Search results for: swiss albino mice
Commenced in January 2007
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Edition: International
Paper Count: 728

Search results for: swiss albino mice

248 Traumatic Brain Injury Induced Lipid Profiling of Lipids in Mice Serum Using UHPLC-Q-TOF-MS

Authors: Seema Dhariwal, Kiran Maan, Ruchi Baghel, Apoorva Sharma, Poonam Rana

Abstract:

Introduction: Traumatic brain injury (TBI) is defined as the temporary or permanent alteration in brain function and pathology caused by an external mechanical force. It represents the leading cause of mortality and morbidity among children and youth individuals. Various models of TBI in rodents have been developed in the laboratory to mimic the scenario of injury. Blast overpressure injury is common among civilians and military personnel, followed by accidents or explosive devices. In addition to this, the lateral Controlled cortical impact (CCI) model mimics the blunt, penetrating injury. Method: In the present study, we have developed two different mild TBI models using blast and CCI injury. In the blast model, helium gas was used to create an overpressure of 130 kPa (±5) via a shock tube, and CCI injury was induced with an impact depth of 1.5mm to create diffusive and focal injury, respectively. C57BL/6J male mice (10-12 weeks) were divided into three groups: (1) control, (2) Blast treated, (3) CCI treated, and were exposed to different injury models. Serum was collected on Day1 and day7, followed by biphasic extraction using MTBE/Methanol/Water. Prepared samples were separated on Charged Surface Hybrid (CSH) C18 column and acquired on UHPLC-Q-TOF-MS using ESI probe with inhouse optimized parameters and method. MS peak list was generated using Markerview TM. Data were normalized, Pareto-scaled, and log-transformed, followed by multivariate and univariate analysis in metaboanalyst. Result and discussion: Untargeted profiling of lipids generated extensive data features, which were annotated through LIPID MAPS® based on their m/z and were further confirmed based on their fragment pattern by LipidBlast. There is the final annotation of 269 features in the positive and 182 features in the negative mode of ionization. PCA and PLS-DA score plots showed clear segregation of injury groups to controls. Among various lipids in mild blast and CCI, five lipids (Glycerophospholipids {PC 30:2, PE O-33:3, PG 28:3;O3 and PS 36:1 } and fatty acyl { FA 21:3;O2}) were significantly altered in both injury groups at Day 1 and Day 7, and also had VIP score >1. Pathway analysis by Biopan has also shown hampered synthesis of Glycerolipids and Glycerophospholipiods, which coincides with earlier reports. It could be a direct result of alteration in the Acetylcholine signaling pathway in response to TBI. Understanding the role of a specific class of lipid metabolism, regulation and transport could be beneficial to TBI research since it could provide new targets and determine the best therapeutic intervention. This study demonstrates the potential lipid biomarkers which can be used for injury severity diagnosis and identification irrespective of injury type (diffusive or focal).

Keywords: LipidBlast, lipidomic biomarker, LIPID MAPS®, TBI

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247 Pollution Challenges in the Akaki Catchment, Upper Awash Basin, Ethiopia: Potential Health Implications for Vegetables

Authors: Minbale Aschale, Bitew K. Dessie, Endaweke Assegide, Yosef Abebe, Tena Alamirew, Claire L. Walsh, Gete Zeleke

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The upper Awash Basin faces pollution challenges due to urbanization, population growth, and expanding industries. It receives various pollutants from its catchments. The study aimed to assess the impact of wastewater irrigation on vegetables and inform stakeholders about pollution challenges and consequences. Eighty-two composite samples of matured vegetables were randomly collected from twenty-one agricultural farm sites. These samples were analyzed for potentially toxic elements, including Cd, Pb, Cr, Hg, As, Ni, Sr, B, Co, Cu, Mn, Fe, Zn, and Se. The results indicated significant variations in concentrations across different sites, with localized contributions from various contaminants. Cr, Cd, and Pb concentrations in most vegetables exceeded recommended levels. Pollution levels varied with metals and vegetable types. Different vegetables contribute differently to health risks. The relative contributions of Ethiopian kale, cabbage, red beet, lettuce, Swiss chard, Gurage cabbage, tomato, zucchini, carrot, onion, watermelon, and potato to the aggregated risk were 12.69%, 12.25%, 11.83%, 11.20%, 10.21%, 9.91%, 8.49%, 5.66%, 3.96%, 3.35%, 3.10%, and 2.72%, respectively. Comparison with permissible standards revealed inadequate environmental management by relevant regulatory bodies and industries. Despite good laws and standards at the federal and regional levels, they are ineffectively implemented or enforced to prevent environmental pollution. Mitigation measures are urgently recommended to address the potential health implications of toxic substances.

Keywords: pollution, upper Awash Basin, health risk, Ethiopia

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246 Potential Impact of Sodium Salicylate Nanoemulsion on Expression of Nephrin in Nephrotoxic Experimental Rat

Authors: Nadia A. Mohamed, Zakaria El-Khayat, Wagdy K. B. Khalil, Mehrez E. El-Naggar

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Drug nephrotoxicity is still a problem for patients who have taken drugs for elongated periods or permanently. Ultrasound-assisted sol−gel method was used to prepare hollow structured poroussilica nanoemulsion loaded with sodium salicylate as a model drug. The work was extended to achieve the target of the current work via investigating the protective role of this nanoemulsion model as anti-inflammatory drug or ginger for its antioxidant effect against cisplatin-induced nephrotoxicity in male albino rats. The results clarify that the nanoemulsion model was synthesized using ultrasonic assisted with small size and well stabilization as proved by TEM and DLS analysis. Additionally, blood urea nitrogen (BUN), Serum creatinine (SC) and Urinary total protein (UTP) were increased, and the level of creatinine clearance (Crcl) was decreased. All those were met with disorders in oxidative stress and downregulation in the expression of the nephrin gene. Also, histopathological changes of the kidney tissue were observed. These changes back to normal by treatment with silica nanoparticles loaded sodium salicylate (Si-Sc-NPs), ginger or both. Conclusions oil/water nanoemulsion of (Si-Sc NPs) and ginger showed a protective and promising preventive strategy against nephrotoxicity due to their antioxidant and anti-inflammatory effects, and that offers a new approach in attenuating drug induced nephrotoxicity.

Keywords: sodium salicylate nanoencapsulation, nephrin mRNA, drug nephrotoxicity, cisplatin, experimental rats

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245 Zingiberofficinale Potential Effect on Nephrin mRNA Expression in Cisplatin Induced Nephrotoxicity

Authors: Nadia A. Mohamed, Mehrevan M. Abdel-Moniem

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Zingiber officinale (ginger) has been cultivated for medicinal purposes due to their various proprieties both in vitro and in vivo, so we designed to evaluate the ginger’s potential effect on nephrin m RNA expression in cisplatin-induced nephrotoxic rats. Method: Forty male albino rats were divided into group I was injected (IP) with one ml saline, group II(cisplatin) injected (IP) with a single dose of 12 mg/kg cisplatin, group III (ginger) received (PO) 310 mg/kg for 30 successive days, and group IV(cisplatin and ginger) rats received ginger extract (310 mg/kg) daily for 20 successive days (PO), and then on day 20 of ginger extract administration each rat was injected(IP) with a single dose of 12 mg/kg cisplatin. The blood was sampled to assess urea, creatinine (SC), while the levels of malondialdehyde (MDA), nitric oxide (NO) and paraoxonase (PON1) were measured in kidney tissue homogenate. Expression of urinary nephrin gene (nephrin mRNA) was detected using qRT-PCR. Results: Treatment with ginger significantly decreased the levels of kidney function parameters as well as MDA and NO elevated by cisplatin injection, while PON1 was significantly reduced in the cisplatin group. However, the protection of male rats with ginger significantly increased the levels of nephrin gene expression and PON1 compared with the cisplatin-treated group. Our results generated a proposal on the ameliorating effect of ginger on nephrin mRNA gene expression reduction in cisplatin-induced nephrotoxicity.

Keywords: nephrin mRNA, ginger, cisplatin, nephrotoxicity

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244 Histopathological and Biochemical Evaluation of Hydroxyurea-Induced Hepato-Pulmonary Toxicity and Lymphoid Necrosis in Rats

Authors: Samah Oda, Asmaa Khafaga, Mohammed Hashim, Asmaa Khamis

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Toxicity of hydroxyurea (HU), a treatment for certain tumors, polycythemia, and thrombocytosis, was evaluated in rats in one-month toxicity study. Sixty male albino rats were equally classified into four groups. Rats received daily oral gavage of HU in 0, 250, 500, and 750 mg/kg b.wt. Chemical and histopathological assessment of liver, lung, spleen, and bone marrow was performed at 10, 20, and 30 days of the experiment. No significant change was reported in alanine aminotransferase (ALT), aspartate aminotransferase (AST), globulin, and albumin/ globulin ratio during the experiment. Significant decreases in alkaline phosphatase (ALP) and total albumin were reported in rats received 500 and 750 mg/kg b.wt of HU. In addition, total cholesterol level increased significantly after 10 days; however, it significantly decreased after 20 and 30 days of the experiment. Moreover, hepatocytic vacuolation and necrosis with portal inflammatory infiltrates were reported along experimental periods. Pulmonary congestion, hemorrhage, interstitial mononuclear infiltration, peribronchitis, and bronchial epithelial necrosis were also reported. Severe lymphocytic necrosis in spleen and severe loss of hematopoietic cells and replacement with corresponding adipose tissue in bone marrow tissues was demonstrated. In conclusion, HU could be able to induce severe dose and time-dependent hepato-pulmonary toxicity and lymphoid depression in rats.

Keywords: hydroxyurea, hepato-pulmonary toxicity, lymphoid depression, histopathology

Procedia PDF Downloads 149
243 Histological and Ultrastructural Study on the Effect

Authors: Olfat Mohamed Hussien Yousef

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Tamoxifen (TM) is a synthetic non-steroidal antiestrogen. It is one of the most effective drugs for treatment of estrogen-dependent cancer by binding to estrogen receptors, suppressing of epithelial proliferation and as a chemotherapeutic agent. Recently, more attention has been paid to the protective effects of natural antioxidants against toxicities induced by anti-cancer drugs involving free radical-mediated oxidative stress and tissue injury. Vitamin C is a potent antioxidant that has the ability to scavenge factors causing free radical formation in animals receiving tamoxifen. The present study aims at pinpointing the TM-induced histopathological and ultrastructural changes in the kidneys and to assess the possible chemoprotective role of vitamin C against such TM-induced microscopic changes. Thirty adult male CD-1 mice, 25-30 g in weight and 3 months old, were divided into three groups. The first group served as control. The second group received the therapeutic dose of TM at daily oral dose of 40 mg/kg body weight for 28 days. The third group received the therapeutic dose of vitamin C at a daily dose of 500 mg/kg body weight simultaneously with the therapeutic dose of TM used in group two for 28 days. Animals were sacrificed and kidney samples were obtained and processed for histological and ultrastructural examination. Histological changes induced by TM included damage of the renal corpuscles including obliteration of the subcapsular space, congestion of the glomerular blood capillaries, segmental mesangial cell proliferation with matrix expansion, capsular adhesions with the glomerular tuft especially at the urinary pole of the corpuscles. Moreover, some proximal and distal tubules suffered various degrees of degeneration in some lining cells. Haemorrhage and inflammatory cell infiltration were also observed in the intertubular spaces. Ultrastructural observations revealed damage of the parietal epithelium of Bowman’s capsule, fusion and destruction of the foot processes of podocytes and great increase of mesangial cells and mesangial matrix. The cells of the proximal convoluted tubules displayed marked destruction of the microvilli constituting the brush borders and degeneration of the mitochondria; besides, abundant lysosomes, numerous vacuoles and pyknotic nuclei were observed. The distal convoluted tubules displayed marked distruction of both the basal infolding and the mitochondria in some areas. Histological and ultrastructural results revealed that treatment of male mice with TM simultaneously with vitamin C led to apparent repair of the injured renal tissue. This might suggest that vitamin C (an antioxidant agent) can minimize the toxic effects of TM (an antiestrogen).

Keywords: tamoxifen, vitamin c, mammalian kidney, histology, ultrastructure

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242 MicroRNA Expression Distinguishes Neutrophil Subtypes

Authors: R. I. You, C. L. Ho, M. S. Dai, H. M. Hung, S. F. Yen, C. S. Chen, T. Y. Chao

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Neutrophils are the most abundant innate immune cells to against invading microorganisms. Numerous data shown neutrophils have plasticity in response to physiological and pathological conditions. Tumor-associated neutrophils (TAN) exist in distinct types of tumor and play an important role in cancer biology. Different transcriptomic profiles of neutrophils in tumor and non-tumor samples have been identified. Several miRNAs have been recognized as regulators of gene expression in neutrophil, which may have key roles in neutrophil activation. However, the miRNAs expression patterns in TAN are not well known. To address this question, magnetic bead isolated neutrophils from tumor-bearing mice were used in this study. We analyzed production of reactive oxygen species (ROS) by luminol-dependent chemiluminescence assay. The expression of miRNAs targeting NADPH oxidase, ROS generation and autophagy was explored using quantitative real-time polymerase chain reaction. Our data suggest that tumor environment influence neutrophil develop to differential states of activation via miRNAs regulation.

Keywords: tumor-associated neutrophil, miRNAs, neutrophil, ROS

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241 Protective Role of CoQ10 or L-Carnitine on the Integrity of the Myocardium in Doxorubicin Induced Toxicity

Authors: Gehan A. Hegazy, Hesham N. Mustafa, Sally A. El Awdan, Marawan AbdelBaset

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Doxorubicin (DOX) is a chemotherapeutic agent used for the treatment of different cancers and its clinical usage is hindered by the oxidative injury-related cardiotoxicity. This work aims to declare if the harmful effects of DOX on the heart can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study was performed on seventy-two female Wistar albino rats divided into six groups, 12 animals each: Control group; DOX group (10 mg/kg); CoQ10 group (200 mg/kg); L-carnitine group (100 mg/kg); DOX + CoQ10 group; DOX + L-carnitine group. CoQ10 and L-carnitine treatment orally started five days before a single dose of 10 mg/kg DOX that injected intraperitoneally (IP) then the treatment continued for ten days. At the end of the study, serum biochemical parameters of cardiac damage, oxidative stress indices, and histopathological changes were investigated. CoQ10 or L-carnitine showed noticeable effects in improving cardiac functions evidenced reducing serum enzymes as serum interleukin-1 beta (IL-1), tumor necrosis factor alpha (TNF-), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1, Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced glutathione levels to normal levels. Both corrected the cardiac alterations histologically and ultrastructurally. With visible improvements in -SMA, vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine supplementation improves the functional and structural integrity of the myocardium.

Keywords: CoQ10, doxorubicin, L-Carnitine, cardiotoxicity

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240 The Effect of Calcium Phosphate Composite Scaffolds on the Osteogenic Differentiation of Rabbit Dental Pulp Stem Cells

Authors: Ling-Ling E, Lin Feng, Hong-Chen Liu, Dong-Sheng Wang, Zhanping Shi, Juncheng Wang, Wei Luo, Yan Lv

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The objective of this study was to compare the effects of the two calcium phosphate composite scaffolds on the attachment, proliferation and osteogenic differentiation of rabbit dental pulp stem cells (DPSCs). One nano-hydroxyapatite/collagen/poly (L-lactide) (nHAC/PLA), imitating the composition and the micro-structure characteristics of the natural bone, was made by Beijing Allgens Medical Science & Technology Co., Ltd. (China). The other beta-tricalcium phosphate (β-TCP), being fully interoperability globular pore structure, was provided by Shanghai Bio-lu Biomaterials Co, Ltd. (China). We compared the absorption water rate and the protein adsorption rate of two scaffolds and the characterization of DPSCs cultured on the culture plate and both scaffolds under osteogenic differentiation media (ODM) treatment. The constructs were then implanted subcutaneously into the back of severe combined immunodeficient (SCID) mice for 8 and 12 weeks to compare their bone formation capacity. The results showed that the ODM-treated DPSCs expressed osteocalcin (OCN), bone sialoprotein (BSP), type I collagen (COLI) and osteopontin (OPN) by immunofluorescence staining. Positive alkaline phosphatase (ALP) staining, calcium deposition and calcium nodules were also observed on the ODM-treated DPSCs. The nHAC/PLA had significantly higher absorption water rate and protein adsorption rate than ß-TCP. The initial attachment of DPSCs seeded onto nHAC/PLA was significantly higher than that onto ß-TCP; and the proliferation rate of the cells was significantly higher than that of ß-TCP on 1, 3 and 7 days of cell culture. DPSCs+ß-TCP had significantly higher ALP activity, calcium/phosphorus content and mineral formation than DPSCs+nHAC/PLA. When implanted into the back of SCID mice, nHAC/PLA alone had no new bone formation, newly formed mature bone and osteoid were only observed in β-TCP alone, DPSCs+nHAC/PLA and DPSCs+β-TCP, and this three groups displayed increased bone formation over the 12-week period. The percentage of total bone formation area had no difference between DPSCs+β-TCP and DPSCs+nHAC/PLA at each time point,but the percentage of mature bone formation area of DPSCs+β-TCP was significantly higher than that of DPSCs+nHAC/PLA. Our results demonstrated that the DPSCs on nHAC/PLA had a better proliferation and that the DPSCs on β-TCP had a more mineralization in vitro, much more newly formed mature bones in vivo were presented in DPSCs+β-TCP group. These findings have provided a further knowledge that scaffold architecture has a different influence on the attachment, proliferation and differentiation of cells. This study may provide insight into the clinical periodontal bone tissue repair with DPSCs+β-TCP construct.

Keywords: dental pulp stem cells, nano-hydroxyapatite/collagen/poly(L-lactide), beta-tricalcium phosphate, periodontal tissue engineering, bone regeneration

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239 Synthesis of Human Factors Theories and Industry 4.0

Authors: Andrew Couch, Nicholas Loyd, Nathan Tenhundfeld

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The rapid emergence of technology observably induces disruptive effects that carry implications for internal organizational dynamics as well as external market opportunities, strategic pressures, and threats. An examination of the historical tendencies of technology innovation shows that the body of managerial knowledge for addressing such disruption is underdeveloped. Fundamentally speaking, the impacts of innovation are unique and situationally oriented. Hence, the appropriate managerial response becomes a complex function that depends on the nature of the emerging technology, the posturing of internal organizational dynamics, the rate of technological growth, and much more. This research considers a particular case of mismanagement, the BP Texas City Refinery explosion of 2005, that carries notable discrepancies on the basis of human factors principles. Moreover, this research considers the modern technological climate (shaped by Industry 4.0 technologies) and seeks to arrive at an appropriate conceptual lens by which human factors principles and Industry 4.0 may be favorably integrated. In this manner, the careful examination of these phenomena helps to better support the sustainment of human factors principles despite the disruptive impacts that are imparted by technological innovation. In essence, human factors considerations are assessed through the application of principles that stem from usability engineering, the Swiss Cheese Model of accident causation, human-automation interaction, signal detection theory, alarm design, and other factors. Notably, this stream of research supports a broader framework in seeking to guide organizations amid the uncertainties of Industry 4.0 to capture higher levels of adoption, implementation, and transparency.

Keywords: Industry 4.0, human factors engineering, management, case study

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238 Saponins from the Fruits of Solanum anguivi Reverse Hyperglycemia, Hyperlipidemia and Increase Antioxidant Status in Stretozotocin Induced Diabetic Rats

Authors: Isaac Gbadura Adanlawo, Olusola Olalekan Elekofehinti

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This work investigated the antihyperglycemic, antioxidant and antihyperlipidemic effects of saponins from the fruit of Solanum anguivi, a plant generally used in folk medicine to treat diabetes and hypertension and to compare its effect with metformin in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in albino rats by administration of STZ (65 mg/kg) intraperitoneally. Saponin (40 and 100 mg/kg) was administered by oral gavage once daily for 21 days. Metformin (200 mg/kg b.w.) was administered as the positive control. The effect of saponin on blood glucose, serum lipids and enzymatic antioxidants defense systems, like superoxide dismutase (SOD), catalase (CAT), as well as MDA levels in serum, liver and pancreas were studied. Saponins from S. anguivi fruits reduced the blood glucose, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein (LDL) levels in STZ-diabetic rats. They also significantly abolished the increase in MDA level in serum, liver and pancreas of diabetic rats. The activities of SOD and CAT in serum, liver and pancreas were significantly increased as well as concentration of HDL in the serum. Metformin had the same effect as saponin but saponins seems to be more potent in reducing serum TC, TG, LDL, and MDA, and increasing SOD and CAT. Conclusions: These results suggest that saponins from S. anguivi fruits have anti-diabetic and antihypercholesterolemic, antihypertriglyceridemic antiperoxidative activities mediated through their antioxidant properties. Also, saponins appeared to have more hypolipidemic, antiperoxidative and antioxidant activity than metformin.

Keywords: saponin, diabetes, metformin, streptozotocin, Solanum anguivi

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237 Sphingosomes: Potential Anti-Cancer Vectors for the Delivery of Doxorubicin

Authors: Brajesh Tiwari, Yuvraj Dangi, Abhishek Jain, Ashok Jain

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The purpose of the investigation was to evaluate the potential of sphingosomes as nanoscale drug delivery units for site-specific delivery of anti-cancer agents. Doxorubicin Hydrochloride (DOX) was selected as a model anti-cancer agent. Sphingosomes were prepared and loaded with DOX and optimized for size and drug loading. The formulations were characterized by Malvern zeta-seizer and Transmission Electron Microscopy (TEM) studies. Sphingosomal formulations were further evaluated for in-vitro drug release study under various pH profiles. The in-vitro drug release study showed an initial rapid release of the drug followed by a slow controlled release. In vivo studies of optimized formulations and free drug were performed on albino rats for comparison of drug plasma concentration. The in- vivo study revealed that the prepared system enabled DOX to have had enhanced circulation time, longer half-life and lower elimination rate kinetics as compared to free drug. Further, it can be interpreted that the formulation would selectively enter highly porous mass of tumor cells and at the same time spare normal tissues. To summarize, the use of sphingosomes as carriers of anti-cancer drugs may prove to be a fascinating approach that would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.

Keywords: sphingosomes, anti-cancer, doxorubicin, formulation

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236 Hepatoprotective Effects of Parsley, Basil, and Chicory Aqueous Extracts against Dexamethasone-Induced in Experimental Rats

Authors: Hanan A. Soliman, Mohamed A. El-Desouky, Walaa G. Hozayen, Rasha R. Ahmed, Amal K . Khaliefa

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Aim: The objective of this study is to investigate the hypoglycemic, hypolipidemic, and hepatoprotective effects of the aqueous extract of parsley, basil, and chicory whole plant in normal and dexamethasone (Dex) rats. Materials and Methods: 50 female albino rats were used in this study and divided into 5 groups (for each 10). Group (1) fed basal diet and maintained as negative control group. Group (2) received Dex in a dose of (0.1 mg/kg b. wt.). Groups 3, 4, and 5 were treated with Dex along with three different plant extracts of parsley, basil, and chicory (2 g/kg b. wt.), (400 mg/kg b. wt.), and (100 mg/kg b. wt.), respectively. Results: All these groups were treated given three times per week for 8 consecutive weeks. Dex-induced alterations in the levels of serum glucose, triglyceride, cholesterol, low-density lipoprotein-cholesterol levels and cardiovascular indices and serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, liver thiobarbituric acid (TBARS) levels increased, while high-density lipoprotein-cholesterol, total protein, albumin, and liver glutathione (GSH) levels decreased. On the other hand, plant extracts succeeded to modulate these observed abnormalities resulting from Dex as indicated by the reduction of glucose, cholesterol, TBARS, and the pronounced improvement of the investigated biochemical and antioxidant parameters. Conclusions: It was concluded that probably, due to its antioxidant property, parsley, basil, and chicory extracts have hepatoprotective effects in Dex-induced in rats.

Keywords: antioxidants, dexamethasone, hyperglycemia, hyperlipidemia

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235 Trigonelline: A Promising Compound for The Treatment of Alzheimer's Disease

Authors: Mai M. Farid, Ximeng Yang, Tomoharu Kuboyama, Chihiro Tohda

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Trigonelline is a major alkaloid component derived from Trigonella foenum-graecum L. (fenugreek) and has been reported before as a potential neuroprotective agent, especially in Alzheimer’s disease (AD). However, the previous data were unclear and used model mice were not well established. In the present study, the effect of trigonelline on memory function was investigated in Alzheimer’s disease transgenic model mouse, 5XFAD which overexpresses the mutated APP and PS1 genes. Oral administration of trigonelline for 14 days significantly enhanced object recognition and object location memories. Plasma and cerebral cortex were isolated at 30 min, 1h, 3h, and 6 h after oral administration of trigonelline. LC-MS/MS analysis indicated that trigonelline was detected in both plasma and cortex from 30 min after, suggesting good penetration of trigonelline into the brain. In addition, trigonelline significantly ameliorated axonal and dendrite atrophy in Amyloid β-treated cortical neurons. These results suggest that trigonelline could be a promising therapeutic candidate for AD.

Keywords: alzheimer’s disease, cortical neurons, LC-MS/MS analysis, trigonelline

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234 Effects of Ethanolic Purslane Shoot and Seed Extracts on Doxorubicin-Induced Hepatotoxicity in Albino Rats

Authors: Osama M. Ahmed, Walaa G. Hozayen, Haidy Tamer Abo Sree

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Doxorubicin (DOX), an anthracycline antibiotic is a broad-spectrum antineoplastic agent, which is commonly used in the treatment of uterine, ovarian, breast and lung cancers, Hodgkin's disease and soft tissue sarcomas as well as in several other cancer types. The effect of doxorubicin (4 mg/kg b.w.week) without or with oral administration of ethanolic purslane (Portulaca oleracea) shoot (leaves and stems) extract (50 mg/kg b.w. day) or ethanolic purslane seeds extract (50 mg/kg b.w.day) co-treatments for 6 weeks was evaluated in adult male rats. Serum ALT, AST, ALP, GGT, total bilirubin, total protein, and albumin levels were assayed. Lipid peroxidation (indexed by MDA) and antioxidants like hepatic glutathine, glutathione transferase, peroxidase, SOD, and CAT were assessed. There was an increase in serum levels of ALT, AST, ALP, GGT and total bilirubin. In addition, hepatic glutathine, glutathione transferase, peroxidase, SOD, and CAT activities were decreased while lipid peroxidation in the liver was increased. Co-administration of ethanolic purslane and seed extracts successfully improved the adverse changes in the liver functions with an increase in antioxidants activities and reduction of lipid peroxidation. In conclusion, it can be supposed that dietary purslane extract supplementation may provide a cushion for a prolonged therapeutic option against DOX hepatopathy without harmful side effects. However, further clinical studies are required to assess the safety and efficacy of these extract in human beings.

Keywords: doxorubicin, purslane, hepatotoxicity, antioxidants

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233 Resistin Mediates Tomato and Broccoli Extracts Effects on Glucose Homeostasis in High Fat Diet Induced Obesity in Rats

Authors: N. M. Aborehab, M. Helmy, N. E. Waly

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Resistin was identified as an adipocyte hormone that participates in regulation of glucose metabolism. Elevated levels of Resistin are postulated to cause insulin resistance. This may link obesity, and increased fat mass to type II diabetes and insulin resistance. We hypothesized that tomato and broccoli extract treatment regulates glucose homeostasis via modulation of resistin levels in high fat diet induced obesity rats (HFD). 63 male albino rats were divided into 8 groups as follows: control, HFD, stop fat diet (SD), Tomato 200 mg/kg (T200), Tomato 400mg/kg (T400), Broccoli 200 mg/kg (B200), Broccoli 400 mg/kg (B400), Chromax (CX). Treatment continued for 1 month. Serum levels of resistin, leptin, adiponectin, glucose and insulin were measured using ELISA, and spectrophotometry. Serum level of resistin was significantly reduced in T 200, T 400, B 200, B 400 and CX groups to: 4.13 ± 0.22 ng/ml, 1.51 ± 0.04 ng/ml, 4.13 ± 0.22 ng/ml, 2.32 ± 0.15 ng/ml and 1.37 ± 0.03 ng/ml respectively compared to HFD group and SD group (P value < 0.0001). Non-significant difference was found between T 400, B 400 and CX groups. Mean serum level of leptin was significantly reduced in T 400 (22.7 ± 0.84 Pg/ml) group compared to B 400 (41 ± 2.45 Pg/ml) and CX groups (45.7 ± 2.91 Pg/ml), P value < 0.001.The mean serum level of adiponectin was significantly increased in T 400 group (131 ± 3.84 Pg/ml) compared to CX group (112 ± 4.77 Pg/ml), P value was < 0.01. Our results demonstrate that tomato and broccoli extract treatment regulates glucose homeostasis via reduction of serum resistin and may be a useful non-pharmacological therapy for obesity. Further studies are required to assess the potential use of these extract as a treatment for type II diabetes and obesity.

Keywords: broccoli, obesity, resistin, tomato

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232 Lucilia Sericata Netrin-A: Secreted by Salivary Gland Larvae as a Potential to Neuroregeneration

Authors: Hamzeh Alipour, Masoumeh Bagheri, Tahereh Karamzadeh, Abbasali Raz, Kourosh Azizi

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Netrin-A, a protein identified for conducting commissural axons, has a similar role in angiogenesis. In addition, studies have shown that one of the netrin-A receptors is expressed in the growing cells of small capillaries. It will be interesting to study this new group of molecules because their role in wound healing will become clearer in the future due to angiogenesis. The greenbottle blowfly Luciliasericata (L. sericata) larvae are increasingly used in maggot therapy of chronic wounds. This aim of this was the identification of moleculareatures of Netrin-A in L. sericata larvae. Larvae were reared under standard maggotarium conditions. The nucleic acid sequence of L. sericataNetrin-A (LSN-A) was then identified using Rapid Amplification of cDNA Ends (RACE) and Rapid Amplification of Genomic Ends (RAGE). Parts of the Netrin-A gene, including the middle, 3′-, and 5′-ends were identified, TA cloned in pTG19 plasmid, and transferred into DH5ɑ Escherichia coli. Each part was sequenced and assembled using SeqMan software. This gene structure was further subjected to in silico analysis. The DNA of LSN-A was identified to be 2407 bp, while its mRNA sequence was recognized as 2115 bp by Oligo0.7 software. It translated the Netrin-A protein with 704 amino acid residues. Its molecular weight is estimated to be 78.6 kDa. The 3-D structure ofNetrin-A drawn by SWISS-MODEL revealed its similarity to the Netrin-1 of humans with 66.8% identity. The LSN-A protein conduces to repair the myelin membrane in neuronal cells. Ultimately, it can be an effective candidate in neural regeneration and wound healing. Furthermore, our next attempt is to deplore recombinant proteins for use in medical sciences.

Keywords: maggot therapy, netrin-A, RACE, RAGE, lucilia sericata

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231 African Mesquite Exerts Neuroprotective Activity Against Quaternary Metal Mixture -Induced Olfactory Bulb-Hippocampal Oxido-Inflammatory Stress via NRF2-HMOX-1-TNF-Alpha Pathway Pathway

Authors: Orish E. Orisakwe, Chinna N. Orish, Anthonet N. Ezejiofor

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African mesquite has been recognized for its antimicrobial, anti-inflammatory, and potential anticarcinogenic activities. However, its neuroprotective benefits against heavy metal-induced neurotoxicity remain largely unexplored. Therefore, the objective of this study was to investigate the neuroprotective properties of African mesquite in the hippocampus and olfactory bulb against common environmental pollutants, including Cd, As, Hg, and Pb. Thirty-five albino Sprague Dawley rats were divided into five groups for the experiment. Group 1 served as the control and did not receive either the heavy metal mixture (HMM) or African mesquite. Group 2 was orally administered HMM, consisting of PbCl2 (20 mg/kg), CdCl2 (1.61 mg/kg), HgCl2 (0.40 mg/kg), and NaAsO3 (10 mg/kg), for 960 days. Meanwhile, groups 3, 4, and 5 were treated with HMM along with African mesquite at doses of 500 mg/kg, 1000 mg/kg, and 1500 mg/kg, respectively. African mesquite reduced heavy metal accumulation in the hippocampus and olfactory bulb. Additionally, Sprague Dawley rats exhibited improved performance in the Passive avoidance and Cincinnati Maze tests. Furthermore, treatment with African mesquite significantly alleviated inflammation macromolecules peroxidation. It also restored the concentrations of SOD, CAT, GSH, GPx, Hmox-1, and reduced the activity of AChE, NRF2 and NFkB and improved histopathological findings. African mesquite exhibits a multifaceted neuroprotective effect with the potential to mitigate various aspects of heavy metal-induced neurotoxicity.

Keywords: African mesquite, heavy metal mixture;, neurotoxicity;, chemoprevention

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230 Transdermal Therapeutic System of Lercanıdipine Hydrochloride: Fabrication and in Vivo Evaluation

Authors: Jiji Jose, R. Narayanacharyulu, Molly Mathew, Jisha Prems

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Introduction: Lercanidipine hydrochloride (LD), an effective calcium channel blocker, widely used for the treatment of chronic stable angina and hypertension seems to be potential transdermal therapeutic system candidate, mainly due to its low oral bio availability, short half life and high first-pass metabolism. Objective: To develop transdermal therapeutic systems for LD and to evaluate its in vivo performance in rabbits. Methodology: Transdermal patches of LD were formulated using the polymer blend of eudragit RL100 (ERL) and polyvinyl pyrolidone (PVP) by casting method Propylene glycol (PG) and tween 80 were used as plasticizer and permeation enhancer respectively. The pharmaco kinetic parameters of LD after the administration of transdermal patches was compared with that of oral administration. The study was carried out in a two way crossover design in male New Zealand albino rabbits. Results: The formulation with ERL: PVP ratio 1:4 with 15% w/w PG as plasticizer and 4% w/w tween 80 as permeation enhancer showed the best drug release results. The pharmacokinetic parameters such as Cmax, tmax, mean residence time (MRT) and area under the curve (AUC 0-∞) were significantly different following transdermal administration compared to oral administration. The terminal half life of transdermally administered LD was found to similar that of oral administration. A sustained drug release over a period of 24 hrs was observed after transdermal administration. Conclusion: The fabricated transdermal delivery system have the potential to provide controlled and extended drug release, better bio availability and thus, this may improve the patient compliance.

Keywords: transdermal therapeutic system, lercanidipine hydrochloride, eudragit, skinpermeation

Procedia PDF Downloads 615
229 Production and Quality Control of a Novel 153Sm-Complex for Radiotherapy of Bone-Metastases

Authors: H. Yousefnia, R. Enayati, M. Hosntalab, S. Zolghadri, A. Bahrami-Samani

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Bone metastases occur in many cases at an early stage of the tumour disease, however their symptoms are recognized rather late. The aim of this study was the preparation of 153Sm-(4-{[bis-(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl) 1,4,7,10-tetraazacyclododec-1-yl) acetic acid (BPAMD) for bone pain palliation therapy. 153Sm was produced at Tehran research reactor via 152Sm(n,γ)153Sm reaction. 200 µl of 1mg/ml BPAMD solution was added to the vial containing 1 mCi 153Sm and the mixture was heated up to 90 0C for 1 h. The radiochemical purity of the complex was measured by ITLC method. The final solution with radiochemical purity of more than 95% was injected to BALB mice and bio distribution was determined up to 48 h. SPECT images were acquired after 2 and 24 h post injection. While high bone uptake was confirmed by both the bio distribution studies and SPECT imaging, accumulation in other organs was approximately negligible. The results show that 153Sm-BPAMD can be used as an excellent tracer for bone pain palliation therapy.

Keywords: bone metastases, BPAMD, 153Sm, radiotherapy

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228 Protective Effect of L-Carnitine against Gentamicin-Induced Nephrotoxicity in Rats

Authors: Mohamed F. Ahmed, Mabruka S. Elashheb, Fatma M. Ben Rabha

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This study aimed to determine the possible protective effects of L‐carnitine against gentamicin‐induced nephrotoxicity. Forty male albino rats were divided into 4 groups (10 rats each); Group 1: normal control, group 2: induced nephrotoxicity (gentamicin 50 mg/kg/day S.C; 8 days) , group 3: treated with L‐carnitine (40 mg/kg/d SC for 12 days) and group 4: treated with L‐carnitine 4 days before and for 8 days in concomitant with gentamicin. Gentamicin‐induced nephrotoxicity (group 2): caused significant increase in serum urea, creatinine, urinary N‐acetyl‐B‐D‐glucosaminidase (NAG), gamma glutamyl transpeptidase (GGT), urinary total protein and kidney tissue malondialdehyde (MDA) with significant decrease in serum superoxide dismutase (SOD), serum catalase and creatinine clearance and marked tubular necrosis in the proximal convoluted tubules with interruption in the basement membrane around the necrotic tubule compared to the normal control group. L‐carnitine 4 days before and for 8 days in concomitant with gentamicin (group 4) offered marked decrease in serum urea, serum creatinine, urinary NAG, urinary GGT, urinary proteins and kidney tissue MDA, with marked increase in serum SOD, serum catalase and creatinine clearance with marked improvement in the tubular damage compared to gentamicin‐induced nephrotoxicity group. L‐carnitine administered for 12 days produced no change in the above-mentioned parameters as compared to the normal control group. In conclusion: L‐carnitine could reduce most of the biochemical parameters and also improve the histopathological features of the kidney associated with gentamicin-induced nephrotoxicity.

Keywords: gentamicin, nephrotoxicity, L‐carnitine, kidney disease

Procedia PDF Downloads 357
227 Can Bone Resorption Reduce with Nanocalcium Particles in Astronauts?

Authors: Ravi Teja Mandapaka, Prasanna Kumar Kukkamalla

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Poor absorption of calcium, elevated levels in serum and loss of bone are major problems of astronauts during space travel. Supplementation of calcium could not reveal this problem. In normal condition only 33% of calcium is absorbed from dietary sources. In this paper effect of space environment on calcium metabolism was discussed. Many surprising study findings were found during literature survey. Clinical trials on ovariectomized mice showed that reduction of calcium particles to nano level make them more absorbable and bioavailable. Control of bone loss in astronauts in critical important In Fortification of milk with nana calcium particles showed reduces urinary pyridinoline, deoxypyridinoline levels. Dietary calcium and supplementation do not show much retention of calcium in zero gravity environment where absorption is limited. So, the fortification of foods with nano calcium particles seemed beneficial for astronauts during and after space travel in their speedy recovery.

Keywords: nano calcium, astronauts, fortification, supplementation

Procedia PDF Downloads 494
226 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 550
225 Effects of Purslane Shoot and Seed Ethanolic Extracts on Doxorubicin-Induced Testicular Toxicity in Albino Rats

Authors: Walaa G. Hozayen, Osama M. Ahmed, Haidy T. Abo Sree

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The clinical usefulness of anthracycline antineoplastic antibiotic, doxorubicin (DOX) is restricted since it has several acute and chronic side effects. The effect of doxorubicin (4 mg/kg b.w/week) without or with oral administration of purslane (Portulaca oleracea) shoot ethanolic extract (50mg/kg b.w./day) and purslane seed ethanolic extract (50mg/kg b.w./day) co-treatments for 6 weeks was evaluated in adult male rats. Serum testosterone luteinizing hormone (LH), follicle stimulating hormone (FSH) level were assayed. Testis lipid peroxidation (indexed by MDA) and antioxidants like glutathione (GSH), glutathione-S-transferase (GST), peroxidase (POX), superoxide dismutase (SOD), catalase (CAT) levels in testis were assessed. The data revealed a significant decrease in serum levels concentration of testosterone, LH and FSH levels in doxorubicin-injected rats. In addition, testis glutathione, glutathione transferase, peroxidase, SOD and CAT levels were decreased while lipid peroxidation concentration in the testis was increased as a result of doxorubicin injection. Co-administration of ethanolic purslane and seed extracts potentially improved the adverse changes in serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) levels with an increase in testis antioxidants levels and reduction in lipid peroxidation. In conclusion, it can be suggested that dietary purslane extract supplementation may provide a cushion for a prolonged therapeutic option against DOX testicular toxicity without harmful side effects.

Keywords: doxorubicin, purslane, testis function, antioxidants

Procedia PDF Downloads 335
224 Histopathological Alterations in Liver of Mice Exposed to Different Doses of Diclofenac Sodium

Authors: Deepak Mohan, Sushma Sharma

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Diclofenac sodium, a member of the acetic acid family of non-steroidal anti-inflammatory drugs, is used to retard inflammation, arthritis pain and ankylosing spondylitis. The drug is known to cause severe injury in different tissues due to formation of reactive oxygen species. The present study is focused on the effect of different doses of diclofenac (4 mg/kg/body weight and 14 mg/kg/body weight on histoarchitecture of the liver from 7-28 days of the investigation. Diclofenac administration resulted in distorted hepatic degeneration and formation of wide areas in the form of sinusoidal gaps. Hepatic fibrosis noticed in different stages of investigation could be attributed to chronic inflammation and reactive oxygen species which results in deposition of extracellular matrix proteins. The abrupt degenerative changes observed during later stages of the experiment showed maximum damage to the liver, and there was enlargement of sinusoidal gaps accompanied by maximum necrosis in the tissues.

Keywords: arthritis, diclofenac, histoarchitecture, sinusoidal

Procedia PDF Downloads 271
223 Analyzing the Food as a Form of Creativity: The Case of the Bijlmermeer in Amsterdam-Zuidoost

Authors: Marc Polo, Núria Arbonés Arán

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Amsterdam is considered one of the great European capitals, which concentrates the headquarters of various multinational companies and which, in addition, enjoys a huge tourist attraction. Its typical residential buildings next to the canals, the museums, or its striking "Red Light District" are a great focus of attraction. In 2019 almost 9 million tourists visited it, but few of them traveled to the farthest neighborhood in the city: Amsterdam-Zuidoost (Amsterdam-Southeast). This neighborhood is geographically separated from the urban core, which makes it an exclave of Amsterdam as it does not border any of the other boroughs. Bijlmermeer neighborhood is the largest of the Amsterdam-Zuidoost, and it was born in the 1960s with the expectations of becoming the city of the future. Its main architect, Siegfried Nassuth, was inspired by the Swiss Le Corbusier to design nearly 18,000 homes, most of which were in high-rise tower blocks and built together, forming a recognizable "honeycombed" pattern. For more than 40 years, a series of infrastructure and social vicissitudes have made the neighborhood outline quite different as it was expected to be. It helped also varied elements such as ethnicity, demolitions, or unoccupied apartments. The called “city of the future” became home to immigrants, drug addicts, and vandals, and the conflicts denigrated the Amsterdam-Zuidoost. This work analyzes the evolution of the Bijlmermeer from its origins and illustrates relevant international referents able to help the area. The purpose of the work is to show how different variations along the recent history didn't help enough, but how there are positive perspectives for the future taking advantage of the food as a creative issue. The research, based on academic literature, existing material in different stadiums, plus the analysis of the city imaginaries, will help to concrete relevant elements in terms of innovation, creativity, and disruption. Despite of radical renewal that is taking place, the research will demonstrate that there are still new opportunities for the old Bijlmermeer.

Keywords: amsterdam, bijlmermeer, creativity, food

Procedia PDF Downloads 117
222 Camel Thorn Has Hepatoprotective Activity Against Carbon Tetrachloride or Acetaminophen-Induced Hepatotoxicity but Enhances the Cardiac Toxicity of Adriamycin in Rodents

Authors: Awad G. Abdellatif, Huda M. Gargoum, Abdelkader A. Debani, Mudafara Bengleil, Salmin Alshalmani, N. El Zuki, Omran El Fitouri

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In this study, the administration of 660 mg/kg of the ethanolic extract of the Alhgigraecorum (camel thorn) to mice, showed a significant decrease in the level of transaminases in animals treated with a combination of CTE plus carbon tetrachloride (CCl4) or acetaminophen as compared to animals receiving CCl4 or acetaminophen alone. The histopathological investigation also confirmed that camel thorn extract protects the liver against damage-induced either by carbon tetrachloride or acetaminophen. On the other hand, the cardiac toxicity produced by adriamycin was significantly increased in the presence of the ethanolic extract of camel thorn. Our study suggested that camel thorn can protect the liver against the injury produced by carbon tetrachloride or acetaminophen, with an unexpected increase in the cardiac toxicity–induced by adriamycin in rodents.

Keywords: ethanolic, alhgigraecorum, tetrachloride, acetaminophen

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221 INCIPIT-CRIS: A Research Information System Combining Linked Data Ontologies and Persistent Identifiers

Authors: David Nogueiras Blanco, Amir Alwash, Arnaud Gaudinat, René Schneider

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At a time when the access to and the sharing of information are crucial in the world of research, the use of technologies such as persistent identifiers (PIDs), Current Research Information Systems (CRIS), and ontologies may create platforms for information sharing if they respond to the need of disambiguation of their data by assuring interoperability inside and between other systems. INCIPIT-CRIS is a continuation of the former INCIPIT project, whose goal was to set up an infrastructure for a low-cost attribution of PIDs with high granularity based on Archival Resource Keys (ARKs). INCIPIT-CRIS can be interpreted as a logical consequence and propose a research information management system developed from scratch. The system has been created on and around the Schema.org ontology with a further articulation of the use of ARKs. It is thus built upon the infrastructure previously implemented (i.e., INCIPIT) in order to enhance the persistence of URIs. As a consequence, INCIPIT-CRIS aims to be the hinge between previously separated aspects such as CRIS, ontologies and PIDs in order to produce a powerful system allowing the resolution of disambiguation problems using a combination of an ontology such as Schema.org and unique persistent identifiers such as ARK, allowing the sharing of information through a dedicated platform, but also the interoperability of the system by representing the entirety of the data as RDF triplets. This paper aims to present the implemented solution as well as its simulation in real life. We will describe the underlying ideas and inspirations while going through the logic and the different functionalities implemented and their links with ARKs and Schema.org. Finally, we will discuss the tests performed with our project partner, the Swiss Institute of Bioinformatics (SIB), by the use of large and real-world data sets.

Keywords: current research information systems, linked data, ontologies, persistent identifier, schema.org, semantic web

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220 In-silico Target Identification and Molecular Docking of Withaferin A and Withanolide D to Understand their Anticancer Therapeutic Potential

Authors: Devinder Kaur Sugga, Ekamdeep Kaur, Jaspreet Kaur, C. Rajesh, Preeti Rajesh, Harsimran Kaur

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Withanolides are steroidal lactones and are highly oxygenated phytoconstituents that can be developed as potential anti-carcinogenic agents. The two main withanolides, namely Withaferin A and Withanolides D, have been extensively studied for their pharmacological activities. Both these withanolides are present in the Withania somnifera (WS) leaves belonging to the family Solanaceae, also known as “Indian ginseng .”In this study effects of WS leaf extract on the MCF7 breast cancer cell line were investigated by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects and in vitro wound-healing assay to study the effect on cancer cell migration. Our data suggest WS extracts have cytotoxic effects and are effective anti-migrating agents and thus can be a source of potential candidates for the development of potential agents against metastasis. Thus, it can be a source of potential candidates for the development of potential agents against metastasis. Insight into these results, the in-silico approach to identify the possible protein targets interacting with withanolides was taken. Protein kinase C alpha (PKCα) was among the selected 5 top-ranked target proteins identified by the Swiss Target Prediction tool. PKCα is known to promote the growth and invasion of cancer cells and is being evaluated as a prognostic biomarker and therapeutic target in clinically aggressive tumors. Molecular docking of Withaferin A and Withanolides D was performed using AutoDock Vina. Both the bioactive compounds interacted with PKCα. The targets predicted using this approach will serve as leads for the possible therapeutic potential of withanolides, the bioactive ingredients of WS extracts, as anti-cancer drugs.

Keywords: withania somnifera, withaferin A, withanolides D, PKCα

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219 Oncogenic Role of MicroRNA-346 in Human Non-Small Cell Lung Cancer by Regulation of XPC/ERK/Snail/E-Cadherin Pathway

Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

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Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here, we report the definition of miR-346 as an oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3'-UTR of XPC mRNA. Blocking miR-346 by an antagomiR was sufficient to inhibit NSCLC cell growth and metastasis, an effect that could be phenol-copied by RNAi-mediated silencing of XPC. In vivo studies established that miR-346 overexpression was sufficient to promote tumor growth by A549 cells in xenografts mice, relative to control cells. Overall, our results defined miR-346 as an oncogenic miRNA in NSCLC, the levels of which contributed to tumor growth and invasive aggressiveness.

Keywords: microRNA-346, miR-346, XPC, non-small cell lung cancer, oncogenesis

Procedia PDF Downloads 312