47 research outputs found
The dual-active histamine H3 receptor antagonist and acetylcholine esterase inhibitor E100 Alleviates Autistic-Like behaviors and oxidative stress in valproic acid induced autism in mice
No full textThe histamine H3 receptor (H3R) functions as auto- and hetero-receptors, regulating the release of brain histamine (HA) and acetylcholine (ACh), respectively. The enzyme acetylcholine esterase (AChE) is involved in the metabolism of brain ACh. Both brain HA and ACh are implicated in several cognitive disorders like Alzheimer’s disease, schizophrenia, anxiety, and narcolepsy, all of which are comorbid with autistic spectrum disorder (ASD). Therefore, the novel dual-active ligand E100 with high H3R antagonist affinity (hH3R: Ki = 203 nM) and balanced AChE inhibitory effect (EeAChE: IC50 = 2 µM and EqBuChE: IC50 = 2 µM) was investigated on autistic-like sociability, repetitive/compulsive behaviour, anxiety, and oxidative stress in male C57BL/6 mice model of ASD induced by prenatal exposure to valproic acid (VPA, 500 mg/kg, intraperitoneal (i.p.)). Subchronic systemic administration with E100 (5, 10, and 15 mg/kg, i.p.) significantly and dose-dependently attenuated sociability deficits of autistic (VPA) mice in three-chamber behaviour (TCB) test (all p < 0.05). Moreover, E100 significantly improved repetitive and compulsive behaviors by reducing the increased percentage of marbles buried in marble-burying behaviour (MBB) (all p < 0.05). Furthermore, pre-treatment with E100 (10 and 15 mg/kg, i.p.) corrected decreased anxiety levels (p < 0.05), however, failed to restore hyperactivity observed in elevated plus maze (EPM) test. In addition, E100 (10 mg/kg, i.p.) mitigated oxidative stress status by increasing the levels of decreased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), and decreasing the elevated levels of malondialdehyde (MDA) in the cerebellar tissues (all p < 0.05). Additionally, E100 (10 mg/kg, i.p.) significantly reduced the elevated levels of AChE activity in VPA mice (p < 0.05). These results demonstrate the promising effects of E100 on in-vivo VPA-induced ASD-like features in mice, and provide evidence that a potent dual-active H3R antagonist and AChE inhibitor (AChEI) is a potential drug candidate for future therapeutic management of autistic-like behaviours
An Analysis of the Computational Efficiency Gains from the Incorporation of Importance Sampling in Determining Optimal Sound Source Location
No full textA novel approach for determining the optimal location of a sound source within an acoustic environment is proposed. This approach involves the application of Importance Sampling to improve the efficiency of the existing method of acoustic ray-tracing for finding the frequency response at various listening locations. The results of this study do not conclusively demonstrate the superiority of the proposed method over existing techniques, and further research is necessary to determine its viability.https://github.com/djosh34/ImportanceSamplingBasedAcousticRayTracer published codeCSE3000 Research ProjectComputer Science and Engineerin
Neuroprotective potential of ferulic acid in the rotenone model of Parkinson’s disease
No full textShreesh Ojha,1,* Hayate Javed,2,* Sheikh Azimullah,1 Salema B Abul Khair,2 M Emdadul Haque2 1Department of Pharmacology and Therapeutics, 2Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE *These authors contributed equally to this work Abstract: Parkinson’s disease (PD) is a chronic, progressive, and the second most common form of neurodegenerative disorders. In order to explore novel agents for the treatment of PD, in the current study, we have evaluated the neuroprotective efficacy of ferulic acid (FA) using rotenone (ROT)-induced rat model of PD. ROT was administered 2.5 mg/kg body weight to male Wistar rats for 4 weeks to induce the PD. Since PD is progressive and chronic in nature, the paradigm for evaluating FA was based on chronic administration for 4 weeks at the dose of 50 mg/kg, 30 minutes prior to ROT administration. ROT administration caused significant reduction in endogenous antioxidants such as superoxide dismutase, catalase, and glutathione. ROT challenge-induced lipid peroxidation evidenced by increased malondialdehyde following perturbation of antioxidant defense. Apart from oxidative stress, ROT also activated proinflammatory cytokines and enhanced inflammatory mediators such as cyclooxygenase-2 and inducible nitric oxide synthase. The immunofluorescence analysis revealed a significant increase in the number of activated microglia and astrocytes accompanied by a significant loss of dopamine (DA) neurons in the substantia nigra pars compacta area upon ROT injection. However, treatment with FA rescued DA neurons in substantia nigra pars compacta area and nerve terminals in the striatum from the ROT insult. FA treatment also restored antioxidant enzymes, prevented depletion of glutathione, and inhibited lipid peroxidation. Following treatment with FA, the inflammatory mediators such as cyclooxygenase-2 and inducible nitric oxide synthase and proinflammatory cytokines were also reduced. Further, the results were supported by a remarkable reduction of Iba-1 and GFAP hyperactivity clearly suggests attenuation of microglial and astrocytic activation. Results of our study suggest that FA has promising neuroprotective effect against degenerative changes in PD, and the protective effects are mediated through its antioxidant and anti-inflammatory properties. Keywords: neurodegeneration, neurotoxicity, neuroinflammation, reactive oxygen specie
Inflammation and cytokine production in experimental neuroinflammatory disorders
No full textGlutamate excitotoxicity is involved in the pathogenesis of a variety of neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Kainic acid (KA), an analogue of excitotoxic glutamate, can elicit selective neuronal death in the brain of rodents, of which the pathological changes partially mimic the neurodegenerative disorders in humans. Experimental autoimmune neuritis (EAN) is an immune-mediated acute inflammatory disease of peripheral nervous system (PNS) and shares many characteristics of human Guillain-Barré syndrome (GBS). Thus EAN is considered to represent as an animal model to study pathogenesis and therapy of human GBS. Cytokines play a key role in neuroinflammatory disorders. In our studies, we attempted to explore the possible roles of tumor necrosis factor (TNF)-α and interferon gamma (IFN-γ) in experimental neurodegenerative and neuroinflammatory disorders.In Paper I, the role of TNF-α in KA-induced hippocampal neurodegeneration was studied by comparing TNF-α knockout (KO) mice with C57BL/6 wild type (WT) mice. After KA treatment, TNF-α KO mice showed more sensitivity to KA-induced neurotoxicity than WT mice, as demonstrated by more severe seizures, measurable behavior changes, greater neuronal degeneration and enhanced glial cell activation, as well as nitric oxide (NO) production. Additionally, KA-treatment up-regulated the expression of nuclear factor kappa B (NFκB) in TNF-α KO mice to a greater degree as compared to that in KA-treated WT mice. In Paper II, we aimed to further clarify the protective role of TNF-α in KA-induced hippocampal neuronal death in vitro and elucidated the potential signaling pathways. After 24-hours treatment with KA, comparing with WT mice, TNF-α KO mice showed more susceptibility to KA-induced neurotoxicity, as demonstrated by higher expression of lactate dehydrogenase (LDH) and lower neuronal survival rates, as well as elevated NO production. It is also evidenced that pretreated with anti-TNF-α antibody increased the production of LDH and NO, and decreased the neuronal survival rate. In contrast, neurons from WT mice pretreated with recombinant TNF-α were more resistant to KA induced neurotoxicity. TNF-α deficiency induced down-regulation of phospho-IκBα, total AKT and phospho-AKT, as well as up-regulation of phospho-p38 MAPK expressions after KA treatment. The reverse results can be achieved in WT hippocampal neurons with TNF-α treatment, i.e. up-regulation of phospho-IκBα and AKT. In Paper III, to further explore the role of TNF-α in the pathogenesis of neuroinflammation, the animal model-EAN was introduced. TNF-α deficiency significantly attenuated the clinical signs of EAN. Further, anti-TNF-α receptor 1 (TNFR1) antibodies markedly suppressed the clinical severity of EAN. TNF-α deficiency down-regulated the production of interleukin (IL)-12 and NO, as well as enhanced the production of IL-10 in macrophages. In Paper IV, the role of IFN-γ in the pathogenesis of EAN was investigated. The clinical signs of IFN-γ KO EAN mice were aggravated when compared with WT EAN mice. At the peak of EAN course, the IL-17A expressing cells in cauda equine (CE) and the levels of IL-17A in sera were elevated in IFN-γ KO mice. The proportions of MHC II, macrosialin, and IL-12 expressing cells, relative to total CE infiltrating cells were correspondingly higher in IFN-γ KO than WT mice with EAN.In summary, TNF-α may play a protective role in KA-induced excitotoxic neurodegeneration, while TNF-α exacerbates EAN via TNFR1 by inducing the proinflammatory phenotype of macrophage. IFN-γ deficiency enhanced the clinical severity of EAN via upregulating of IL-17A and Th2 cytokines production. These findings have relevance for future studies on pathogenesis and treatment of neurodegenerative and neuroinflammatory disorders in humans.List of scientific papersI. Xing-Mei, Zhang , Xiang-Yu Zheng, Sara Shaaban Sharkawi, Yang Ruan, Naheed Amir, Sheikh Azimullah, Mohammed Y Hasan, Jie Zhu, Abdu Adem. Possible Protecting Role of TNF-α in Kainic Acid-induced Neurotoxicity Via Down-Regulation of NFκB Signaling Pathway. Current Alzheimer Research. 2013, 10(6): 660-9. https://doi.org/10.2174/15672050113109990007 II. Xiang-Yu Zheng, Naheed Amir, Hong-Liang Zhang, Sheikh Azimullah, Bengt Winblad, Abdu Adem, Jie Zhu. TNF-α protects hippocampal neurons from kainic acid-induced neurodegeneration via up-regulation of AKT and down-regulation of p38 MAPK signaling pathways. [Manuscript]III. Hong-Liang Zhang, Mohammed Y Hassan, Xiang-Yu Zheng, Sheikh Azimullah, Hernan Concha Quezada, Naheed Amir, Mohamed Elwasila, Eilhard Mix, Abdu Adem, Jie Zhu. Attenuated EAN in TNF-α deficient mice is associated with an altered balance of M1/M2 macrophages. PLoS ONE. 2012, 7(5): e38157. https://doi.org/10.1371/journal.pone.0038157 IV. Hong-Liang Zhang, Sheikh Azimullah, Xiang-Yu Zheng, Xiao-Ke Wang, Naheed Amir, Eric P Mensah-Brown, Mariam Al Shamsi, Allen Shahin, Rayomand Press, Jie Zhu, Abdu Adem. IFN-γ deficiency exacerbates experimental autoimmune neuritis in mice despite a mitigated systemic Th1 immune response. Journal of Neuroimmunology. 2012; 246(1-2): 18-26. https://doi.org/10.1016/j.jneuroim.2012.02.011 </p
α-Bisabolol mitigates rotenone-induced dopaminergic neurodegeneration by suppressing oxidative stress, neuroinflammation and apoptosis in rat model of Parkinson’s disease : [abstract]
No full textA Look at the Translation Process in Afghanistan's Higher Education Institutions in 2019
No full textIn this research, an analytical-statistical method was used, and our main goal was to show the extent of the use of the translation process in the academic system of Afghanistan. The findings of this research indicate that the year (2019) had the highest number of subjects registered for translation compared to recent years. So, a difference of about 30% can be seen between the mentioned year and the previous year. Although the number of translated works has not been impressive so far, it is a good step towards strengthening the materials and resources for the researches of the country's academic system. The main question that was addressed was how to start the translation process in Afghanistan's higher education institutions in order to use the works and researches of other nations. So, it can be seen that the restoration process in the year (2019) was unprecedented in Afghanistan's higher education institutions compared to the 90s.Keywords: Translation, Goals, Motivation, Scientific Needs, Higher Education Institutions. IntroductionTranslation is considered an excellent and vital approach in the process of teaching and transferring data and solving problems from one language and culture to another language and culture.Also, translation causes the sharing of theories, viewpoints, mindsets, and methods of scientific-literary studies among nations.Today's Afghanistan society, especially the academic and scientific generation needs access to academic texts more than ever. Undoubtedly, it is translation that can give a suitable answer to many of these needs and introduce relevant, enriched, and important texts for us.Translation has a history of thousands of years. Humans have used this approach since time immemorial to exchange their thoughts and opinions. Translation has always been used as a principle of interaction between living languages. But sometimes, due to its necessity, translation becomes an important matter, the denial of which causes unforeseeable losses in that society. Although many books from other languages have been translated into Farsi and other languages in different eras, in the mentioned periods, the passion for translation was so great that the activity of translation in those periods was called (translation movement). After the arrival of Islam, Muslim translators have played a very prominent role in translating from other languages into Arabic as the language of government, religion, and science. The process of translation has had many ups and downs in different periods of history. However, the chaotic situation and the ever-increasing disturbances have always prevented translation activity in Afghanistan. Despite the fact that some people called Afghan translators residing in other countries or within Afghanistan have tried to translate, there has been no effort to meet the needs of the society. If it is carefully considered, the practice of translation in other countries has specific goals and motivations that have made it flourish. In the absence of goals and motivation, one can never reach the destination, for example, Mohammad Ghazi says his motivation for translation is primarily (love for translation) and then (material needs). Languages are limited. In the same way, whoever has done the act of translation has also expressed his motivation. Although the historical course of translation in Afghanistan has been examined from different perspectives by translators abroad, we have explored and examined the translations of 2019 in state institutions of higher education led by the Ministry of Higher Education. The result obtained from it showed that in the early 90s due to the problems that affected the people of Afghanistan, the translation process was not taken care of much, but in the last half of this decade, we have witnessed the relative growth of this process; a number of books have been translated from international languages into the national languages of Pashto and Dari Farsi, for example, we can refer to books translated from Arabic, for example, Türkiye Meydan al-Sara' bein al-Sharq va al-Gharb was translated by a professor at Badakhshan University. From a literary point of view, this translation has some errors, because the translator is a history professor and does not know much about Persian grammar, which is why it has some literary errors. I have read this work once. Similarly, other works that have been translated into Pashto in other universities of the country are not free of literary errors. Because those who translate the books are not experts in the mentioned languages in terms of expertise. For example, the following books have been translated from Arabic to Pashto: the rules of fasting and philosophy in Dhu al-Qur'an and Sunnah, al-Zahreh fi fan al-Takhrij and Drasa al-Asatid, Taysir al-Qava'ed al-Narhulllambtadiin and the book of al-Qava’ed al-Ulama, Al-Adab and Fanoonah, Nizam al-Syasi fi al-Islam, which were translated by professors in Nangarhar and Kandahar universities, the only flawless translations that have been translated by language experts, among which the number of language experts is limited.Literature ReviewWe did not come across any articles about translation in Afghanistan's higher education institutions. Therefore, we decided to write an article about the activities carried out regarding the translation from other living languages to national languages.Significance of the StudyThis article has examined and researched the process of scientific-research translations in Afghanistan's higher education institutions in the year (2018). Moreover, it discussed some points about the translation services in higher education institutions which are done for scientific promotion of professors. For this reason, the present article is new in terms of content and is of great importance.Purpose of the StudyThe main purpose of translation research in higher education institutions is to reveal the services of Afghanistan's higher education academic staff members. Its partial goals are to estimate the amount of translation services provided according to the conditions, whether it is in accordance with the needs of the present age or not. Whether so many different works from living languages have been translated by the academic staff members of Afghan universities to meet the academic needs or not.Another secondary goal of this research has been to reveal this process with its importance and path along with objective evidence, so that every student and researcher can easily understand how many necessary works have been translated by the scientific staff members of higher education.Research Questions:What was the main purpose of starting translation in Afghanistan's academic institutions?How many of the desired works of Afghanistan's academic field have been provided through translation so far?To what extent can works translated from foreign languages into national languages of Afghanistan help in the scientific process of Afghanistan?MethodologyA statistical method has been used to investigate the problem. The statistical population of the mentioned research was the source of data from the Department of Research, Compilation, and Translation of the Ministry of Higher Education. Our way of working was that we first presented each university in separate tables, and then at the end of it, we analyzed the received data of works translated in all universities of Afghanistan in the year (2019).FindingsSo, we talked about the definition, literature review, purpose, significance, and questions of translation. The findings of this research show that the motivation for translation has increased among the academic staff members of some universities. This increase will bring hope for the translation process in the following years.Among the educational institutions, the professors of Kabul University have the highest motivation for translating the work from international languages to the national language, and in the second step is Nangarhar University, followed by academic members of Harat and Balkh universities. The experience of academic members and researchers shows that there have been significant considerations in the quantity and quality of the translated works. The most frequent and expressive translations in the year (2019) are the translations that have been translated using the semantic method (free meaning).The Importance of the Translation Process in Academic FieldsTranslation, as one of the simplest and most effective tools and means of communication between humans, has always received special and public attention throughout history. The requirements of the current era (technology) and the revolution of communication in the current century have made the lives of countries dependent on each other. The multi-dimensional reliance of the age of communication has forced contemporary people to be aware of each other's conditions and understand each other's needs.Therefore, the universities of Afghanistan, which are the cradle of science, and the members of its scientific staff are considered among the scientific and academic assets of the same society and expected to play their valuable part in the development of this process.ConlusionAfter many efforts for the present research and due to an agreement with the translation management department Research, Compilation, and Translation Department of the Ministry of Higher Education, we were able to obtain a relative database in which the scientific topics of the professors are recorded. The works of professors are registered in the database of scientific subjects based on the name of the translator, academic institution, and academic rank. But we proceeded by removing some things, and we only mentioned the name of the works, faculty, group, and year. Regarding the translated topics, it should be said that most of the translated topics are specialized and they have been translated according to the expertise of the group or field that was mentioned. In general, it can be said that the most translated works are from English and then from Arabic. Translators of works in Afghanistan's institutions of higher education have mostly used semantic methods (conceptual translation) and this is the usual and acceptable method of the Ministry of Higher Education of Afghanistan. The results obtained from the present research show that the most works for translation in the year (2019) were first registered at Kabul University, followed by Nangarhar University, Harat University, University of Medical Sciences, Sheikh Zayed University, Balkh University, and others, which is summarized in the diagram below
Nerolidol Attenuates Oxidative Stress, Inflammation, and Apoptosis by Modulating Nrf2/MAPK Signaling Pathways in Doxorubicin-Induced Acute Cardiotoxicity in Rats
No full textThe clinical usage of doxorubicin (DOX), a potent anthracycline antineoplastic drug, is often limited by its cardiotoxic effects. Thus, for improving usage of DOX, the aim of this study was to assess the cardioprotective effects of nerolidol (NERO) in a rat model of DOX-induced acute cardiotoxicity and examine underlying molecular mechanisms that contribute to these effects. To induce acute cardiotoxicity male albino Wistar rats were injected with single dose intraperitoneal DOX (12.5 mg/kg). The rats were treated with NERO (50 mg/kg, orally) for five days. DOX-injected rats showed elevated levels of cardiac marker enzymes and enhanced oxidative stress markers along with altered Nrf2/Keap1/HO-1 signaling pathways. DOX administration also induced the activation of NF-κB/MAPK signaling and increased the levels and expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) as well as expression of inflammatory mediators (iNOS and COX-2) in the heart. DOX also triggered DNA damage and apoptotic cell death in the myocardium. Additionally, histological studies revealed structural alterations of the myocardium. NERO treatment exhibited protection against the deleterious results of DOX on myocardium, as evidenced by the restoration of altered biochemical parameters, mitigated oxidative stress, inflammation, and apoptosis. The findings of the present study demonstrate that NERO provides cardioprotective effects against DOX-induced acute cardiotoxicity attributed to its potent antioxidant, anti-inflammatory, and antiapoptotic activities through modulating cellular signaling pathways
Neuroprotective Effects of Thymol, a Dietary Monoterpene Against Dopaminergic Neurodegeneration in Rotenone-Induced Rat Model of Parkinson’s Disease
No full textParkinson’s disease (PD), a multifactorial movement disorder that involves progressive degeneration of the nigrostriatal system affecting the movement ability of the patient. Oxidative stress and neuroinflammation both are shown to be involved in the etiopathogenesis of PD. The aim of this study was to evaluate the therapeutic potential of thymol, a dietary monoterpene phenol in rotenone (ROT)-induced neurodegeneration in rats that precisely mimics PD in humans. Male Wistar rats were injected ROT at a dose of 2.5 mg/kg body weight for 4 weeks, to induce PD. Thymol was co-administered for 4 weeks at a dose of 50 mg/kg body weight, 30 min prior to ROT injection. The markers of dopaminergic neurodegeneration, oxidative stress and inflammation were estimated using biochemical assays, enzyme-linked immunosorbent assay, western blotting and immunocytochemistry. ROT challenge increased the oxidative stress markers, inflammatory enzymes and cytokines as well as caused significant damage to nigrostriatal dopaminergic system of the brain. Thymol treatment in ROT challenged rats appears to significantly attenuate dopaminergic neuronal loss, oxidative stress and inflammation. The present study showed protective effects of thymol in ROT-induced neurotoxicity and neurodegeneration mediated by preservation of endogenous antioxidant defense networks and attenuation of inflammatory mediators including cytokines and enzymes
Pharmacological Properties and Molecular Mechanisms of Thymol: Prospects for Its Therapeutic Potential and Pharmaceutical Development
No full textTannic Acid Mitigates Rotenone-Induced Dopaminergic Neurodegeneration by Inhibiting Inflammation, Oxidative Stress, Apoptosis, and Glutamate Toxicity in Rats
No full textParkinson’s disease (PD), a movement disorder, is a neurodegenerative disease characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) region of the brain. The etiopathogenesis of PD involves increased oxidative stress, augmented inflammation, impaired autophagy, accumulation of α-synuclein, and α-Glutamate neurotoxicity. The treatment of PD is limited and there is a lack of agents to prevent the disease/delay its progression and inhibit the onset of pathogenic events. Many agents of natural and synthetic origin have been investigated employing experimental models of PD, mimicking human PD. In the present study, we assessed the effect of tannic acid (TA) in a rodent model of PD induced by rotenone (ROT), a pesticide and an environmental toxin of natural origin reported to cause PD in agricultural workers and farmers. Rotenone (2.5 mg/kg/day, i.p.) was administered for 28 days, and TA (50 mg/kg, orally) was administered 30 min before ROT injections. The study results showed an increase in oxidative stress, as evidenced by the depletion of endogenous antioxidants and enhanced formation of lipid peroxidation products, along with the onset of inflammation following a rise in inflammatory mediators and proinflammatory cytokines. ROT injections have also augmented apoptosis, impaired autophagy, promoted synaptic loss, and perturbed α-Glutamate hyperpolarization in rats. ROT injections also induced the loss of dopaminergic neurons subsequent to the activation of microglia and astrocytes. However, TA treatment was observed to reduce lipid peroxidation, prevent loss of endogenous antioxidants, and inhibit the release and synthesis of proinflammatory cytokines, in addition to the favorable modulation of apoptosis and autophagic pathways. Treatment with TA also attenuated the activation of microglia and astrocytes along with preservation of dopaminergic neurons following reduced loss of dopaminergic neurodegeneration and inhibition of synaptic loss and α-Glutamate cytotoxicity. The effects of TA in ROT-induced PD were attributed to the antioxidant, anti-inflammatory, antiapoptotic, and neurogenesis properties. Based on the present study findings, it can be concluded that TA may be a promising novel therapeutic candidate for pharmaceutical as well as nutraceutical development owing to its neuroprotective properties in PD. Further regulatory toxicology and translational studies are suggested for future clinical usage in PD
