the first and all chews in the two food types were determined and compared with the side of the dominant hand. Results indicated the two lateralities in the same side considerably (60%-70%), implying the solidarity in the control of the dominant hemisphere of the brain. The unilaterality was more prominent in the assessment of all chews in hard food, with higher statistical agreement and correlation. Thereupon masticatory preference is found with probable origins in the dominant hemisphere of the brain.