Search results for: neuronal plasticity

Authors: M. Tehranizadeh, E. Shoushtari Rezvani

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Seismic performance of steel moment-resisting frame structures is investigated considering nonlinear soil-structure interaction (SSI) effects. 10-, 15-, and 20-story planar building frames with aspect ratio of 3 are designed in accordance with current building codes. Inelastic seismic demands of the superstructure are considered using concentrated plasticity model. The raft foundation system is designed for different soil types. Beam-on-nonlinear Winkler foundation (BNWF) is used to represent dynamic impedance of the underlying soil. Two sets of pulse-like as well as no-pulse near-fault earthquakes are used as input ground motions. The results show that the reduction in drift demands due to nonlinear SSI is characterized by a more uniform distribution pattern along the height when compared to the fixed-base and linear SSI condition. It is also concluded that beneficial effects of nonlinear SSI on displacement demands is more significant in case of pulse-like ground motions and performance level of the steel moment-resisting frames can be enhanced.

Keywords: soil-structure interaction, uplifting, soil plasticity, near-fault earthquake, tall building

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Authors: Amos Sunday Onikanni, Bashir Lawal, Babatunji Emmanuel Oyinloye, Gomaa Mostafa-Hedeab, Mohammed Alorabi, Simona Cavalu, Augustine O. Olusola, Chih-Hao Wang, Gaber El-Saber Batiha

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The increasing global burden of diabetes mellitus has called for the search for a therapeutic alternative that offers better activities and safety than conventional chemotherapy. Herein, we evaluated the neuroprotective and antioxidant properties of different fractions (ethyl acetate, N-butanol and residual aqueous) of Clompanus pubescens leaves in streptozotocin (STZ)-induced diabetic rats. Our results revealed a significant elevation in the levels of blood glucose, pro-inflammatory cytokines, lipid peroxidation, neuronal activities of acetylcholinesterase, butyrylcholinesterase, nitric oxide, epinephrine, norepinephrine, and Na+/K+-ATPase in diabetic non treated rats. In addition, decreased levels of enzymatic and non-enzymatic antioxidants were observed. Treatment with different fractions of C. pubescens leaves resulted in a significant reversal of the biochemical alteration and improved the neurocognitive deficit in STZ-induced diabetic rats. However, the ethyl-acetate fraction demonstrated higher activities than the other fractions and was characterized for its phytoconstituents, revealing the presence of Gallic acid (713.00 ppm), catechin (0.91 ppm), ferulic acid (0.98 ppm), rutin (59.82 ppm), quercetin (3.22 ppm) and kaempferol (4.07 ppm). Our molecular docking analysis revealed that these compounds exhibited different binding affinities and potentials for targeting BChE/AChE/ IL-1 β/Na+-K+-ATPase. However, only Kampferol and ferulic exhibited good drug-like, ADMET, and permeability properties suitable for use as a neuronal drug target agent. Hence, the ethyl-acetate fraction of C. pubescent leaves could be considered a source of promising bioactive metabolite for the treatment and management of cognitive impairments related to type II diabetes mellitus.

Keywords: diabetes mellitus, neuroprotective, antioxidant, pro-inflammatory cytokines

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Authors: Alireza Shams, Ali Zamanian, Atefehe Shamosi, Farnaz Ghorbani

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Introduction: Although the application of a new strategy remains a remarkable challenge for treatment of disabilities due to neuronal defects, progress in Nanomedicine and tissue engineering, suggesting the new medical methods. One of the promising strategies for reconstruction and regeneration of nervous tissue is replacing of lost or damaged cells by specific scaffolds after Compressive, ischemic and traumatic injuries of central nervous system. Furthermore, ultrastructure, composition, and arrangement of tissue scaffolds are effective on cell grafts. We followed implantation and differentiation of mesenchyme stem cells to neural cells on Gelatin Polylactic-co-glycolic acid (PLGA) scaffolds coated with iron nanoparticles. The aim of this study was to evaluate the capability of stem cells to differentiate into motor neuron-like cells under topographical cues and morphogenic factors. Methods and Materials: Bone marrow mesenchymal stem cells (BMMSCs) was obtained by primary cell culturing of adult rat bone marrow got from femur bone by flushing method. BMMSCs were incubated with DMEM/F12 (Gibco), 15% FBS and 100 U/ml pen/strep as media. Then, BMMSCs seeded on Gel/PLGA scaffolds and tissue culture (TCP) polystyrene embedded and incorporated by Fe Nano particles (FeNPs) (Fe3o4 oxide (M w= 270.30 gr/mol.). For neuronal differentiation, 2×10 5 BMMSCs were seeded on Gel/PLGA/FeNPs scaffolds was cultured for 7 days and 0.5 µ mol. Retinoic acid, 100 µ mol. Ascorbic acid,10 ng/ml. Basic fibroblast growth factor (Sigma, USA), 250 μM Iso butyl methyl xanthine, 100 μM 2-mercaptoethanol, and 0.2 % B27 (Invitrogen, USA) added to media. Proliferation of BMMSCs was assessed by using MTT assay for cell survival. The morphology of BMMSCs and scaffolds was investigated by scanning electron microscopy analysis. Expression of neuron-specific markers was studied by immunohistochemistry method. Data were analyzed by analysis of variance, and statistical significance was determined by Turkey’s test. Results: Our results revealed that differentiation and survival of BMMSCs into motor neuron-like cells on Gel/PLGA/FeNPs as a biocompatible and biodegradable scaffolds were better than those cultured in Gel/PLGA in absence of FeNPs and TCP scaffolds. FeNPs had raised physical power but decreased capacity absorption of scaffolds. Well defined oriented pores in scaffolds due to FeNPs may activate differentiation and synchronized cells as a mechanoreceptor. Induction effects of magnetic FeNPs by One way flow of channels in scaffolds help to lead the cells and can facilitate direction of their growth processes. Discussion: Progression of biological properties of BMMSCs and the effects of FeNPs spreading under magnetic field was evaluated in this investigation. In vitro study showed that the Gel/PLGA/FeNPs scaffold provided a suitable structure for motor neuron-like cells differentiation. This could be a promising candidate for enhancing repair and regeneration in neural defects. Dynamic and static magnetic field for inducing and construction of cells can provide better results for further experimental studies.

Keywords: differentiation, mesenchymal stem cells, nano particles, neuronal defects, Scaffolds

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Authors: Brwa Abdulrahman Abubaker

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Recently, there has been a lot of interest in the difficult task of applying reinforcement learning to autonomous mobile robots. Conventional reinforcement learning (TRL) techniques have many drawbacks, such as lengthy computation times, intricate control frameworks, a great deal of trial and error searching, and sluggish convergence. In this paper, a modified Spiking Neural Network (SNN) is used to offer a distinct method for autonomous mobile robot learning and control in unexpected surroundings. As a learning algorithm, the suggested model combines dopamine modulation with spike-timing-dependent plasticity (STDP). In order to create more computationally efficient, biologically inspired control systems that are adaptable to changing settings, this work uses the effective and physiologically credible Izhikevich neuron model. This study is primarily focused on creating an algorithm for target tracking in the presence of obstacles. Results show that the SNN trained with three obstacles yielded an impressive 96% success rate for our proposal, with collisions happening in about 4% of the 214 simulated seconds.

Keywords: spiking neural network, spike-timing-dependent plasticity, dopamine modulation, reinforcement learning

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Authors: Mansi Srivastava, Uzma Saqib, Adnan Naim, Anjali Roy, Dongfang Liu, Deepak Bhatnagar, Ravinder Ravinder, Mirza S. Baig

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Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1 to M2 phenotypes decides the nature, duration, and severity of an inflammatory response. However, inspite of a substantial understanding of the fate of these phenotypes, the underlying molecular mechanisms are not well understood. We have investigated the role of Neuronal nitric oxide synthase (NOS1) mediated regulation of Activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change. Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of jun, Fos, and ATF family proteins. We determined that NOS1-derived nitric oxide (NO) facilitate Fos and jun interaction which induces IL12 & IL23 expression. Pharmacological inhibition of NOS1 inhibits Fos and jun interaction but increases ATF2 and Fos dimerization. Switching of Fos and jun dimer to ATF2 and jun dimerization switches phenotype from IL–12high IL-23high IL-10low to IL–12low IL-23lowIL-10high phenotype, respectively. Together, these findings highlight a key role of the TLR4-NOS1-AP1 signaling axis in regulating macrophage polarization.

Keywords: inflammation, macrophage, lipopolysaccharide (LPS), proinflammatory cytokines, activator protein 1 (AP-1), neuronal nitric oxide synthase (NOS1)

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Authors: Yan Lu, Song Hong, Janakiraman Udaiyappan, Aarti Nagayach, Quoc-Viet A. Duong, Masao Morita, Shun Saito, Yuichi Kobayashi, Yuhai, Zhao, Hongying Peng, Nicholas B. Pham, Walter J Lukiw, Christopher A. Vuong, Nicolas G. Bazan

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Aims: Neurodegeneration and behavior dysfunction occurs in patients with Alzheimer's Disease (AD), and as the disease progresses many patients develop cognitive impairment. 5XFAD mouse model of AD is widely used to study AD pathogenesis and treatment. This study aimed to investigate the effect of maresin like 1 (MaR-L1) treatment in AD pathology using 5XFAD mice. Methods: We tested 12-month-old male 5XFAD mice and wild type control mice treated with MaR-L1 in a battery of behavioral tasks. We performed open field test, beam walking test, clasping test, inverted grid test, acetone test, marble burring test, elevated plus maze test, cross maze test and novel object recognition test. We also studied neuronal loss, amyloid β burden, and inflammation in the brains of 5XFAD mice using immunohistology and Western blotting. Results: MaR-L1 treatment to the 5XFAD mice showed improved cognitive function of 5XFAD mice. MaR-L1 showed decreased anxiety behavior in open field test and marble burring test, increased muscular strength in the beam walking test, clasping test and inverted grid test. Cognitive function was improved in MaR-L1 treated 5XFAD mice in the novel object recognition test. MaR-L1 prevented neuronal loss and aberrant inflammation. Conclusion: Our finding suggests that behavioral abnormalities were normalized by the administration of MaR-L1 and the neuroprotective role of MaR-L1 in the AD. It also indicates that MaR-L1 treatment is able to prevent and or ameliorate neuronal loss and aberrant inflammation. Further experiments to validate the results are warranted using other AD models in the future.

Keywords: Alzheimer's disease, motor and cognitive behavior, 5XFAD mice, Maresin Like 1, microglial cell, astrocyte, neurodegeneration, inflammation, resolution of inflammation

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Authors: Ali̇ Bayram, Semih Dalkilic, Remzi Yigiter

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N-methyl-D-aspartate (NMDA) receptor is a subtype of glutamate receptor and plays a pivotal role in learning, memory, neuronal plasticity, neurotoxicity and synaptic mechanisms. Animal experiments were suggested that glutamate-induced excitotoxic injuriy and NMDA receptor blockage lead to amnesia and other neurodegenerative diseases including Alzheimer’s disease (AD), Huntington’s disease, amyotrophic lateral sclerosis. Aim of this study is to investigate association between NMDA receptor coding gene GRIN2B expression level and Alzheimer disease. The study was approved by the local ethics committees, and it was conducted according to the principles of the Declaration of Helsinki and guidelines for the Good Clinical Practice. Peripheral blood was collected 50 patients who diagnosed AD and 49 healthy control individuals. Total RNA was isolated with RNeasy midi kit (Qiagen) according to manufacturer’s instructions. After checked RNA quality and quantity with spectrophotometer, GRIN2B expression levels were detected by quantitative real time PCR (QRT-PCR). Statistical analyses were performed, variance between two groups were compared with Mann Whitney U test in GraphpadInstat algorithm with 95 % confidence interval and p < 0.05. After statistical analyses, we have determined that GRIN2B expression levels were down regulated in AD patients group with respect to control group. But expression level of this gene in each group was showed high variability. İn this study, we have determined that NMDA receptor coding gene GRIN2B expression level was down regulated in AD patients when compared with healthy control individuals. According to our results, we have speculated that GRIN2B expression level was associated with AD. But it is necessary to validate these results with bigger sample size.

Keywords: Alzheimer’s disease, N-methyl-d-aspartate receptor, NR2B, GRIN2B, mRNA expression, RT-PCR

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Authors: Omar Khan, Shana Krstevska, Edwin George, Veronica Gorden, Fen Bao, Christina Caon, NP-C, Carla Santiago, Imad Zak, Navid Seraji-Bozorgzad

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Objective: To quantify cellular injury in the substantia nigra (SN) in patients with Parkinson's disease (PD) and to examine the effect of rasagiline of tissue injury in the SN in patients with PD. Background: N-acetylaspartate (NAA) quantified with MRS is a reliable marker of neuronal metabolic function. Fractional anisotropy (FA) and mean diffusivity (MD) obtained with DTI, characterize tissue alignment and integrity. Rasagline, has been shown to exert anti-apototic effect. We applied these advanced MRI techniques to examine: (i) the effect of rasagiline on cellular injury and metabolism in patients with early PD, and (ii) longitudinal changes seen over time in PD. Methods: We conducted a prospective longitudinal study in patients with mild PD, naive to dopaminergic treatment. The imaging protocol included multi-voxel proton-MRS and DTI of the SN, acquired on a 3T scanner. Scans were performed at baseline and month 3, during which the patient was on no treatment. At that point, rasagiline 1 mg orally daily was initiated and MRI scans are were obtained at 6 and 12 months after starting rasagiline. The primary objective was to compare changes during the 3-month period of “no treatment” to the changes observed “on treatment” with rasagiline at month 12. Age-matched healthy controls were also imaged. Image analysis was performed blinded to treatment allocation and period. Results: 25 patients were enrolled in this study. Compared to the period of “no treatment”, there was significant increase in the NAA “on treatment” period (-3.04 % vs +10.95 %, p= 0.0006). Compared to the period of “no treatment”, there was significant increase in following 12 month in the FA “on treatment” (-4.8% vs +15.3%, p<0.0001). The MD increased during “no treatment” and decreased in “on treatment” (+2.8% vs -7.5%, p=0.0056). Further analysis and clinical correlation are ongoing. Conclusions: Advanced MRI techniques quantifying cellular injury in the SN in PD is a feasible approach to investigate dopaminergic neuronal injury and could be developed as an outcome in exploratory studies. Rasagiline appears to have a stabilizing effect on dopaminergic cell loss and metabolism in the SN in PD, that warrants further investigation in long-term studies.

Keywords: substantia nigra, Parkinson's disease, MRI, neuronal loss, biomarker

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Authors: A. Ghasemipanah, R. Ziaie Moayed, H. Niroumand

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Improving the geotechnical properties of soil has always been one of the issues in geotechnical engineering. Traditional materials have been used to improve and stabilize soils to date, each with its own advantages and disadvantages. Although the soil stabilization by adding materials such as cement, lime, bitumen, etc. is one of the effective methods to improve the geotechnical properties of soil, but nanoparticles are one of the newest additives which can improve the loose soils. This research is intended to study the effect of adding nanobentonite on soil engineering properties, especially the unconfined compression strength and maximum dry unit weight, using clayey soil with low liquid limit (CL) from Kerman (Iran). Nanobentonite was mixed with soil in three different percentages (i.e. 3, 5, 7% by weight of the parent soil) with different curing time (1, 7 and 28 days). The unconfined compression strength, liquid and plastic limits and plasticity index of treated specimens were measured by unconfined compression and Atterberg limits test. It was found that increase in nanobentonite content resulted in increase in the unconfined compression strength, liquid and plastic limits of the clayey soil and reduce in plasticity index.

Keywords: nanobentonite particles, clayey soil, unconfined compression stress, soil improvement.

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Authors: Hassnen M. Jafer, W. Atherton, F. Ruddock, E. Loffill

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This study represents the results of an experimental work using two types of fly ashes as a cement replacement in soft soil stabilisation. The fly ashes (FA1 and FA2) used in this study are by-products resulting from an incineration processes between 800 and 1200 ˚C. The stabilised soil in this study was an intermediate plasticity silty clayey soil with medium organic matter content. The experimental works were initially conducted on soil treated with different percentages of FA1 (0, 3, 6, 9, 12, and 15%) to identify the optimum FA1 content. Then FA1 was chemically activated by FA2 which has high alkalinity by blending the optimum content of FA1 with different portions of FA2. The improvement levels were evaluated dependent on the results obtained from consistency limits and compaction tests along with the results of unconfined compressive strength (UCS) tests which were conducted on specimens of soil treated with FA1 and FA2 and exposed to different periods of curing (zero, 7, 14, and 28 days). The results indicated that the FA1 and FA2 used in this study effectively improved the physical and geotechnical properties of the soft soil where the index of plasticity (IP) was decreased significantly from 21 to 13.17 with 12% of FA1; however, there was a slight increase in IP with the use of FA2. Meanwhile, 12% of FA1 was identified as the optimum percentage improving the UCS of stabilised soil significantly. Furthermore, FA2 was found effective as a chemical activator to FA1 where the UCS was improved significantly after using FA2.

Keywords: fly ashes, soft soil stabilisation, waste materials, unconfined compressive strength

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Authors: I. A Tijani, Y. F Wu, C.W. Lim

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Concrete Damaged Plasticity Model (CDPM) is capable of modeling the stress-strain behavior of confined concrete. Nevertheless, the accuracy of the model largely depends on its parameters. To date, most research works mainly focus on the identification and modification of the parameters for fiber reinforced polymer (FRP) confined concrete prior to damage. And, it has been established that the FRP-strengthened concrete behaves differently to FRP-repaired concrete. This paper presents a modified plastic damage model within the context of the CDPM in ABAQUS for modelling of a uniformly FRP-confined repaired concrete under monotonic loading. The proposed model includes infliction damage, elastic stiffness, yield criterion and strain hardening rule. The distinct feature of damaged concrete is elastic stiffness reduction; this is included in the model. Meanwhile, the test results were obtained from a physical testing of repaired concrete. The dilation model is expressed as a function of the lateral stiffness of the FRP-jacket. The finite element predictions are shown to be in close agreement with the obtained test results of the repaired concrete. It was observed from the study that with necessary modifications, finite element method is capable of modeling FRP-repaired concrete structures.

Keywords: Concrete, FRP, Damage, Repairing, Plasticity, and Finite element method

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Authors: Yan Yu, Wang Yu, Chen Xintong, Liu Yi, Zhang Yanzhong, Wang Yanji, Chen Xingyu, Zhang Miaocheng, Tong Yi

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Neuromorphic computing based on spiking neural networks (SNNs) has emerged as a promising avenue for building the next generation of intelligent computing systems. Owing to its high-density integration, low power, and outstanding nonlinearity, memristors have attracted emerging attention on achieving SNNs. However, fabricating a low-power and robust memristor-based spiking neuron without extra electrical components is still a challenge for brain-inspired systems. In this work, we demonstrate a TiO₂-based threshold switching (TS) memristor to emulate a leaky integrate-and-fire (LIF) neuron without auxiliary circuits, used to realize single layer fully connected (FC) SNNs. Moreover, our TiO₂-based resistive switching (RS) memristors realize spiking-time-dependent-plasticity (STDP), originating from the Ag diffusion-based filamentary mechanism. This work demonstrates that TiO2-based memristors may provide an efficient method to construct hardware neuromorphic computing systems.

Keywords: leaky integrate-and-fire, memristor, spiking neural networks, spiking-time-dependent-plasticity

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Authors: Thanh N. Do

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This paper addresses the modeling of two critical behaviors of concrete material in reinforced concrete components: (1) the increase in strength and ductility due to confining stresses from surrounding transverse steel reinforcements, and (2) the progressive deterioration in strength and stiffness due to high strain and/or cyclic loading. To improve the state-of-the-art, the author presents a new 3D constitutive model of concrete material based on plasticity and continuum damage mechanics theory to simulate both the confinement effect and the strength deterioration in reinforced concrete components. The model defines a yield function of the stress invariants and a compressive damage threshold based on the level of confining stresses to automatically capture the increase in strength and ductility when subjected to high compressive stresses. The model introduces two damage variables to describe the strength and stiffness deterioration under tensile and compressive stress states. The damage formulation characterizes well the degrading behavior of concrete material, including the nonsymmetric strength softening in tension and compression, as well as the progressive strength and stiffness degradation under primary and follower load cycles. The proposed damage model is implemented in a general purpose finite element analysis program allowing an extensive set of numerical simulations to assess its ability to capture the confinement effect and the degradation of the load-carrying capacity and stiffness of structural elements. It is validated against a collection of experimental data of the hysteretic behavior of reinforced concrete columns and shear walls under different load histories. These correlation studies demonstrate the ability of the model to describe vastly different hysteretic behaviors with a relatively consistent set of parameters. The model shows excellent consistency in response determination with very good accuracy. Its numerical robustness and computational efficiency are also very good and will be further assessed with large-scale simulations of structural systems.

Keywords: concrete, damage-plasticity, shear wall, confinement

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Authors: Gobinathan Devathasan, Kezia Devathasan

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Objective: To improve the current modified Broca-Wernicke-Lichtheim-Kussmaul speech schema and provide insight into autism. Methods: We reviewed the pertinent literature. Current findings, involving Brodmann areas 22, 46, 9,44,45,6,4 are based on neuropathology and functional MRI studies. However, in primary autism, there is no lucid explanation and changes described, whether neuropathology or functional MRI, appear consequential. Findings: We forward an enhanced model which may explain the enigma related to autism. Vowel output is subcortical and does need cortical representation whereas consonant speech is cortical in origin. Left lateralization is needed to commence the circuitry spin as our life have evolved with L-amino acids and left spin of electrons. A fundamental species difference is we are capable of three syllable-consonants and bi-syllable expression whereas cetaceans and songbirds are confined to single or dual consonants. The 4 key sites for speech are superior auditory cortex, Broca’s two areas, and the supplementary motor cortex. Using the Argand’s diagram and Reimann’s projection, we theorize that the Euclidean three dimensional synaptic neuronal circuits of speech are quantized to coherent waves, and then decoherence takes place at area 6 (spherical representation). In this quantum state complex, 3-consonant languages are instantaneously integrated and multiple languages can be learned, verbalized and differentiated. Conclusion: We postulate that evolutionary human speech is elevated to quantum interaction unlike cetaceans and birds to achieve the three consonants/bi-syllable speech. In classical primary autism, the sudden speech switches off and on noted in several cases could now be explained not by any anatomical lesion but failure of coherence. Area 6 projects directly into prefrontal saccadic area (8); and this further explains the second primary feature in autism: lack of eye contact. The third feature which is repetitive finger gestures, located adjacent to the speech/motor areas, are actual attempts to communicate with the autistic child akin to sign language for the deaf.

Keywords: quantum neuronal paradigm, cetaceans and human speech, autism and rapid magnetic stimulation, coherence and decoherence of speech

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Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

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Authors: Bahar Ayhan

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The present paper is concerned with the numerical modeling of the inelastic behavior of the anisotropically damaged ductile materials, which are based on a generalized macroscopic theory within the framework of continuum damage mechanics. Kinematic decomposition of the strain rates into elastic, plastic and damage parts is basis for accomplishing the structure of continuum theory. The evolution of the damage strain rate tensor is detailed with the consideration of anisotropic effects. Helmholtz free energy functions are constructed separately for the elastic and inelastic behaviors in order to be able to address the plastic and damage process. Additionally, the constitutive structure, which is based on the standard dissipative material approach, is elaborated with stress tensor, a yield criterion for plasticity and a fracture criterion for damage besides the potential functions of each inelastic phenomenon. The finite element method is used to approximate the linearized variational problem. Stress and strain outcomes are solved by using the numerical integration algorithm based on operator split methodology with a plastic and damage (multiplicator) variable separately. Numerical simulations are proposed in order to demonstrate the efficiency of the formulation by comparing the examples in the literature.

Keywords: anisotropic damage, finite element method, plasticity, coupling

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Authors: Hassnen M. Jafer, Khalid S. Hashim, W. Atherton, Ali W. Alattabi

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This study investigates the effect of two important parameters (length of curing period and percentage of the added binder) on the strength of soil treated with OPC. An intermediate plasticity silty clayey soil with medium organic content was used in this study. This soft soil was treated with different percentages of a commercially available cement type 32.5-N. laboratory experiments were carried out on the soil treated with 0, 1.5, 3, 6, 9, and 12% OPC by the dry weight to determine the effect of OPC on the compaction parameters, consistency limits, and the compressive strength. Unconfined compressive strength (UCS) test was carried out on cement-treated specimens after exposing them to different curing periods (1, 3, 7, 14, 28, and 90 days). The results of UCS test were used to develop a non-linear multi-regression model to find the relationship between the predicted and the measured maximum compressive strength of the treated soil (qu). The results indicated that there was a significant improvement in the index of plasticity (IP) by treating with OPC; IP was decreased from 20.2 to 14.1 by using 12% of OPC; this percentage was enough to increase the UCS of the treated soil up to 1362 kPa after 90 days of curing. With respect to the statistical model of the predicted qu, the results showed that the regression coefficients (R2) was equal to 0.8534 which indicates a good reproducibility for the constructed model.

Keywords: cement admixtures, soft soil stabilisation, geotechnical parameters, multi-regression model

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Authors: Vera Karla S. Caingles, Glen A. Lorenzo

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Soil, as the main material of landslides, plays a vital role in landslide assessment. An efficient and accurate method of doing an assessment is significantly important to prevent damage of properties and loss of lives. The study has two phases: to establish an empirical correlation of the residual soil thickness with the slope angle and to investigate the geotechnical characteristics of residual soil. Digital Elevation Model (DEM) in Geographic Information System (GIS) was used to establish the slope map and to program sampling points for field investigation. Physical and index property tests were undertaken on the 20 soil samples obtained from the area with Pliocene-Pleistocene geology and different slope angle in Kibawe, Bukidnon. The regression analysis result shows that the best fitting model that can describe the soil thickness-slope angle relationship is an exponential function. The physical property results revealed that soils contain a high percentage of clay and silts ranges from 41% - 99.52%. Based on the index properties test results, the soil exhibits a high degree of plasticity and expansion but not collapsible. It is deemed that this compendium will serve as primary data for slope stability analysis and deterministic landslide assessment.

Keywords: collapsibility, correlation, expansiveness, landslide, plasticity

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Authors: Burak Bal

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Mechanical characterization tests might come with a remarkable cost of time and money for both companies and academics. The inquiry to transform laboratory experiments to the computational media is getting a trend; accordingly, the literature supplies many analytical ways to explain the mechanics of deformation. In our work, we focused on the crystal plasticity finite element modeling (CPFEM) analysis on various materials in various crystal structures to predict the stress-strain curve without tensile tests. For FEM analysis, which we used in this study was ABAQUS, a standard user-defined material subroutine (UMAT) was prepared. The geometry of a specimen was created via DREAM 3D software with the inputs of Euler angles taken by Electron Back-Scattered Diffraction (EBSD) technique as orientation, or misorientation angles. The synthetic crystal created with DREAM 3D is also meshed in a way the grains inside the crystal meshed separately, and the computer can realize interaction of inter, and intra grain structures. The mechanical deformation parameters obtained from the literature put into the Fortran based UMAT code to describe how material will response to the load applied from specific direction. The mechanical response of a synthetic crystal created with DREAM 3D agrees well with the material response in the literature.

Keywords: crystal plasticity finite element modeling, ABAQUS, Dream.3D, microstructure

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Authors: G. A. Rombach, A. Faron

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Crack formation and growth in reinforced concrete members are, in many cases, the cause of the collapse of technical structures. Such serious failures impair structural behavior and can also damage property and persons. An intensive investigation of the crack propagation is indispensable. Numerical methods are being developed to analyze crack growth in an element and to detect fracture failure at an early stage. For reinforced concrete components, however, further research and action are required in the analysis of shear cracks. This paper presents numerical simulations and continuum mechanical modeling of bending shear crack propagation in a three-dimensional reinforced concrete beam without transverse reinforcement. The analysis will provide a further understanding of crack growth and redistribution of inner forces in concrete members. As a numerical method to map discrete cracks, the extended finite element method (XFEM) is applied. The crack propagation is compared with the smeared crack approach using concrete damage plasticity. For validation, the crack patterns of real experiments are compared with the results of the different finite element models. The evaluation is based on single span beams under bending. With the analysis, it is possible to predict the fracture behavior of concrete members.

Keywords: concrete damage plasticity, crack propagation, extended finite element method, fracture mechanics

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Authors: Lalita Subedi, Jae Kyoung Chae, Yong Un Park, Cho Kyo Hee, Lee Jae Hyuk, Kang Min Cheol, Sun Yeou Kim

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Neuroinflammation may mediate the relationship between low levels of estrogens and neurodegenerative disease. Estrogens are neuroprotective and anti-inflammatory in neurodegenerative disease models. Due to the long term side effects of estrogens, researches have been focused on finding an effective phytoestrogens for biological activities. Daidzein present in soybeans and its active metabolite equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) bears strong antioxidant and anticancer showed more potent anti-inflammatory and neuroprotective role in neuroinflammatory model confirmed its in vitro activity with molecular mechanism through NF-κB pathway. Three major CNS cells Microglia (BV-2), Astrocyte (C6), Neuron (N2a) were used to find the effect of equol in inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), MAPKs signaling proteins, apoptosis related proteins by western blot analysis. Nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Gries method and ELISA, respectively. Cytokines like tumor necrosis factor-α (TNF-α) and IL-6 were also measured in the conditioned medium of LPS activated cells with or without equol. Equol inhibited the NO production, PGE-2 production and expression of COX-2 and iNOS in LPS-stimulated microglial cells at a dose dependent without any cellular toxicity. At the same time Equol also showed promising effect in modulation of MAPK’s and nuclear factor kappa B (NF-κB) expression with significant inhibition of the production of proinflammatory cytokine like interleukin -6 (IL-6), and tumor necrosis factor -α (TNF-α). Additionally, it inhibited the LPS activated microglia-induced neuronal cell death by downregulating the apoptotic phenomenon in neuronal cells. Furthermore, equol increases the production of neurotrophins like NGF and increase the neurite outgrowth as well. In conclusion the natural daidzein metabolite equol are more active than daidzein, which showed a promising effectiveness as an anti-neuroinflammatory and neuroprotective agent via downregulating the LPS stimulated microglial activation and neuronal apoptosis. This work was supported by Brain Korea 21 Plus project and High Value-added Food Technology Development Program 114006-4, Ministry of Agriculture, Food and Rural Affairs.

Keywords: apoptosis, equol, neuroinflammation, phytoestrogen

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Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

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Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

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Authors: Tomer Gans-Or, Shmulik Pinkert

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The determination of lateral pile capacity per unit length is a key aspect in geotechnical engineering. Traditional approaches for assessing piles lateral capacity in cohesive soils involve the application of upper-bound and lower-bound plasticity theorems. However, a comprehensive solution encompassing the entire spectrum of soil strength parameters, particularly in frictional soils with or without cohesion, is still lacking. This research introduces an innovative implementation of the slice method limit equilibrium solution for lateral capacity assessment. For any given numerical discretization of the soil's domain around the pile, the lateral capacity evaluation is based on mobilized strength concept. The critical failure geometry is then found by a unique optimization procedure which includes both factor of safety minimization and geometrical optimization. The robustness of this suggested methodology is that the solution is independent of any predefined assumptions. Validation of the solution is accomplished through a comparison with established plasticity solutions for cohesive soils. Furthermore, the study demonstrates the applicability of the limit equilibrium method to address unresolved cases related to frictional and cohesive-frictional soils. Beyond providing capacity values, the method enables the utilization of the mobilized strength concept to generate safety-factor distributions for scenarios representing pre-failure states.

Keywords: lateral pile capacity, slice method, limit equilibrium, mobilized strength

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Authors: Bhuvanesh Baniya

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Alzheimer disease is illnesses that are responsible for neuronal cell death and resulting in lifelong cognitive problems. Due to their unclear mechanism, there are no effective drugs available for the treatment. For a long time, herbal drugs have been used as a role model in the field of the drug discovery process. Holy basil in the Indian medicinal system (Ayurveda) is used for several neuronal disorders like insomnia and memory loss for decades. This study aims to identify active components of holy basil as potential inhibitors for the treatment of Alzheimer disease. To fulfill this objective, the Network pharmacology approach, gene ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics simulation (MDS) studies were performed. A total of 7 active components in holy basil, 12 predicted neurodegenerative targets of holy basil, and 8063 Alzheimer-related targets were identified from different databases. The network analysis showed that the top ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B were found as significant target related to Alzheimer disease. On the basis of gene ontology and topology analysis results, APP was found as a significant target related to Alzheimer’s disease pathways. Further, the molecular docking results to found that various compounds showed the best binding affinities. Further, MDS top results suggested could be used as potential inhibitors against APP protein and could be useful for the treatment of Alzheimer’s disease.

Keywords: holy basil, network pharmacology, neurodegeneration, active phytochemicals, molecular docking and simulation

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Authors: Dina Kon Mushid, Kabutakapua Kakanda, Dibu Dave Mbako

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The failure of material usually involves elastoplastic deformation and fracturing. Continuum mechanics can effectively deal with plastic deformation by using a yield function and the flow rule. At the same time, it has some limitations in dealing with the fracture problem since it is a theory based on the continuous field hypothesis. The lattice model can simulate the fracture problem very well, but it is inadequate for dealing with plastic deformation. Based on the discretized virtual internal bond model (DVIB), this paper proposes a lattice model that can account for plasticity. DVIB is a lattice method that considers material to comprise bond cells. Each bond cell may have any geometry with a finite number of bonds. The two-body or multi-body potential can characterize the strain energy of a bond cell. The two-body potential leads to the fixed Poisson ratio, while the multi-body potential can overcome the limitation of the fixed Poisson ratio. In the present paper, the modified Stillinger-Weber (SW), a multi-body potential, is employed to characterize the bond cell energy. The SW potential is composed of two parts. One part is the two-body potential that describes the interatomic interactions between particles. Another is the three-body potential that represents the bond angle interactions between particles. Because the SW interaction can represent the bond stretch and bond angle contribution, the SW potential-based DVIB (SW-DVIB) can represent the various Poisson ratios. To embed the plasticity in the SW-DVIB, the plasticity is considered in the two-body part of the SW potential. It is done by reducing the bond stiffness to a lower level once the bond reaches the yielding point. While before the bond reaches the yielding point, the bond is elastic. When the bond deformation exceeds the yielding point, the bond stiffness is softened to a lower value. When unloaded, irreversible deformation occurs. With the bond length increasing to a critical value, termed the failure bond length, the bond fails. The critical failure bond length is related to the cell size and the macro fracture energy. By this means, the fracture energy is conserved so that the cell size sensitivity problem is relieved to a great extent. In addition, the plasticity and the fracture are also unified at the bond level. To make the DVIB able to simulate different Poisson ratios, the three-body part of the SW potential is kept elasto-brittle. The bond angle can bear the moment before the bond angle increment is smaller than a critical value. By this method, the SW-DVIB can simulate the plastic deformation and the fracturing process of material with various Poisson ratios. The elastoplastic SW-DVIB is used to simulate the plastic deformation of a material, the plastic fracturing process, and the tunnel plastic deformation. It has been shown that the current SW-DVIB method is straightforward in simulating both elastoplastic deformation and plastic fracture.

Keywords: lattice model, discretized virtual internal bond, elastoplastic deformation, fracture, modified stillinger-weber potential

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Authors: Muhammad Munawar

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Pavement destruction is normally associated with the horizontal relocation of subgrade because of pavement engrossing water and inordinate avoidance and differential settlement of material underneath the pavement. The aim of the research is to study the effect of the additives (rockdust) on the stability and the increase of bearing capacity of selected soils in Mardan City. The physical, chemical and designing properties of soil were contemplated, and the soil was treated with added admixture rockdust with the goal of stabilizing the local soil. The stabilization or modification of soil is done by blending of rock dust to soils in the scope of 0 to 85% by the rate increment of 5%, 10%, and 15% individually. The following test was done for treated sample: Atterberg limits (liquid limit, plasticity index, plastic limit), standard compaction test, the California bearing test and the direct shear test. The results demonstrated that the gradation of soil is narrow from the particle size analysis. Plasticity index (P.I), Liquid limit (L.L) and plastic limit (P.L) were shown reduction with the addition of Rock dust. It was concluded that the maximum dry density is increasing with the addition of rockdust up to 10%, beyond 10%, it shows reduction in their content. It was discovered that the Cohesion C diminished, the angle of internal friction and the California bearing ratio (C.B.R) was improved with the addition of Rock dust. The investigation demonstrated that the best stabilizer for the contextual investigation (Toru road Mardan) is the rock dust and the ideal dosage is 10 %.

Keywords: rockdust, stabilization, modification, CBR

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Authors: Dogan Cetin, Omar Hamdi Jasim

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Using some additives is very common method to improve the soil properties such as shear strength, bearing capacity; and to reduce the settlement and lateral deformation. Soil reinforcement with natural materials is an attractive method to improve the soil properties because of their low cost. However, the studies conducted by using natural additive are very limited. This paper presents the results of an investigation on the immediate and long-term effects of the sawdust on the shear strength behavior of a clayey silt soil obtained in Arnavutkoy in Istanbul with sawdust. Firstly, compaction tests were conducted to be able to optimum moisture content for every percentage of sawdust. The samples were obtained from compacted soil at optimum moisture content. UU Triaxial Tests were conducted to evaluate the response of randomly distributed sawdust on the strength of low plasticity clayey silt soil. The specimens were tested with 1%, 2% and 3% content of sawdust. It was found that the undrained shear strength of clay soil with 1%, 2% and 3% sawdust were increased respectively 4.65%, 27.9% and 39.5% higher than the soil without additive. At 5%, shear strength of clay soil decreased by 3.8%. After 90 days cure period, the shear strength of the soil with 1%, 2%, 3% and %5 increased respectively 251%, 302%, 260% and 153%. It can be said that the effect of the sawdust usage has a remarkable effect on the undrained shear strength of the soil. Besides the increasing undrained shear strength, it was also found that the sawdust decreases the liquid limit, plastic limit and plasticity index by 5.5%, 2.9 and 10.9% respectively.

Keywords: compaction test, sawdust, shear strength, UU Triaxial Test

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Authors: Taek Hwan Lee, Moon Ho Do, Lalita Subedi, Young Un Park, Sun Yeou Kim

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Natural and artificial toxic substances namely neurotoxins induce the bitter effect in the nervous system termed as neurotoxicity. It can modulate the normal functioning of the nervous system either hyperactivate it or damage homeostasis of neuronal system. Neurotoxins induced toxicity ultimately kills the neuron. The present study investigated the neuroprotective effects of germinated Dolichos lablab on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity using SH-SY5Y neuroblastoma cells. Germination is a process of plant growth from a seed. Sprouting of a seedling from a seed induced many molecular changes in the seed in order to prepare it for further growth. Because of these molecular and chemical changes, the neuroprotective effect of Dolichos lablab is higher in the germinated form than in the normal condition. SH-SY5Y cells were treated with Dolichos lablab extract (50, 100 g/ml) followed by 6-OHDA (25M) induced toxicity. Cell Viability was measured to check the cell survival against 6-OHDA induced toxicity using MTT assay. Dolichos lablab showed a neuroprotective effect against 6-OHDA induced neuronal cell death in neuroblastoma cell at a higher concentration of 100g/ml however the effect is much better even at the lower concentration after germination 50g/ml. Cell survival was increased dramatically after 15 h of germination and increased with time of germination in concentration dependent manner. Trigonelline as a representative compound was validated in germinated Dolichos lablab by HPLC analysis that might enhance the neuroprotective effect of Dolichos lablab. This result suggests that Dolichos lablab possess neuroprotective effect in neuroblastoma cells against 6-OHDA however its activity was more potent in the germinated form.

Keywords: dolichos lablab, germination, neuroprotection, trigonelline

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Authors: Chanya Inprasit, Yi-Wen Lin

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Inflammation causes changes of peripheral and central nervous system properties, affecting both neuronal and non-neuronal cells, resulting in inflammatory pain. Acupoint injection (AI) was developed in the 1950s and has been widely used for relieving pain. It is an acupoint-stimulating technique that utilizes anatomically based meridians derived from Chinese medicine theory. AI has been accepted as an effective treatment and is thought to display superior results when compared to traditional acupuncture methods. However, the mechanism of AI needs to be ratified by more scientific evidence in order to support the theory and its therapeutic development. In this study, we explored the effect of AI on the comorbidity of chronic pain and depression. Mice hindpaw was injected by complete Freund’s adjuvant (CFA) to induce the condition of chronic pain. Measurements of mechanical and thermal hyperalgesia and depression-like behavior were analyzed. The results indicated a positive tendency to AI treatment. The comorbidity of chronic pain and depression was investigated with relation to transient receptor potential V1 (TRPV1) mechanism through the use of TRPV1 gene deletion. The expression of nociceptors such as voltage-gated sodium channels (Navs) or TRPV1, was significantly down-regulated by AI. The expression of inflammation-activated molecules: astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, and related kinases, were reversed by AI in both the peripheral and central nervous system. Taken together, these data provided a detailed molecular mechanism of AI-induced analgesia and anti-inflammatory properties. This finding may be utilized for clinical practice to treat chronic pain and depression comorbidity.

Keywords: inflammatory pain, acupoint injection, TRPV1, GFAP, S100B

Procedia PDF Downloads 149

Authors: Imdad Ullah Khan, Yongseok Yoon, Kyeung Uk Choi, Kwang Rae Jo, Namyul Kim, Eunbee Lee, Wan Hee Kim, Oh-Kyeong Kweon

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The primary spinal cord injury (SCI) causes mechanical damage to the neurons and blood vessels. It leads to secondary SCI, which activates multiple pathological pathways, which expand neuronal damage at the injury site. It is characterized by vascular disruption, ischemia, excitotoxicity, oxidation, inflammation, and apoptotic cell death. It causes nerve demyelination and disruption of axons, which perpetuate a loss of impulse conduction through the injured spinal cord. It also leads to the production of myelin inhibitory molecules, which with a concomitant formation of an astroglial scar, impede axonal regeneration. The pivotal role regarding the neuronal necrosis is played by oxidation and inflammation. During an early stage of spinal cord injury, there occurs an abundant expression of reactive oxygen species (ROS) due to defective mitochondrial metabolism and abundant migration of phagocytes (macrophages, neutrophils). ROS cause lipid peroxidation of the cell membrane, and cell death. Abundant migration of neutrophils, macrophages, and lymphocytes collectively produce pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β), matrix metalloproteinase, superoxide dismutase, and myeloperoxidases which synergize neuronal apoptosis. Therefore, it is crucial to control inflammation and oxidation injury to minimize the nerve cell death during secondary spinal cord injury. Therefore, in response to oxidation and inflammation, heme oxygenase-1 (HO-1) is induced by the resident cells to ameliorate the milieu. In the meanwhile, neurotrophic factors are induced to promote neuroregeneration. However, it seems that anti-stress enzyme (HO-1) and neurotrophic factor (BDNF) do not significantly combat the pathological events during secondary spinal cord injury. Therefore, optimum healing can be induced if anti-inflammatory and neurotrophic factors are administered in a higher amount through an exogenous source. During the first experiment, the inflammation and neuroregeneration were selectively targeted. HO-1 expressing MSCs (HO-1 MSCs) and BDNF expressing MSCs (BDNF MSC) were co-transplanted in one group (combination group) of dogs with subacute spinal cord injury to selectively control the expression of inflammatory cytokines by HO-1 and induce neuroregeneration by BDNF. We compared the combination group with the HO-1 MSCs group, BDNF MSCs group, and GFP MSCs group. We found that the combination group showed significant improvement in functional recovery. It showed increased expression of neural markers and growth-associated proteins (GAP-43) than in other groups, which depicts enhanced neuroregeneration/neural sparing due to reduced expression of pro-inflammatory cytokines such as TNF-alpha, IL-6 and COX-2; and increased expression of anti-inflammatory markers such as IL-10 and HO-1. Histopathological study revealed reduced intra-parenchymal fibrosis in the injured spinal cord segment in the combination group than in other groups. Thus it was concluded that selectively targeting the inflammation and neuronal growth with the combined use of HO-1 MSCs and BDNF MSCs more favorably promote healing of the SCI. HO-1 MSCs play a role in controlling the inflammation, which favors the BDNF induced neuroregeneration at the injured spinal cord segment of dogs.

Keywords: HO-1 MSCs, BDNF MSCs, neuroregeneration, inflammation, anti-inflammation, spinal cord injury, dogs

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