Oral consumption of α-linolenic acid increases serum BDNF levels in healthy adult humans

Background aims: Dietary omega-6 and omega-3 fatty acids have remarkable impacts on the levels of DHA in the brain and retina. Low levels of DHA in plasma and blood hamper visual and neural development in children and cause dementia and cognitive decline in adults. The level of brain-derived neurotrophic factors (BDNF) changes with dietary omega-3 fatty acid intake. BDNF is known for its effects on promoting neurogenesis and neuronal survival. Methods: In this study, we examined the effect of the oral consumption of α-Linolenic acid (ALA) on blood levels of BDNF and Malondialdehyde (MDA) in healthy adult humans. 30 healthy volunteers, 15 men and 15 women, were selected randomly. Each individual served as his or her own control. Before consuming the Flaxseed oil capsules, 5cc blood from each individual was sampled in order to measure the plasma levels of BDNF and MDA as baseline controls. During the experiment, each individual was given 3 oral capsules of flaxseed oil, containing 500mg of alpha linolenic acid, daily for one week. Then, plasma levels of BDNF and MDA were tested. Results: The plasma levels of BDNF and MDA significantly (P < 0.05) increased in individuals who received the oral capsules of ALA. Plasma levels of BDNF increased more in the women in comparison with the men. Conclusion: ALA treatment could be a feasible approach to reduce size of infarcts in stroke patients. Thus, ALA could be used in adjunction with routine stroke therapies to minimize brain lesions caused by stroke. © 2015 Hadjighassem et al.; licensee BioMed Central

Hydrodynamic modelling of free water-surface constructed storm water wetlands using a finite volume technique

One of the key factors in designing free water-surface constructed wetlands (FWS CW) is the hydraulic efficiency (λ), which depends primarily on the retention time of the polluted storm water. Increasing the hydraulic retention time (HRT) at various flow levels will increase λ of the overall constructed wetland (CW). The effects of characteristic geometric features that increase HRT were explored through the use of a two-dimensional depth-average hydrodynamic model. This numerical model was developed to solve the equations of continuity and motions on an unstructured triangular mesh using the Galerkin finite volume formulation and equations of the k–ε turbulence model. Eighty-nine diverse forms of artificial FWS CW with 11 different aspect ratios were numerically simulated and subsequently analysed for four scenarios: rectangular CW, modified rectangular CW with rounded edges, different inlet/outlet configurations of CW, and surface and submerged obstructions in front of the inlet part of the CW. Results from the simulations showed that increasing the aspect ratio has a direct influence on the enhancement of λ in all cases. However, the aspect ratio should be at least 9 in order to achieve an appropriate rate for λ in rectangular CW. Modified rounded rectangular CW improved λ by up to 23%, which allowed for the selection of a reduced aspect ratio. Simulation results showed that CW with low aspect ratios benefited from obstructions and optimized inlet/outlet configurations in terms of improved HRT

Exosome-inspired targeting of cancer cells with enhanced affinity

One of the major challenges in the area of novel drug delivery systems (NDDSs) is finding distinguished ligands for specific receptors represented by many cancer cells in order to enhance their cancer homing efficacy. Exosomes, the so-called natural nanocarriers or "Trojan horses,'' are secreted by the majority of cancer cells. These carriers exchange biomolecular information (e.g. proteins, siRNA, enzymes) between cancer cells and their stromal compartments in order to adjust a variety of cellular behaviours, including metastasis, apoptosis in T cells and angiogenesis. By exhibiting exosomal smart functions and biomimetic traits, exosome-mimicking nanocarriers will be one step ahead of the conventional targeted DDSs for the efficient delivery of antitumor drugs. In the present study, we tried to describe an engineering route to make some surface-functionalized nanoparticles that can mimic the targeting mechanism recruited by tumor-derived exosomes. The ligand-receptor interactions were investigated by molecular dynamics (MD) simulations. In addition, the selected ligand was experimentally studied to verify its improved targeting efficacy. The present study describes a novel targeting method that forces the mucin-domain-containing molecule-4 (TIM4)-embellished nanoparticles (NPs) to swarm towards the cancerous cells. These NPs can interact with the phosphatidylserine (PS) receptor on the surface of several kinds of cancer cells, such as U-87 MG (glioblastoma cell line). The molecular affinity between TIM4 as a homing device and PS, the target receptor, was investigated using MD simulations and surface plasmon resonance (SPR). According to the calculated free energies and the cellular uptake of TIM4-functionalized NPs, it seems that the TIM4/PS complex releases enough free energy to induce endocytosis. Our results emphasize on the potential of the proposed ligand as a good candidate for many targeted drug delivery applications. In this report, we present our proof-of-concept results in order to spotlight the importance of using computer-based simulating methods at the molecular level for the next-generation nanomedicine

Four novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations

Masoumeh Dehghan Manshadi,1 Behnam Kamalidehghan,2,3 Omid Aryani,1 Elham Khalili,1 Sepideh Dadgar,1 Mahdi Tondar,4 Fatemeh Ahmadipour,5 Goh Yong Meng,6 Massoud Houshmand1,31Department of Medical Genetics, Special Medical Center, Tehran, Iran; 2Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran; 4Department of Biochemistry and Molecular &amp; Cellular Biology, School of Medicine, Georgetown University, Washington, DC, USA; 5Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 6Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia Abstract: Metachromatic leukodystrophy (MLD) disorder is a rare lysosomal storage disorder that leads to severe neurological symptoms and an early death. MLD occurs due to the deficiency of enzyme arylsulfatase A (ARSA) in leukocytes, and patients with MLD excrete sulfatide in their urine. In this study, the ARSA gene in 12 non-consanguineous MLD patients and 40 healthy individuals was examined using polymerase chain reaction sequencing. Furthermore, the structural and functional effects of new mutations on ARSA were analyzed using SIFT (sorting intolerant from tolerant), I-Mutant 2, and PolyPhen bioinformatics software. Here, 4 new pathogenic homozygous mutations c.585G&gt;T, c.661T&gt;A, c.849C&gt;G, and c.911A&gt;G were detected. The consequence of this study has extended the genotypic spectrum of MLD patients, paving way to a more effective method for carrier detection and genetic counseling. Keywords: psychomotor regression, demyelinating, gait abnormality and impairment, metachromatic leukodystrophy (MLD), behavioral disturbance

Four novel <em>ARSA</em> gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations

Metachromatic leukodystrophy (MLD) disorder is a rare lysosomal storage disorder that leads to severe neurological symptoms and an early death. MLD occurs due to the deficiency of enzyme arylsulfatase A (ARSA) in leukocytes, and patients with MLD excrete sulfatide in their urine. In this study, the ARSA gene in 12 non-consanguineous MLD patients and 40 healthy individuals was examined using polymerase chain reaction sequencing. Furthermore, the structural and functional effects of new mutations on ARSA were analyzed using SIFT (sorting intolerant from tolerant), I-Mutant 2, and PolyPhen bioinformatics software. Here, 4 new pathogenic homozygous mutations c.585G>T, c.661T>A, c.849C>G, and c.911A>G were detected. The consequence of this study has extended the genotypic spectrum of MLD patients, paving way to a more effective method for carrier detection and genetic counseling

Intravenous injection of human umbilical cord matrix stem cell (Wharton jelly stem cell) provides functional recovery in a rat model of traumatic brain injury

Objective: This study was designed to examine the effects of human umbilical cord matrix stem cell (hUCMSC) administration in rats for 6 weeks after traumatic brain injury (TBI). Materials and Methods: Adult male Wistar rats (n = 30) were injured with controlled cortical impact device and divided into three groups. The treatment group (n = 10) was injected with 2 � 106 hUCMSC intravenously, the vehicle group (n=10) received phosphate buffered saline (PBS) whereas the control group (n = 10) receive nothing. All injections were performed one day after injury into the tail veins of the rats. All cells were labelled with Brdu before injection. Evaluation of the neurological function of the rats was performed before and after injury using Neurological Severity Scores (NSS). The rats were sacrificed 6 weeks after TBI and brain sections were stained using Brdu immunohistochemistry. Results: Statistically significant improvement in functional outcome was observed in the treatment group compared with the control group (p &lt; 0.01). This benefit was visible 1 week after TBI and persisted for six weeks (end of trial). Histological analysis showed that hUC-MSC were present in the lesion boundary zone at 6 weeks in all cell injected animals. Conclusion: Rats injected with hUCMSC after TBI survive for at least six weeks and show functional improvemnt