Search results for: umbilical cord blood derived mesenchymal stem cells (UC-MSCs)

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

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

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

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Authors: B. El Fadil, R. Najar

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STEM education is promoted by many scholars and curricula around the world, but it is not yet well established in the province of Quebec in Canada. In addition, effective instructional STEM activities and design methods are required to ensure that students and teachers' needs are being met. One potential method is the Engineering Design Process (EDP), a methodology that emphasizes the importance of creativity and collaboration in problem-solving strategies. This article reports on a case study that focused on using the EDP to develop instructional materials by means of making a technological artifact to teach mathematical variables and functions at the secondary level. The five iterative stages of the EDP (design, make, test, infer, and iterate) were integrated into the development of the course materials. Data was collected from different sources: pre- and post-questionnaires, as well as a working document dealing with pupils' understanding based on designing, making, testing, and simulating. Twenty-four grade seven (13 years old) students in Northern Quebec participated in the study. The findings of this study indicate that STEM activities have a positive impact not only on students' engagement in classroom activities but also on learning new mathematical concepts. Furthermore, STEM-focused activities have a significant effect on problem-solving skills development in an interdisciplinary approach. Based on the study's results, we can conclude, inter alia, that teachers should integrate STEM activities into their teaching practices to increase learning outcomes and attach more importance to STEM-focused activities to develop students' reflective thinking and hands-on skills.

Keywords: engineering design process, motivation, stem, integration, variables, functions

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Authors: Lauren B. Birney

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Summer STEM Institute for Middle and High School Students at Pace University The STEM Collaboratory NYC® Summer Fellows Institute takes place on Pace University’s New York City campus during July and provides the following key features for all participants: (i) individual meetings with Pace faculty to discuss and refine future educational goals; (ii) mentorship, guidance, and new friendships with program leaders; and (iii) guest lectures from professionals in STEM disciplines and businesses. The Summer STEM Institute allows middle school and high school students to work in teams to conceptualize, develop, and build native mobile applications that teach and reinforce skills in the sciences and mathematics. These workshops enhance students’STEM problem solving techniques and teach advanced methods of computer science and engineering. Topics include: big data and analytics at the Big Data lab at Seidenberg, Data Science focused on social and environmental advancement and betterment; Natural Disasters and their Societal Influences; Algal Blooms and Environmental Impacts; Green CitiesNYC; STEM jobs and growth opportunities for the future; renew able energy and sustainable infrastructure; and climate and the economy. In order to better align the existing Summer STEM, Institute with the CCERS model and expand the overall network, Pace is actively recruiting new content area specialists from STEM industries and private sector enterprises to participate in an enhanced summer institute in order to1) nurture student progress and connect summer learning to school year curriculum, 2) increase peer-to-peer collaboration amongst STEM professionals and private sector technologists, and 3) develop long term funding and sponsorship opportunities for corporate sector partners to support CCERS schools and programs directly.

Keywords: environmental restoration science, citizen science, data science, STEM

Procedia PDF Downloads 61

Authors: Pakize Neslihan Taslı, Alev Cumbul, Gul Merve Yalcın, Fikrettin Sahin

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A key experimental trial in the regeneration of large oral and craniofacial defects is the neogenesis of osseous and ligamentous interfacial structures. Currently, oral regenerative medicine strategies are unpredictable for repair of tooth supporting tissues destroyed as a consequence of trauma, chronic infection or surgical resection. A different approach combining the gel-casting method with Hydroxy Apatite HA-based scaffold and different cell lineages as a hybrid system leads to successively mimic the early stage of tooth development, in vitro. HA is widely accepted as a bioactive material for guided bone and tooth regeneration. In this study, it was reported that, HA porous scaffold preparation, characterization and evaluation of structural and chemical properties. HA is the main factor that exists in tooth and it is in harmony with structural, biological, and mechanical characteristics. Here, this study shows mimicking immature tooth at the late bell stage design and construction of HA scaffolds for cell transplantation of human Adipose Stem Cells (hASCs), human Bone Marrow Stem Cells (hBMSCs) and Gingival Epitelial cells for the formation of human tooth dentin-pulp-enamel complexes in vitro. Scaffold characterization was demonstrated by SEM, FTIR and pore size and density measurements. The biological contraction of dental tissues against each other was demonstrated by mRNA gene expressions, histopatologic observations and protein release profile by ELISA tecnique. The tooth shaped constructs with a pore size ranging from 150 to 300 µm arranged by gathering right amounts of materials provide interconnected macro-porous structure. The newly formed tissue like structures that grow and integrate within the HA designed constructs forming tooth cementum like tissue, pulp and bone structures. These findings are important as they emphasize the potential biological effect of the hybrid scaffold system. In conclusion, this in vitro study clearly demonstrates that designed 3D scaffolds shaped as a immature tooth at the late bell stage were essential to form enamel-dentin-pulp interfaces with an appropriate cell and biodegradable material combination. The biomimetic architecture achieved here is providing a promising platform for dental tissue engineering.

Keywords: tooth regeneration, tissue engineering, adipose stem cells, hydroxyapatite tooth engineering, porous scaffold

Procedia PDF Downloads 209

Authors: A. M. Malagon Escandon, J. A. Arenas Alatorre, C. P. Chaires Rosas, N. A. Vazquez Torres, B. Hernandez Tellez, G. Pinon Zarate, M. Herrera Enriquez, A. E. Castell Rodriguez

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The current approach to the treatment of bone defects involves the use of scaffolds that provide a biological and mechanically stable niche to favor tissue repair. Despite the significant progress in the field of bone tissue engineering, several main problems associated are attributed to giving a low biodegradation degree, does not promote osseointegration and regeneration, if the bone is not healing as well as expected or fails to heal, will not be given a proper ossification or new bone formation. The actual approaches of bone tissue regeneration are directed to the use of decellularized native extracellular matrices, which are able of retain their own architecture, mechanic properties, biodegradability and promote new bone formation because they are capable of conserving proteins and other factors that are founded in physiological concentrations. Therefore, we propose an extracellular matrix-based bioscaffolds derived from bovine cancellous bone, which is processed by decellularization, demineralization, and hydrolysis of the collagen protein, these protocols have been successfully carried out in other organs and tissues; the effectiveness of its biosafety has also been previously evaluated in vivo and Food and Drug Administration (FDA) approved. In the specific case of bone, a more complex treatment is needed in comparison with other organs and tissues because is necessary demineralization and collagen denaturalization. The present work was made in order to obtain a temporal scaffold that succeed in degradation in an inversely proportional way to the synthesis of extracellular matrix and the maturation of the bone by the cells of the host.

Keywords: bioactive, biodegradable, bone, extracellular matrix-based bioscaffolds, stem cells, tissue engineering

Procedia PDF Downloads 127

Authors: Dinoo Kirthinanda, Sujani Wijeratne

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Pseudohyperkalaemia is a common benign in vitro phenomenon caused by the release of potassium ions (K+) from cells during specimen processing. Analysis of haemolysed blood samples for predominantly intracellular electrolytes may lead to re-investigation and potentially harmful interventions. We report a case of a 52-year male with myeloproliferative disease manifested as Polycythaemia Rubra Vera, Hypertension and hypertensive nephropathy with stage 3 chronic kidney disease admitted to Neuro-intensive care unit (NICU) with an intra-cerebral haemorrhage secondary to hypertensive bleed. His initial blood investigations showed hyperkalemia with serum K+ 6.2 mmol/L yet the bedside arterial blood gas analysis yielded K+ of 4.6 mmol/L. The patient was however given hyperkalemia regime twice based on venous electrolyte analysis. The discrepancy between the bedside electrolyte analysis using arterial blood and venous blood prompted further evaluation. The 12 lead Electrocardiogram showed U waves and sinus bradycardia corresponding to the serum K+ of 2.8 mmol/L on arterial blood gas analysis. Immediate K+ replacement ensured the patient did not develop life-threatening cardiac complications. Pseudohyperkalaemia may pose diagnostic challenges in the absence of detectable haemolysis and should be suspected in susceptible patients with normal Electrocardiogram and Glomerular Filtration Rate to avoid potentially life-threatening interventions. When in doubt, rapid analysis of arterial blood gas may be useful for accurate quantification of potassium.

Keywords: patient safety, pseudohyperkalaemia, haemolysis, myeloproliferative disorder

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Authors: Nahid Eskandari, Marjan Ghagozolo, Ehsan Almasi

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

Keywords: silymarin, immunosuppressive effect, rapamycin, immunology

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Authors: Abdullah Özköse, Ahmet Tamkoç

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The present study was conducted to determine the yield and yield components of smooth bromegrass lines under the environmental conditions of the Konya region during the growing seasons between 2011 and 2013. The experiment was performed in the randomized complete block design (RCBD) with four replications. It was found that the selected lines had a statistically significant effect on all the investigated traits, except for the main stem length and the number of nodes in the main stem. According to the two-year average calculated for various parameters checked in the smooth bromegrass lines, the main stem length ranged from 71.6 cm to 79.1 cm, the main stem diameter from 2.12 mm from 2.70 mm, the number of nodes in the main stem from 3.2 to 3.7, the internode length from 11.6 cm to 18.9 cm, flag leaf length from 9.7 cm to 12.7 cm, flag leaf width from 3.58 cm to 6.04 mm, herbage yield from 221.3 kg da^–1 to 354.7 kg da^–1 and hay yield from 100.4 kg da^–1 to 190.1 kg da^–1. The study concluded that the smooth bromegrass lines differ in terms of yield and yield components. Therefore, it is very crucial to select suitable varieties of smooth bromegrass to obtain optimum yield.

Keywords: semiarid region, smooth bromegrass, yield, yield components

Procedia PDF Downloads 251

Authors: H. M. Abdelmoneim, N. A. Babtain, A. S. Barhamain, A. Z. Kufiah, A. S. Malibari, S. F. Munassar, R. S. Rawa

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Introduction: Prostate cancer is one of the most common causes of morbidity and mortality in men in developed countries. Cancer Stem Cells (CSCs) could be responsible for the progression and relapse of cancer. Therefore, CSCs markers could provide a prognostic strategy for human malignancies. Aldehyde dehydrogenase 1A1 (ALDH1A1) activity has been shown to be associated with tumorigenesis and proposed to represent a functional marker for tumor initiating cells in various tumor types including prostate cancer. Material & Methods: We analyzed the immunohistochemical expression of ALDH1A1 in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma and assessed their significant correlations in 50 TURP sections. They were microscopically interpreted and the results were correlated with histopathological types and tumor grade. Results: In different prostatic histopathological lesions we found that ALDH1A1 expression was low in BPH (13.3%) and PIN (6.7%) and then its expression increased with prostatic adenocarcinoma (40%), and this was statistically highly significant (P value = 0.02). However, in different grades of prostatic adenocarcinoma we found that the higher the Gleason grade the higher the expression for ALDH1A1 and this was statistically significant (P value = 0.02). We compared the expression of ALDH1A1 in PIN and prostatic adenocarcinoma. ALDH1A1 expression was decreased in PIN and highly expressed in prostatic adenocarcinoma and this was statistically significant (P value = 0.04). Conclusion: Increasing ALDH1A1 expression is correlated with aggressive behavior of the tumor. Immunohistochemical expression of ALDH1A1 might provide a potential approach to study tumorigenesis and progression of primary prostate carcinoma.

Keywords: ALDH1A1, BPH, PIN, prostatic adenocarcinoma

Procedia PDF Downloads 237

Authors: Jeounghee Kim

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Objective: To describe the incidence of complication, according to the stage of Traumatic Spinal Cord Injury (TSCI) which was treated at Asan Medical Center (AMC), Korea. Hereafter, it should be developed in nursing management protocol of traumatic SCI. Methods. Retrospectively reviewed hospital records about the patients who were admitted AMC Patients with traumatic spinal cord injury until January 2005 and December 2016 were analyzed (n=97). AMC is a single institution of 2,700 beds where patients with trauma and severe trauma can be treated. Patients who were admitted to the emergency room due to spinal cord injury and who underwent intensive care unit, general ward, and rehabilitation ward. To identify long-term complications, we excluded patients who were operated on to other hospitals after surgery. Complications such as respiratory(pneumonia, atelectasis, pulmonary embolism, and others), cardiovascular (hypotension), urinary (autonomic dysreflexia, urinary tract infection (UTI), neurogenic bladder, and others), and skin systems (pressure ulcers) from the time of admission were examined through medical records and images. Results: SCI was graded according to ASIA scale. The initial grade was checked at admission. (grade A 55(56.7%), grade B 14(14.4)%, grade C 11(11.3%), grade D 15(15.5%), and grade E 2(2.1%). The grade was rechecked when the patient was discharged after treatment. (grade A 43(44.3%), grade B 15(15.5%), grade C 12(12.4%), grade D 21(21.6%), and grade E 6(6.2%). The most common complication after SCI was UTI 24cases (mean 36.5day), sore 24cases (40.5day), and Pneumonia which was 23 cases after 10days averagely. The other complications after SCI were neuropathic pain 19 cases, surgical site infection 4 cases. 53.6% of patient who had SCI were educated about intermittent catheterization at discharge from hospital. The mean hospital stay of all SCI patients was 61days. Conclusion: The Complications after traumatic SCI were developed at various stages from acute phase to chronic phase. Nurses need to understand fully the time-course of complication in traumatic SCI to provide evidence-based practice.

Keywords: spinal cord injury, complication, nursing, rehabilitation

Procedia PDF Downloads 191

Authors: Muhammad Fiaz Qamar, Ahmad Faraz, Muhammad Arfan Zaman, Kazim Ali, Waleed Akram

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Babesiosis is reflected as the most important disease of cattle that are transmitted by arthropods. In Pakistan, its prevalence is up to 29% in the cattle and buffalo population in different regions. Cattle show a long lasting and durable immunity by giving an infection of B.bovis, B. bigemina, or Babesiadivergens. this is used in cattle to immunize them in a few countries as anti-babesiosis vaccine. Development of frozen vaccine allows for complete testing after production of each batch, However, once thawed, its reduced its shelf life, frozen vaccines are more difficult to transport as well as expensive to produce as compared to chilled vaccine. The contamination of blood derived vaccine has the potential risk that makes pre-production and post-production quality control necessary. For the trail master seed production of whole blood frozen bivalent Babesia(Babesiabovis and Babesiabigemina), 100 blood samples of Babesial positive suspected cattle was taken and processed for separation microscopic detection and rectification by PCR. Vaccine passages were done to reduce the parasitaemiasis in live calves. After 8 passages, parasitemia of Babesia reduced from 80% to 15%. Infected donor calf’s blood was taken by jugular cannulation by using preservative free lithium heparin as an anticoagulant (5 International Units IU heparin/ml blood). In lab, parasite containing blood was mixed in equal volumes with 3 M glycerol in PBS supplemented with 5 mM glucose (final concentration of glycerol 1.5 M) at 37°C. The mixture was then equilibrized at 37°C for 30 minutes and were dispensed in required containers (e.g., 5 ml cryovials).

Keywords: distribution, babesia, primer sequences, PCV

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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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Authors: Ana M. Korol, Bibiana Riquelme, Osvaldo A. Rosso

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Since erythrocyte deformability analysis is mostly qualitative, the development of quantitative nonlinear methods is crucial for restricting subjectivity in the study of cell behaviour. An electro-optic mechanic system called erythrodeformeter has been developed and constructed in our laboratory in order to evaluate the erythrocytes' viscoelasticity. A numerical method formulated on the basis of fractal approximation for ordinary (OBM) and fractionary Brownian motion (FBM), as well as wavelet transform analysis, are proposed to distinguish chaos from noise based on the assumption that diffractometric data involves both deterministic and stochastic components, so it could be modelled as a system of bounded correlated random walk. Here we report studies on 25 donors: 4 alpha thalassaemic patients, 11 beta thalassaemic patients, and 10 healthy controls non-alcoholic and non-smoker individuals. The Correlation Coefficient, a nonlinear parameter, showed evidence of the changes in the erythrocyte deformability; the Wavelet Entropy could quantify those differences which are detected by the light diffraction patterns. Such quantifiers allow a good deal of promise and the possibility of a better understanding of the rheological erythrocytes aspects and also could help in clinical diagnosis.

Keywords: red blood cells, deformability, nonlinear dynamics, chaos theory, wavelet trannsform

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Authors: Daria Grechishnikova, Maria Poptsova

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Transposable elements play an important role in the evolution of various species from bacteria to human. Long Interspersed Nuclear Elements (LINEs) and Short Interspersed Nuclear Elements (SINEs) are two major classes of retrotransposons that occupy a considerable part of any genome and their copy numbers can range form several hundreds to a million. Both LINEs and SINEs multiply through a copy-and-paste mechanism. LINEs encode proteins, which make them capable of self-propagation while SINEs are parasitic and require the machinery of LINEs to multiply. The mechanisms how LINE and SINE RNA is recognized by the LINE-encoded reverse transcriptase (RT) remain unclear. For some SINE-LINE pairs, it was shown that they share a common 3’-end with a stem-loop structure. Majority of the SINE-LINE pairs do not have a common 3’-end. Recently we have shown that in the human genome Alu-L1 pairs have structurally similar stem-loop structure at the 3’-end. Here we extended our analysis to a wide range of species and analyzed LINEs from 161 different species from Repbase and 217 SINE sequences from SINEBase. It appeared that all of the analyzed sequences contained stem-loop structures at the 3’-end. Here we conclude that it is very likely that a common evolutionary mechanism of transposon RNA recognition requires the presence of stem-loop structures at their 3’-end.

Keywords: LINE, SINE, mechanisms of retrotransposition, retrotransposons, stem-loop, stem-loop structures, transposons

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Authors: Y. Abdulmumin, K. I. Matazu, A. M. Wudil, A. J. Alhassan, A. A. Imam

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Phytochemical analysis of Boswellia papryfera confirms the presence of various phytochemicals such as alkaloids, flavonoids, tannins, saponins and cardiac glycosides in its aqueous stem bark extract at different concentration, with tannins being the highest (0.611 ± 0.002 g %). Acute toxicity test (LD50, oral, rat) of the extract showed no mortality at up to 5000 mg/kg and the animals were found active and healthy. The extract was declared as practically non-toxic, this suggest the safety of the extract in traditional medicine.

Keywords: acute toxicity, aqueous extract, boswellia papryfera, phytochemicals and stem bark

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Authors: Demmiele Matu Kiiza, Constantine Steven Labongo Loum, Julaina Obika Asinasi

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Background: The use of traditional medicine in Uganda forms the preliminary therapeutic approaches among many people. Traditional medicines have been used in Uganda for many years, not only for the management of pregnancy-related complications but also for the management of other physical and psychological illnesses. Traditional medicines are always considered the first line of treatment by a considerable number of people. This study, therefore, sought to explore the lived experiences of pregnant women by assessing their perceptions of the transitional use of traditional medicine. Methods: Ethnography was used to capture data from an emic perspective. The ethnographic approach involved visiting a few selected pregnant women to observe and participate in the identification of traditional medicines. The ethnographic fieldwork was carried out within a period of three months. In-depth interviews were carried out and audio recorded and later transcribed verbatim. Data was thereafter analyzed thematically. The thematic analysis involved identifying statements made by research participants by transcribing audio and reading through field notes, coding was done, and themes were generated according to commonly mentioned experiences of using traditional medicine. Results: The findings revealed that women performed a ritual of ‘cutting the cord’ by making a small horizontal incision on the belly across the linea Nigra (also known as a pregnancy line) at around six months of pregnancy to avoid producing a baby with an umbilical cord tied around the baby’s neck. They also used crushed egg shells, crushed snail shells and herbs such as pawpaw roots, Entarahompo (crassocephalum vitelline), Ekyoganyanja (Erlangea tomentose), to manage Omushohokye (a term used by the study participants to refer to a situation where women pass out too much water when giving birth, producing a child with mold and oozing out of a milky liquid through the breasts before giving births); prepare for safe delivery and also to manage pregnancy-related complications. The study recommends the implementation of a traditional medicine use policy using a bottom-up approach. Designing and implementing of culturally sensitive maternal healthcare intervention programs and involving village health teams and the elderly in health education.

Keywords: traditional medicine, pregnant women, uganda, perceptions

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Authors: Ali Taher Othman Ali

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The aim of this research is to provide a draft proposal for the professional development of mathematics teachers in accordance with the orientation of science, technology, engineering and mathematics which is known by the abbreviation STEM, as a modern and contemporary orientation in the teaching and learning of mathematics and in order to achieve the objective of the research, the researcher used the theoretical descriptive method through the induction of the literature of education and the previous studies and experiments related to the topic. The researcher concluded by providing the proposal according to five basic axes, the first axe: professional development as a system, and its requirements include: development of educational systems, and allocate sufficient budgets to support the requirements of teaching STEM, identifying mechanisms for incentives and rewards for teachers attending professional development programs based on STEM; the second: development of in-depth knowledge content and its requirements include: basic sciences content development for STEM, linking the scientific understanding of teachers with real-world issues and problems, to provide the necessary resources to expand teachers' knowledge in this area; the third: the necessary pedagogical skills of teachers in the field of STEM, and its requirements include: identification of the required training and development needs and the mechanism of determining these needs, the types of professional development programs and the mechanism of designing it, the mechanisms and places of execution, evaluation and follow-up; the fourth: professional development strategies and mechanisms in the field of STEM, and its requirements include: using a variety of strategies to enable teachers to design and transfer effective educational experiences which reflect their scientific mastery in the fields of STEM, provide learning opportunities, and developing the skills of procedural research to generate new knowledge about the STEM; the fifth: to support professional development in the area of STEM, and its requirements include: support leadership within the school, provide a clear and appropriate opportunities for professional development for teachers within the school through professional learning communities, building partnerships between the Ministry of education and the local and international community institutions. The proposal includes other factors that should be considered when implementing professional development programs for mathematics teachers in the field of STEM.

Keywords: professional development, mathematics teachers, the orientation of science, technology, engineering and mathematics (STEM)

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Authors: Ainia Nurul Aqida

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Lead is one of the sources of air pollution. The use of lead on motor vehicle fuels resulted in the increasing contamination of lead in the air. The polluted air that has been inhaled by many people, especially guards and sellers of retail gasoline filling stations. The impact is increased levels of lead in blood. One result is an increase in blood pressure that causes hypertension. This research would like to know the relationship between blood lead levels in the incidence of hypertension in Indonesia. The method used in this study is a systematic review of the three journals have been published in the year 2007 to the year 2010 with the total sample is 312 samples. Odd ratio values obtained in the first article was OR = 6.50 pvalue = 0.000, CI = 95 % (2.89 to 14.60), and the second article was obtained OR 2.619 (95 % CI: 0.944 to 7.625) pvalue = 0.028, and the third article was obtained 0.002 r = 0.324 R2 = 10.5 %. Over all, there is a relationship between blood lead levels with the incidence of hypertension in Indonesia.

Keywords: lead, blood, air pollution, hypertension

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Authors: Qasem Qananwah, Ahmad Dagamseh, Hiam AlQuran, Khalid Shaker Ibrahim

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Blood pressure helps the physicians greatly to have a deep insight into the cardiovascular system. The determination of individual blood pressure is a standard clinical procedure considered for cardiovascular system problems. The conventional techniques to measure blood pressure (e.g. cuff method) allows a limited number of readings for a certain period (e.g. every 5-10 minutes). Additionally, these systems cause turbulence to blood flow; impeding continuous blood pressure monitoring, especially in emergency cases or critically ill persons. In this paper, the most important statistical features in the photoplethysmogram (PPG) signals were extracted to estimate the blood pressure noninvasively. PPG signals from more than 40 subjects were measured and analyzed and 12 features were extracted. The features were fed to principal component analysis (PCA) to find the most important independent features that have the highest correlation with blood pressure. The results show that the stiffness index means and standard deviation for the beat-to-beat heart rate were the most important features. A model representing both features for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) was obtained using a statistical regression technique. Surface fitting is used to best fit the series of data and the results show that the error value in estimating the SBP is 4.95% and in estimating the DBP is 3.99%.

Keywords: blood pressure, noninvasive optical system, principal component analysis, PCA, continuous monitoring

Procedia PDF Downloads 138

Authors: Afshin Zahedi, Keivan Jamshidi

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This study was conducted to determine the neurotoxic effects of different doses of ACR on the thoracic axons of the spinal cord of rat. To evaluate this hypothesis in the thoracic axons, amino-cupric silver staining technique of the de Olmos was conducted to define the histopathologic characteristic (argyrophilia) of axonal damage following ACR exposure. For this purpose 60 adult male rats (Wistar, approximately 250 g) were selected. Rats were hosed in polycarbonate boxes as two per each. Randomly assigned groups of rats (10 rats per exposure group, total 5 exposure groups as A, B, C, D and E) were exposed to 0.5, 5, 50, 100 and 500 mg/kg per day×11days intraperitoneal injection (IP injection) respectively. The remaining 10 rats were housed in group (F) as control group. Control rats received daily injections of 0.9% saline (3ml/kg). As indices of developing neurotoxicity, weight gain, gait scores and landing hindlimb foot splay (LHF) were determined. Weight gains were measured daily prior to injection. Gait scoring involved observation of spontaneous open field locomotion, included evaluations of ataxia, hopping, rearing and hind foot placement, and hindlimb foot splay were determined 3-4 times per week. Gait score was assigned from 1-4. After 11 days, two rats for silver stain, were randomly selected, dissected and proper samples were collected from thoracic portion of the spinal cord of rat. Results did show no neurological behavior in groups A, B and F, whereas severe neurotoxicity was observed in groups C and D. Rats in groups E died within 1-2 hours due to severe toxemia. In histopathological studies based on the de Olmos technique no argyrophilic neurons or processes were observed in stained sections obtained from the thoracic portion of the spinal cord of rats belong to groups A, B and F, while moderate to severe argyrophilic changes were observed in different stained sections obtained from the thoracic portion of the spinal cord of rats belong to groups C and D.

Keywords: acrylamide, rat, axonopathy, argyrophily, de Olmos

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Authors: Jimmy Jiun-Ming Su, Yuan-Min Lin

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Bioprinting has been applied to produce 3D cellular constructs for tissue engineering. Microextrusion printing is the most common used method. However, printing low viscosity bioink is a challenge for this method. Herein, we developed a new 3D printing system to fabricate cell-laden hydrogels via a DLP-based projector. The bioprinter is assembled from affordable equipment including a stepper motor, screw, LED-based DLP projector, open source computer hardware and software. The system can use low viscosity and photo-polymerized bioink to fabricate 3D tissue mimics in a layer-by-layer manner. In this study, we used gelatin methylacrylate (GelMA) as bioink for stem cell encapsulation. In order to reinforce the printed construct, surface modified hydroxyapatite has been added in the bioink. We demonstrated the silanization of hydroxyapatite could improve the crosslinking between the interface of hydroxyapatite and GelMA. The results showed that the incorporation of silanized hydroxyapatite into the bioink had an enhancing effect on the mechanical properties of printed hydrogel, in addition, the hydrogel had low cytotoxicity and promoted the differentiation of embedded human bone marrow stem cells (hBMSCs) and retinal pigment epithelium (RPE) cells. Moreover, this bioprinting system has the ability to generate microchannels inside the engineered tissues to facilitate diffusion of nutrients. We believe this 3D bioprinting system has potential to fabricate various tissues for clinical applications and regenerative medicine in the future.

Keywords: bioprinting, cell encapsulation, digital light processing, GelMA hydrogel

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Authors: Magda I. Hassan

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This paper aims to investigate the health effects of aspartame on weanling male hamsters. 20 Golden Syrian hamsters drank only water (control) or water with 6, 11, and 18 mg aspartame/kg of body weight per day for 42 days. Food intake, weight gain, glucose blood level, and lipid profile were determined at the end of the experiment. The animals were sacrificed and histopathological examination of organs (liver, brain and heart) was done. Results revealed that animals in Asp.groups consumed significantly larger amount of food than the control (13.4±5.9, 8.6±2.5 and 8.8±3.0 vs 4.2±2.5 g/day, in succession). Hamsters in the control group showed higher total cholesterol and HDL levels than hamsters in aspartame 6, 11, 18 groups (160±19 vs 101±13, 130±22, 141±15 mg/dl & 144±9 vs 120±12, 118±13, 99±17 respectively (P<0•05)). The control group showed a glucose concentration below those of aspartame groups, indicating no effect of aspartame on glucose blood level. While, there were no significant differences in the triglycerides and LDL levels between control group and Asp.groups. Histopathological changes were observed, especially in brain and liver cells. Aspartame increases appetite and weight gain of young hamsters. Therefore, FDA should reconsider the acceptable daily intake (ADI) of aspartame for children.

Keywords: aspartame, brain, food intake, hamsters

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Authors: Hiroki Tsuneda, Takamasa Suzuki, Hideki Yamamoto, Kimito Kawamura, Eiji Tamura, Katharina Wochner, Roberto Plasenzotti

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Flow property of human blood is one of the important factors on the prevention of the circulatory condition such as a high blood pressure, a diabetes mellitus, and a cardiac infarction. However, the measurement of flow property of human blood, especially blood viscosity, is not so easy, because of their coagulation or aggregation behaviors after taking a sample from blood vessel. In the experiment, some kinds of anticoagulant were added into the human blood to avoid its solidification. Anticoagulant used in the blood test has been chosen for each purpose of blood test, for anticoagulant effect on blood is different mechanism for each. So that, there is a problem that the evaluation of measured blood property with different anticoagulant is so difficult. Therefore, it is so important to make clear the difference of anticoagulant effect on the blood property. In the previous work, a compact-size falling needle rheometer (FNR) has been developed in order to measure the flow property of human blood such as a flow curve, an apparent viscosity. It was found that FNR system can apply to a rheometer or a viscometry for various experimental conditions for not only human blood but also mammalians blood. In this study, the measurements of human blood viscosity with different anticoagulant (EDTA and Heparin) were carried out using newly developed FNR system. The effect of anticoagulant on blood viscosity was also tested by using the standard liquid for each. The accuracy on the viscometry was also tested by using the standard liquid for calibrating materials (JS-10, JS-20) and observed data have satisfactory agreement with reference data around 1.0% at 310K. The flow curve of six males and females with different anticoagulant were measured using FNR. In this experiment, EDTA and Heparin were chosen as anticoagulant for blood. Heparin can inhibit the coagulation of human blood by activating the body of anti-thrombin. To examine the effect of human blood viscosity on anticoagulant, flow curve was measured at high shear rate (＞350s-1), and apparent viscosity of each person were determined with different anticoagulant. The apparent viscosity of human blood with heparin was 2%-9% higher than that with EDTA. However, the difference of blood viscosity for two anticoagulants for same blood was different for each. Further discussion, we need the consideration of effect on other physical property, such as cellular component and plasma component.

Keywords: falling-needle rheometer, human blood, viscosity, anticoagulant

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Authors: Abdul-Monim Batiha, Manar AlAzzam, Mohammed ALBashtawy, Loai Tawalbeh, Ahmad Tubaishat, Fadwa N. Alhalaiqa

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Background: Obesity is the major modifiable risk factor for many chronic illnesses especially high blood pressure. Objectives: To evaluate the relationship between anthropometric indices and high blood pressure, and which one was most strongly correlated with high blood pressure in Jordanian population. Methods: A cross-sectional study was conducted with a total 622 students and workers from three Jordanian universities. Results: Nearly half of the participant are overweight (34.7%) and obese (15.4%) and hypertension was detected among 138 (22.2%) of the participants. Linear correlation was significant (p<0.01) between both systolic blood pressure and diastolic blood pressure for all anthropometric indices, except for A body shape index and diastolic blood pressure was significant at p< 0.05. Stepwise multiple linear regression analysis was used to assess the influence of age and anthropometric measurements. Conclusions: The waist circumference was the only independent predictor of hypertension, showing that this simple measurement may be an importance marker of high blood pressure in Jordanian population.

Keywords: anthropometric indices, Jordan, blood pressure, cross-sectional study, obesity, hypertension, waist circumference

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Authors: Y. Abdulmumin, K. I. Matazu, A. M. Wudil, A. J. Alhassan, A. A. Imam

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Phytochemical analysis of Boswellia papryfera confirms the presence of various phytochemicals such as alkaloids, flavonoids, tannins, saponins and cardiac glycosides in its aqueous stem bark extract at different concentration, with tannins being the highest (0.611 ± 0.002 g %). Acute toxicity test (LD50,oral, rat) of the extract showed no mortality at up to 5000 mg/kg and the animals were found active and healthy. The extract was declared as practically non-toxic, this suggest the safety of the extract in traditional medicine.

Keywords: acute toxicity, aqueous extract, boswellia papryfera, phytochemicals, stem bark extract

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Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

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Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

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Authors: Anjali Roy, Mirza S. Baig

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Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.

Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL

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Authors: Atitallah Sofien, Bouyahia Olfa, Romdhani Meriam, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Spondylothoracic dysostosis, also known as Jarcho-Levin syndrome, is defined by a shortened neck and thorax, a protruding abdomen, inguinal and umbilical hernias, atypical spinal structure and rib fusion, leading to restricted chest movement or difficulty in breathing, along with urinary tract abnormalities and, potentially severe scoliosis. Aim: This is the case of a patient diagnosed with Jarcho-Levin syndrome, aiming to detail the range of abnormalities observed in this syndrome, the observed complications, and the therapeutic approaches employed. Results: A three-month-old male infant, born of a consanguineous marriage, delivered at full term by cesarean section, was admitted to the pediatric department for severe acute bronchiolitis. In his prenatal history, morphological ultrasound revealed macrosomia, a shortened spine, irregular vertebrae with thickened skin, normal fetal cardiac ultrasound, and the absence of the right kidney. His perinatal history included respiratory distress, requiring ventilatory support for five days. Upon physical examination, he had stunted growth, scoliosis, a short neck and trunk, longer upper limbs compared to lower limbs, varus equinus in the right foot, a neural tube defect, a low hairline, and low-set ears. Spondylothoracic dysostosis was suspected, leading to further investigations, including a normal transfontaneous ultrasound, a spinal cord ultrasound revealing a lipomyelocele-type closed dysraphism with a low-attached cord, an abdominal ultrasound indicating a single left kidney, and a cardiac ultrasound identifying Kommerell syndrome. Due to a lack of resources, genetic testing could not be performed, and the diagnosis was based on clinical criteria. Conclusion: Jarcho-Levin syndrome can result in a mortality rate of about 50%, primarily due to respiratory complications associated with thoracic insufficiency syndrome. Other complications, like heart and neural tube defects, can also lead to premature mortality. Therefore, early diagnosis and comprehensive treatment involving various specialists are essential.

Keywords: Jarcho-Levin syndrome, congenital disorder, scoliosis, spondylothoracic dysostosis, neural tube defect

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Authors: N. H. Harun, A. S. Abdul Nasir, M. Y. Mashor, R. Hassan

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Leukaemia is a blood cancer disease that contributes to the increment of mortality rate in Malaysia each year. There are two main categories for leukaemia, which are acute and chronic leukaemia. The production and development of acute leukaemia cells occurs rapidly and uncontrollable. Therefore, if the identification of acute leukaemia cells could be done fast and effectively, proper treatment and medicine could be delivered. Due to the requirement of prompt and accurate diagnosis of leukaemia, the current study has proposed unsupervised pixel segmentation based on clustering algorithm in order to obtain a fully segmented abnormal white blood cell (blast) in acute leukaemia image. In order to obtain the segmented blast, the current study proposed three clustering algorithms which are k-means, fuzzy c-means and moving k-means algorithms have been applied on the saturation component image. Then, median filter and seeded region growing area extraction algorithms have been applied, to smooth the region of segmented blast and to remove the large unwanted regions from the image, respectively. Comparisons among the three clustering algorithms are made in order to measure the performance of each clustering algorithm on segmenting the blast area. Based on the good sensitivity value that has been obtained, the results indicate that moving k-means clustering algorithm has successfully produced the fully segmented blast region in acute leukaemia image. Hence, indicating that the resultant images could be helpful to haematologists for further analysis of acute leukaemia.

Keywords: acute leukaemia images, clustering algorithms, image segmentation, moving k-means

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Authors: Liang Ning, Chung Hau Yin

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Angiogenesis is the process of new blood vessel development. It has been recognized as a therapeutic target for blocking cancer growth four decades ago. Vascular sprouting is initiated by pro-angiogenic factors. Vascular endothelial cell growth factor (VEGF) plays a central role in angiogenic initiation, many patients with cancer or ocular neovascularization have been benefited from anti-VEGF therapy. Emerging approaches impacting in the later stages of vessel remodeling and maturation are expected to improve clinical efficacy. TIE receptor as well as the corresponding angiopoietin ligands, were identified as another endothelial cell specific receptor tyrosine kinase signaling system. Much efforts were made to reduce the activity of angiopoietin-TIE receptor axis. Two eudesmane-type sesquiterpenes from laggera alata, namely, 15-dihydrocostic acid and ilicic acid were found with strong anti-angiogenic properties in zebrafish model. Meanwhile, the mRNA expression levels of VEGFR2 and TIE2 pathway related genes were down-regulated in the sesquiterpenes treated zebrafish embryos. Besides, in human umbilical vein endothelial cells (HUVECs), the sesquiterpenes have the ability to inhibit VEGF-induced HUVECs proliferation and migration at non-toxic concentration. Moreover, angiopoietin-2 induced TIE2 phosphorylation was inhibited by the sesquiterpenes, the inhibitory effect was detected in angiopoietin-1 induced HUVECs proliferation as well. Thus, we hypothesized the anti-angiogenic activity of the compounds may via the inhibition of VEGF and TIE2 related pathways. How the compounds come into play as the pathways inhibitors need to be evaluated in the future.

Keywords: Laggera alata, eudesmane-type sesquiterpene, anti-angiogenesis, VEGF, angiopoietin, TIE2

Procedia PDF Downloads 185