Search results for: mechanically induced cavitation
2157 Validation and Fit of a Biomechanical Bipedal Walking Model for Simulation of Loads Induced by Pedestrians on Footbridges
Authors: Dianelys Vega, Carlos Magluta, Ney Roitman
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The simulation of loads induced by walking people in civil engineering structures is still challenging It has been the focus of considerable research worldwide in the recent decades due to increasing number of reported vibration problems in pedestrian structures. One of the most important key in the designing of slender structures is the Human-Structure Interaction (HSI). How moving people interact with structures and the effect it has on their dynamic responses is still not well understood. To rely on calibrated pedestrian models that accurately estimate the structural response becomes extremely important. However, because of the complexity of the pedestrian mechanisms, there are still some gaps in knowledge and more reliable models need to be investigated. On this topic several authors have proposed biodynamic models to represent the pedestrian, whether these models provide a consistent approximation to physical reality still needs to be studied. Therefore, this work comes to contribute to a better understanding of this phenomenon bringing an experimental validation of a pedestrian walking model and a Human-Structure Interaction model. In this study, a bi-dimensional bipedal walking model was used to represent the pedestrians along with an interaction model which was applied to a prototype footbridge. Numerical models were implemented in MATLAB. In parallel, experimental tests were conducted in the Structures Laboratory of COPPE (LabEst), at Federal University of Rio de Janeiro. Different test subjects were asked to walk at different walking speeds over instrumented force platforms to measure the walking force and an accelerometer was placed at the waist of each subject to measure the acceleration of the center of mass at the same time. By fitting the step force and the center of mass acceleration through successive numerical simulations, the model parameters are estimated. In addition, experimental data of a walking pedestrian on a flexible structure was used to validate the interaction model presented, through the comparison of the measured and simulated structural response at mid span. It was found that the pedestrian model was able to adequately reproduce the ground reaction force and the center of mass acceleration for normal and slow walking speeds, being less efficient for faster speeds. Numerical simulations showed that biomechanical parameters such as leg stiffness and damping affect the ground reaction force, and the higher the walking speed the greater the leg length of the model. Besides, the interaction model was also capable to estimate with good approximation the structural response, that remained in the same order of magnitude as the measured response. Some differences in frequency spectra were observed, which are presumed to be due to the perfectly periodic loading representation, neglecting intra-subject variabilities. In conclusion, this work showed that the bipedal walking model could be used to represent walking pedestrians since it was efficient to reproduce the center of mass movement and ground reaction forces produced by humans. Furthermore, although more experimental validations are required, the interaction model also seems to be a useful framework to estimate the dynamic response of structures under loads induced by walking pedestrians.Keywords: biodynamic models, bipedal walking models, human induced loads, human structure interaction
Procedia PDF Downloads 1322156 Effect of Visnagin on Altered Steroidogenesis and Spermatogenesis, and Testicular Injury Induced by the Heavy Metal Lead
Authors: Saleh N. Maodaa
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Background: Lead (Pb) is an environmental pollutant causing serious health problems, including impairment of reproduction. Visnagin (VIS) is a furanochromone with promising antioxidant and anti-inflammatory effects; however, its protective efficacy against Pb toxicity has not been investigated. Objective: This study evaluated the protective effect of VIS on Pb reproductive toxicity, impaired steroidogenesis and spermatogenesis, oxidative stress and inflammation. Methods: Rats received VIS (30 or 60 mg/kg) and 50 mg/kg lead acetate for 3 weeks, and blood and testes samples were collected. Results: Pb intoxication impaired the pituitary-testicular axis (PTA), manifested by the decreased serum levels of gonadotropins and testosterone. Pb decreased sperm count, motility and viability, increased sperm abnormalities, and downregulated the steroidogenesis markers StAR, CYP17A1, 3β-HSD and 17β-HSD in the testis of rats. VIS significantly increased serum gonadotropins and testosterone, alleviated sperm parameters and upregulated steroidogenesis. In addition, VIS decreased pro-inflammatory cytokines, testicular lipid peroxidation and DNA fragmentation, downregulated Bax, and enhanced antioxidants and Bcl-2 Conclusion: These results demonstrate the protective effect of VIS against Pb reproductive toxicity in rats. VIS improved serum gonadotropins and testosterone, enhanced steroidogenesis and spermatogenesis, and attenuated oxidative injury, inflammation and apoptosis. Therefore, VIS is a promising candidate for the protection against Pb-induced reproduction impairment.Keywords: pituitary-gonadal axis, cytokines, DNA damage, apoptosis
Procedia PDF Downloads 982155 Allium Cepa Extract Provides Neuroprotection Against Ischemia Reperfusion Induced Cognitive Dysfunction and Brain Damage in Mice
Authors: Jaspal Rana, Alkem Laboratories, Baddi, Himachal Pradesh, India Chitkara University, Punjab, India
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Oxidative stress has been identified as an underlying cause of ischemia-reperfusion (IR) related cognitive dysfunction and brain damage. Therefore, antioxidant based therapies to treat IR injury are being investigated. Allium cepa L. (onion) is used as culinary medicine and is documented to have marked antioxidant effects. Hence, the present study was designed to evaluate the effect of A. cepa outer scale extract (ACE) against IR induced cognition and biochemical deficit in mice. ACE was prepared by maceration with 70% methanol and fractionated into ethylacetate and aqueous fractions. Bilateral common carotid artery occlusion for 10 min followed by 24 h reperfusion was used to induce cerebral IR injury. Following IR injury, ACE (100 and 200 mg/kg) was administered orally to animals for 7 days once daily. Behavioral outcomes (memory and sensorimotor functions) were evaluated using Morris water maze and neurological severity score. Cerebral infarct size, brain thiobarbituric acid reactive species, reduced glutathione, and superoxide dismutase activity was also determined. Treatment with ACE significantly ameliorated IR mediated deterioration of memory and sensorimotor functions and rise in brain oxidative stress in animals. The results of the present investigation revealed that ACE improved functional outcomes after cerebral IR injury, which may be attributed to its antioxidant properties.Keywords: stroke, neuroprotection, ischemia reperfusion, herbal drugs
Procedia PDF Downloads 1062154 Ultrasonic Treatment of Baker’s Yeast Effluent
Authors: Emine Yılmaz, Serap Fındık
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Baker’s yeast industry uses molasses as a raw material. Molasses is end product of sugar industry. Wastewater from molasses processing presents large amount of coloured substances that give dark brown color and high organic load to the effluents. The main coloured compounds are known as melanoidins. Melanoidins are product of Maillard reaction between amino acid and carbonyl groups in molasses. Dark colour prevents sunlight penetration and reduces photosynthetic activity and dissolved oxygen level of surface waters. Various methods like biological processes (aerobic and anaerobic), ozonation, wet air oxidation, coagulation/flocculation are used to treatment of baker’s yeast effluent. Before effluent is discharged adequate treatment is imperative. In addition to this, increasingly stringent environmental regulations are forcing distilleries to improve existing treatment and also to find alternative methods of effluent management or combination of treatment methods. Sonochemical oxidation is one of the alternative methods. Sonochemical oxidation employs ultrasound resulting in cavitation phenomena. In this study, decolorization of baker’s yeast effluent was investigated by using ultrasound. Baker’s yeast effluent was supplied from a factory which is located in the north of Turkey. An ultrasonic homogenizator used for this study. Its operating frequency is 20 kHz. TiO2-ZnO catalyst has been used as sonocatalyst. The effects of molar proportion of TiO2-ZnO, calcination temperature and time, catalyst amount were investigated on the decolorization of baker’s yeast effluent. The results showed that prepared composite TiO2-ZnO with 4:1 molar proportion treated at 700°C for 90 min provides better result. Initial decolorization rate at 15 min is 3% without catalyst, 14,5% with catalyst treated at 700°C for 90 min respectively.Keywords: baker’s yeast effluent, decolorization, sonocatalyst, ultrasound
Procedia PDF Downloads 4742153 Study of Therapeutic Potential of Dodonaea Viscosa Against Rheumatoid Arthritis in Collagen Induced Arthritic Mouse Model
Authors: Peter John, Zainab Ali, Attya Bhatti
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Rheumatoid Arthritis (RA) is a systemic autoimmune inflammatory disease that primarily affects the joints. RA is caused in many cases by the interaction between genes and environmental factors, including tobacco, that primarily involves synovial joints. It typically starts in small peripheral joints, is usually symmetric, and progresses to involve proximal joints if left untreated. The prevalence of rheumatoid arthritis varies substantially around the globe, ranging from 0·25% to 1%.3. Rheumatoid arthritis can affect individuals of any age, with an increased incidence in people older than 40 years. Women are affected two to three times more frequently than men. The present work involved evaluating the toxicity and therapeutic potential of Dodonaea viscosa in a collagen-induced arthritic mouse model. Chemical analysis exhibited that Dodonaea viscosa has high levels of beneficial compounds, including phenols, flavonoids, and other phytochemicals. The Dodonaea viscosa showed significant antioxidant, anti-inflammatory, and anti-arthritic potential without toxic effects. Arthritic mice treated with Dodonaea viscosa showed reduced levels of rheumatoid factor and paw edema, while no significant effects on spleen indices and radiological examination of paws were found compared to control untreated arthritic mice. In summary, the Dodonaea viscosa treatment results in improvement in Arthritic Mice Model for which further studies are required.Keywords: rheumatoid arthritis, dodonaea viscisa, anti-inflammatory, anti-rheumatic
Procedia PDF Downloads 232152 Reactive Oxygen Species-Mediated Photoaging Pathways of Ultrafine Plastic Particles under UV Irradiation
Authors: Jiajun Duan, Yang Li, Jianan Gao, Runzi Cao, Enxiang Shang, Wen Zhang
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Reactive oxygen species (ROS) generation is considered as an important photoaging mechanism of microplastics (MPs) and nanoplastics (NPs). To elucidate the ROS-induced MP/NP aging processes in water under UV365 irradiation, we examined the effects of surface coatings, polymer types, and grain sizes on ROS generation and photoaging intermediates. Bare polystyrene (PS) NPs generated hydroxyl radicals (•OH) and singlet oxygen (¹O₂), while coated PS NPs (carboxyl-modified PS (PS-COOH), amino-modified PS (PS-NH₂)) and PS MPs generated fewer ROS due to coating scavenging or size effects. Polypropylene, polyethylene, polyvinyl chloride, polyethylene terephthalate, and polycarbonate MPs only generated •OH. For aromatic polymers, •OH addition preferentially occurred at benzene rings to form monohydroxy polymers. Excess •OH resulted in H abstraction, C-C scission, and phenyl ring opening to generate aliphatic ketones, esters, aldehydes, and aromatic ketones. For coated PS NPs, •OH preferentially attacked the surface coatings to result in decarboxylation and deamination reactions. For aliphatic polymers, •OH attack resulted in the formation of carbonyl groups from peracid, aldehyde, or ketone via H abstraction and C-C scission. Moreover, ¹O₂ might participate in phenyl ring opening for PS NPs and coating degradation for coated PS NPs. This study facilitates understanding the ROS-induced weathering process of NPs/MPs in water under UV irradiation.Keywords: microplastics, nanoplastics, photoaging, reactive oxygen species, surface coating
Procedia PDF Downloads 1572151 Luteolin Exhibits Anti-Diabetic Effects by Increasing Oxidative Capacity and Regulating Anti-Oxidant Metabolism
Authors: Eun-Young Kwon, Myung-Sook Choi, Su-Jung Cho, Ji-Young Choi, So Young Kim, Youngji Han
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Overweight and obesity have been linked to a low-grade chronic inflammatory response and an increased risk of developing metabolic syndrome including insulin resistance, type 2 diabetes mellitus and certain types of cancers. Luteolin is a dietary flavonoid with anti-inflammatory, anti-oxidant, anti-cancer and anti-diabetic properties. However, little is known about the detailed mechanism associated with the effect of luteolin on inflammation-related obesity and its complications. The aim of the present study was to reveal the anti-diabetic effect of luteolin in diet-induced obesity mice using “transcriptomics” tool. Thirty-nine male C57BL/6J mice (4-week-old) were randomly divided into 3 groups and were fed normal diet, high-fat diet (HFD, 20% fat) and HFD+0.005% (w/w) luteolin for 16 weeks. Luteolin improved insulin resistance, as measured by HOMA-IR and glucose tolerance, along with preservation action of pancreatic β-cells, compared to the HFD group. Luteoiln was significantly decreased the levels of leptin and ghrelin that play a pivotal role in energy balance, and the macrophage low-grade inflammation marker sCD163 (soluble Cd antigen 163) in plasma. Activities of hepatic anti-oxidant enzymes (catalase and glutathione peroxidase) were increased, while the levels of plasma transaminase (GOT and GPT) and oxidative damage markers (hepatic mitochondria H2O2 and TBARS) were markedly decreased by luteolin supplementation. In addition, luteolin increased oxidative capacity and fatty acid utilization by presenting decrease in enzyme activities of citrate synthase, cytochrome C oxidase and β-hydroxyacyl CoA dehydrogenase and UCP3 gene expression compared to high-fat diet. Moreover, our microarray results of muscle also revealed down-regulated gene expressions associated with TCA cycle by HFD were reversed to normal level by luteolin treatment. Taken together, our results indicate that luteolin is one of bioactive components for improving insulin resistance by increasing oxidative capacity, modulating anti-oxidant metabolism and suppressing inflammatory signaling cascades in diet-induced obese mice. These results provide possible therapeutic targets for prevention and treatment of diet-induced obesity and its complications.Keywords: anti-oxidant metabolism, diabetes, luteolin, oxidative capacity
Procedia PDF Downloads 3372150 Whey Protein: A Noval Protective Agent against Oto-Toxicity Induced by Cis-Platin in Male Rat
Authors: Eitedal Daoud, Reda M.Daoud, Khaled Abdel-Wahhab, Maha M.Saber, Lobna Saber
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Background: Cis-platin is a widely used chemotherapeutic drug to treat many malignant disorders including head and neck malignancies. Oto-nephrotxicity is an important and dose - limiting side effect of cis - platin therapy. Nowadays, more attention had been paid to oto-toxicity caused with cis-platin. Aim of the Work: This study was designed to investigate the potential protective effect of Whey protein (WP) against cis-platin induced ototoxicity compared to the effect of N-acetylcysteine (NAC) in rats. Methodology: Male albino rats were randomly divided into 6 groups: untreated rats (control), rats orally treated with whey protein (1g/kg b.w/day) for seven executive days, rats treated orally with N-acetylcysteine (500 mg/kgb.w /day) for seven executive days, rates intoxicated intraperitoneal (ip) with cis- platin (10 mg/kgb.w. once), rats treated with whey protein (1g/kgb.w./day) for seven executive days) followed by one injection (ip) of cis-platin(10 mg/kg b.w.) one hour after the last oral administration of whey protein, rats treated with N- acetylcysteine (for seven executive days followed by one injection (ip) of cis-platin (10 mg/kgb.w) one hour after the last oral administration of N-acetylcysteine. The organ of Corti, the stria vascularis and spiral ganglia were visualized by light microscopy at different magnifications. Results: Cis-platin intoxicated animals showed a significant decrease in serum level of total antioxidant capacity (TAC),with inhibition in the activity of serum glutathione-s transferase(GST) and paraoxonnase-1 (PON-1) in comparison with control. Group treated with either NAC or WP with cis-platin showed significant elevation in the activity of both GST & PON-1 with increased serum level of TAC when compared with cis-platin intoxicated rats. Animals treated with NAC or WP with cis-platin compared to those treated with cis-platin alone showed marked degree of improvement towards control rats as there was significant drop in the serum level of cortecosterone, nitric oxide (NO), and melandialdehyde (MDA).Histopathologic, in NAC pretreated group there was no changes in stria vascularis or spiral ganglia. In group pretreated with WP, there was no histopathologic alteration detected in the organ of Corti and Reissers membrane but oedema and haemorrhage were founded in the stria vascularis in small focal manner. Conclusion: Our finding showed that Whey protein is a natural dietary supplement product proved its ability of protection of anti-oxidant system and the cochlea against cis-platin induced ototoxicity.Keywords: anti-oxidant, cis-platin, N-acetylcysteine, ototoxicity, whey protein
Procedia PDF Downloads 5232149 Applications of High Intensity Ultrasound to Modify Millet Protein Concentrate Functionality
Authors: B. Nazari, M. A. Mohammadifar, S. Shojaee-Aliabadi, L. Mirmoghtadaie
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Millets as a new source of plant protein were not used in food applications due to its poor functional properties. In this study, the effect of high intensity ultrasound (frequency: 20 kHz, with contentious flow) (US) in 100% amplitude for varying times (5, 12.5, and 20 min) on solubility, emulsifying activity index (EAI), emulsion stability (ES), foaming capacity (FC), and foaming stability (FS) of millet protein concentrate (MPC) were evaluated. In addition, the structural properties of best treatments such as molecular weight and surface charge were compared with the control sample to prove the US effect. The US treatments significantly (P<0.05) increased the solubility of the native MPC (65.8±0.6%) at all sonicated times with the maximum solubility that is recorded at 12.5 min treatment (96.9±0.82 %). The FC of MPC was also significantly affected by the US treatment. Increase in sonicated time up to 12.5 min significantly increased the FC of native MPC (271.03±4.51 ml), but higher increase reduced it significantly. Minimal improvements were observed in the FS of all sonicated MPC compared to the native MPC. Sonicated time for 12.5 min affected the EAI and ES of the native MPC more markedly than 5 and 20 min that may be attributed to higher increase in proteins tendency to adsorption at the oil and water interfaces after the US treatment at this time. SDS-PAGE analysis showed changes in the molecular weight of MPC that attributed to shearing forces created by cavitation phenomenon. Also, this phenomenon caused an increase in the exposure of more amino acids with negative charge in the surface of US treated MPC, that was demonstrated by Zetasizer data. High intensity ultrasound, as a green technology, can significantly increase the functional properties of MPC and can make this usable for food applications.Keywords: functional properties, high intensity ultrasound, millet protein concentrate, structural properties
Procedia PDF Downloads 2412148 Co-Administration Effects of Conjugated Linoleic Acid and L-Carnitine on Weight Gain and Biochemical Profile in Diet Induced Obese Rats
Authors: Maryam Nazari, Majid Karandish, Alihossein Saberi
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Obesity as a global health challenge motivates pharmaceutical industries to produce anti-obesity drugs. However, effectiveness of these agents is remained unclear. Because of popularity of dietary supplements, the aim of this study was tp investigate the effects of Conjugated Linoleic Acid (CLA) and L-carnitine (LC) on serum glucose, triglyceride, cholesterol and weight changes in diet induced obese rats. 48 male Wistar rats were randomly divided into two groups: Normal fat diet (n=8), and High fat diet (HFD) (n=32). After eight weeks, the second group which was maintained on HFD until the end of study, was subdivided into four categories: a) 500 mg Corn Oil (as control group), b) 500 mg CLA, c) 200 mg LC, d) 500 mg CLA+ 200 mg LC.All doses are planned per kg body weights, which were administered by oral gavage for four weeks. Body weights were measured and recorded weekly by means of a digital scale. At the end of the study, blood samples were collected for biochemical markers measurement. SPSS Version 16 was used for statistical analysis. At the end of 8th week, a significant difference in weight was observed between HFD and NFD group. After 12 weeks, LC significantly reduced weight gain by 4.2%. Trend of weight gain in CLA and CLA+LC groups was insignificantly decelerated. CLA+LC reduced triglyceride level significantly, but just CLA had significant influence on total cholesterol and insignificant decreasing effect on FBS. Our results showed that an obesogenic diet in a relative short time led to obesity and dyslipidemia which can be modified by LC and CLA to some extent.Keywords: conjugated linoleic acid, high fat diet, L-Carnitine, obesity
Procedia PDF Downloads 1572147 Screening the Growth Inhibition Mechanism of Sulfate-Reducing Bacteria by Chitosan/Lignosulfonate Nanocomposite in Seawater Media
Authors: K. Rasool
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Sulfate-reducing bacteria (SRBs) induced biofilm formation is a global industrial concern due to its role in the development of microbial-induced corrosion (MIC). Herein, we have developed a biodegradable chitosan/lignosulfonate nanocomposite (CS@LS) as an efficient green biocide for the inhibition of SRBs biofilms. We investigated in detail the inhibition mechanism of SRBs by CS@LS in seawater media. Stable CS@LS-1:1 with 150–200 nm average size and zeta potential of + 34.25 mV was synthesized. The biocidal performance of CS@LS was evaluated by sulfate reduction profiles coupled with analysis of extracted extracellular polymeric substances (EPS) and lactate dehydrogenase (LDH) release assays. As the nanocomposite concentration was increased from 50 to 500 µg/mL, the specific sulfate reduction rate (SSRR) decreased from 0.278 to 0.036 g-sulfate/g-VSS*day showing a relative sulfate reduction inhibition of 86.64% as compared to that of control. Similarly, the specific organic uptake rate (SOUR) decreased from 0.082 to 0.039 0.036 g-TOC/g-VSS*day giving a relative co-substrate oxidation inhibition of 52.19% as compared to that of control. The SRBs spiked with 500 µg/mL CS@LS showed a reduction in cell viability to 1.5 × 106 MPN/mL. To assess the biosafety of the nanocomposite on the marine biota, the 72-hours acute toxicity assays using the zebrafish embryo model revealed that the LC50 for the CS@LS was 103.3 µg/mL. Thus, CS@LS can be classified as environmentally friendly. The nanocomposite showed long-term stability and excellent antibacterial properties against SRBs growth and is thus potentially useful for combating the problems of biofilm growth in harsh marine and aquatic environments.Keywords: green biocides, chitosan/lignosulfonate nanocomposite, SRBs, toxicity
Procedia PDF Downloads 1202146 Model Evaluation of Action Potential Block in Whole-Animal Nerves Induced by Ultrashort, High-Intensity Electric Pulses
Authors: Jiahui Song
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There have been decades of research into the action potential block in nerves. To our best knowledge electrical voltages can reversibly block the conduction of action potentials across whole animal nerves. Blocking biological electrical signaling pathways can have a variety of applications in muscular and sensory incapacitation and clinical research, including urethral pressure reduction and relieving chronic pain relief from a peripheral nerve injury. The cessation ability has been used in muscle activation and fatigue reduction. Ultrashort, high-intensity electric pulses modulate the membrane conductivity to block nerve conduction through the electroporation process. Nanopore formation on the membrane surface would increase the local membrane conductivity and effectively "short-out" the trans-membrane potential of a nerve that inhibits action potential propagation. This block would be similar in concept to stopping the propagation of an air-pressure wave down a "leaky" pipe. This research focuses on a distributed electrical model with an additional time-dependent membrane conductance to calculate the poration induced by the ultrashort, high-intensity electric pulses. The changes in membrane conductivity are used to predict changes in action potential transmission. A "strength-duration (SD)" curve is generated for action potential blockage and would be used as a design guide for benchmarking safety thresholds or setting the pulse voltage and/or durations necessary for neuro-muscular incapacitation.Keywords: action potential, ultrashort, high-intensity, nerve, strength-duration
Procedia PDF Downloads 182145 Interferon-Induced Transmembrane Protein-3 rs12252-CC Associated with the Progress of Hepatocellular Carcinoma by Up-Regulating the Expression of Interferon-Induced Transmembrane Protein 3
Authors: Yuli Hou, Jianping Sun, Mengdan Gao, Hui Liu, Ling Qin, Ang Li, Dongfu Li, Yonghong Zhang, Yan Zhao
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Background and Aims: Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. IFITM3 has been recognized as a key signal molecule regulating cell growth in some tumors. However, the function of IFITM3 rs12252-CC genotype in the hepatocellular carcinoma (HCC) remains unknown to author’s best knowledge. A cohort study was employed to clarify the relationship between IFITM3 rs12252-CC genotype and HCC progression, and cellular experiments were used to investigate the correlation of function of IFITM3 and the progress of HCC. Methods: 336 candidates were enrolled in study, including 156 with HBV related HCC and 180 with chronic Hepatitis B infections or liver cirrhosis. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3. The functions of IFITM3 were detected in PLC/PRF/5 cell with different treated:LV-IFITM3 transfected with lentivirus to knockdown the expression of IFITM3 and LV-NC transfected with empty lentivirus as negative control. The IFITM3 expression, proliferation and migration were detected by Quantitative reverse transcription polymerase chain reaction (qRT-PCR), QuantiGene Plex 2.0 assay, western blotting, immunohistochemistry, Cell Counting Kit(CCK)-8 and wound healing respectively. Six samples (three infected with empty lentiviral as control; three infected with LV-IFITM3 vector lentiviral as experimental group ) of PLC/PRF/5 were sequenced at BGI (Beijing Genomics Institute, Shenzhen,China) using RNA-seq technology to identify the IFITM3-related signaling pathways and chose PI3K/AKT pathway as related signaling to verify. Results: The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC compared with the patients with chronic HBV infection or liver cirrhosis. The distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Patients with CC genotype found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes. The expression of IFITM3 was higher in HCC tissues than adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic than high/medium differentiation and without metastatic. Higher RNA level of IFITM3 was found in CC genotype than TT genotype. In PLC/PRF/5 cell with knockdown, the ability of cell proliferation and migration was inhibited. Analysis RNA sequencing and verification of RT-PCR found out the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) pathway was associated with knockdown IFITM3.With the inhibition of IFITM3, the expression of PI3K/AKT/mTOR signaling pathway was blocked and the expression of vimentin was decreased. Conclusions: IFITM3 rs12252-CC with the higher expression plays a vital role in the progress of HCC by regulating HCC cell proliferation and migration. These effects are associated with PI3K/AKT/mTOR signaling pathway.Keywords: IFITM3, interferon-induced transmembrane protein 3, HCC, hepatocellular carcinoma, PI3K/ AKT/mTOR, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin
Procedia PDF Downloads 1242144 Preparation of Magnetothermally Responsive Polymer Multilayer Films for Controlled Release Applications from Surfaces
Authors: Eda Cagli, Irem Erel Goktepe
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Externally triggered and effective release of therapeutics from polymer nanoplatforms is one of the key issues in cancer treatment. In this study, we aim to prepare polymer multilayer films which are stable at physiological conditions (little or no drug release) but release drug molecules at acidic pH and via application of AC magnetic field. First, novel stimuli responsive diblock copolymers composed of pH- and temperature-responsive blocks were synthesized. Then, block copolymer micelles with pH-responsive core and temperature responsive coronae will be obtained via pH-induced self-assembly of these block copolymers in aqueous environment. A model anticancer drug, e.g. Doxorubicin will be loaded in the micellar cores. Second, superparamagnetic nanoparticles will be synthesized. Magnetic nanoparticles and drug loaded block copolymer micelles will be used as building blocks to construct the multilayers. To mimic the acidic nature of the tumor tissues, Doxorubicin release from the micellar cores will be induced at acidic conditions. Moreover, Doxorubicin release from the multilayers will be facilitated via magnetothermal trigger. Application of AC magnetic field will induce the heating of magnetic nanoparticles resulting in an increase in the temperature of the polymer platform. This increase in temperature is expected to trigger conformational changes on the temperature-responsive micelle coronae and facilitate the release of Doxorubicin from the surface. Such polymer platform may find use in biomedical applications.Keywords: layer-by-layer films, magnetothermal trigger, smart polymers, stimuli responsive
Procedia PDF Downloads 3642143 Study on the Effect Cabbage (Brassica oleracea) and Ginger (Zingiber officinale) Extracts on Rat Liver Injuries Induced by Carbon tetrachloride (CCl4)
Authors: Asmaa F. Hamouda, Randa M Shrourou
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Cabbage (Brassica oleracea) and Ginger (Zingiber officinale) constitute apportion of regular human diet. The effect of Cabbage(CE) and Ginger extracts(GE) separately on liver nitric oxide (NO), malondialdehyde (MDA), as well as serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, total cholesterol(TC), triglyceride(T.G), high density lipoprotein(HDL cholesterol), low density lipoprotein (LDL cholesterol), thyroid-stimulating hormone (TSH), Triiodothyronine (T3), Thyroxine (T4) in rats treated and untreated with carbon tetrachloride (CCl4) was studied. The levels of NO, MDA, as well as serum AST, ALT, total bilirubin, TC, T.G, LDLand TSH showed an elevation and decline in HDL, T3, and T4 in rats treated with CCl4 as compared to control. Treatment of rats with GE pre, during, and post CCl4 administration improved NO, MDA, as well as serum AST, ALT, total bilirubin, TC, T.G, HDL, LDL, TSH, T3, T4 as compared to CCl4, indicates that GE improve thyroid function and reduced oxidative stress as well as injuries induced by CCl4. Treatment of rats with CE pre, during, and post CCl4 administration did not improved in the thyroid hormones and lipid profile levels as compared to CCl4. These findings suggest that ginger treatment exerts a protective effect on metabolic disorders by decreasing oxidative stress.Keywords: liver injuries, carbon tetrachloride (CCl4), cabbage (Brassica oleracea), ginger (Zingiber officinale), thyroid function
Procedia PDF Downloads 2652142 Effect of Sodium Arsenite Exposure on Pharmacodynamic of Meloxicam in Male Wistar Rats
Authors: Prashantkumar Waghe, N. Prakash, N. D. Prasada, L. V. Lokesh, M. Vijay Kumar, Vinay Tikare
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Arsenic is a naturally occurring metalloid with potent toxic effects. It is ubiquitous in the environment and released from both natural and anthropogenic sources. It has the potential to cause various health hazards in exposed populations. Arsenic exposure through drinking water is considered as one of the most serious global environmental threats including Southeast Asia. The aim of present study was to evaluate the modulatory role of subacute exposure to sodium (meta) arsenite on the antinociceptive, anti-inflammatory and antipyretic responses mediated by meloxicam in rats. Rats were exposed to arsenic as sodium arsenite through drinking water for 28 days. A single dose of meloxicam (2 mg/kg b. wt.) was administered by oral gavage on the 29th day. The exact time of meloxicam administration depended on the type of test. Rats were divided randomly into 5 groups (n=6). Group I served as normal control and received arsenic free drinking water, while rats in group II were maintained similar to Group I but received meloxicam on 29th day. Groups III, IV and V were pre-exposed to arsenic through drinking water at 0.5, 5.0 and 50 ppm, respectively, for 28 days and was administered meloxicam next day and; pain and inflammation carried out by using formalin-induced nociception and carrageenan-induced inflammatory model(s), respectively by using standard protocol. For assessment of antipyretic effects, one more additional group (Group VI) was taken and given LPS @ 1.8 mg/kg b. wt. for induction of pyrexia (LPS control). Higher dose of arsenic inhibited the meloxicam mediated antinociceptive, anti-inflammatory and antipyretic responses. Further, meloxicam inhibited the arsenic induced level of tumor necrosis factor-α, inetrleukin-1β, interleukin -6 and COX2 mediated prostaglandin E2 in hind paw muscle. These results suggest a functional antagonism of meloxicam by arsenic. This may relate to arsenic mediated local release of tumor necrosis factor-α, inetrleukin-1β, interleukin -6 releases COX2 mediated prostaglandin E2. Based on the experimental study, it is concluded that sub-acute exposure to arsenic through drinking water aggravate pyrexia, inflammation and pain at environment relevant concentration and decrease the therapeutic efficacy of meloxicam at higher level of arsenite exposure. Thus, the observation made has clinical relevance in situations where animals are exposed to arsenite epidemic geographical locations.Keywords: arsenic, analgesic activity, meloxicam, Wistar rats
Procedia PDF Downloads 1852141 Energy Metabolites Show Cross-Protective Plastic Responses for Stress Resistance in a Circumtropical Drosophila Species
Authors: Ankita Pathak, Ashok Munjal, Ravi Parkash
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Plastic responses to multiple environmental stressors in wet or dry seasonal populations of tropical Drosophila species have received less attention. We tested plastic effects of heat hardening, acclimation to drought or starvation; and changes in trehalose, proline and body lipids in D. ananassae flies reared under wet or dry season specific conditions. Wet season flies revealed significant increase in heat knockdown, starvation resistance and body lipids after heat hardening. However, accumulation of proline was observed only after desiccation acclimation of dry season flies while wet season flies elicited no proline but trehalose only. Therefore, drought-induced proline can be a marker metabolite for dry season flies. Further, partial utilization of proline and trehalose under heat hardening reflects their possible thermoprotective effects. Heat hardening elicited cross-protection to starvation stress. Stressor-specific accumulation or utilization, as well as rates of metabolic change for each energy metabolite, were significantly higher in wet season flies than dry season flies. Energy metabolite changes due to inter-related stressors (heat vs. desiccation or starvation) resulted in possible maintenance of energetic homeostasis in wet or dry season flies. Thus, low or high humidity induced plastic changes in energy metabolites can provide cross-protection to seasonally varying climatic stressors.Keywords: wet-dry seasons, plastic changes, stress related traits, energy metabolites, cross protection
Procedia PDF Downloads 1702140 Hepatoprotective Activity of Sharbat Deenar, against Carbon Tetrachloride-Induced Hepatotoxicity in Rats
Authors: Nazmul Huda, Ashik Mosaddik, Abdul Awal, Shafiqur Rahman, Rukhsana Shaheen, Mustofa Nabi
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Polyherbal formulation Sharbat Deenar is a very popular unani medicine in Bangladesh. It is usually used for different kinds of liver disorders. In absence of reliable and inadequate hepatoprotective agents in conventional medicine, the herbal preparations are preferred for liver diseases. The present study was designed to evaluate the hepatoprotective activity of Sharbat Deenar on carbon tetrachloride (CCl4) induced hepatotoxicity in male Long-Evans albino rats. Group I served as normal control and received neither formulation nor carbon tetrachloride. Group II received only CCl4 1mL/kg body weight of rat intraperitoneally for consecutive 14 days. Group III received CCl4 1mL/kg body weight of rat intraperitoneally and Silymarin, in dose 50mg/kg body weight of rat orally. Group IV received CCl4 1mL/kg body weight of rat intraperitoneally and Sharbat Deenar 1mL/kg body weight of rat for the same 14 consecutive days. At the end of the study, hepatoprotective activity was evaluated by the levels of total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Histopathological study of rat liver was also carried out. The results showed that polyherbal formulation Sharbat Deenar exhibited a significant hepatoprotective effect. Such an outcome seems to be the synergistic effect of all ingredients of tested herbal formulation. Although this study suggests that Sharbat Deenar may be used to cure or minimize various liver diseases, it needs further study to attain the clarity of mechanism and safety.Keywords: polyherbal formulation, sharbat deenar, carbon tetrachloride, silymarin, hepatoprotective
Procedia PDF Downloads 5502139 Anti-Arthritic Effect of a Herbal Diet Formula Comprising Fruits of Rosa Multiflora and Flowers of Lonicera Japonica
Authors: Brian Chi Yan Cheng, Hui Guo, Tao Su, Xiu‐qiong Fu, Ting Li, Zhi‐ling Yu
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Rheumatoid arthritis (RA) affects around 1% of the globe population. Yet, there is still no cure for RA. Toll-like receptor 4 (TLR4) signalling has been found to be involved in the pathogenesis of RA, making it a potential therapeutic target for RA treatment. A herbal formula (RL) consisting of fruits of Rosa Multiflora (Eijitsu rose) and flowers of Lonicera Japonica (Japanese honeysuckle) has been used in treating various inflammatory disorders for more than a thousand year. Both of them are rich sources of nutrients and bioactive phytochemicals, which can be used in producing different food products and supplements. In this study, we would evaluate the anti-arthritic effect of RL on collagen-induced arthritis (CIA) in rats and investigate the involvement of TLR4 signaling in the mode of action of RL. Anti-arthritic efficacy was evaluated using CIA rats induced by bovine type II collagen. The treatment groups were treated with RL (82.5, 165, and 330 mg/kg bw per day, p.o.) or positive control indomethacin (0.25 mg/kg bw per day, p.o.) for 35 days. Clinical signs (hind paw volume and arthritis severity scores), changes in serum inflammatory mediators, pro-/antioxidant status, histological and radiographic changes of joints were investigated. Spleens and peritoneal macrophages were used to determine the effects of RL on innate and adaptive immune responses in CIA rats. The involvement of TLR4 signalling pathways in the anti-arthritic effect of RL was examined in cartilage tissue of CIA rats, murine RAW264.7 macrophages and human THP-1 monocytic cells. The severity of arthritis in the CIA rats was significantly attenuated by RL. Antioxidant status, histological score and radiographic score were efficiently improved by RL. RL could also dose-dependently inhibit pro-inflammatory cytokines in serum of CIA rats. RL significantly inhibited the production of various pro-inflammatory mediators, the expression and/or activity of the components of TLR4 signalling pathways in animal tissue and cell lines. RL possesses anti-arthritic effect on collagen-induced arthritis in rats. The therapeutic effect of RL may be related to its inhibition on pro-inflammatory cytokines in serum. The inhibition of the TAK1/NF-κB and TAK1/MAPK pathways participate in the anti-arthritic effects of RL. This provides a pharmacological justification for the dietary use of RL in the control of various arthritic diseases. Further investigation should be done to develop RL into a anti-arthritic food products and/or supplements.Keywords: japanese honeysuckle, rheumatoid arthritis, rosa multiflora, rosehip
Procedia PDF Downloads 4322138 Effects of Egg Yolk Peptide on the Retardation of Bone Growth Induced by Low-Calcium Diets
Authors: Kang-Hyun Leem, Myung-Gyou Kim, Hye Kyung Kim
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Eggs have long been an important contributor to the nutritional quality of the human, and recognized as a very valuable source of proteins for human nutrition. Egg yolk is composed of various important chemical substances for human health. Growth means not only the increase of body weight but also the elongation of height and the enlargement of each organ's anatomical and morphological size. A calcium shortage causes the growth retardation on the body growth. In this study, we examined the therapeutic effects of egg yolk peptide (EYP) on the retardation of the longitudinal bone growth induced by low-calcium diet (0.05%) in adolescent rats. Low calcium diets were administrated for 15 days. During the last five days, calcium and/or vitamin D and/or EYP were administrated. The body weights, longitudinal bone growth rates, the heights of growth plates, and bone morphogenetic protein (BMP)-2 and insulin-like growth factor (IGF)-1 expressions were measured using histochemical analysis. Low calcium diets caused the significant reduction in body weight gains and the longitudinal bone growth. The heights of growth plates and the expressions of BMP-2 and IGF-1 showed the impairment of body growth as well. Calcium and/or vitamin D administration could not significantly increase the longitudinal bone growth. However, calcium, vitamin D, and EYP administration significantly increased the bone growth, the growth plate height, and BMP-2 and IGF-1 expressions. These results suggest that EYP enhances the longitudinal bone growth in the calcium and/or vitamin D deficiency and it could be a promising agent for the treatment of children suffering from malnutrition.Keywords: egg yolk peptide, low-calcium diet, longitudinal bone growth, morphogenetic protein-2, insulin-like growth factor-1, vitamin D
Procedia PDF Downloads 4492137 Analysis of the Homogeneous Turbulence Structure in Uniformly Sheared Bubbly Flow Using First and Second Order Turbulence Closures
Authors: Hela Ayeb Mrabtini, Ghazi Bellakhal, Jamel Chahed
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The presence of the dispersed phase in gas-liquid bubbly flow considerably alters the liquid turbulence. The bubbles induce turbulent fluctuations that enhance the global liquid turbulence level and alter the mechanisms of turbulence. RANS modeling of uniformly sheared flows on an isolated sphere centered in a control volume is performed using first and second order turbulence closures. The sphere is placed in the production-dissipation equilibrium zone where the liquid velocity is set equal to the relative velocity of the bubbles. The void fraction is determined by the ratio between the sphere volume and the control volume. The analysis of the turbulence statistics on the control volume provides numerical results that are interpreted with regard to the effect of the bubbles wakes on the turbulence structure in uniformly sheared bubbly flow. We assumed for this purpose that at low void fraction where there is no hydrodynamic interaction between the bubbles, the single-phase flow simulation on an isolated sphere is representative on statistical average of a sphere network. The numerical simulations were firstly validated against the experimental data of bubbly homogeneous turbulence with constant shear and then extended to produce numerical results for a wide range of shear rates from 0 to 10 s^-1. These results are compared with our turbulence closure proposed for gas-liquid bubbly flows. In this closure, the turbulent stress tensor in the liquid is split into a turbulent dissipative part produced by the gradient of the mean velocity which also contains the turbulence generated in the bubble wakes and a pseudo-turbulent non-dissipative part induced by the bubbles displacements. Each part is determined by a specific transport equation. The simulations of uniformly sheared flows on an isolated sphere reproduce the mechanisms related to the turbulent part, and the numerical results are in perfect accordance with the modeling of the transport equation of the turbulent part. The reduction of second order turbulence closure provides a description of the modification of turbulence structure by the bubbles presence using a dimensionless number expressed in terms of two-time scales characterizing the turbulence induced by the shear and that induced by bubbles displacements. The numerical simulations carried out in the framework of a comprehensive analysis reproduce particularly the attenuation of the turbulent friction showed in the experimental results of bubbly homogeneous turbulence subjected to a constant shear.Keywords: gas-liquid bubbly flows, homogeneous turbulence, turbulence closure, uniform shear
Procedia PDF Downloads 4602136 Rapid Mitochondrial Reactive Oxygen Species Production Precedes NF-κB Activation and Pro-inflammatory Responses in Macrophages
Authors: Parinaz Tavakoli Zaniani, Dimitrios Balomenos
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Mitochondrial reactive oxygen species (mROS) play a crucial role in macrophage pro-inflammatory activation, although a detailed understanding of the mechanism and kinetics by which mROS drive signaling molecules is still lacking. In general, it is thought that NF-κB activation drives mROS and general ROS production. Here, We performed a detailed kinetic analysis of mROS production during macrophage activation. We found early mROS generation after LPS (lipopolysaccharide) stimulation. Remarkably as early as 5 minutes, mROS signaling promoted initial NF-κB, MAPK activation and pro-inflammatory cytokine production, as established through inhibition or quenching of mROS. On the contrary, NF-κB inhibition had no effect on mROS production. Our findings point to a mechanism by which mROS increase TRAF-6 ubiquitination and, thus NF-κB activity. mROS inhibition reduced LPS-induced lethality in an in vivo septic shock model by controlling pro-inflammatory cytokine production. Overall, our research provides novel insights into the role of mROS as a primary messenger in the pathway of macrophage and as a regulator of inflammatory responses. We found that early mROS production promotes initial NF-κB, and MAPK activation by regulating TRAF-6 ubiquitination and that mROS inhibition can reduce LPS-induced inflammatory cytokines and lethality in a septic shock model. These findings might lead to novel immunotherapeutic strategies targeting early mROS production and control of extreme inflammation in the context of sepsis and other inflammatory diseases.Keywords: mitochondria, reactive oxygen species, nuclear factor κB, lipopolysaccharide, macrophages
Procedia PDF Downloads 752135 Antistress Effects of Hydrangeae Dulcis Folium on Net Handing Stress-Induced Anxiety-Like Behavior in Zebrafish: Possible Mechanism of Action of Adrenocorticotropin Hormone (ACTH) Receptor
Authors: Lee Seungheon, Kim Ba-Ro
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In this study, the anti-stress effects of the ethanolic extract of Hydrangeae Dulcis Folium (EHDF) were investigated. To determine the effects of EHDF on physical stress, changes in the whole-body cortisol level and behaviour were monitored in zebrafish. To induce physical stress, we used the net handling stress (NHS). Fish were treated with EHDF for 6 min before they were exposed to stress, and the fish were either evaluated via behavioural tests, including a novel tank test and an open field test or sacrificed to collect body fluid from the whole body. The results indicate that increased anxiety-like behaviours in the novel tank test and open field test under stress were recovered by treatment with EHDF at 5, 10 and 20 mg/L (P < 0.05). Moreover, compared with the normal group, which was not treated with NHS, the whole-body cortisol level was significantly increased by treatment with NHS in the control group. Compared with the control group, pre-treatment with EHDF at concentrations of 5, 10 and 20 mg/L for 6 min significantly prevented the increase in the whole-body cortisol level induced by NHS (P < 0.05). In addition, adrenocorticotropin hormone (ACTH) challenge studies showed that EHDF completely blocked the effects of ACTH (0.2 IU/g, IP) on cortisol secretion. These results suggest that EHDF may be a good anti-stress candidate and that its mechanism of action may be related to its positive effects on cortisol release.Keywords: net handling stress, zebrafish, hydrangeae dulcis folium, whole-body cortisol, novel tank test, open field test
Procedia PDF Downloads 2992134 Multifunctional β-Cyclodextrin-EDTA-Chitosan Polymer Adsorbent Synthesis for Simultaneous Removal of Heavy Metals and Organic Dyes from Wastewater
Authors: Monu Verma, Hyunook Kim
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Heavy metals and organic dyes are the major sources of water pollution. Herein, a trifunctional β−cyclodextrin−ethylenediaminetetraacetic acid−chitosan (β−CD−EDTA−CS) polymer was synthesized using an easy and simple chemical route by the reaction of activated β−CD with CS through EDTA as a cross-linker (amidation reaction) for the removal of inorganic and organic pollutants from aqueous solution under different parameters such as pH, time effect, initial concentration, reusability, etc. The synthesized adsorbent was characterized using powder X-ray diffraction, Fourier transform infrared spectroscopy, field scanning electron microscopy, energy dispersive spectroscopy, Brunauer-Emmett-Teller (BET), thermogravimetric analyzer techniques to investigate their structural, functional, morphological, elemental compositions, surface area, and thermal properties, respectively. Two types of heavy metals, i.e., mercury (Hg²⁺) and cadmium (Cd²⁺), and three organic dyes, i.e., methylene blue (MB), crystal violet (CV), and safranin O (SO), were chosen as inorganic and organic pollutants, respectively, to study the adsorption capacity of β-CD-EDTA-CS in aqueous solution. The β-CD-EDTA-CS shows a monolayer adsorption capacity of 346.30 ± 14.0 and 202.90 ± 13.90 mg g−¹ for Hg²⁺ and Cd²⁺, respectively, and a heterogeneous adsorption capacity of 107.20 ± 5.70, 77.40 ± 5.30 and 55.30 ± 3.60 mg g−¹ for MB, CV and SO, respectively. Kinetics results followed pseudo-second order (PSO) kinetics behavior for both metal ions and dyes, and higher rate constants values (0.00161–0.00368 g mg−¹ min−¹) for dyes confirmed the cavitation of organic dyes (physisorption). In addition, we have also demonstrated the performance of β-CD-EDTA-CS for the four heavy metals, Hg²⁺, Cd²⁺, Ni²⁺, and Cu²⁺, and three dyes MB, CV, and SO in secondary treated wastewater. The findings of this study indicate that β-CD-EDTA-CS is simple and easy to synthesize and can be used in wastewater treatment.Keywords: adsorption isotherms, adsorption mechanism, amino-β-cyclodextrin, heavy metal ions, organic dyes
Procedia PDF Downloads 1072133 DNA Hypomethylating Agents Induced Histone Acetylation Changes in Leukemia
Authors: Sridhar A. Malkaram, Tamer E. Fandy
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Purpose: 5-Azacytidine (5AC) and decitabine (DC) are DNA hypomethylating agents. We recently demonstrated that both drugs increase the enzymatic activity of the histone deacetylase enzyme SIRT6. Accordingly, we are comparing the changes H3K9 acetylation changes in the whole genome induced by both drugs using leukemia cells. Description of Methods & Materials: Mononuclear cells from the bone marrow of six de-identified naive acute myeloid leukemia (AML) patients were cultured with either 500 nM of DC or 5AC for 72 h followed by ChIP-Seq analysis using a ChIP-validated acetylated-H3K9 (H3K9ac) antibody. Chip-Seq libraries were prepared from treated and untreated cells using SMARTer ThruPLEX DNA- seq kit (Takara Bio, USA) according to the manufacturer’s instructions. Libraries were purified and size-selected with AMPure XP beads at 1:1 (v/v) ratio. All libraries were pooled prior to sequencing on an Illumina HiSeq 1500. The dual-indexed single-read Rapid Run was performed with 1x120 cycles at 5 pM final concentration of the library pool. Sequence reads with average Phred quality < 20, with length < 35bp, PCR duplicates, and those aligning to blacklisted regions of the genome were filtered out using Trim Galore v0.4.4 and cutadapt v1.18. Reads were aligned to the reference human genome (hg38) using Bowtie v2.3.4.1 in end-to-end alignment mode. H3K9ac enriched (peak) regions were identified using diffReps v1.55.4 software using input samples for background correction. The statistical significance of differential peak counts was assessed using a negative binomial test using all individuals as replicates. Data & Results: The data from the six patients showed significant (Padj<0.05) acetylation changes at 925 loci after 5AC treatment versus 182 loci after DC treatment. Both drugs induced H3K9 acetylation changes at different chromosomal regions, including promoters, coding exons, introns, and distal intergenic regions. Ten common genes showed H3K9 acetylation changes by both drugs. Approximately 84% of the genes showed an H3K9 acetylation decrease by 5AC versus 54% only by DC. Figures 1 and 2 show the heatmaps for the top 100 genes and the 99 genes showing H3K9 acetylation decrease after 5AC treatment and DC treatment, respectively. Conclusion: Despite the similarity in hypomethylating activity and chemical structure, the effect of both drugs on H3K9 acetylation change was significantly different. More changes in H3K9 acetylation were observed after 5 AC treatments compared to DC. The impact of these changes on gene expression and the clinical efficacy of these drugs requires further investigation.Keywords: DNA methylation, leukemia, decitabine, 5-Azacytidine, epigenetics
Procedia PDF Downloads 1492132 The Analgesic Effect of Electroacupuncture in a Murine Fibromyalgia Model
Authors: Bernice Jeanne Lottering, Yi-Wen Lin
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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception
Procedia PDF Downloads 1392131 Hepatoprotective Evaluation of Potent Antioxidant Fraction from Urtica dioica L.: In vitro and In vivo Studies
Authors: Bhuwan C. Joshi, Atish Prakash, Ajudhia N. Kalia
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Ethnopharmacological relevance: The plant Urtica dioica L. (Urticaceae) is used in various diseases including hepatic ailments. Traditionally, the leaves and roots of the plant are used in jaundice. Objective: The aim of the present work was to evaluate hepatoprotective potential of potent antioxidant from Urtica dioica L. against CCl4 induced hepatotoxicity in-vitro and in-vivo model. Materials and methods: Antioxidant activity of hydro alcoholic extract and its fractions petroleum ether fraction (PEF), ethyl acetate fraction (EAF), n-butanol fraction (NBF) and aqueous fraction (AF) were determined by DPPH radicals scavenging assay. Fractions were subjected to in-vitro cell line study. Further, the most potent fraction (EAF) was subjected to in-vivo study. The in-vivo hepatoprotective active fraction was chromatographed on silica column to isolate the bioactive constituent(s). Structure elucidation was done by using various spectrophotometric techniques like UV, IR, 1H NMR, 13C NMR and MS spectroscopy. Results and conclusion: The ethyl acetate fraction (EAF) of Urtica. dioica L. possessed the potent antioxidant activity viz. DPPH (IC50 78.99 ± 0.17 µg/ml). The in-vitro cell line study showed EAF prevented the cell damage. The EAF significantly attenuated the increased liver enzymes activities in serum and tissue. Column chromatography of most potent antioxidant fraction (EAF) leads to the isolation of 4-hydroxy-3-methoxy cinnamic acid which is responsible for its hepatoprotective potential. Hence, the present study suggests that EAF has significant antioxidant and hepatoprotective potential on CCl4 induced hepatotoxicity in-vitro and in-vivo.Keywords: Urtica dioica L., antioxidant, HepG2 cell line, hepatoprotective
Procedia PDF Downloads 4252130 The Effect of Nepodin-Enrich Plant on Dyslipidemia and Hyperglycemia in High-Fat Diet-Induced Obese C57BL/6J Mice
Authors: Mi Kyeong Yu, Seon Jeong Lee, So Young Kim, Bora Choi, Young Mi Lee, Su-Jung Cho, Je Tae Woo, Myung-Sook Choi
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A high-fat diet (HFD) induces excessive fat accumulation in white adipose tissue (WAT), which increases metabolic disorders such as obesity, dyslipidemia and type 2 diabetes. Many plants are known to have effects that improve metabolic disorders. Therefore, the aim of this present study is to investigate the effect of nepodin-enrich plant extract on dyslipidemia, hyperglycemia in high fat diet-induced C57BL/6J mice. Male C57BL/6J mice were randomly divided into two groups, and fed HFD (20% fat, w/w) or HFD supplemented with nepodin-enrich plant extract (NPE 0.005%, w/w) for 16 weeks. Body weight and food intake were measured every week. And we also analysed metabolic rates (respiratory quotient), blood glucose level, and plasma high-density lipoprotein (HDL)-cholesterol, free fatty acid, apolipoprotein (apo) A-1 and apo B levels. Food intakes and body weights were not different between NPE group and HFD group, while plasma apo B, free fatty acid levels, and blood glucose concentration were significantly decreased in NPE group than in HFD group. Furthermore, plasma apo A and HDL-cholesterol levels in NPE group were remarkably increased than in HFD group. Metabolic rates (respiratory quotient) were significantly increased in NPE group than in HFD group. These results indicate that NPE can alleviate dyslipidemia, hyperglycemia. Further studies are required to identify the effects of NPE on metabolic disorders.Keywords: dyslipidemia, hyperglycemia, metabolic disorders, nepodin enrich plant extract
Procedia PDF Downloads 3732129 Hydrogen Induced Fatigue Crack Growth in Pipeline Steel API 5L X65: A Combined Experimental and Modelling Approach
Authors: H. M. Ferreira, H. Cockings, D. F. Gordon
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Climate change is driving a transition in the energy sector, with low-carbon energy sources such as hydrogen (H2) emerging as an alternative to fossil fuels. However, the successful implementation of a hydrogen economy requires an expansion of hydrogen production, transportation and storage capacity. The costs associated with this transition are high but can be partly mitigated by adapting the current oil and natural gas networks, such as pipeline, an important component of the hydrogen infrastructure, to transport pure or blended hydrogen. Steel pipelines are designed to withstand fatigue, one of the most common causes of pipeline failure. However, it is well established that some materials, such as steel, can fail prematurely in service when exposed to hydrogen-rich environments. Therefore, it is imperative to evaluate how defects (e.g. inclusions, dents, and pre-existing cracks) will interact with hydrogen under cyclic loading and, ultimately, to what extent hydrogen induced failure will limit the service conditions of steel pipelines. This presentation will explore how the exposure of API 5L X65 to a hydrogen-rich environment and cyclic loads will influence its susceptibility to hydrogen induced failure. That evaluation will be performed by a combination of several techniques such as hydrogen permeation testing (ISO 17081:2014), fatigue crack growth (FCG) testing (ISO 12108:2018 and AFGROW modelling), combined with microstructural and fractographic analysis. The development of a FCG test setup coupled with an electrochemical cell will be discussed, along with the advantages and challenges of measuring crack growth rates in electrolytic hydrogen environments. A detailed assessment of several electrolytic charging conditions will also be presented, using hydrogen permeation testing as a method to correlate the different charging settings to equivalent hydrogen concentrations and effective diffusivity coefficients, not only on the base material but also on the heat affected zone and weld of the pipelines. The experimental work is being complemented with AFGROW, a useful FCG modelling software that has helped inform testing parameters and which will also be developed to ultimately help industry experts perform structural integrity analysis and remnant life characterisation of pipeline steels under representative conditions. The results from this research will allow to conclude if there is an acceleration of the crack growth rate of API 5L X65 under the influence of a hydrogen-rich environment, an important aspect that needs to be rectified instandards and codes of practice on pipeline integrity evaluation and maintenance.Keywords: AFGROW, electrolytic hydrogen charging, fatigue crack growth, hydrogen, pipeline, steel
Procedia PDF Downloads 1052128 Assessment of Climate Induced Hazards in Coastal Zone of Bangladesh: A Case Study of Koyra Upazilla under Khulna District and Shyamnagar Upazilla under Satkhira District
Authors: Kazi Ashief Mahmood
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Geographically Bangladesh is located in a natural hazard prone area. Compared to the rest of the areas, the coastal sub-districts are more vulnerable to climate variability and change. However, the hydro-geophysical reality of the sub-districts predominantly determines their contexts of vulnerability and its nature differs accordingly. Intriguingly enough, the poorest of the areas appear to be the most cornered among the different vulnerable sectors. Among of these deprived segments; however, the women, the persons with disability and the minorities are generally more vulnerable and they face a high risk of marginalized. The most threatening hydro-geophysical climate vulnerability have been created by prolonged dry season as observed at Koyra Upazilla in Khulna districts and Shyamnagar in Satkhira districts. The prolonged dry season creates severe surface salinity by which farmers cannot produce or use their to cultivate. The absence of land-based production and employment in the area has led to severe food insecurity. As a result, farmers tend to change their livelihood option and many of them are forced to migrate to the other areas of the country in search of livelihood. Besides salinity intrusion, water logging, drought and different climate change induced hazards are endangering safe drinking water sources and putting small-holders out of agriculture-based livelihoods in the Koyra and Shyamnagar Upazilla. A sizeable fraction of small-holders are still trying to hold on to their small scale shrimp production, despite being under pressure to sell off their cultivating lands to their influential shrimp merchants. While their desperate effort to take advantage of the increasing salinity is somewhat successful, their families still face a greater risk of health hazards owing to the lack of safe drinking water. Unless the issues of salinity in drinking water cannot be redressed, the state of the affected people will be in great jeopardy. Most of the inhabitants of oKyra and Shyamnagar Upazilla are living under the poverty line. Thus, poverty is a major factor that intensifies the vulnerability caused by hydro-geophysical climatic conditions. The government and different NGOs are trying to improve the present scenario by implementing different disaster risk reduction projects along with poverty reduction for community empowerment.Keywords: assessment, climate change, climate induced hazards, coastal zone
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