Search results for: swiss albino mice

Authors: R. Schweighoffer, N. Nagy, E. Reeves, B. Liebig

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Due to aging populations, the need for seamless palliative care provision is of central interest for western societies. An essential aspect of palliative care delivery is the quality of collaboration amongst palliative care providers. Therefore, the current research is based on Bainbridge’s conceptual framework, which provides an outline for the evaluation of palliative care provision. This study is the first one to investigate the predictive validity of spatial distribution on the quantity of interaction amongst various palliative care providers. Furthermore, based on the familiarity principle, we examine whether the extent of collaboration influences the perceived quality of collaboration among palliative care providers in urban versus rural areas of Switzerland. Based on a population-representative survey of Swiss palliative care providers, the results of the current study show that professionals in densely populated areas report higher absolute numbers of interactions and are more satisfied with their collaborative practice. This indicates that palliative care providers who work in urban areas are better embedded into networks than their counterparts in more rural areas. The findings are especially important, considering that efficient collaboration is a prerequisite to achieve satisfactory patient outcomes. Conclusively, measures should be taken to foster collaboration in weakly interconnected palliative care networks.

Keywords: collaboration, healthcare networks, palliative care, Switzerland

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Authors: Majed Al Otaibi, Melissa Lessard-Beaudoin, Amel Loudghi, Raphael Chouinard-Watkins, Melanie Plourde, Frederic Calon, C. Alexandre Castellano, Stephen Cunnane, Helene Payette, Pierrette Gaudreau, Denis Gris, Rona K. Graham

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Introduction: Alzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction, and also alterations in attention, planning, language and overall cognitive function. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may therefore lead to the discovery of potential biomarkers and/or treatments for neurodegenerative diseases. Objectives: To determine if olfactory dysfunction predicts future cognitive impairment in the aging population and to characterize the olfactory system in a murine model expressing a genetic factor of AD. Method: For the human study, quantitative olfactory tests (UPSIT and OMT) have been done on 93 subjects (aged 80 to 94 years) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) cohort accepting to participate in the ORCA secondary study. The telephone Modified Mini Mental State examination (t-MMSE) was used to assess cognition levels, and an olfactory self-report was also collected. In a separate cohort, olfactory cortical volume was calculated using MRI results from healthy old adults (n=25) and patients with AD (n=18) using the AAL single-subject atlas and performed with the PNEURO tool (PMOD 3.7). For the murine study, we are using Western blotting, RT-PCR and immunohistochemistry. Result: Human Study: Based on the self-report, 81% of the participants claimed to not suffer from any problem with olfaction. However, based on the UPSIT, 94% of those subjects showed a poor olfactory performance and different forms of microsmia. Moreover, the results confirm that olfactory function declines with age. We also detected a significant decrease in olfactory cortical volume in AD individuals compared to controls. Murine study: Preliminary data demonstrate there is a significant decrease in expression levels of the proform of caspase-3 and the caspase substrate STK3, in the olfactory bulb of mice expressing human APOE4 compared with controls. In addition, there is a significant decrease in the expression level of the caspase-9 proform and caspase-8 active fragment. Analysis of the mature neuron marker, NeuN, shows decreased expression levels of both isoforms. The data also suggest that Iba-1 immunostaining is increased in the olfactory bulb of APOE4 mice compared to wild type mice. Conclusions: The activation of caspase-3 may be the cause of the decreased levels of STK3 through caspase cleavage and may play role in the inflammation observed. In the clinical study, our results suggest that seniors are unaware of their olfactory function status and therefore it is not sufficient to measure olfaction using the self-report in the elderly. Studying olfactory function and cognitive performance in the aging population will help to discover biomarkers in the early stage of the AD.

Keywords: Alzheimer's disease, APOE4, cognition, caspase, brain atrophy, neurodegenerative, olfactory dysfunction

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Authors: Jianming Cai

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Exposure to ionizing radiation causes severe damage to human body and an safe and effective radioprotector is urgently required for alleviating radiation damage. In 2008, flagellin, an agonist of TLR5, was found to exert radioprotective effects on radiation injury through activating NF-kB signaling pathway. From then, the radioprotective effects of TLR ligands has shed new lights on radiation protection. CpG-ODN is an unmethylated oligonucleotide which activates TLR9 signaling pathway. In this study, we demonstrated that CpG-ODN has therapeutic effects on radiation injuries induced by γ ray and 12C6+ heavy ion particles. Our data showed that CpG-ODN increased the survival rate of mice after whole body irradiation and increased the number of leukocytes as well as the bone marrow cells. CpG-ODN also alleviated radiation damage on intestinal crypt through regulating apoptosis signaling pathway including bcl2, bax, and caspase 3 etc. By using a radiation-induced pulmonary fibrosis model, we found that CpG-ODN could alleviate structural damage, within 20 week after whole–thorax 15Gy irradiation. In this model, Th1/Th2 imbalance induced by irradiation was also reversed by CpG-ODN. We also found that TGFβ-Smad signaling pathway was regulated by CpG-ODN, which accounts for the therapeutic effects of CpG-ODN in radiation-induced pulmonary injury. On another hand, for high LET radiation protection, we investigated protective effects of CpG-ODN against 12C6+ heavy ion irradiation and found that after CpG-ODN treatment, the apoptosis and cell cycle arrest induced by 12C6+ irradiation was reduced. CpG-ODN also reduced the expression of Bax and caspase 3, while increased the level of bcl2. Then we detected the effect of CpG-ODN on heavy ion induced immune dysfunction. Our data showed that CpG-ODN increased the survival rate of mice and also the leukocytes after 12C6+ irradiation. Besides, the structural damage of immune organ such as thymus and spleen was also alleviated by CpG-ODN treatment. In conclusion, we found that TLR9 ligand, CpG-ODN reduced radiation injuries in response to γ ray and 12C6+ heavy ion irradiation. On one hand, CpG-ODN inhibited the activation of apoptosis induced by radiation through regulating bcl2, bax and caspase 3. On another hand, through activating TLR9, CpG-ODN recruit MyD88-IRAK-TRAF6 complex, activating TAK1, IRF5 and NF-kB pathway, and thus alleviates radiation damage. This study provides novel insights into protection and therapy of radiation damages.

Keywords: TLR9, CpG-ODN, radiation injury, high LET radiation

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Authors: Michela Terlizzi, Chiara Colarusso, Aldo Pinto, Rosalinda Sorrentino

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Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid exerting a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer, although its exact role is still elusive. Based on our previous study in which we found that S1P/S1PR3 is involved in an inflammatory pattern via the activation of Toll-like Receptor 9 (TLR9), highly expressed on lung cancer cells, the main goal of the current study was to better understand the involvement of S1P/S1PR3 pathway/signaling during lung carcinogenesis, taking advantage of a mouse model of first-hand smoke exposure and of carcinogen-induced lung cancer. We used human samples of Non-Small Cell Lung Cancer (NSCLC), a mouse model of first-hand smoking, and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. We found that the intranuclear, but not the membrane, localization of S1PR3 was associated to the proliferation of lung adenocarcinoma cells, the mechanism that was correlated to human and mouse samples of smoke-exposure and carcinogen-induced lung cancer, which were characterized by higher utilization of S1P. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after TLR9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the enzyme responsible for the catalysis of the S1P last step synthesis, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. These results prove that the endogenous TLR9-induced S1P can on one side favor pro-inflammatory mechanisms in the tumor microenvironment via the activation of cell surface receptors, but on the other tumor progression via the nuclear S1PR3/SPHK II axis, highlighting a novel molecular mechanism that identifies S1P as one of the crucial mediators for lung carcinogenesis-associated inflammatory processes and that could provide differential therapeutic approaches especially in non-responsive lung cancer patients.

Keywords: sphingosine-1-phosphate (S1P), S1P Receptor 3 (S1PR3), smoking-mice, lung inflammation, lung cancer

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Authors: Sahar B. Ahmed, M. Mostafa Said, Mona I. Mohamed

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Streptozotocin (STZ) caused a significant increase in blood glucose and malondialdehyde (MDA) levels in serum accompanied by a significant decrease in blood reduced glutathione (GSH) and superoxide dismutase (SOD) activities. Also, ALT, AST, albumin and urea were markedly affected by STZ injection. The oral administration of Mango leaves extract (MLE) one hour before STZ injection was significantly improved the blood glucose level, ALT, AST activities, albumin and urea that associated with the regulation of MDA, GSH and SOD levels. The antimicrobial activity of MLE showed a significant inhibitory activity against multidrug resistant gram positive and gram negative bacteria isolated from patients in Egyptian hospitals especially Salmonella typhi and typhimurium. In conclusion, results revealed the antioxidant, hypoglycemic effect and antimicrobial potentials of MLE under investigation. Further studies will be needed to investigate the prolonged period of MLE administration and its possible side effects.

Keywords: aqueous extract of mango leaves, STZ, antioxidant, hypoglycemic effect, antimicrobial potentials.

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Authors: Ravinder Singh, Ankita Gurao, Saroj Bandhan, Sudhir Kumar Kashyap

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The Bos taurus Beta defensin 3 is a defensin peptide secreted by neutrophils and epithelial that exhibits anti-microbial activity. It is one of the crucial components forming an innate defense against intra mammary infections in livestock. The beta defensin 3 by virtue of its anti-microbial activity inhibits major mastitis pathogens including Staphylococcus aureus and Pseudomonas aeruginosa etc, which are also responsible for biofilm formation leading to antibiotic resistance phenomenon. Therefore, the defensin may prove as a non-conventional option to treat mastitis. In this study, computational analysis has been performed including sequence comparison among species and homology modeling of Bos taurus beta defensin 3 protein. The assessments of protein structure were done using the protein structure and model assessment tools integrated in Swiss Model server, which employs various local and global quality evaluation parameters. Further, molecular docking was also carried out between the defensin peptide and the components of biofilm to gain insight into various interactions and structural differences crucial for functionality of this protein.

Keywords: beta defensin 3, bos taurus, docking, homology modeling

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Authors: João Pedro Albino, Ana Cláudia Pires Ferreira de Lima

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Humanity has undergone a transformation from the physical to the virtual world, generating an enormous amount of data on the world wide web, known as big data. Many facts that occur in the physical world or in the digital world are proven through records made on the internet, such as digital photographs, posts on social media, contract acceptances by digital platforms, email, banking, and messaging applications, among others. These data recorded on the internet have been used as evidence in judicial proceedings. The identification of internet users is essential for the security of legal relationships. This research was carried out on scientific articles and materials from courses and lectures, with an analysis of Brazilian legislation and some judicial decisions on the request of static data from logs and Internet Protocols (IPs) from application and connection providers. In this article, we will address the determination of authorship of data processing on the internet by obtaining the IP address and the appropriate judicial procedure for this purpose under Brazilian law.

Keywords: IP address, digital forensics, big data, data analytics, information and communication technology

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Authors: Shouta Sora, Shizuki Kuriu, Radhika Mishra, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

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Lymph node (LN) metastasis accounts for 20 - 30 % of all deaths in patients with head and neck cancer. Therefore, the control of metastatic lymph nodes (MLNs) is necessary to improve the life prognosis of patients with cancer. In a classical metastatic theory, tumor cells are thought to metastasize hematogenously through a bead-like network of lymph nodes. Recently, a lymph node-mediated hematogenous metastasis theory has been proposed, in which sentinel LNs are regarded as a source of distant metastasis. Therefore, the treatment of MLNs at the early stage is essential to prevent distant metastasis. Radiation therapy is one of the primary therapeutic modalities in cancer treatment. In addition, total body irradiation (TBI) has been reported to act as activation of natural killer cells and increase of infiltration of CD4+ T-cells to tumor tissues. However, the treatment effect of TBI for MLNs remains unclear. This study evaluated the possibilities of low-dose total body irradiation (L-TBI) and middle-dose total body irradiation (M-TBI) for the treatment of MLNs. Mouse breast cancer FM3A-Luc cells were injected into subiliac lymph node (SiLN) of MXH10/Mo/LPR mice to induce the metastasis to the proper axillary lymph node (PALN) and lung. Mice were irradiated for the whole body on 4 days after tumor injection. The L-TBI and M-TBI were defined as irradiations to the whole body at 0.2 Gy and 1.0 Gy, respectively. Tumor growth was evaluated by in vivo bioluminescence imaging system. In the non-irradiated group, tumor activities on SiLN and PALN significantly increased over time, and the metastasis to the lung from LNs was confirmed 28 days after tumor injection. The L-TBI led to a tumor growth delay in PALN but did not control tumor growth in SiLN and metastasis to the lung. In contrast, it was found that the M-TBI significantly delayed the tumor growth of both SiLN and PALN and controlled the distant metastasis to the lung compared with non-irradiated and L-TBI groups. These results suggest that the M-TBI is an effective treatment method for MLNs in the early stage and distant metastasis from lymph nodes via blood vessels connected with LNs.

Keywords: metastatic lymph node, lung metastasis, radiation therapy, total body irradiation, lymphatic system

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Authors: Bouzidi Abdelouahab, Ghadjati Nadhra, Bettihi Sara, Mahdeb Nadia, Daamouche Z. El Youm

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The effects of acute administration of TOTAL alkaloids, the main active principle of Datura stramonium, with toxic properties, were studied in female Albino-Wistar rats. After acute intraperitoneal administration of dose 120 mg kg-1 (≈1/3 DL50) of total alkaloids to the seeds of D. stramonium, there were no remarkable changes in general appearance and no deaths occurred in any experimental group. After 5 days a significant reduction was observed in total alkaloids of seeds. The Red Blood Cells (RBC), Hematocrit (HCT) and Hemoglobin (HGB) show significant changes in the treated groups. There were no statistical differences in Glutamic-pyruvic Transaminase (GPT), Alkaline Phosphatase (ALP), urea, glucose and total protein observed between groups. After 24 h Glutamic-Oxaloacetic Transaminase (GOT) and creatinine were significantly higher in the treated male rats than the control group histological examination of liver showed no histopathological changes.

Keywords: datura stramonium, rat, liver, kidney, alkaloids, toxicity

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Authors: Ibrahim Abdulla Labib, Medhat Mohamed Morsy, Gamal Hosny, Hanan Dawood Yassa, Gaber Hassan

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Amiodarone is a very effective drug, widely used for arrhythmia. Unfortunately it has many side effects involving many organs especially thyroid gland. The current work was conducted to elucidate the effect of amiodarone on the thyroid gland and the possible protective role of vitamin E. Fifty adult male albino rats weighed 200 – 250 grams were divided into five groups; ten rats each. Group I (Control): Five rats were sacrificed after three weeks and five rats were sacrificed after six weeks. Group II (Sham control): Each rat received sunflower oil orally; the solvent of vitamin E for three weeks. Group III (Amiodarone-treated): each rat received an oral dose of amiodarone; 150 mg/kg/day for three weeks. Group IV (Recovery): Each rat received amiodarone as group III then the drug was stopped for three weeks to evaluate recovery. Group V (Amiodarone + Vitamin E-treated): Each rat received amiodarone as group III followed by 100 mg/kg/day vitamin E orally for three weeks. Thyroid gland of the sacrificed animals were dissected out and prepared for light and electron microscopic studies. Amiodarone administration resulted in loss of normal follicular architecture as many follicles appeared either shrunken, empty or contained scanty pale colloid. Some follicles appeared lined by more than one layer of cells while others showed interruption of their membrane. Masson's Trichrome stained sections showed increased collagen fibers in between the thyroid follicles. Ultrastructurally, the apical border of the follicular cells showed few irregular detached microvilli. The nuclei of the follicular cells were almost irregular with chromatin condensation. The cytoplasm of most follicular cells revealed numerous dilated rough endoplasmic reticulum with numerous lysosomes. After three weeks of stopping amiodarone, the follicles were nearly regular in outline. Some follicles were filled with homogenous eosinophilic colloid and others had shrunken pale colloid or were empty. Some few follicles showed exfoliated cells in their lumina and others were still lined by more than one layer of follicular cells. Moderate amounts of collagen fibers were observed in-between thyroid follicles. Ultrastructurally, many follicular cells had rounded euchromatic nucleui, moderate number of lysosomes and moderately dilated rough endoplasmic reticulum. However, few follicular cells still showing irregular nucleui, dilated rough endoplasmic reticulum and many cytoplasmic vacuoles. Administration of vitamin E with amiodarone for three weeks resulted in obvious structural improvement. Most of the follicles were lined by a single layer of cuboidal cells and the lumina were filled with homogenous eosinophilic colloid with very few vacuolations. The majority of follicular cells had rounded nuclei with occasional detection of ballooned cells and dark nuclei. Scanty collagen fibers were detected among thyroid follicles. Ultrastructurally, most follicular cells exhibited rounded euchromatic nuclei with few short microvilli were projecting into the colloid. Few lysosomes were also noticed. It was concluded that amiodarone administration leads to many adverse histological changes in the thyroid gland. Some of these changes are reversible during the recovery period however concomitant vitamin E administration with amiodarone has a major protective role in preventing many of these changes.

Keywords: amiodarone, recovery, ultrastructure, vitamin E.

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Authors: Manal E. A Elhalwagy, Nadia Amin Abdulmajeed, Hanan S. Alnahdi, Enas N. Danial

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Baron is herbicide includes (48% glyphosate) widely used in Egypt. The present study assesses the cytotoxic and genotoxic effect of baron on rats liver. Two groups of rats were treated orally with 1/10 LD 50, (275.49 mg kg -1) and 1/40 LD 50, (68.86 mg kg-1) glyphosate for 28 days compared with control group. Serum and liver tissues were taken at 14 and 28 days of treatment. An inhibition in Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were recorded at both treatment periods and reduction in total serum protein (TP) and albumin (ALB). However, non-significant changes in serum acetylcholinesterase (AChE). Elevation in oxidative stress biomarker malondyaldehyde (MDA) and the decline in detoxification biomarker total reduced glutathione (GSH), Glutathione S-transferase (GST) and superoxide dismutase (SOD) in liver tissues led to increase in percentage of DNA damage. Destruction in liver tissue architecture was observed . Although, Baron was classified in the safe category pesticides repeated exposure to small doses has great danger effect.

Keywords: glyphosate, liver toxicity, oxidative stress, DNA damage, commet assay

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Authors: H. Jeries, N. Volkova, C. G. Iglesias, M. Najjar, M. Rosenblat, M. Aviram, T. Hayek

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Background: Synthetic forms of glucocorticoids (e.g., prednisone, prednisolone) are anti-inflammatory drugs which are widely used in clinical practice. The role of glucocorticoids (GCs) in cardiovascular diseases including atherosclerosis is highly controversial, and their impact on macrophage foam cell formation is still unknown. Our aim was to investigate the effects of prednisone or its active metabolite, prednisolone, on macrophage oxidative stress and lipid metabolism using in-vivo, ex-vivo and in-vitro systems. Methods: The in-vivo study included C57BL/6 mice which were intraperitoneally injected with prednisone or prednisolone (5mg/kg) for 4 weeks, followed by lipid metabolism analyses in the mice aorta, and in peritoneal macrophages (MPM). In the ex-vivo study, we analyzed the effect of serum samples obtained from 9 healthy volunteers before or after treatment with oral prednisone (20mg for 5 days), on J774A.1 macrophage atherogenicity. In-vitro studies were conducted using J774A.1 macrophages, human monocyte derived macrophages (HMDM) and fibroblasts. Cells were incubated with increasing concentrations (0-200 ng/ml) of prednisone or prednisolone, followed by determination of cellular oxidative status, triglyceride and cholesterol metabolism. Results: Prednisone or prednisolone treatment resulted in a significant reduction in triglycerides and mainly in cholesterol cellular accumulation in MPM or in J774A.1 macrophages incubated with human serum. Similar resulted were noted in HMDM or in J774A.1 macrophages which were directly incubated with the GCs. These effects were associated with GCs inhibitory effect on triglycerides and cholesterol biosynthesis rates, throughout downregulation of diacylglycerol acyltransferase1 (DGAT1) expression, and of the sterol regulatory element binding protein (SREBP2) and HMGCR expression, respectively. In parallel to prednisone or prednisolone induced reduction in macrophage triglyceride content, paraoxonase 2 (PON2) expression was significantly upregulated. GCs-induced reduction of cellular triglyceride and cholesterol mass was mediated by the GCs receptors on macrophages since the GCs receptor antagonist (RU 486) abolished these effects. In fibroblasts, unlike macrophages, prednisone or prednisolone showed no anti-atherogenic effects. Conclusions: Prednisone or prednisolone are anti-atherogenic since they protected macrophages from lipid accumulation and foam cell formation.

Keywords: atherosclerosis, cholesterol, foam cell, macrophage, prednisone, prednisolone, triglycerides

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Authors: Joulié Aurélien, Jourdain Elsa, Bailly Xavier, Gasqui Patrick, Yang Elise, Leblond Agnès, Rousset Elodie, Sidi-Boumedine Karim

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Q fever is a worldwide zoonosis caused by the gram-negative obligate intracellular bacterium Coxiella burnetii. Following the recent outbreaks in the Netherlands, a hyper virulent clone was found to be the cause of severe human cases of Q fever. In livestock, Q fever clinical manifestations are mainly abortions. Although the abortion rates differ between ruminant species, C. burnetii’s virulence remains understudied, especially in enzootic areas. In this study, the infectious potential of three C. burnetii isolates collected from French farms of small ruminants were compared to the reference strain Nine Mile (in phase II and in an intermediate phase) using an in vivo (CD1 mice) model. Mice were challenged with 105 live bacteria discriminated by propidium monoazide-qPCR targeting the icd-gene. After footpad inoculation, spleen and popliteal lymph node were harvested at 10 days post-inoculation (p.i). The strain invasiveness in spleen and popliteal nodes was assessed by qPCR assays targeting the icd-gene. Preliminary results showed that the avirulent strains (in phase 2) failed to pass the popliteal barrier and then to colonize the spleen. This model allowed a significant differentiation between strain’s invasiveness on biological host and therefore identifying distinct virulence profiles. In view of these results, we plan to go further by testing fifteen additional C. burnetii isolates from French farms of sheep, goat and cattle by using the above-mentioned in vivo model. All 15 strains display distant MLVA (multiple-locus variable-number of tandem repeat analysis) genotypic profiles. Five of the fifteen isolates will bee also tested in vitro on ovine and bovine macrophage cells. Cells and supernatants will be harvested at day1, day2, day3 and day6 p.i to assess in vitro multiplication kinetics of strains. In conclusion, our findings might help the implementation of surveillance of virulent strains and ultimately allow adapting prophylaxis measures in livestock farms.

Keywords: Q fever, invasiveness, ruminant, virulence

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Authors: Bawa Inalegwu, Jacob A. Jato, Ovye Akyengo, John Akighir

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All humans will experience some type of wound in every lifetime. Most wounds heal quickly with little or no attention but, many people suffer from wounds that are complex and/or persistent therefore posing a burden. This study was designed to assess the efficacy of Mitrcarpus villous ointment against honey in diabetic rats. To achieve this, percentage wound closure and collagen assessments were used to express treatment efficacy. Results show that on day 21, rats treated with M. villosus ointment had the highest percentage closure (94.5%) while honey treated and non-treated recorded 90.0% and 83.3% respectively. Similarly, a significant difference (p < 0.05) was observed on day 21 in the total collagen deposited in wounds of diabetic rats (10.57 ± 0.7) and M. villous ointment treated wounds (11.77 ± 0.4) as compared with the non-treated diabetic rats. M. villosus ointment was efficacious in healing wounds in diabetic rats and heals wound faster than honey and may hold potential for wound healing in diabetes mellitus sufferers. However, the wound healing mechanism of this ointment

Keywords: collagen, diabetic rats, honey, Mitracarpus villosus, ointment, wound healing

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Authors: Zine Kechrid

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This study was carried out to investigate the antioxidant effect of vitamin C on oxidative stress induced by dietary Zn-deficiency in albino diabetic rats. Thirty two males alloxan-diabetic rats divided into two groups of 16 individuals each; the first group was fed a zinc adequate diet (54 mg zinc/kg). The second group had given low zinc diet (1 mg zinc/kg). Then, half of each group was treated with vitamin C (1 g/l) in drinking water. After four weeks, animals were sacrificed and different parameters were determined. The findings showed that dietary deficiency zinc intake significantly increased serum glucose. Zn-deficiency was also led to an increase in oxidative stress, which was indicated by an increase of MDA level and glutathione-S-transferase activity. Meanwhile it was result in a decrease of reduced glutathione (GSH) content, glutathione peroxidase GSH-Px and catalase activities in liver. However, the administration of vitamin C restored all the previous parameters approximately to their normal values. In conclusion, vitamin C probably played a key role strong as antioxidant factor against oxidative stress provoked by dietary zinc inadequate. Therefore, it might be contributed in reduction diabetes complications.

Keywords: vitamin C, oxidative stress, zinc, experimental diabetes, rats

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Authors: Omolola Soji-Omoniwa, Babasoji Omoniwa

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The hypolipidemic effect of leaf essential oil of Citrus sinensis in alloxan–induced diabetic rats was evaluated. Forty albino rats (150–200 g) were randomly selected into 4 groups of 10 rats each, representing Normal Control, Diabetic Control, Diabetic treated with 14.2 mg/kg body weight Metformin and Diabetic treated with 110 mg/kg body weight leaf essential oil of Citrus sinensis. Diabetes was induced in the animals by intraperitoneal administration of single dose alloxan monohydrate (150 mg/kg body weight). The leaf essential oil of Citrus sinensis was administered every other day to the Diabetic rats for a period of 15 days. The effects of leaf essential oil on High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Trigylcerides and Cholesterol were evaluated. A significant reduction (p <0.05) in LDL, Triglycerides and cholesterol levels and a significant increase (p<0 .05) in HDL was observed. Leaf essential oil of Citrus sinensis possesses hypolipidemic properties.

Keywords: Citrus sinensis, Diabetes mellitus, hypolipidemic, leaf essential oil

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Authors: Sanaa AM Elgayar, Sohair A Eltony, Maha Mahmoud Abd El Rouf

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Background: Retinopathy remains an important complication of diabetes. Aim of work: This work was carried out to evaluate the protective effects of genistein from diabetic retinopathy in rat. Material and Methods: Fifteen adult male albino rats were divided into two groups; Group I: control (n=5) and Group II: streptozotocin induced diabetic group (n=10), which is equally divided into two subgroups; IIa (diabetic vehicle control) and IIb (diabetic genistein-treated). Specimens were taken from the retina 12 weeks post induction, processed and examined using light, immunohistochemical, ultrastructural techniques. Blood samples were assayed for the levels of glucose. Results: In comparison with the diabetic non-treated group, the histological changes in macro and microglial glial cells reactivity and retinal blood capillaries were improved in genistein-treated groups. In addition, GFAP and iNOS expressions in the retina and the blood glucose level were reduced. Conclusion: Genistein ameliorates the histological changes of diabetic retinopathy reaching healing features, which resemble that of a normal retina.

Keywords: diabetic retinopathy, genistein, glia, capillaries.

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Authors: Natalia Strobel, Jan Kratzer

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In this paper, we test whether different types of research and development (R&D) alliances positively impact the radical innovation performance of firms. We differentiate between the R&D alliances without extern R&D orders and embeddedness in knowledge source network. We test the differences between the domestically diversified R&D alliances and R&D alliances diversified abroad. Moreover, we test how non-price competition influences the impact of domestically diversified R&D alliances, and R&D alliance diversified abroad on radical innovation performance. Our empirical analysis is based on the comprehensive Swiss innovation panel, which allowed us to study 3520 firms between the years between 1996 and 2011 in 3 years intervals. We analyzed the data with a linear estimation with Swamy-Aurora transformation using plm package in R software. Our results show as hypothesized a positive impact of R&D alliances diversity abroad as well as domestically on radical innovation performance. The effect of non-price interaction is in contrast to our hypothesis, not significant. This suggests that diversity of R&D alliances is highly advantageous independent of non-price competition.

Keywords: R&D alliances, partner diversity, knowledge source diversity, non-price competition, absorptive capacity

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Authors: Shelly Sharma, Pooja Chadha

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Humans are exposed to pesticides and insecticides either directly or indirectly. Exposure to these pesticides may lead to acute toxicity to mammals and non-target organisms. Chlorpyrifos (CPF) is a broad spectrum organophosphate pesticide widely used in various countries of the world. The aim of the present study was to assess the toxicity associated with chlorpyrifos exposure and possible mitigating effect of cow urine against genotoxic and toxic effects in rat brain induced by chlorpyrifos. For this purpose LD50 was determined and rats were orally administered with 1/8th of LD50 (19mg/kg b.wt). Brain samples were taken after 24hrs, 48hrs and 72hrs of treatment. A significant increase in the % tail DNA was observed along with the increase in MDA levels of brain tissues in chlorpyrifos treated groups as compared to control. Cow urine treated groups show decrease in DNA damage and MDA levels as compared to CPF treated group. The study indicates that cow urine has ameliorative potential against neurotoxicity and genotoxicity induced by CPF. Cow urine is considered rich in vitamin A, E and volatile fatty acids which provide antioxidant potential to it. Thus, it can be used as a genoprotective agent.

Keywords: comet assay, brain, cow urine, genotoxicity, toxicity

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Authors: Natalia Hordynska, Magdalena Szechynska-Hebda, Miroslaw Sobczak, Elzbieta Rozanska, Joanna Troczynska, Zofia Banaszak, Maria Wedzony

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Albinism is a common problem encountered in wheat and triticale breeding programs, which require in vitro culture steps e.g. generation of doubled haploids via androgenesis process. Genetic factor is a major determinant of albinism, however, environmental conditions such as temperature and media composition influence the frequency of albino plant formation. Cold incubation of wheat and triticale spikes induced a switch from gametophytic to sporophytic development. Further, androgenic structures formed from anthers of the genotypes susceptible to androgenesis or treated with cold stress, had a pool of structurally primitive plastids, with small starch granules or swollen thylakoids. High temperature was a factor inducing andro-genesis of wheat and triticale, but at the same time, it was a factor favoring the formation of albino plants. In genotypes susceptible to albinism or after heat stress conditions, cells formed from anthers were vacuolated, and plastids were eliminated. Partial or complete loss of chlorophyll pigments and incomplete differentiation of chloroplast membranes result in formation of tissues or whole plant unable to perform photosynthesis. Indeed, susceptibility to the andro-genesis process was associated with an increase of total concentration of photosynthetic pigments in anthers, spikes and regenerated plants. The proper balance of the synthesis of various pigments, was the starting point for their proper incorporation into photosynthetic membranes. In contrast, genotypes resistant to the androgenesis process and those treated with heat, contained 100 times lower content of photosynthetic pigments. In particular, the synthesis of violaxanthin, zeaxanthin, lutein and chlorophyll b was limited. Furthermore, deregulation of starch and lipids synthesis, which led to the formation of very complex starch granules and an increased number of oleosomes, respectively, correlated with the reduction of the efficiency of androgenesis. The content of other sugars varied depending on the genotype and the type of stress. The highest content of various sugars was found for genotypes susceptible to andro-genesis, and highly reduced for genotypes resistant to androgenesis. The most important sugars seem to be glucose and fructose. They are involved in sugar sensing and signaling pathways, which affect the expression of various genes and regulate plant development. Sucrose, on the other hand, seems to have minor effect at each stage of the androgenesis. The sugar metabolism was related to metabolic activity of microspores. The genotypes susceptible to androgenesis process had much faster mitochondrium- and chloroplast-dependent energy conversion and higher heat production by tissues. Thus, the effectiveness of metabolic processes, their balance and the flexibility under the stress was a factor determining the direction of microspore development, and in the later stages of the androgenesis process, a factor supporting the induction of androgenic structures, chloroplast formation and the regeneration of green plants. The work was financed by Ministry of Agriculture and Rural Development within Program: ‘Biological Progress in Plant Production’, project no HOR.hn.802.15.2018.

Keywords: androgenesis, chloroplast, metabolism, temperature stress

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Authors: Mohana Babu Amberkar, Meena Kumari K, Ravi, Arjun, Christopher Rockson

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The aim of this research is to evaluate the hepatoprotective activity of Terminalia paniculata (Tp) against ATT induced hepatic damage in rats.Three hepatotoxic ATT drugs Isoniazid + Rifampicin + Pyrazinamide, silymarin as standard hepatoprotective drug and 0.5% carboxymethylcellulose (CMC) as a control were used. Tp extract and silymarin were administered orally with ATT drugs for 90 days. Two doses 250 and 500 mg/kg of Tp extract, ATT drugs and silymarin were administered as suspensions with 0.5% CMC. ATT treated rats showed a significant increase in aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and lipid peroxides in the serum vs. control. Treatment of silymarin and Tp (250mg/kg) extract showed hepatoprotective activity against the hepatic damage by ATT. This was evident from significant reduction in serum liver enzymes levels, and also there was a significant increase in serum proteins, albumin and total liver tissue thiols as compared to the ATT treated groups. Tp was found to possess hepatoprotective property.

Keywords: antitubercular drugs, hepatoprotective, liver enzymes, Terminalia paniculata

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Authors: U. P. Rathnakar, Sejpal Jaykumar, Shenoy K. Ashok

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The effect of Shilajit was investigated for lipid lowering activity and its effect on weight gain in Wistar albino rats. Shilajit, semi-hard brownish black resin formed through long-term humidification of several plant types, mainly bryophytes, can be obtained from steep rocks of the Himalayas at altitudes between 1000 to 5000 meters. Hyperlipidemia was produced by feeding the rats with the cholesterol-rich high-fat diet (HFD) for 2 months. This diet contained deoxycholic acid, cholesterol and warm coconut oil in powdered rat chow diet. At the end of study, Shilajit treated rats showed significant decrease in serum LDL, triglyceride and total cholesterol level as well as increase in serum HDL level, in comparison to rats fed on high-fat diet with no treatment. Also during study period, increase in weight in Shilajit treated group was significantly less than in the other group of rats fed on high-fat diet with no treatment. Thus, Shilajit has significantly controlled the development of hyperlipidemia and weight gain in high-fat diet fed rats in the present study.

Keywords: Shilajit, hyperlipidemia, weight control, cholesterol-rich high-fat diet

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Authors: Cinzia Cruder, Deborah Falla, Francesca Mangili, Laura Azzimonti, Liliana Araujo, Aaron Williamon, Marco Barbero

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Background and aims: According to the existing literature, musicians are at risk to experience a range of musculoskeletal painful conditions. Recently, digital technology has been developed to investigate pain location and pain extent. The aim of this study was to describe pain location and pain extent in musicians using a digital method for pain drawing analysis. Additionally, the association between pain drawing (PD) variables and clinical features in musicians with pain were explored. Materials and Methods: One hundred fifty-eight musicians (90 women and 68 men; age 22.4±3.6 years) were recruited from Swiss and UK conservatoires. Participants were asked to complete a survey including both background musical information and clinical features, the Quick Dash (QD) questionnaire and the digital PDs. Results: Of the 158 participants, 126 musicians (79.7%) reported having pain, with more prevalence in the areas of the neck and shoulders, the lower back and the right arm. The mean of pain extent was 3.1% ±6.5. The mean of QD was larger for musicians showing the presence of pain than for those without pain. Additionally, the results indicated a positive correlation between QD score and pain extent, and there were significant correlations between age and pain intensity, as well as between pain extent and pain intensity. Conclusions: The high prevalence of pain among musicians has been confirmed using a digital PD. In addition, positive correlations between pain extent and upper limb disability has been demonstrated. Our findings highlight the need for effective prevention and treatment strategies for musicians.

Keywords: pain location, pain extent, musicians, pain drawings

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Authors: Filip Jaroš

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The Swiss scholar Adolf Portmann (1897-1982) was an outstanding figure in the history of biology and the philosophy of the life sciences. Portmann’s biological theory is primarily focused on the problem of animal form (Gestalt), and it poses a significant counterpart to neo-Darwinian theories about the explanatory primacy of a genetic level over the outer appearance of animals. Besides that, Portmann’s morphological studies related to species-specific ontogeny and the influence of environmental surroundings can be classified as the antecedents of contemporary synthetic approaches such as “eco-evo-devo, “extended synthesis or biosemiotics. The most influential of Portmann’s concepts up to the present is his thesis of a social womb (Soziale Mutterschos): human children are born physiologically premature in comparison with other primates, and they find a second womb in a social environment nurturing their healthy development. It is during the first year of extra-uterine life when a specific human nature is formed, characterized by the strong tie between an individual and a broader historical, cultural whole. In my paper, I will closely analyze: a) the historical coordinates of Portmann’s philosophy of the life sciences (e.g., the philosophical anthropology of A. Gehlen, H. Plessner, and their concept of humans as beings “open to the world”), b) the relation of Portmann’s concept of the social womb to contemporary theories of infant birth evolution.

Keywords: adolf portmann, extended synthesis, philosophical anthropology, social womb

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Authors: Valencia Fernandes, Dharmendra Kumar Khatri, Shashi Bala Singh

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Background and Aim: Epigenetics are the inaudible signatures of several pathological processes in the brain. This study understands the influence of DNA methylation, a major epigenetic modification, in the prefrontal cortex and hippocampus of the diabetic brain and its notable effect on the cellular chaperones and synaptic proteins. Method: Chronic high fat diet and STZ-induced diabetic mice were studied for cognitive dysfunction, and global DNA methylation, as well as DNA methyltransferase (DNMT) activity, were assessed. Further, the cellular chaperones and synaptic proteins were examined using DNMT inhibitor, 5-aza-2′-deoxycytidine (5-aza-dC)-via intracerebroventricular injection. Moreover, % methylation of these synaptic proteins were also studied so as to correlate its epigenetic involvement. Computationally, its interaction with the DNMT enzyme were also studied using bioinformatic tools. Histological studies for morphological alterations and neuronal degeneration were also studied. Neurogenesis, a characteristic marker for new learning and memory formation, was also assessed via the BrdU staining. Finally, the most important behavioral studies, including the Morris water maze, Y maze, passive avoidance, and Novel object recognition test, were performed to study its cognitive functions. Results: Altered global DNA methylation and increased levels of DNMTs within the nucleus were confirmed in the cortex and hippocampus of the diseased mice, suggesting hypermethylation at a genetic level. Treatment with AzadC, a global DNA demethylating agent, ameliorated the protein and gene expression of the cellular chaperones and synaptic fidelity. Furthermore, the methylation analysis profile showed hypermethylation of the hsf1 protein, a master regulator for chaperones and thus, confirmed the epigenetic involvement in the diseased brain. Morphological improvements and decreased neurodegeneration, along with enhanced neurogenesis in the treatment group, suggest that epigenetic modulations do participate in learning and memory. This is supported by the improved behavioral test battery seen in the treatment group. Conclusion: DNA methylation could possibly accord in dysregulating the memory-associated proteins at chronic stages in type 2 diabetes. This could suggest a substantial contribution to the underlying pathophysiology of several metabolic syndromes like insulin resistance, obesity and also participate in transitioning this damage centrally, such as cognitive dysfunction.

Keywords: epigenetics, cognition, chaperones, DNA methylation

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Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

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Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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Authors: Yuanyuan Zhang, Yujuan Zheng, Giuseppina Barutello, Sumako Kameishi, Kungchun Chiu, Katharina Hennig, Martial Balland, Federica Cavallo, Lars Holmgren

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Angiogenesis describes that new blood vessels migrate from pre-existing ones to form 3D lumenized structure and remodeling. During directional migration toward the gradient of pro-angiogenic factors, the endothelial cells, especially the tip cells need filopodia to sense the environment and exert the pulling force. Of particular interest are the integrin proteins, which play an essential role in focal adhesion in the connection between migrating cells and extracellular matrix (ECM). Understanding how these biomechanical complexes orchestrate intrinsic and extrinsic forces is important for our understanding of the underlying mechanisms driving angiogenesis. We have previously identified Angiomotin (Amot), a member of Amot scaffold protein family, as a promoter for endothelial cell migration in vitro and zebrafish models. Hence, we established inducible endothelial-specific Amot knock-out mice to study normal retinal angiogenesis as well as tumor angiogenesis. We found that the migration ratio of the blood vessel network to the edge was significantly decreased in Amotec- retinas at postnatal day 6 (P6). While almost all the Amot defect tip cells lost migration advantages at P7. In consistence with the dramatic morphology defect of tip cells, there was a non-autonomous defect in astrocytes, as well as the disorganized fibronectin expression pattern correspondingly in migration front. Furthermore, the growth of transplanted LLC tumor was inhibited in Amot knockout mice due to fewer vasculature involved. By using MMTV-PyMT transgenic mouse model, there was a significantly longer period before tumors arised when Amot was specifically knocked out in blood vessels. In vitro evidence showed that Amot binded to beta-actin, Integrin beta 1 (ITGB1), Fibronectin, FAK, Vinculin, major focal adhesion molecules, and ITGB1 and stress fibers were distinctly induced by Amot transfection. Via traction force microscopy, the total energy (force indicater) was found significantly decreased in Amot knockdown cells. Taken together, we propose that Amot is a novel partner of the ITGB1/Fibronectin protein complex at focal adhesion and required for exerting force transition between endothelial cell and extracellular matrix.

Keywords: angiogenesis, angiomotin, endothelial cell migration, focal adhesion, integrin beta 1

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Authors: Dalal Alghawas, Jetty Lee, Kaisa Poutanen, Hani El-Nezami

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Oat β-glucan a water soluble non starch linear polysaccharide has been approved as a cholesterol lowering agent by various food safety administrations and is commonly used to reduce the risk of heart disease. The molecular weight of oat β-glucan can vary depending on the extraction and fractionation methods. It is not clear whether the molecular weight has a significant impact at reducing the acceleration of atherosclerosis. The aim of this study was to investigate three different oat β-glucan fractionations on the development of atherosclerosis in vivo. With special focus on plaque stability and the intestinal barrier function. To test this, ApoE-/- female mice were fed a high fat diet supplemented with oat bran, high molecular weight (HMW) oat β-glucan fractionate and low molecular weight (LMW) oat β-glucan fractionate for 16 weeks. Atherosclerosis risk markers were measured in the plasma, heart and aortic tree. Plaque size was measured in the aortic root and aortic tree. ICAM-1, VCAM-1, E-Selectin, P-Selectin, protein levels were assessed from the aortic tree to determine plaque stability at 16 weeks. The expression of p22phox at the aortic root was evaluated to study the NADPH oxidase complex involved in nitric oxide bioavailability and vascular elasticity. The tight junction proteins E-cadherin and beta-catenin from western blot analyses were analysed as an intestinal barrier function test. Plasma LPS, intestinal D-lactate levels and hepatic FMO gene expression were carried out to confirm whether the compromised intestinal barrier lead to endotoxemia. The oat bran and HMW oat β-glucan diet groups were more effective than the LMW β-glucan diet group at reducing the plaque size and showed marked improvements in plaque stability. The intestinal barrier was compromised for all the experimental groups however the endotoxemia levels were higher in the LMW β-glucan diet group. The oat bran and HMW oat β-glucan diet groups were more effective at attenuating the development of atherosclerosis. Reasons for this could be due to the LMW oat β-glucan diet group’s low viscosity in the gut and the inability to block the reabsorption of cholesterol. Furthermore the low viscosity may allow more bacterial endotoxin translocation through the impaired intestinal barrier. In future food technologists should carefully consider how to incorporate LMW oat β-glucan as a health promoting food.

Keywords: Atherosclerosis, beta glucan, endotoxemia, intestinal barrier function

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Authors: Jan F. Talts, Amit Saxena, Kåre Engkilde

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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by anti-neoplastic agents, with a prevalence from 19 % to 85 %. Clinically, CIPN is a mostly sensory neuropathy leading to pain and to motor and autonomic changes. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors, especially because currently, there is no single effective method of preventing CIPN. Hearing loss is the most common form of sensory impairment in humans and can be caused by ototoxic chemical compounds such as chemotherapy (platinum-based antineoplastic agents).In rodents, single or repeated cisplatin injections induce peripheral neuropathy and hearing impairment mimicking human disorder, allowing studying the efficacy of new pharmacological candidates in chemotherapy-induced hearing loss and peripheral neuropathy. RNA sequencing data from full term amniotic fluid (TAF) mesenchymal stemcell (MSC) clones was used to identify neural-specific markers present on TAF-MSC. Several prospective neural markers were tested by flow cytometry on cultured TAF-MSC. One of these markers was used for cell-sorting using Tyto MACSQuant cell sorter, and the neural marker positive cell population was expanded for several passages to the final therapeutic product stage. Peripheral neuropathy and hearing loss was induced in mice by administration of cisplatin in three week-long cycles. The efficacy of neural-specific TAF-MSC in treating hearing loss and pain perception was evaluated by administration of three injections of 3 million cells/kg by intravenous route or three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment. Auditory brainstem responses (ABR) are electric potentials recorded from scalp electrodes, and the first ABR wave represents the summed activity of the auditory nerve fibers contacting the inner hair cells. For ABR studies, mice were anesthetized, then earphones were placed in the left ear of each mouse, an active electrode was placed in the vertex of the skull, a reference electrode under the skin of the mastoid bone, and a ground electrode in the neck skin. The stimuli consisted of tone pips of five frequencies (2, 4, 6, 12, 16, and 24 kHz) at various sound levels (from 0 to 90 dB) ranging to cover the mouse auditory frequency range. The von Frey test was used to assess the onset and maintenance of mechanical allodynia over time. Mice were placed in clear plexiglass cages on an elevated mesh floor and tested after 30 min of habituation. Mechanical paw withdrawal threshold was examined using an electronic von Frey anesthesiometer. Cisplatin groups treated with three injections of 3 million cells/kg by intravenous route and three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment presented, a significant increase of hearing acuity characterized by a decrease of ABR threshold and a decrease of neuropathic pain characterized by an increase of von Frey paw withdrawal threshold compared to controls only receiving cisplatin. This study shows that treatment with MSCselected for neural specificity presents significant positive efficacy on the chemotherapy-induced neuropathic pain and the chemotherapy-induced hearing loss.

Keywords: mesenchymal stem cell, peripheral neuropathy, amniotic fluid, regenerative medicine

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Authors: Valeria T. Dilcheva, Svetlozara L. Petkova, Ivelin Vladov

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Trichinellosis is a food-borne parasitic disease caused by nematodes of the genus Trichinella which are zoonotic parasites with cosmopolitan distribution and major socio-economic importance. Human infection is acquired through consumption of undercooked meat from domestic or wild animal. Penetration of Trichinella larvae into striated skeletal muscle cells results in ultrastructural and metabolic changes. Migration of larvae causes the typical symptoms and signs of the disease. The severity of the symptoms depends on the number of ingested Trichinella larvae and the immune response of the host. Eosinophilia is present, with few exceptions, in most cases of human trichinellosis, inasmuch as it is the earliest and most important host response. Even in human asymptomatic cases, increases in eosinophilia of up to 15% have been observed. Eosinophilia appears at an early stage of infection between the second and fifth weeks of infection. By 2005 it was considered that only two species of Trichinella genus were found in the country. After routine trichinelloscopy procedure disseminated single muscle larvae in samples of wild boars and badger were PCR-identified as T. pseudospiralis. The study aimed to observed hematological changes occurring during experimentally induced infection with Trichinella spiralis, T. britovi and T. pseudospiralis in mice. We performed hematological blood profile, tracking 15 blood indicators. In statistical analysis made by Two-way ANOVA, there were significant differences of HGB, MCHC, PLT, Lymph%, Gran% in all three types of trichinellosis compared to control animals. Capsule-forming T. spiralis showed statistically significant differences in HGB, MCHC, Lymph% and PLT compared to the other two species. Non capsule-forming T. pseudospiralis showed statistically significant differences in Lymph%, Gran% relative to the control and in Gran% relative to T. spiralis. It appears rather substantial the process of capsule formation for prolonged immune response and retention of high content of percentage of lymphocytes(Lymph%) and low of granulocyte(Gran%) in T. pseudospiralis, which is contrary to studies for T. spiralis and eosinophilia. Studies and analyzes of some specific blood profile parameters can provide additional data in favor of early diagnosis and adequate treatment as well as provide a better understanding of acute and chronic trichinosis.

Keywords: hematological test, T. britovi, T. spiralis, T. pseudospiralis

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