Search results for: natural killer cells

Authors: Magdalena Maria Rost-Roszkowska, Alina Chachulska-Żymełka, Monika Tarnawska, Maria Augustyniak, Alina Kafel, Agnieszka Babczyńska

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The digestive system of insects is composed of three distinct regions: fore-, mid- and hingut. The middle region (the midgut) is treated as one of the barriers which protects the organism against any stressors which originate from external environment, e.g. toxic metals. Such factors can activate the cell death in epithelial cells to preserve the entire tissue/organs against the degeneration. Different mechanisms involved in homeostasis maintenance have been described, but the studies of animals under field conditions do not give the opportunity to conclude about potential ability of subsequent generation to inherit the tolerance mechanisms. It is possible only by a multigenerational strain of an animal led under laboratory conditions, exposed to a selected toxic factor, present also in polluted ecosystems. The main purpose of the project was to check if changes, which appear in the midgut epithelium after Cd treatment, can be fixed during the following generations of insects with the special emphasis on apoptosis. As the animal for these studies we chose 5th larval stage of the beet armyworm Spodoptera exigua Hübner (Lepidoptera: Noctuidae), which is one of pest of many vegetable crops. Animals were divided into some experimental groups: K, Cd, KCd, Cd1, Cd2, Cd3. A control group (K) fed a standard diet, and was conducted for XX generations, a cadmium group (Cd), fed on standard diet supplemented with cadmium (44 mg Cd per kg of dry weight of food) for XXX generations. A reference Cd group (KCd) has been initiated: control insects were fed with Cd supplemented diet (44 mg Cd per kg of dry weight of food). Experimental groups Cd1, Cd2, Cd3 developed from the control one: 5 mg Cd per kg of dry weight of food, 10 mg Cd per kg of dry weight of food, 20 mg Cd per kg of dry weight of food. We were interested in the activation of apoptosis during following generations in all experimental groups. Therefore, during the 1st year of the experiment, the measurements were done for 6 generations in all experimental group. The intensity and the course of apoptosis have been examined using transmission electron microscope (TEM), confocal microscope and flow cytometry. During apoptosis the cell started to shrink, extracellular spaces appeared between digestive and neighboring cells, the nucleus achieved a lobular shape. Eventually, the apoptotic cells was discharged into the midgut lumen. A quantitative analysis revealed that the number of apoptotic cells depends significantly on the generation, tissue and cadmium concentration in the insect rearing medium. In the following 6 generations, we observed that the percentage of apoptotic cells in the midguts from cadmium-exposed groups decreased gradually according to the following order of strains: Cd1, Cd2, Cd3 and KCd. At the same time, it was still higher than the percentage of apoptotic cells in the same tissues of the insects from the control and multigenerational cadmium strain. The results of our studies suggest that changes caused by cadmium treatment were preserved during 6-generational development of lepidopteran larvae. The study has been financed by the National Science Centre Poland, grant no 2016/21/B/NZ8/00831.

Keywords: cadmium, cell death, digestive system, ultrastructure

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Authors: Nijole Savickiene, Antonella Di Sotto, Gabriela Mazzanti, Rasa Starselskyte, Silvia Di Giacomo, Annabella Vitalone

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Plant lectins are non-enzymic and non-immune origin proteins that specifically recognize and bind to various sugar structures and possess the activity to agglutinate cells and/or precipitate polysaccharides and glycoconjugates. The emerging evidences showed that plant lectins contribute not only to tumour cell recognition but also to cell adhesion and localization, to signal transduction, to mitogenic cytotoxicity and apoptosis. Among chitin-binding lectins, the Urtica dioica agglutinin (UDA), which is a complex of different isoforms, has been poorly studied for its biological activity. In this context and according to the increasing interest for lectins as novel antitumor drugs, present paper aimed at evaluating the potential antimutagenic activity of a lectin-like glycoprotein-enriched fraction from aerial part of Urtica dioica L. Aim: to evaluate the potential chemopreventive properties of a protein - lectin fraction from the aerial part of Urtica dioica. Materials and methods: Protein – lectin fraction has been tested for the antimutagenic activity in bacteria (50–800 mg/plate; Ames test by the preincubation method) and for the cytotoxicity on human hepatoma HepG2 cells (0.06–2 mg/mL; 24 and 48 h incubation). Results: Protein – lectin fraction from stinging nettle was not cytotoxic on HepG2 cells up to 2 mg/mL; conversely, it exhibited a strong antimutagenic activity against the mutagen 2-aminoanthracene (2AA) in all strains tested (maximum inhibition of 56.78 and 61% in TA98, TA100, and WP2uvrA strains, respectively, at 800 mg/plate). Discussion and conclusions: Protein – lectin fraction from Urtica dioica L. possesses antimutagenic and radical scavenging properties. Being 2AA a pro-carcinogenic agent, we hypothesize that the antimutagenicity of it can be due to the inhibition of CYP450-isoenzymes, involved in the mutagen bioactivation.

Keywords: lectins, antimutagenicity, chemoprevention, Urtica dioica

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Authors: Ali Bayram, Burak Uz, Remzi Yiğiter

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The impairment of lipid metabolism in the central nervous system has been suggested as a critical factor of Alzheimer’s disease (AD) pathogenesis. Homo sapiens acyl-coenyme A synthetase short-chain family member 2 (ACSS2) gene encodes the enzyme acetyl-Coenzyme A synthetase (AMP forming; AceCS) providing acetyl-coenzyme A (Ac-CoA) for various physiological processes, such as cholesterol and fatty acid synthesis, as well as the citric acid cycle. We investigated ACSS2, transcript variant 1 (ACSS2*1), mRNA levels in the peripheral blood mononuclear cells (PBMC) of patients with AD and compared them with the controls. The study group comprised 50 patients with the diagnosis of AD who have applied to Gaziantep University Faculty of Medicine, and Department of Neurology. 49 healthy individuals without any neurodegenerative disease are included as controls. ACSS2 mRNA expression in PBMC of AD/control patients was 0.495 (95% confidence interval: 0.410-0.598), p= .000000001902). Further studies are needed to better clarify this association.

Keywords: Alzheimer’s disease, ACSS2 Genes, mRNA expression, RT-PCR

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Authors: Amelia J. McFarland, Andrew K. Davey, Shailendra Anoopkumar-Dukie

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Microglia are the resident macrophage population of the central nervous system (CNS), contributing to both innate and adaptive immune response, and brain homeostasis. Activation of microglia occurs in response to a multitude of pathogenic stimuli in their microenvironment; this induces morphological and functional changes, resulting in a state of acute neuroinflammation which facilitates injury resolution. Adequate microglial function is essential for the health of the neuroparenchyma, with microglial dysfunction implicated in numerous CNS pathologies. Given the critical role that these macrophage-derived cells play in CNS homeostasis, there is a high demand for microglial models suitable for use in neuroscience research. The isolation of primary human microglia, however, is both difficult and costly, with microglial activation an unwanted but inevitable result of the extraction process. Consequently, there is a need for the development of alternative experimental models which exhibit morphological, biochemical and functional characteristics of human microglia without the difficulties associated with primary cell lines. In this study, our aim was to evaluate whether THP-1 human peripheral blood monocytes would display microglial-like qualities following an induced differentiation, and, therefore, be suitable for use as surrogate microglia. To achieve this aim, THP-1 human peripheral blood monocytes from acute monocytic leukaemia were differentiated with a range of phorbol 12-myristate 13-acetate (PMA) concentrations (50-200 nM) using two different protocols: a 5-day continuous PMA exposure or a 3-day continuous PMA exposure followed by a 5-day rest in normal media. In each protocol and at each PMA concentration, microglial-like cell morphology was assessed through crystal violet staining and the presence of CD-14 microglial / macrophage cell surface marker. Lipopolysaccharide (LPS) from Escherichia coli (055: B5) was then added at a range of concentrations from 0-10 mcg/mL to activate the PMA-differentiated THP-1 cells. Functional microglial-like behavior was evaluated by quantifying the release of prostaglandin (PG)-E2 and pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α using mediator-specific ELISAs. Furthermore, production of global reactive oxygen species (ROS) and nitric oxide (NO) were determined fluorometrically using dichlorodihydrofluorescein diacetate (DCFH-DA) and diaminofluorescein diacetate (DAF-2-DA) respectively. Following PMA-treatment, it was observed both differentiation protocols resulted in cells displaying distinct microglial morphology from 10 nM PMA. Activation of differentiated cells using LPS significantly augmented IL-1β, TNF-α and PGE2 release at all LPS concentrations under both differentiation protocols. Similarly, a significant increase in DCFH-DA and DAF-2-DA fluorescence was observed, indicative of increases in ROS and NO production. For all endpoints, the 5-day continuous PMA treatment protocol yielded significantly higher mediator levels than the 3-day treatment and 5-day rest protocol. Our data, therefore, suggests that the differentiation of THP-1 human monocyte cells with PMA yields a homogenous microglial-like population which, following stimulation with LPS, undergo activation to release a range of pro-inflammatory mediators associated with microglial activation. Thus, the use of PMA-differentiated THP-1 cells represents a suitable microglial model for in vitro research.

Keywords: differentiation, lipopolysaccharide, microglia, monocyte, neuroscience, THP-1

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Authors: Kumar Dron Shrivastav, Ankan Mukherjee Das, Arti Taneja, Harpreet Singh, Priya Ranjan, Rajiv Janardhanan

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Cervical cancer is one of the most common cancer among women worldwide which can be cured if detected early. Manual pathology which is typically utilized at present has many limitations. The current gold standard for cervical cancer diagnosis is exhaustive and time-consuming because it relies heavily on the subjective knowledge of the oncopathologists which leads to mis-diagnosis and missed diagnosis resulting false negative and false positive. To reduce time and complexities associated with early diagnosis, we require an interactive diagnostic tool for early detection particularly in developing countries where cervical cancer incidence and related mortality is high. Incorporation of digital pathology in place of manual pathology for cervical cancer screening and diagnosis can increase the precision and strongly reduce the chances of error in a time-specific manner. Thus, we propose a robust and interactive cervical cancer image analysis and diagnostic tool, which can categorically process both histopatholgical and cytopathological images to identify abnormal cells in the least amount of time and settings with minimum resources. Furthermore, incorporation of a set of specific parameters that are typically referred to for identification of abnormal cells with the help of open source software -’R’ is one of the major highlights of the tool. The software has the ability to automatically identify and quantify the morphological features, color intensity, sensitivity and other parameters digitally to differentiate abnormal from normal cells, which may improve and accelerate screening and early diagnosis, ultimately leading to timely treatment of cervical cancer.

Keywords: cervical cancer, early detection, digital Pathology, screening

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Authors: Nahid Eskandari, Marjan Ghagozolo, Ehsan Almasi

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Introduction: Silymarin, as a polyphenolic flavonoid derived from milk thistle (Silybum marianum), is known to have antioxidant, immunomodulatory, antiproliferative, antifibrotic, and antiviral effects. The goal of this study was to determine immunosuppressive effect of Silymarin on proliferation and apoptosis of human T cells in comparison with Rapamycin and FK506. Methods: Peripheral Blood Mononuclear Cells (PBMCs) from healthy individuals were activated with Con A (5µg/ml) and then treated with Silymarin, Rapamycin and FK506 in various concentrations (0.001, 0.01, 0.1, 1, 10,100 and 200M) for 5 days. PBMCs were examined for proliferation using CFSE assay and the concentration that inhibited 50% of the cell proliferation (IC50) was determined for each treatment. For apoptosis assay using flow cytometry, PBMCs were activated with Con A and treated with IC50 dose of Silymarin, Rapamycin and FK506 for 5 days, then cell apoptosis was analysed by FITC-annexin V/PI staining and flow cytometry. The effects of Silymarin, Rapamycin and FK506 on the activation of PARP (poly ADP ribose polymerase) pathway in PBMCs stimulated with Con A and treated with IC50 dose of drugs for 5 days evaluated using the PathScan cleaved PARP sandwich ELISA kit. Results: This study showed that Silymarin had the ability to inhibit T cell proliferation in vitro. Moreover, our results indicated that 100 μM (P < 0.001) and 200 μM (P < 0.001) of Silymarin has more inhibitory effect on T cells proliferation than FK506 and Rapamycin. Our data showed that the effective doses (IC50) of Silymarin, FK506 and Rapamycin were 3×10-5 µM, 10-8 µM and 10-6 µM respectively. Data showed that the inhibitory effect of Silymarin, FK506 and Rapamycin on T cell proliferation was not due to cytotoxicity and none of these drugs at IC50 concentration had not affected the level of cleaved PARP. Conclusion: Silymarin could be a good candidate for immunosuppressive therapy for certain medical conditions with superior efficacy and lesser toxicity in comparison with other immunosuppressive drugs.

Keywords: silymarin, immunosuppressive effect, rapamycin, immunology

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Authors: Doo Ki Lee, Man Young Kim

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The Urea-Selective Catalytic Reduction (SCR) system is considered to be the most promising technology to fulfill the stringent emission regulation. In the Urea-SCR system, the urea solutions are used as the reducing agent, which is a eutectic composition (32.5wt% of urea). The advantage of this eutectic compositions is that it has a low freezing point approximately at -11 ℃, however, the problem of freezing occurs at low-temperature levels below that freezing point. To prevent freezing of urea solutions, we need heating systems that can melt by heating the frozen urea solutions in urea storage tank at low-temperature environment. In this study, therefore, a numerical investigation of three-dimensional unsteady heating problems analyzed to find the melting characteristics of the urea solutions on melting process. In this work, it can be found that the urea melting initiated by heat conduction from the heater is enhanced by the natural convection inside the melted liquid urea solutions due to the temperature difference. Also, liquid urea solutions are initially concentrated on the upper parts of the urea sender module.

Keywords: urea solution, melting, heat conduction, natural convection, liquid fraction, phase change

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Authors: Tamer M. Shehata, Heba S. Elsewedy, Mashel Al Dosary, Alaa Elshehry, Mohamed A. Khedr, Maged E. Mohamed

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Objective: 2,4-Dichlorophenoxy acetic acid (2,4-D) is a well-known herbicide widely used as a weed killer. Recently, 2,4-D was rediscovered as a new anti-inflammatory agent through in silico as well as in-vivo experiments. However, poor solubility of 2,4-D could represent a problems during pharmaceutical development in addition to lower bioavailability. Solid dispersion (SD) refers to a group of solid products consisting of at least two different components, usually a hydrophobic drug and hydrophilic matrix. It is well known technique for enhancing drug solubility. Therefore, selecting SD as a tool for enhancing 2,4-D could be of great interest to the formulator. Method: In our project, several polymers were investigated (such as PEG, HPMC, citric acid and others) in addition to drug polymer ratios and its effect on solubility. Evaluation of drug polymer interaction was investigated through both Fourier Transform Infrared (FTIR) and Differential Scanning Calorimetry (DSC). Finally, in-vivo evaluation was performed for the best selected preparation through inflammatory response of rat induce hind paw. Results: Results indicated that, citric acid 2,4-D and in ratio of 0.75 : 1 showed modified the dissolution profile of the drug. The FTIR resltes indicated no significant chemical interaction, however DSC showed shifting of the drug melting point. Finally, Carragenan induced rat hind paw edema showed significant reduction of the drug solid dispersion in comparison to the pure drug, indicating rapid and complete absorption of the drug in solid dispersion form. Conclusion: Solid dispersion technology can be utilized efficiently to enhance the solubility of 2,4-D.

Keywords: solid dispersion, 2, 4-D solubility, carragenan induced edema

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Authors: R. Denkova

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Nowadays, aesthetic and psychological researches in some countries show that the aesthetic ideal for women is built by the same pattern of big volumes – lips, cheek, facial disproportions. They all look like made of a matrix. And they lose their unique and emotional aspects of beauty. How to escape this matrix and find the balance? The secret to being a unique injector is good assessment, creating a treatment plan and flawless injection strategy. The newest concepts in this new injection era which meet the requirements of a modern society and deliver balanced and natural looking results are based on the concept of injecting not the consequence, but the reason. Three case studies are presented with full face assessment, treatment plan and before/after pictures. Using different approaches and techniques of the MD codes concept, lights and shadows concept in order to preserve the emotional beauty and identity of the women. In conclusion, the cases demonstrate that beauty exists even beyond the matrix and it is the injector’s mission and responsibility is to preserve and highlight the natural beauty and unique identity of every different patient.

Keywords: beyond the matrix, emotional beauty, face assessment, injector, treatment plan

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Authors: Hye Kyung Kim, Myung-Gyou Kim, Kang-Hyun Leem

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Postmenopausal osteoporosis is characterized by low bone density which leads to increased bone fragility and greater susceptibility to fracture. Current treatments for osteoporosis are dominated by drugs that inhibit bone resorption although they also suppress bone formation that may contribute to pathogenesis of osteonecrosis. To restore the extensive bone loss, there is a great need for anabolic treatments that induce osteoblasts to build new bone. Pre-osteoblastic cells produce proteins of the extra-cellular matrix, including type I collagen at first, and then to successively produce alkaline phosphatase (ALP) and osteocalcin during differentiation to osteoblasts. Finally, osteoblasts deposit calcium. Present study investigated the effects of egg yolk peptide (EYP) on osteogenic activities and bone matrix gene expressions in human osteoblastic MG-63 cells. The effects of EYP on cell proliferation, alkaline phosphatase (ALP) activity, collagen synthesis, and mineralization were measured. The expression of osteogenic genes including COL1A1 (collagen, type I, alpha 1), ALP, BGLAP (osteocalcin), and SPP1 (secreted phosphoprotein 1, osteopontin) were measured by quantitative realtime PCR. EYP dose-dependently increased MG-63 cell proliferation, ALP activity, collagen synthesis, and calcium deposition. Furthermore, COL1A1, ALP, and SPP1 gene expressions were increased by EYP treatment. Present study suggested that EYP treatment enhanced osteogenic activities and increased bone matrix osteogenicgenes. These results could provide a mechanistic explanation for the bone-strengthening effects of EYP.

Keywords: egg yolk peptide, osteoblastic MG-63 cells, alkaline phosphatase, collagen synthesis, osteogenic genes, COL1A1, osteocalcin, osteopontin

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Authors: H. Chabalala, A. Grootboom, M. Tang

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The innovative development, production, and clinical utilisation of African natural medicines requires frameworks from systematisation, innovation, registration. Afrika faces challenges when it comes to these sectors. The opposite is the case as is is evident in ancient Asian (Traditional Chinese Medicine and Indian Ayurveda and Siddha) medical systems, which are interfaced into their respective national health and educational systems. Afrikan Natural Medicines (ANMs) are yet to develop systematisation frameworks, i.e. disease characterisation and medicines classification. This paper explores classical medical systems drawn from Afrikan and Chinese experts in natural medicines. An Afrikological research methodology was used to conduct in-depth interviews with 20 key respondents selected through purposeful sampling technique. Data was summarised into systematisation frameworks for classical disease theories, patient categorisation, medicine classification, aetiology and pathogenesis of disease, diagnosis and prognosis techniques and treatment methods. It was discovered that ancient Afrika had systematic medical cosmologies, remnants of which are evident in most Afrikan cultural health practices. Parallels could be drawn from classical medical concepts of antiquity, like Chinese Taoist and Indian tantric health systems. Data revealed that both the ancient and contemporary ANM systems were based on living medical cosmologies. The study showed that African Natural Healing Systems have etiological systems, general pathogenesis knowledge, differential diagnostic techniques, comprehensive prognosis and holistic treatment regimes. Systematisation models were developed out of these frameworks, and this could be used for evaluation of clinical research, medical application including development of curriculum for high-education. It was envisaged that frameworks will pave way towards the development, production and commercialisation of ANMs. This was piloted in inclusive innovation, technology transfer and commercialisation of South African natural medicines, cosmeceuticals, nutraceuticals and health infusions. The central model presented here in will assist in curriculum development and establishment of Afrikan Medicines Hospitals and Pharmaceutical Industries.

Keywords: African Natural Medicines, Indigenous Knowledge Systems, Medical Cosmology, Clinical Application

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Authors: Iman Adnan Annon, Kadhim F. Alsultan

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This study investigate the internal corrosion of low carbon steel pipelines in the crude oil, as well as prepare and use natural and locally available plant as a natural corrosion inhibiter, the nature extraction achieved by two types of solvents in order to show the solvent effect on inhibition process, the first being distilled water and the second is diethyl ether. FT-IR spectra and using a chemical reagents achieved to detection the presence of many active groups and the presence of tannins, phenols, and alkaloids in the natural extraction. Some experiments were achieved to estimate the performance of a new inhibitor, one of these tests include corrosion measurement by simple immersion in crude oil within and without inhibitors which added in different amounts 30,40,50and 60 ppm at tow temperature 300 and 323k, where the best inhibition efficiencies which get when added the inhibitors in a critical amounts or closest to it, since for the aqueous extract (EB-A) the inhibition efficiency reached (94.4) and (86.71)% at 300 and 323k respectively, and for diethyl ether extract (EB-D) reached (82.87) and (84.6)% at 300 and 323k respectively. Optical microscopy examination have been conducted to evaluate the corrosion nature where it show a clear difference in the topography of the immersed samples surface after add the inhibitors at two temperatures. The results show that the new corrosion inhibitor is not only equivalent to a chemical inhibitor but has greatly improvement properties such as: high efficiency, low cost, non-toxic, easily to produce, and nonpolluting as compared with chemical inhibitor.

Keywords: corrosion in pipeline, inhibitors, crude oil, carbon steel, types of solvent

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Authors: Szymon Kuczynski, Krystian Liszka, Mariusz Laciak, Andrii Oliinyk, Adam Szurlej

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Currently, in automotive transport to power vehicles, almost exclusively hydrocarbon based fuels are used. Due to increase of hydrocarbon fuels consumption, quality parameters are tightend for clean environment. At the same time efforts are undertaken for development of alternative fuels. The reasons why looking for alternative fuels for petroleum and diesel are: to increase vehicle efficiency and to reduce the environmental impact, reduction of greenhouse gases emissions and savings in consumption of limited oil resources. Significant progress was performed on development of alternative fuels such as methanol, ethanol, natural gas (CNG / LNG), LPG, dimethyl ether (DME) and biodiesel. In addition, biggest vehicle manufacturers work on fuel cell vehicles and its introduction to the market. Alcohols such as methanol and ethanol create the perfect fuel for spark-ignition engines. Their advantages are high-value antiknock which determines their application as additive (10%) to unleaded petrol and relative purity of produced exhaust gasses. Ethanol is produced in distillation process of plant products, which value as a food can be irrational. Ethanol production can be costly also for the entire economy of the country, because it requires a large complex distillation plants, large amounts of biomass and finally a significant amount of fuel to sustain the process. At the same time, the fermentation process of plants releases into the atmosphere large quantities of carbon dioxide. Natural gas cannot be directly converted into liquid fuels, although such arrangements have been proposed in the literature. Going through stage of intermediates is inevitable yet. Most popular one is conversion to methanol, which can be processed further to dimethyl ether (DME) or olefin (ethylene and propylene) for the petrochemical sector. Methanol uses natural gas as a raw material, however, requires expensive and advanced production processes. In relation to pollution emissions, the optimal vehicle fuel is LPG which is used in many countries as an engine fuel. Production of LPG is inextricably linked with production and processing of oil and gas, and which represents a small percentage. Its potential as an alternative for traditional fuels is therefore proportionately reduced. Excellent engine fuel may be biogas, however, follows to the same limitations as ethanol - the same production process is used and raw materials. Most essential fuel in the campaign of environment protection against pollution is natural gas. Natural gas as fuel may be either compressed (CNG) or liquefied (LNG). Natural gas can also be used for hydrogen production in steam reforming. Hydrogen can be used as a basic starting material for the chemical industry, an important raw material in the refinery processes, as well as a fuel vehicle transportation. Natural gas can be used as CNG which represents an excellent compromise between the availability of the technology that is proven and relatively cheap to use in many areas of the automotive industry. Natural gas can also be seen as an important bridge to other alternative sources of energy derived from fuel and harmless to the environment. For these reasons CNG as a fuel stimulates considerable interest in the worldwide.

Keywords: alternative fuels, CNG (Compressed Natural Gas), LNG (Liquefied Natural Gas), NGVs (Natural Gas Vehicles)

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Authors: Akterono Budiyati, Gita Kusumo, Teguh Putra, Fritzie Rexana, Antonius Kurniawan, Aru Sudoyo, Ahmad Utomo, Andi Utama

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The presence of the programmed death ligand-1 (PD-L1) has been used in multiple clinical trials and approved as biomarker for selecting patients more likely to respond to immune checkpoint inhibitors. However, the expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence. Positive PD-L1 within tumors may result from two mechanisms, induced PD-L1 expression by T-cell presence or genetic mechanism that lead to constitutive PD-L1 expression. Amplification of PD-L1 genes was found as one of genetic mechanism which causes an increase in PD-L1 expression. In case of colorectal cancer (CRC), targeting immune checkpoint inhibitor has been recommended for patients with microsatellite instable (MSI). Although the correlation between PD-L1 expression and MSI status has been widely studied, so far the precise mechanism of PD-L1 gene activation in CRC patients, particularly in MSI population have yet to be clarified. In this present study we have profiled 61 archived formalin fixed paraffin embedded CRC specimens of patients from Medistra Hospital, Jakarta admitted in 2010 - 2016. Immunohistochemistry was performed to measure expression of PD-L1 in tumor cells as well as MSI status using antibodies against PD-L1 and MMR (MLH1, MSH2, PMS2 and MSH6), respectively. PD-L1 expression was measured on tumor cells with cut off of 1% whereas loss of nuclear MMR protein expressions in tumor cells but not in normal or stromal cells indicated presence of MSI. Subset of PD-L1 positive patients was then assessed for copy number variations (CNVs) using single Tube TaqMan Copy Number Assays Gene CD247PD-L1. We also observed KRAS mutation to profile possible genetic mechanism leading to the presence or absence of PD-L1 expression. Analysis of 61 CRC patients revealed 15 patients (24%) expressed PD-L1 on their tumor cell membranes. The prevalence of surface membrane PD-L1 was significantly higher in patients with MSI (87%; 7/8) compared to patients with microsatellite stable (MSS) (15%; 8/53) (P=0.001). Although amplification of PD-L1 gene was not found among PD-L1 positive patients, low-level amplification of PD-L1 gene was commonly observed in MSS patients (75%; 6/8) than in MSI patients (43%; 3/7). Additionally, we found 26% of CRC patients harbored KRAS mutations (16/61), so far the distribution of KRAS status did not correlate with PD-L1 expression. Our data suggest genetic mechanism through amplification of PD-L1 seems not to be the mechanism underlying upregulation of PD-L1 expression in CRC patients. However, further studies are warranted to confirm the results.

Keywords: colorectal cancer, gene amplification, microsatellite instable, programmed death ligand-1

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Authors: Ahmad K. Samaila, Basant K. Jha

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This paper presents the effects of suction/injection of transient/steady natural convection flow of reactive viscous fluid in a vertical porous pipe. The mathematical model capturing the time dependent flow of viscous reactive fluid is solved using implicit finite difference method while the corresponding steady state model is solved using regular perturbation technique. Results of analytical and numerical solutions are reported for various parametric conditions to illustrate special features of the solutions. The coefficient of skin friction and rate of heat transfer are obtained and illustrated graphically. The numerical solution is shown to be in excellent agreement with the closed form analytical solution. It is interesting to note that time required to reach steady state is higher in case of injection in comparison to suction.

Keywords: porous pipe, reactive viscous fluid, transient natural-convective flow, analytical solution

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Authors: Hairin Taha, Aditya Arya, M. A. Hapipah, A. M. Mustafa

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Plants have been an important source of medicine since ancient times. Pseuduvaria monticola is a rare montane forest species from the Annonaceae family. Traditionally, the plant was used to cure symptoms of fever, inflammation, stomach-ache and also to reduce the elevated levels of blood glucose. Scientifically, we have evaluated the antidiabetic potential of the Pseuduvaria monticola bark methanolic extract on certain in vitro cell based assays, followed by in vivo study. Results from in vitro models displayed PMm upregulated glucose uptake and insulin secretion in mouse pancreatic β-cells. In vivo study demonstrated the PMm down-regulated hyperglycaemia, oxidative stress and elevated levels of pro-inflammatory cytokines in type 2 diabetic rat models. Altogether, the study revealed that Pseuduvaria monticola might be used as a potential candidate for the management of type 2 diabetes and its related complications.

Keywords: type 2 diabetes, Pseuduvaria monticola, insulin secretion, glucose uptake

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Authors: Rita Hairani, Warinthorn Chavasiri

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Naphthoquinones are secondary metabolites widespread in nature and can be produced by plants, fungi and actinomycetes. The interest of naphthoquinones is not only limited as organic dyes, but also their wide variety of biological activities such as antitumor, antibacterial, and cytotoxic activities. Typical 1,2-naphthoquinones such as mansonones can be found in Mansonia gagei Drumm. (“chan-cha-mod”), Sterculaceae family. This plant has been used traditionally to treat some diseases such as antiemetic and antidepressant. In this study, some natural mansonones isolated from the CH2Cl2 extract of M. gagei heartwood have been assessed for their antibacterial activities using agar well diffusion method. According to the antibacterial activity results of four natural mansonones (mansonones C, E, G and H), mansonones E and G showed higher activities than the others against Staphylococcus aureus, Propionibacterium acnes and Salmonella typhi, respectively. Since mansonone G exhibited good antibacterial activity and was obtained in the highest yield, we decided to derivertize mansonone G into five ether analogues. Based on the antibacterial activities of these synthesized compounds, four ether analogues (compounds 1-4) revealed higher antibacterial activities than its natural mansonone G against S. aureus and S. typhi.

Keywords: Mansonia gagei Drumm., antibacterial activities, mansonone G, ether analogues

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Authors: William Burdick

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Manmade climate change is an existential threat that must be mitigated at the earliest opportunity. The role of government in climate change mitigation is enacting and enforcing law and policy to affect substantial reductions in greenhouse gasses, in the short and long term, without substantial increases in the cost of energy. To be optimally effective those laws and policies must be established and enforced based on peer reviewed evidence and scientific facts and result in substantial outcomes in years, not decades. Over the next fifty years, New York’s 2019 Climate Change and Community Protection Act and 2021 All Electric Building Act that mandate replacing natural gas heating systems with heat pumps will, immediately double annual heating costs and by 2075, yield less than 16.2% reduction in CO₂ emissions from heating systems in new housing units, less than a 13% reduction in total CO₂ emissions, and affect a $40B in cumulative additional heating cost, compared to natural gas fueled heating systems.

Keywords: climate change, mandate, heat pump, natural gas

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Authors: Ahmad Taghinia, Negar Gholamishaker

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GaAs (gallium arsenide) solar cells have gained significant attention for their use in space applications. These solar cells have the potential for efficient energy conversion and are being explored as potential power sources for electronic devices, satellites, and telecommunication equipment. In this study, the aim is to investigate the effect of adding a window layer and a back surface field (BSF) layer made of InₓGa₍₁₋ₓ₎P material to a GaAs single junction solar cell. In this paper, we first obtain the important electrical parameters of a single-junction GaAs solar cell by utilizing a two-dimensional simulator software for virtual investigation of the solar cell; then, we analyze the impact of adding a window layer and a back surface field layer made of InₓGa₍₁₋ₓ₎P on the solar cell. The results show that the incorporation of these layers led to enhancements in Jsc, Voc, FF, and the overall efficiency of the solar cell.

Keywords: back surface field layer, solar cell, GaAs, InₓGa₍₁₋ₓ₎P, window layer

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Authors: Dalila Souilem, Salma Boumiza, Abdelkarim Abdelkader

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The Clarifier Dialogue Interface (CDI) is a part of an online teaching system based on human-machine communication in learning situation. This interface used in the system during the learning action specifically in the evaluation step, to clarify ambiguities in the learner's response. The CDI can generate patterns allowing access to an information system, using the selectors associated with lexical units. To instantiate these patterns, the user request (especially learner’s response), must be analyzed and interpreted to deduce the canonical form, the semantic form and the subject of the sentence. For the efficiency of this interface at the interpretation level, a set of substitution operators is carried out in order to extend the possibilities of manipulation with a natural language. A second approach that will be presented in this paper focuses on the object languages with new prospects such as combination of natural language with techniques of handling information system in the area of online education. So all operators, the CDI and other interfaces associated to the domain expertise and teaching strategies will be unified using FRAME representation form.

Keywords: dialogue, e-learning, FRAME, information system, natural language

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Authors: T. Garba, Y. Y. Sabo A. Babanyara, K. G. Ilellah, A. K. Mutari

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This study used the Normalized Difference Vegetation Index (NDVI) and maps compiled from the classification of Landsat TM and Landsat ETM images of 1986 and 1999 respectively and Nigeria sat 1 images of 2007 to quantify changes in land use and land cover in selected areas of Nigeria covering 143,609 hectares that are threatened by the encroaching Sahara desert. The results of this investigation revealed a decrease in natural vegetation over the three time slices (1986, 1999 and 2007) which was characterised by an increase in high positive pixel values from 0.04 in 1986 to 0.22 and 0.32 in 1999 and 2007 respectively and, a decrease in natural vegetation from 74,411.60ha in 1986 to 28,591.93ha and 21,819.19ha in 1999 and 2007 respectively. The same results also revealed a periodic trend in which there was progressive increase in the cultivated area from 60,191.87ha in 1986 to 104,376.07ha in 1999 and a terminal decrease to 88,868.31ha in 2007. These findings point to expansion of vegetated and cultivated areas in in the initial period between 1988 and 1996 and reversal of these increases in the terminal period between 1988 and 1996. The study also revealed progressive expansion of built-up areas from 1, 681.68ha in 1986 to 2,661.82ha in 1999 and to 3,765.35ha in 2007. These results argue for the urgent need to protect and conserve the depleting natural vegetation by adopting sustainable human resource use practices i.e. intensive farming in order to minimize persistent depletion of natural vegetation.

Keywords: changes, classification, desertification, vegetation changes

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Authors: Amal Alshahrani, Allan Ramsay

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Paraphrasing is one of the important tasks in natural language processing; i.e. alternative ways to express the same concept by using different words or phrases. Paraphrases can be used in many natural language applications, such as Information Retrieval, Machine Translation, Question Answering, Text Summarization, or Information Extraction. To obtain pairs of sentences that are paraphrases we create a system that automatically extracts paraphrases from a corpus, which is built from different sources of news article since these are likely to contain paraphrases when they report the same event on the same day. There are existing simple standard approaches (e.g. TF-IDF vector space, cosine similarity) and alignment technique (e.g. Dynamic Time Warping (DTW)) for extracting paraphrase which have been applied to the English. However, the performance of these approaches could be affected when they are applied to another language, for instance Arabic language, due to the presence of phenomena which are not present in English, such as Free Word Order, Zero copula, and Pro-dropping. These phenomena will affect the performance of these algorithms. Thus, if we can analysis how the existing algorithms for English fail for Arabic then we can find a solution for Arabic. The results are promising.

Keywords: natural language processing, TF-IDF, cosine similarity, dynamic time warping (DTW)

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Authors: M.S. Ashraf, Raja Rizwan Hussain, A. M. Alhozaimy

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The effect of supplementary cementitious materials (SCMs) with concrete pore solution on the protective properties of the oxide films that form on reinforcing steel bars has been experimentally investigated using electrochemical impedance spectroscopy (EIS) and Tafel Scan. The tests were conducted on oxide films grown in saturated calcium hydroxide solutions that included different representative amounts of NaOH and KOH. In addition to that, commonly used supplementary cementitious materials (natural pozzolan and fly ash) were also added. The results of electrochemical tests show that supplementary cementitious materials do have an effect on the protective properties of the passive oxide film. In particular, natural pozzolans has been shown to have a highly positive influence on the film quality. Fly ash also increases the protective qualities of the passive film.

Keywords: supplementary cementitious materials (SCMs), passive film, EIS, Tafel scan, rebar, concrete, simulated concrete pore solution (SPS)

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Authors: Sylvester Akpah, Selasi Vondee

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Unmanned Aerial Vehicles (UAV) as they are also known, drones have attracted increasing attention in recent years due to their ubiquitous nature and boundless applications in the areas of communication, surveying, aerial photography, weather forecasting, medical delivery, surveillance amongst others. Operated remotely in real-time or pre-programmed, drones can fly autonomously or on pre-defined routes. The application of these aerial vehicles has successfully penetrated the world due to technological evolution, thus a lot more businesses are utilizing their capabilities. Unfortunately, while drones are replete with the benefits stated supra, they are riddled with some problems, mainly attributed to the complexities in learning how to master drone flights, collision avoidance and enterprise security. Additional challenges, such as the analysis of flight data recorded by sensors attached to the drone may take time and require expert help to analyse and understand. This paper presents an autonomous drone control system using a chatbot. The system allows for easy control of drones using conversations with the aid of Natural Language Processing, thus to reduce the workload needed to set up, deploy, control, and monitor drone flight missions. The results obtained at the end of the study revealed that the drone connected to the chatbot was able to initiate flight missions with just text and voice commands, enable conversation and give real-time feedback from data and requests made to the chatbot. The results further revealed that the system was able to process natural language and produced human-like conversational abilities using Artificial Intelligence (Natural Language Understanding). It is recommended that radio signal adapters be used instead of wireless connections thus to increase the range of communication with the aerial vehicle.

Keywords: artificial ntelligence, chatbot, natural language processing, unmanned aerial vehicle

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Authors: Subrata Kar, Banani Kundu, Papiya Nandy, Ruma Basu, Sukhen Das

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Natural montmorilollite clay is a common ingredient in pharmaceutical products, both as excipients and active support; hence considered as suitable candidate for Drug Delivery System. In this work, cationic detergent CTAB is used to increase the interlayer spacing of Na+-Montmoriollite clay to intercalate curcumin and methotrexate. Methotrexate is a folic acid antagonist, anti-proliferative and immunosuppressive agent; while curcumin is a bioactive constituent of rhizomes of Curcuma longa, possessing remarkable chemo-preventive and anti-inflammatory properties. The resultant inorganic-organic hybrids are characterized by X-ray diffraction (XRD), Infrared spectroscopy (FTIR) and Thermo Gravimetric Analysis (TGA) to confirm successful intercalation of curcumin and Methotrexate within clay layers. Pharmaceutical investigation of the hybrids is explored by studying the drug loading (%), encapsulation efficiency and release kinetics. Finally in-vitro studies are performed using cancer cells to find the effect of released curcumin to improve the sensitivity of clay bound methotrexate to ameliorate cell death compared to their effectiveness when used without the inorganic aluminosilicate vehicle.

Keywords: montmorillonite, methotrexate, curcumin, loading efficiency, release kinetics, anticancer activity

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Authors: Mark Gavriel, Ariel J. Jaffa, Dan Grisaru, David Elad

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The human endometrium-myometrium interface (EMI) is the uterine inner barrier without a separatig layer. It is composed of endometrial epithelial cells (EEC) and endometrial stromal cells (ESC) in the endometrium and myometrial smooth muscle cells (MSMC) in the myometrium. The EMI undergoes structural remodeling during the menstruation cycle which are essential for human reproduction. Recently, we co-cultured a layer-by-layer in vitro model of EEC, ESC and MSMC on a synthetic membrane for mechanobiology experiments. We also treated the model with progesterone and β-estradiol in order to mimic the in vivo receptive uterus In the present study we analyzed the cytokines profile in a single layer of EEC the hormonal treated in vitro model of the EMI. The methodologies of this research include simple tissue-engineering . First, we cultured commercial EEC (RL95-2, ATCC® CRL-1671™) in 24-wellplate. Then, we applied an hormonal stimuli protocol with 17-β-estradiol and progesterone in time dependent concentration according to the human physiology that mimics the menstrual cycle. We collected cell supernatant samples of control, pre-ovulation, ovulation and post-ovulaton periods for analysis of the secreted proteins and cytokines. The cytokine profiling was performed using the Proteome Profiler Human XL Cytokine Array Kit (R&D Systems, Inc., USA) that can detect105 human soluble cytokines. The relative quantification of all the cytokines will be analyzed using xMAP – LUMINEX. We conducted a fishing expedition with the 4 membranes Proteome Profiler. We processed the images, quantified the spots intensity and normalized these values by the negative control and reference spots at the membrane. Analyses of the relative quantities that reflected change higher than 5% of the control points of the kit revealed the The results clearly showed that there are significant changes in the cytokine level for inflammation and angiogenesis pathways. Analysis of tissue-engineered models of the uterine wall will enable deeper investigation of molecular and biomechanical aspects of early reproductive stages (e.g. the window of implantation) or developments of pathologies.

Keywords: tissue-engineering, hormonal stimuli, reproduction, multi-layer uterine model, progesterone, β-estradiol, receptive uterine model, fertility

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Authors: A. Almohammedi, A. J. Hudson, N. M. Storey

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Following ischaemia/reperfusion injury, as in a myocardial infraction, cardiac myocytes undergo oxidative stress which leads to several potential outcomes including; necrotic or apoptotic cell death or dysregulated calcium homeostasis or disruption of the electron transport chain. Several studies have shown that nitric oxide donors protect cardiomyocytes against ischemia and reperfusion. However until present, the mechanism of cardioprotective effect of nitric oxide donor in isolated ventricular cardiomyocytes is not fully understood and has not been investigated before using Raman spectroscopy. For these reasons, the aim of this study was to develop a novel technique, pre-resonance Raman spectroscopy, to investigate the mechanism of cardioprotective effect of nitric oxide donor in isolated ventricular cardiomyocytes exposed to metabolic inhibition and re-energisation. The results demonstrated the first time that Raman microspectroscopy technique has the capability to monitor the metabolic inhibition of cardiomyocytes and to monitor the effectiveness of cardioprotection by nitric oxide donor prior to metabolic inhibition of cardiomyocytes. Metabolic inhibition and reenergisation were used in this study to mimic the low and high oxygen levels experienced by cells during ischaemic and reperfusion treatments. A laser wavelength of 488 nm used in this study has been found to provide the most sensitive means of observe the cellular mechanisms of myoglobin during nitric oxide donor preconditioning, metabolic inhibition and re-energisation and did not cause any damage to the cells. The data also highlight the considerably different cellular responses to metabolic inhibition to ischaemia. Moreover, the data has been shown the relationship between the release of myoglobin and chemical ischemia where that the release of myoglobin from the cell only occurred if a cell did not recover contractility.

Keywords: ex vivo biospectroscopy, Raman spectroscopy, biophotonics, cardiomyocytes, ischaemia / reperfusion injury, cardioprotection, nitric oxide donor

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Authors: Otokiti Mojeed Jimoh

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This work investigates the possibility of using recycled polyethylene LDPE as a base polymer in production of different products (shoe sole, foot mat, and many more) using carbon black as a filler to improve its mechanical properties, like hardness, tensile stress properties and elongation at break properties, from the result so far gotten there is a possibility that there is an increase in the mechanical properties of the sample compare to natural rubber sample.

Keywords: recycled polyethylene, base polymer, hardness, stress properties

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Authors: Heba M. Saad Eldien, Ola Abdel-Tawab Hussein, Ahmed Yassein Nassar

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Background: Indomethacin is a non-steroidal anti inflammatory drug. Indomethacin induces an injury to gastrointestinal mucosa in experimental animals and humans and their use is associated with a significant risk of hemorrhage, erosions and perforation of both gastric and intestinal ulcers. The anti-inflammatory action of copper complexes is an important activity of their anti-ulcer effect achieved by their intermediary role as a transport form of copper that allow activation of the several copper-dependent enzymes. Therefore, several copper complexes were synthesized and investigated as promising alternative anti-ulcer therapy. Aim of the work: The purpose of this study was to evaluate a copper chelating complex consisting of egg albumin and copper as one of the copper peptides that can be used as anti-inflammatory agent and effective in ameliorates the hazards of the indomethacin on the histological structure of the fundus of the stomach that could be added to raise the efficacy of the currently used simple and cheap gastric anti-inflammatory drug mucogel. Material &methods: This study was carried out on 40 adult male albino rats,divided equally into 4 groups;Group I(control group) received distilled water,Group II(indomethacin treated group) received (25 mg/kg body weight, oral intubation) once, Group III (mucogel treated group)2 mL/rat once daily, oral incubation, Group IV(copper complex group) 1 mL /rat of 30 gm of copper albumin complex was mixed uniformly with mucogel to 100 mL. Treatment has been started six hour after Induction of Ulcers and continued till the 3rd day. The animals sacrificed and was processed for light, transmission electron microscopy(TEM) and immunostaining for inducible nitric oxide synthase(iNOS). Results: Fundic mucosa of group II, showed exfoliation of epithelial cells lining the gland, discontinuity of surface epithelial cells (ulcer formation), vacuolation and detachment of cells, eosinophilic infiltration and congestion of blood vessels in the lamina propria and submucosa. There was thickening and disarrangement of mucosa, weak positive reaction for PAS and marked increase in the collagen fibers lamina propria and the submucosa of the fundus. TEM revealed degeneration of cheif and parietal cells.Marked increase positive reactive of iNOS in all cells of the fundic gland. Group III showed reconstruction of gastric gland with cystic dilatation and vacuolation, moderate decrease of collagen fibers, reduced the intensity of iNOS while in Group IV healthy mucosa with normal surface lining epithelium and fundic glands, strong positive reaction for PAS, marked decrease of collagen fibers and positive reaction for iNOS. TEM revealed regeneration of cheif and parietal cells. Conclusion: Co treatment of copper-albumin complex seems to be useful for gastric ulcer treatment and ameliorates most of hazards of indomethacin.

Keywords: copper complex, gastric ulcer, indomethacin, rat

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Authors: Ihtisham Bukhari

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In the current study, we enrolled a 46, XY phenotypically female patient bearing testes in her inguinal canal. DNA sequencing of the AR gene detected a missense mutation C.1715A > G (p. Y572C) in exon 2 which is already known to cause Complete androgen insensitivity syndrome (CAIS). We further studied the effects of this mutation on the testicular histopathology of the patient. No spermatocytes were seen in the surface spreading of testicular tissues while H&E staining showed that seminiferous tubules predominantly have only Sertoli cells. To confirm this meiotic failure is likely due to the current AR mutation we performed mRNA expression of genes associated with AR pathway, expression and location of the associated proteins in testicular tissues. Western blot and real-time PCR data showed that the patient had high levels of expression of AMH, SOX9, and INNB in testis. Tubules were stained with SOX9 and AMH which revealed Sertoli cell maturation arrest. Therefore, we suggest that AR mutation enhances AMH expression which ultimately leads to failure in the maturation of Sertoli cells and failure in spermatogenesis.

Keywords: androgen receptor, spermatogenesis, infertility, Sertoli cell only syndrome

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