Upregulation of retinal VEGF and connexin 43 in murine nonarteritic anterior ischemic optic neuropathy induced with 577 nm laser.

Nonarteritic anterior ischemic optic neuropathy (NAION) is a common acute optic neuropathy and cause of irreversible vision loss in those older than 50 years of age. There is currently no effective treatment for NAION and the biological mechanisms leading to neuronal loss are not fully understood. Promising novel targets include glial cells activation and intercellular communication mediated by molecules such as gap junction protein Connexin 43 (Cx43), which modulate neuronal fate in central nervous system disorders. In this study, we investigated retinal glial changes and neuronal loss following a novel NAION animal model using a 577 nm yellow laser. We induced unilateral photochemical thrombosis using rose bengal at the optic nerve head vasculature in adult C57BL/6 mice using a 577 nm laser and performed morphometric analysis of the retinal structure using serial in vivo optical coherence tomography (OCT) and histology for glial and neuronal markers. One day after experimental NAION, in acute phase, OCT imaging revealed peripapillary thickening of the retinal ganglion cell complex (GCC, baseline: 79.5 ±â€¯1.0 µm, n = 8; NAION: 93.0 ±â€¯2.5 µm, n = 8, P < 0.01) and total retina (baseline: 202.9 ±â€¯2.4 µm, n = 8; NAION: 228.1 ±â€¯6.8 µm, n = 8, P < 0.01). Twenty-one days after ischemia, at a chronic phase, there was significant GCC thinning (baseline 78.3 ±â€¯2.1 µm, n = 6; NAION: 72.2 ±â€¯1.9 µm, n = 5, P < 0.05), mimicking human disease. Examination of molecular changes in the retina one day after ischemia revealed that NAION induced a significant increase in retinal VEGF levels (control: 2319 ±â€¯195, n = 5; NAION: 4549 ±â€¯683 gray mean value, n = 5, P < 0.05), which highly correlated with retinal thickness (r = 0.89, P < 0.05). NAION also led to significant increase in mRNA level for Cx43 (Gj1a) at day 1 (control: 1.291 ±â€¯0.38; NAION: 3.360 ±â€¯0.58 puncta/mm2, n = 5, P < 0.05), but not of glial fibrillary acidic protein (Gfap) at the same time (control: 2,800 ±â€¯0.59; NAION: 4,690 ±â€¯0.90 puncta/mm2 n = 5, P = 0.19). Retinal ganglion cell loss at day 21 was confirmed by a 30% decrease in Brn3a+ cells (control: 2,844 ±â€¯235; NAION: 2,001 ±â€¯264 cells/mm2, n = 4, P < 0.05). We described a novel protocol of NAION induction by photochemical thrombosis using a 577 nm laser, leading to retinal edema and VEGF increase at day 1 and RGCs loss at day 21 after injury, consistent with the pathophysiology of human NAION. Early changes in glial cells intercommunication revealed by increased Cx43+ gap junctions are consistent with a retinal glial role in mediating cell-to-cell signaling after an ischemic insult. Our study demonstrates an early glial response in a novel NAION animal model and reveals glial intercommunication molecules such as Cx43 as a promising therapeutic target in acute NAION.

A clinically friendly viscoelastic finite element analysis model of the mandible with Herbst appliance.

INTRODUCTION: As a powerful numerical approximation tool, finite element analysis (FEA) has been widely used to predict stress and strain distributions in facial bones generated by orthodontic appliances. Previous FEA models were constructed on the basis of a linear elastic phase of the bone response (eg, elastic bone strains to loading). However, what is more useful for clinical understanding would be predicting long-term strains and displacements of bone-segments responding to loading, yet tissue responses are (1) not promptly observable and (2) hard to predict in nature. METHODS: Viscoelastic property of the mandibular bone was incorporated into FEA models to visualize long-term, time-dependent stress and strain patterns in the mandible after being exposed to orthopedic stress. A mandible under loading by a Herbst appliance was modeled, and outcomes of the constructed elastic and viscoelastic models were compared. RESULTS: Patterns and magnitudes of the displacement throughout the mandible predicted by the viscoelastic model were exhibited in accordance with previous clinical outcomes of Herbst appliance therapy. The elastic models exhibited similar displacement patterns; however, the magnitude of the displacements in the models was invariably small (approximately 1 per 100) compared with those outputs of corresponding viscoelastic models. The corresponding maximum stress level in our viscoelastic mandible subjected to the Herbst appliance with the same loading was considerably low and relaxed in various regions when compared with the elastic model. CONCLUSIONS: We suggest that a viscoelastic model of the mandible mimics our general prediction of orthopedic treatment outcomes better than those by elastic models.

[Type of vascular anastomosis and early outcome after kidney transplantation].

There are usually two main techniques of vessel anastomosis called as; end-to-end or end-to-side. The aim of this study was to investigate surgical vascular anastomotic and its correlation with early outcome after kidney transplantation. Data including gender, age, hospital stay, living or deceased donor, evidence of acute tubular necrosis, preference of artery or vein in addition to biochemical variables were noted analysed by SPSS. The study population was comprised of 84 females and 176 males (174 living versus 86 deceased donor). Surgical vascular anastomic techniques were based on; first artery second vein (FASV; n=209) or first vein second artery (FVSA; n=51). Vascular anastomic were performed as follow; group 1 (FASV with end-to-end; n= 52%), group 2 (FASV with end-to-side; n=29%), group 3 (FVSA with end-to-end; n=15%) and group 4 (FVSA with end-to-side; n= 5%). Comparison of groups showed that; deceased/living donor (group 1 versus group 3; p=0.02), ATN (group 1 versus group 2; p=0.002, group 1 versus group 4; p=0.03). Despite the higher use of deceased donors, those with vascular anastomic technique based on FASV (end-to-end) revealed a lower rate of ATN when compared to other techniques. Further studies in this direction recommended.

Mesenchymal stromal cells; a new horizon in regenerative medicine.

In recent decades, mesenchymal stromal cells (MSCs) biomedical utilizing has attracted worldwide growing attention. After the first report of the human MSCs obtaining from the bone marrow (BM) tissue, these cells were isolated from wide types of the other tissues, ranging from adipose tissue to dental pulp. Their specific characteristics, comprising self-renewality, multipotency, and availability accompanied by their immunomodulatory properties and little ethical concern denote their importance in the context of regenerative medicine. Considering preclinical studies, MSCs can modify immune reactions during tissue repair and restoration, providing suitable milieu for tissue recovery; on the other hand, they can be differentiated into comprehensive types of the body cells, such as osteoblast, chondrocyte, hepatocyte, cardiomyocyte, fibroblast, and neural cells. Though a large number of studies have investigated MSCs capacities in regenerative medicine in varied animal models, the oncogenic capability of unregulated MSCs differentiation must be more assessed to enable their application in the clinic. In the current review, we provide a brief overview of MSCs sources, isolation, and expansion as well as immunomodulatory activities. More important, we try to collect and discuss recent preclinical and clinical research and evaluate current challenges in the context of the MSC-based cell therapy for regenerative medicine.

Antigenic targets of CAR T Cell Therapy. A retrospective view on clinical trials.

Chimeric antigen receptor (CAR) T cell therapy is anticipated to be increasingly implemented in the context of cancer treatment after two current FDA approval of anti-CD19 CAR-T cells (Kymriah™ & Yescarta™). The success of CD19 is mainly attributable to the proper selection of the antigen, CD19, as the target of the disease, highlighting the importance of target selection for other CAR therapies. Therefore, here we performed a global analysis of targets that are the prime focus for various CAR T cell therapies in human clinical trials.

SDS-Aluminum Oxide Nanofluid for Enhanced Oil Recovery: IFT, Adsorption, and Oil Displacement Efficiency.

Surfactant flooding is one of the most promising chemical enhanced oil recovery (CEOR) methods to produce residual oil in reservoirs. Recently, nanoparticles (NPs) have attracted extensive attention because of their significant characteristics and capabilities to improve oil recovery. The aim of this study is to scrutinize the synergistic effect of sodium dodecyl sulfate (SDS) as an anionic surfactant and aluminum oxide (Al2O3) on the efficiency of surfactant flooding. Extensive series of interfacial tension and surfactant adsorption measurements were conducted at different concentrations of SDS and Al2O3 NPs. Furthermore, different surfactant adsorption isotherm models were fitted to the experimental data, and constants for each model were calculated. Additionally, oil displacement tests were performed at 25 °C and atmospheric pressure to indicate the suitability of SDS-Al2O3 for CEOR. Analysis of this study shows that the interfacial tension (IFT) reduction between aqueous phase and crude oil is enhanced considerably by 76%, and the adsorption density of SDS onto sandstone rock is decreased remarkably from 1.76 to 0.49 mg/g in the presence of these NPs. Although the effectiveness of NPs gradually increases with the increase of their concentration, there is an optimal value of Al2O3 NP concentration. Moreover, oil recovery was increased from 48.96 to 64.14% by adding 0.3 wt % NPs to the surfactant solution, which demonstrates the competency of SDS-Al2O3 nanofluids for CEOR.

The potential use of mesenchymal stem cells and their exosomes in Parkinson's disease treatment.

Parkinson's disease (PD) is the second most predominant neurodegenerative disease worldwide. It is recognized clinically by severe complications in motor function caused by progressive degeneration of dopaminergic neurons (DAn) and dopamine depletion. As the current standard of treatment is focused on alleviating symptoms through Levodopa, developing neuroprotective techniques is critical for adopting a more pathology-oriented therapeutic approach. Regenerative cell therapy has provided us with an unrivalled platform for evaluating potentially effective novel methods for treating neurodegenerative illnesses over the last two decades. Mesenchymal stem cells (MSCs) are most promising, as they can differentiate into dopaminergic neurons and produce neurotrophic substances. The precise process by which stem cells repair neuronal injury is unknown, and MSC-derived exosomes are suggested to be responsible for a significant portion of such effects. The present review discusses the application of mesenchymal stem cells and MSC-derived exosomes in PD treatment.

Stem cell in neurodegenerative disorders; an emerging strategy.

Neurodegenerative disorders are a diversity of disorders, surrounding Alzheimer's (AD), Parkinson's (PD), Huntington's diseases (HD), and amyotrophic lateral sclerosis (ALS) accompanied by some other less common diseases generally characterized by either developed deterioration of central or peripheral nervous system structurally or functionally. Today, with the viewpoint of an increasingly aging society, the number of patients with neurodegenerative diseases and sociomedical burdens will spread intensely. During the last decade, stem cell technology has attracted great attention for treating neurodegenerative diseases worldwide because of its unique attributes. As acknowledged, there are several categories of stem cells being able to proliferate and differentiate into various cellular lineages, highlighting their significance in the context of regenerative medicine. In preclinical models, stem cell therapy using mesenchymal stem/stromal cells (MSCs), hematopoietic stem cells (HSCs), and neural progenitor or stem cells (NPCs or NSCs) along with pluripotent stem cells (PSCs)-derived neuronal cells could elicit desired therapeutic effects, enabling functional deficit rescue partially. Regardless of the noteworthy progress in our scientific awareness and understanding of stem cell biology, there still exist various challenges to defeat. In the present review, we provide a summary of the therapeutic potential of stem cells and discuss the current status and prospect of stem cell strategy in neurodegenerative diseases, in particular, AD, PD, ALS, and HD.

Mesenchymal stromal cells (MSCs) for neurodegenerative disease: A promising frontier.

Neurodegenerative disorders are a variety of diseases including Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) along with some other less common diseases generally described by the advanced deterioration of central or peripheral nervous system, structurally or functionally. In the last two decades, mesenchymal stromal cells (MSCs) due to their unique assets encompassing self-renewal, multipotency and accessibility in association with low ethical concern open new frontiers in the context of neurodegenerative diseases therapy. Interestingly, MSCs can be differentiated into endodermal and ectodermal lineages (e.g., neurons, oligodendrocyte, and astrocyte), and thus could be employed to advance cell-based therapeutic strategy. Additionally, as inflammation ordinarily ensues as a local response provoked by microglia in the neurodegenerative diseases, MSCs therapy because of their pronounced immunomodulatory properties is noticed as a rational approach for their treatment. Recently, varied types of studies have been mostly carried out in vitro and rodent models using MSCs upon their procurement from various sources and expansion. The promising results of the studies in rodent models have motivated researchers to design and perform several clinical trials, with a speedily rising number. In the current review, we aim to deliver a brief overview of MSCs sources, expansion strategies, and their immunosuppressive characteristics and discuss credible functional mechanisms exerted by MSCs to treat neurodegenerative disorders, covering AD, PD, ALS, MS, and HD.

On the Vibrations and Stability of Moving Viscoelastic Axially Functionally Graded Nanobeams.

In this article, size-dependent vibrations and the stability of moving viscoelastic axially functionally graded (AFG) nanobeams were investigated numerically and analytically, aiming at the stability enhancement of translating nanosystems. Additionally, a parametric investigation is presented to elucidate the influence of various key factors such as axial gradation of the material, viscosity coefficient, and nonlocal parameter on the stability boundaries of the system. Material characteristics of the system vary smoothly along the axial direction based on a power-law distribution function. Laplace transformation in conjunction with the Galerkin discretization scheme was implemented to obtain the natural frequencies, dynamical configuration, divergence, and flutter instability thresholds of the system. Furthermore, the critical velocity of the system was evaluated analytically. Stability maps of the system were examined, and it can be concluded that the nonlocal effect in the system can be significantly dampened by fine-tuning of axial material distribution. It was demonstrated that AFG materials can profoundly enhance the stability and dynamical response of axially moving nanosystems in comparison to homogeneous materials. The results indicate that for low and high values of the nonlocal parameter, the power index plays an opposite role in the dynamical behavior of the system. Meanwhile, it was shown that the qualitative stability of axially moving nanobeams depends on the effect of viscoelastic properties in the system, while axial grading of material has a significant role in determining the critical velocity and natural frequencies of the system.

A sham-controlled trial of acupressure on the quality of sleep and life in haemodialysis patients.

BACKGROUND: Sleep disorder in haemodialysis patients can lead to disturbance in their psychosocial function and interpersonal relations, and reduced quality of life. The aim of the present study was to investigate the effect of acupressure on the quality of sleep of haemodialysis patients. METHODS: In a randomised controlled trial, 108 haemodialysis patients were randomly divided into three groups: true acupressure, placebo acupressure, and no treatment. The two acupressure groups received treatment three times a week for 4 weeks during dialysis. Routine care only was provided for the no treatment group. The main study outcome was sleep quality. RESULTS: The total Pittsburgh Sleep Quality Index score decreased significantly from 11.9±3.13 to 6.2±1.93 in the true acupressure group, from 11.3±3.69 to 10.6±3.82 in the sham acupressure group, and from 10.9±4.10 to 10.7±3.94 in the no treatment group. There was a significant difference between groups (p<0.001). CONCLUSIONS: Acupressure seems to have a positive effect on the sleep quality in haemodialysis patients. CLINICAL TRIAL REGISTRATION: IRCT201106145864N2.