Lack of association between TRAF1/C5 rs10818488 polymorphism and rheumatoid arthritis in Iranian population

Rheumatoid arthritis (RA) is a multifactorial disorder related to the inflammatory response system with debilitating and painful conditions. Both genetic and environmental factors, with unknown etiology, play important roles in this disease pathogenesis. Recently, TRAF1/C5 (Tumor Necrosis Factor Receptor-Associated Factor 1/. Complement Component 5) polymorphism associated with increased risk for RA has been studied in different populations worldwide, and inconsistent results have been obtained. rs10818488 allele is located on TRAF1/C5 intergenic region, and has been predicted to be functional. A total of 100 sex- and age-matched people including RA patients (n= 50) and healthy individuals (n= 50) from Iran have been entered in this study and genotyped for rs10818488 (A/G) polymorphism, using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). In our study, rs10818488 allele was not associated with risk for RA in Iranian population (p>. 0.05, OR = 1.27, 95% CI = 0.72-2.23). Results revealed that this allele might be population-specific and not to be associated with their corresponding gene pool. However, further analyses are required to clarify other RA-associated markers in our community. © 2012

A Roadmap for the Production of a GMP-Compatible Cell Bank of Allogeneic Bone Marrow-Derived Clonal Mesenchymal Stromal Cells for Cell Therapy Applications

Background: Allogeneic mesenchymal stromal cells (MSCs) have been used extensively in various clinical trials. Nevertheless, there are concerns about their efficacy, attributed mainly to the heterogeneity of the applied populations. Therefore, producing a consistent population of MSCs is crucial to improve their therapeutic efficacy. This study presents a good manufacturing practice (GMP)-compatible and cost-effective protocol for manufacturing, banking, and lot-release of a homogeneous population of human bone marrow-derived clonal MSCs (cMSCs). Methods: Here, cMSCs were isolated based on the subfractionation culturing method. Afterward, isolated clones that could reproduce up to passage three were stored as the seed stock. To select proliferative clones, we used an innovative, cost-effective screening strategy based on lengthy serial passaging. Finally, the selected clones re-cultured from the seed stock to establish the following four-tired cell banking system: initial, master, working, and end of product cell banks (ICB, MCB, WCB, and EoPCB). Results: Through a rigorous screening strategy, three clones were selected from a total of 21 clones that were stored during the clonal isolation process. The selected clones met the identity, quality, and safety assessments criteria. The validated clones were stored in the four-tiered cell bank system under GMP conditions, and certificates of analysis were provided for the three-individual ready-to-release batches. Finally, a stability study validated the EoPCB, release, and transport process of the frozen final products. Conclusion: Collectively, this study presents a technical and translational overview of a GMP-compatible cMSCs manufacturing technology that could lead to the development of similar products for potential therapeutic applications. Graphical Abstract: [Figure not available: see fulltext.

Nonordered dendritic mesoporous silica nanoparticles as promising platforms for advanced methods of diagnosis and therapies

Dendritic mesoporous silica nanoparticles (DMSNs) are a new generation of porous materials that have gained great attention compared to other mesoporous silicas due to attractive properties, including straightforward synthesis methods, modular surface chemistry, high surface area, tunable pore size, chemical inertness, particle size distribution, excellent biocompatibility, biodegradability, and high pore volume compared with conventional mesoporous materials. The last years have witnessed a blooming growth of the extensive utilization of DMSNs as an efficient platform in a broad spectrum of biomedical and industrial applications, such as catalysis, energy harvesting, biosensing, drug/gene delivery, imaging, theranostics, and tissue engineering. DMSNs are considered great candidates for nanomedicine applications due to their ease of surface functionalization for targeted and controlled therapeutic delivery, high therapeutic loading capacity, minimizing adverse effects, and enhancing biocompatibility. In this review, we will extensively detail state-of-the-art studies on recent advances in synthesis methods, structure, properties, and applications of DMSNs in the biomedical field with an emphasis on the different delivery routes, cargos, and targeting approaches and a wide range of therapeutic, diagnostic, tissue engineering, vaccination applications and challenges and future implications of DMSNs as cuttingedge technology in medicine

The physiological cost index of walking with a powered knee ankle foot orthosis in subjects with poliomyelitis : A pilot study

Background: A powered knee ankle foot orthosis (KAFO) was developed to provide restriction of knee flexion during stance phase and active flexion and extension of the knee during swing phase of gait. Objectives: The purpose of this study was to determine its effect on the physiological cost index (PCI), walking speed and the distance walked in people with poliomyelitis compared to when walking with a KAFO with drop lock knee joints. Methods: Seven subjects with poliomyelitis volunteered for the study, and undertook gait analysis with both types of KAFO. Results: Walking with the powered KAFO significantly reduced walking speed (p=0.015) and the distance walked (p=0.004), and also it did not improve PCI values (p =0.009) compared to walking with the locked KAFO. Conclusion: Using a powered KAFO did not significantly improve any of the primary outcome measures during walking for poliomyelitis subjects

Nonordered dendritic mesoporous silica nanoparticles as promising platforms for advanced methods of diagnosis and therapies

Dendritic mesoporous silica nanoparticles (DMSNs) are a new generation of porous materials that have gained great attention compared to other mesoporous silicas due to attractive properties, including straightforward synthesis methods, modular surface chemistry, high surface area, tunable pore size, chemical inertness, particle size distribution, excellent biocompatibility, biodegradability, and high pore volume compared with conventional mesoporous materials. The last years have witnessed a blooming growth of the extensive utilization of DMSNs as an efficient platform in a broad spectrum of biomedical and industrial applications, such as catalysis, energy harvesting, biosensing, drug/gene delivery, imaging, theranostics, and tissue engineering. DMSNs are considered great candidates for nanomedicine applications due to their ease of surface functionalization for targeted and controlled therapeutic delivery, high therapeutic loading capacity, minimizing adverse effects, and enhancing biocompatibility. In this review, we will extensively detail state-of-the-art studies on recent advances in synthesis methods, structure, properties, and applications of DMSNs in the biomedical field with an emphasis on the different delivery routes, cargos, and targeting approaches and a wide range of therapeutic, diagnostic, tissue engineering, vaccination applications and challenges and future implications of DMSNs as cutting-edge technology in medicine

Evaluation of gait symmetry in poliomyelitis subjects : Comparison of a conventional knee ankle foot orthosis (KAFO) and a new powered KAFO.

Background: Compared to able-bodied subjects, subjects with post polio syndrome and poliomyelitis demonstrate a preference for weight-bearing on the non-paretic limb, causing gait asymmetry. Objectives: The purpose of this study was to evaluate the gait symmetry of the poliomyelitis subjects when ambulating with either a drop- locked knee ankle foot orthosis (KAFO) or a newly developed powered KAFO. Methods: Seven subjects with poliomyelitis who routinely wore conventional KAFOs participated in this study, and received training to enable them to ambulate with the powered KAFO on level ground, prior to gait analysis. Results: There were no significant differences in the gait symmetry index (SI) of step length (P=0.085), stance time (P=0.082), double limb support time (P=0.929) or speed of walking (p=0.325) between the two test conditions. However, using the new powered KAFO improved the SI in step width (P=0.037), swing time (P=0.014), stance phase percentage (P=0.008) and knee flexion during swing phase (p≤0.001) compared to wearing the dropped locked KAFO. Conclusion: The use of a powered KAFO for ambulation by poliomyelitis subjects affects gait symmetry in the base of support, swing time, stance phase percentage and knee flexion during swing phase

The role of signaling pathways in derivation and maintenance of mouse embryonic stem cells

Background: Stem cells are believed as the premier hope to regenerate the defected tissues. In this regard, enhancing the efficient derivation of mouse embryonic stem (ES) cells, as the best model of pluripotent stem cell, facilitates capturing of the efficient derivation of human ES cells. Small molecules play a critical role in improving the efficiency of generating the pluripotent stem cells by inhibiting signaling pathways related to differentiation. This study aimed to evaluate the role of some molecular signaling pathways (e.g. JAK/STAT, MAPK/ERK, PI3K/AKT, WNT/GSK3 and TGF-β) in the cells involved in producing and maintaining ES cells.Materials and Methods: In this review study, the relevant articles to signaling pathways and embryonic stem cells were selected from PubMed database. In addition, the procedure for the efficient derivation of mouse ES cells was analyzed using small molecules under different conditions, like 2i and R2i culture. Results: The R2i culture condition increases the efficiency of generation and maintenance of ES cell lines from different types of mouse strain. Thus, findings showed that by inhibiting the MEK and TGF-β pathways in this process, the higher frequency of cells would be maintained at ground state of pluripotency with no differentiation. Conclusion: To understand the molecular effects of R2i culture condition on enhancing the efficiency of generating the mouse ES cells, the assessment of key pluripotency and differentiation gene expressions as well as the epigenetic changes within the ES cell derivation process seems to be essential