Search results for: muscle stem cells

Authors: B. Bouadjemi, S. Bentata, T. Lantri, Souidi Amel, W.Bensaali, A. Zitouni, Z. Aziz

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We performed first-principle calculations, the full-potential linearized augmented plane wave (FP-LAPW) method is used to calculate structural, optoelectronic and magnetic properties of cubic halide perovskites CsPbX3 (X= F,I). We employed for this study the GGA approach and for exchange is modeled using the modified Becke-Johnson (mBJ) potential to predicting the accurate band gap of these materials. The optical properties (namely: the real and imaginary parts of dielectric functions, optical conductivities and absorption coefficient absorption make this halide perovskites promising materials for solar cells applications.

Keywords: halide perovskites, mBJ, solar cells, FP-LAPW, optoelectronic properties, absorption coefficient

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Authors: Wadha Alqahtani

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In recent times, polymers have seen a great surge in interest in the field of medicine, particularly chemotherapeutics. One recent innovation is the conversion of polymeric materials into “polymeric nanoparticles”. These nanoparticles can be designed and modified to encapsulate and transport drugs selectively to cancer cells, minimizing collateral damage to surrounding healthy tissues, and improve patient quality of life. In this study, we have synthesized pseudo-branched polyester polymers from bio-based small molecules, including sorbitol, glutaric acid and a propargylic acid derivative to further modify the polymer to make it “click-able" with an azide-modified target ligand. Melt polymerization technique was used for this polymerization reaction, using lipase enzyme catalyst NOVO 435. This reaction was conducted between 90- 95 °C for 72 hours. The polymer samples were collected in 24-hour increments for characterization and to monitor reaction progress. The resulting polymer was purified with the help of methanol dissolving and filtering with filter paper then characterized via NMR, GPC, FTIR, DSC, TGA and MALDI-TOF. Following characterization, these polymers were converted to a polymeric nanoparticle drug delivery system using solvent diffusion method, wherein DiI optical dye and chemotherapeutic drug Taxol can be encapsulated simultaneously. The efficacy of the nanoparticle’s apoptotic effects were analyzed in-vitro by incubation with prostate cancer (LNCaP) and healthy (CHO) cells. MTT assays and fluorescence microscopy were used to assess the cellular uptake and viability of the cells after 24 hours at 37 °C and 5% CO2 atmosphere. Results of the assays and fluorescence imaging confirmed that the nanoparticles were successful in both selectively targeting and inducing apoptosis in 80% of the LNCaP cells within 24 hours without affecting the viability of the CHO cells. These results show the potential of using biodegradable polymers as a vehicle for receptor-specific drug delivery and a potential alternative for traditional systemic chemotherapy. Detailed experimental results will be discussed in the e-poster.

Keywords: chemotherapeutic drug, click chemistry, nanoparticle, prostat cancer

Procedia PDF Downloads 117

Authors: V. M. B. K. T. Malwanage, S. Samita

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Core stability is one of the major determinants that contribute to preventing injuries, enhance performance, and improve quality of life of the human. Endurance of the four major muscle groups of the central ‘core’ of the human body is identified as the most reliable determinant of core stability amongst the other numerous causes which contribute to readily make one’s core stability. This study aimed to develop a ‘Core Stability Index’ to confer a single value for an individual’s core stability based on the four endurance test scores. Since it is possible that at least some of the test scores are not independent, possibility of constructing a single index using the multivariate method exploratory factor analysis was investigated in the study. The study sample was consisted of 400 healthy young individuals with the mean age of 23.74 ± 1.51 years and mean BMI (Body Mass Index) of 21.1 ± 4.18. The correlation analysis revealed highly significant (P < 0.0001) correlations between test scores and thus construction an index using these highly inter related test scores using the technique factor analysis was justified. The mean values of all test scores were significantly different between males and females (P < 0.0001), and therefore two separate core stability indices were constructed for the two gender groups. Moreover, having eigen values 3.103 and 2.305 for males and females respectively, indicated one factor exists for all four test scores and thus a single factor based index was constructed. The 95% reference intervals constructed using the index scores were -1.64 to 2.00 and -1.56 to 2.29 for males and females respectively. These intervals can effectively be used to diagnose those who need improvement in core stability. The practitioners should find that with a single value measure, they could be more consistent among themselves.

Keywords: construction of indices, endurance test scores, muscle endurance, quality of life

Procedia PDF Downloads 164

Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche

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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.

Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells

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Authors: Yi-Feng Kao, Huey-Jine Chai, Chin-I Chang, Yi-Chen Chen, June-Ru Chen

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Microglia is a macrophage that resides in brain, and overactive microglia may result in brain neuron damage or inflammation. In this study, the phospholipids was extracted from squid skin and manufactured into a liposome (SQ liposome) to mimic apoptotic body. We then evaluated anti-inflammatory effects of SQ liposome on mouse microglial cell line (BV-2) by lipopolysaccharide (LPS) induction. First, the major phospholipid constituents in the squid skin extract were including 46.2% of phosphatidylcholine, 18.4% of phosphatidylethanolamine, 7.7% of phosphatidylserine, 3.5% of phosphatidylinositol, 4.9% of Lysophosphatidylcholine and 19.3% of other phospholipids by HPLC-UV analysis. The contents of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the squid skin extract were 11.8 and 28.7%, respectively. The microscopic images showed that microglia cells can engulf apoptotic cells or SQ-liposome. In cell based studies, there was no cytotoxicity to BV-2 as the concentration of SQ-liposome was less than 2.5 mg/mL. The LPS induced pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were significant suppressed (P < 0.05) by pretreated 0.03~2.5mg/ml SQ liposome. Oppositely, the anti-inflammatory cytokines transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10) secretion were enhanced (P < 0.05). The results suggested that SQ-liposome possess anti-inflammatory properties on BV-2 and may be a good strategy for against neuro-inflammatory disease.

Keywords: apoptotic mimicry, neuroinflammation, microglia, squid processing by-products

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Authors: Javed Iqbal

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The growing need for energy by the human society and depletion of conventional energy sources demands a renewable, safe, infinite, low-cost and omnipresent energy source. One of the most suitable ways to solve the foreseeable world’s energy crisis is to use the power of the sun. Photovoltaic devices are especially of wide interest as they can convert solar energy to electricity. Recently the best performing solar cells are silicon-based cells. However, silicon cells are expensive, rigid in structure and have a large timeline for the payback of cost and electricity. Organic photovoltaic cells are cheap, flexible and can be manufactured in a continuous process. Therefore, organic photovoltaic cells are an extremely favorable replacement. Organic photovoltaic cells utilize sunlight as energy and convert it into electricity through the use of conductive polymers/ small molecules to separate electrons and electron holes. A major challenge for these new organic photovoltaic cells is the efficiency, which is low compared with the traditional silicon solar cells. To overcome this challenge, usually two straightforward strategies have been considered: (1) reducing the band-gap of molecular donors to broaden the absorption range, which results in higher short circuit current density (JSC) of devices, and (2) lowering the highest occupied molecular orbital (HOMO) energy of molecular donors so as to increase the open-circuit voltage (VOC) of applications devices.8 Keeping in mind the cost of chemicals it is hard to try many materials on test basis. The best way is to find the suitable material in the bulk. For this purpose, we use computational approach to design molecules based on our organic chemistry knowledge and determine their physical and electronic properties. In this study, we did DFT calculations with different options to get high open circuit voltage and after getting suitable data from calculation we finally did synthesis of a novel D–π–A–π–D type low band-gap small molecular donor material (ZOPTAN-TPA). The Aarylene vinylene based bis(arylhalide) unit containing a cyanostilbene unit acts as a low-band- gap electron-accepting block, and is coupled with triphenylamine as electron-donating blocks groups. The motivation for choosing triphenylamine (TPA) as capped donor was attributed to its important role in stabilizing the separated hole from an exciton and thus improving the hole-transporting properties of the hole carrier.3 A π-bridge (thiophene) is inserted between the donor and acceptor unit to reduce the steric hindrance between the donor and acceptor units and to improve the planarity of the molecule. The ZOPTAN-TPA molecule features a low HOMO level of 5.2 eV and an optical energy gap of 2.1 eV. Champion OSCs based on a solution-processed and non-annealed active-material blend of [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) and ZOPTAN-TPA in a mass ratio of 2:1 exhibits a power conversion efficiency of 1.9 % and a high open-circuit voltage of over 1.0 V.

Keywords: high open circuit voltage, donor, triphenylamine, organic solar cells

Procedia PDF Downloads 243

Authors: B. González-Yebra, B. Flores-Nieto, P. Aguilar-Salinas, M. Preciado Puga, A. L. González Yebra

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The monitoring of populations occupationally exposed to organic solvents has been an important issue for several shoe factories for years since the International Agency for Research on Cancer (IARC) has advised on the potential carcinogenic risk of chemicals related to occupations. In order to detect if exposition to organic solvents used in some Mexican shoe factories contributes to oral carcinogenesis, we performed monitoring in three factories. Occupational exposure was determined by using monitors 3M. Organic solvents were assessed by gas chromatography. Then, we recruited 30 shoe workers (30.2 ± 8.4 years) and 10 unexposed subjects (43.3 ± 11.2 years) for the micronuclei (MN) test and immunodetection of some cancer biomarkers (ki-67, p16, caspase-3) in scraped oral epithelial cells. Monitored solvents detected were acetone, benzene, hexane, methyl ethyl ketone, and toluene in acceptable levels according to Official Mexican Norm. We found by MN test higher incidence of nuclear abnormalities (karyorrhexis, pycnosis, karyolysis, condensed chromatin, and macronuclei) in the exposed group than the non-exposed group. On the other hand, we found, a negative expression for Ki-67 and p16 in exfoliated epithelial cells from exposed and non-exposed to organic solvents subjects. Only caspase-3 shown positive patter of expression in 9/30 (30%) exposed subjects, and we detected high karyolysis incidence in caspase-3 subjects (p = 0.021). The absence of expression of proliferation markers p16 and ki-67 and presence of apoptosis marker caspase-3 are indicating the absence of malignancy in oral epithelial cells and low risk for oral cancer. It is a fact that the MN test is a very effective method to detect nuclear abnormalities in exfoliated buccal cells from subjects that have been exposed to organic solvents in the shoe industry. However, in order to improve this tool and predict cancer risk is it is mandatory to implement complementary tests as other biomarkers that can help to detect malignancy in individuals occupationally exposed.

Keywords: biomarkers, oral cancer, organic solvents, shoe industries

Procedia PDF Downloads 136

Authors: Awol Seid Ebrie

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HIV results as an incurable disease, AIDS. After a person is infected with virus, the virus gradually destroys all the infection fighting cells called CD4 cells and makes the individual susceptible to opportunistic infections which cause severe or fatal health problems. Several studies show that the CD4 cells count is the most determinant indicator of the effectiveness of the treatment or progression of the disease. The objective of this paper is to investigate the progression of the disease over time among patient under HAART treatment. Two main approaches of the generalized multilevel ordinal models; namely the proportional odds model and the nonproportional odds model have been applied to the HAART data. Also, the multilevel part of both models includes random intercepts and random coefficients. In general, four models are explored in the analysis and then the models are compared using the deviance information criteria. Of these models, the random coefficients nonproportional odds model is selected as the best model for the HAART data used as it has the smallest DIC value. The selected model shows that the progression of the disease increases as the time under the treatment increases. In addition, it reveals that gender, baseline clinical stage and functional status of the patient have a significant association with the progression of the disease.

Keywords: nonproportional odds model, proportional odds model, random coefficients model, random intercepts model

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Authors: Z. Khalifa, K. M. Hassan, M. Abdel Azzem

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Potential strategies for deriving useful forms of renewable high density energy from abundant energy stored in carbohydrates is direct conversion of glucose (GLU) to electrical power. A three novel versatile modified electrodes, synthesized by electrochemical polymerization of organic monomers on glassy carbon electrodes (GC), have been developed for biofuel cells results in stable and long-term power production. Electrocatalytic oxidation of glucose in alkaline solution on conducting polymers electrodes modified by incorporation of Ni nanoparticles (NiNPs) onto poly(1,5-aminonaphthalene) (1,5-PDAN), poly(1,8-diaminonaphthalene) (1,8-PDAN) and poly(1-amino-2-methyl-9,10-anthraquinone) (PAMAQ) was investigated. The electrocatalytic oxidation of glucose at NiNPs-modified 1,5-PDAN/GC, 1,8-PDAN/GC and PAMAQ/GC electrodes has been studied using voltammetry technique. The PDAN electrodes show a slight activity in the potential of interest. The prepared NiNPs/PAMAQ/GC catalyst showed a very interesting catalytic activity that was nicely comparable to the NiNPs/1,5-PDAN/GC, NiNPs/1,8-PDAN/GC modified electrodes. In advance, both shows a significant more catalytic activity compared to the reported data for electrodes for glucose electrocatalytic oxidation.

Keywords: biofuel cells, glucose oxidation, electrocatalysis, nanoparticles and modified electrodes

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Authors: Dimakatso B. Gumede, Nicolette N. Houreld

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Diabetic foot ulcers (DFUs) are a complication of diabetes mellitus (DM), a metabolic disease caused by insulin resistance or insufficiency, resulting in hyperglycaemia and low-grade chronic inflammation. Current therapies for treating DFUs include wound debridement, glycaemic control, and wound dressing. However, these therapies are moderately effective as there is a recurrence of these ulcers and an increased risk of lower limb amputations. Photobiomodulation (PBM), which is the application of non-invasive low-level light for wound healing at the spectrum of 660-1000 nm, has shown great promise in accelerating the healing of chronic wounds. However, its underlying mechanisms are not clearly defined. Studies have indicated that PBM induces wound healing via the activation of signaling pathways that are involved in tissue repair, such as the transforming growth factor-β (TGF-β). However, other signaling pathways, such as the WNT/β-catenin pathway, which is also critical for wound repair, have not been investigated. This study aimed to elucidate if PBM at 660 nm and a fluence of 5 J/cm² activates the WNT/β-catenin signaling pathway for wound healing in a diabetic cellular model. Human dermal fibroblasts (WS1) were continuously cultured high-glucose (26.5 mM D-glucose) environment to create a diabetic cellular model. A central scratch was created in the diabetic model to ‘wound’ the cells. The diabetic wounded (DW) cells were thereafter irradiated at 660 nm and a fluence of 5 J/cm². Cell migration, gene expression and protein assays were conducted at 24- and 48-h post-PBM. The results showed that PBM at 660 nm and a fluence of 5 J/cm² significantly increased cell migration in diabetic wounded cells at 24-h post-PBM. The expression of CTNNB1, ACTA2, COL1A1 and COL3A1 genes was also increased in DW cells post-PBM. Furthermore, there was increased cytoplasmic accumulation and nuclear localization of β-catenin at 24 h post-PBM. The findings in this study demonstrate that PBM activates the WNT/β-catenin signaling pathway by inducing the accumulation of β-catenin in diabetic wounded cells, leading to increased cell migration and expression of wound repair markers. These results thus indicate that PBM has the potential to improve wound healing in diabetic ulcers via activation of the WNT/β-catenin signaling pathway.

Keywords: wound healing, diabetic ulcers, photobiomodulation, WNT/β-catenin, signalling pathway

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Authors: Madhu Gupta, G. P. Agrawa, Suresh P. Vyas

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Certain tumor cells overexpress a membrane-spanning molecule aminopeptidase N (CD13) isoform, which is the receptor for peptides containing the NGR motif. NGR-modified Docetaxel (DTX)-loaded PEG-b-PLGA polymeric nanoparticles (cNGR-DNB-NPs) were developed and evaluated for their in vitro potential in HT-1080 cell line. The cNGR-DNB-NPs containing particles were about 148 nm in diameter with spherical shape and high encapsulation efficiency. Cellular uptake was confirmed both qualitatively and quantitatively by Confocal Laser Scanning Microscopy (CLSM) and flow cytometry. Both quantitatively and qualitatively results confirmed the NGR conjugated nanoparticles revealed the higher uptake of nanoparticles by CD13-overexpressed tumor cells. Free NGR inhibited the cellular uptake of cNGR-DNB-NPs, revealing the mechanism of receptor mediated endocytosis. In vitro cytotoxicity studies demonstrated that cNGR-DNB-NPs, formulation was more cytotoxic than unconjugated one, which were consistent well with the observation of cellular uptake. Hence, the selective delivery of cNGR-DNB-NPs formulation in CD13-overexpressing tumors represents a potential approach for the design of nanocarrier-based dual targeted delivery systems for targeting the tumor cells and vasculature.

Keywords: solid Tumor, docetaxel, targeting, NGR ligand

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Authors: Mansa Radhakrishnan, Anwar Ali, Muhammad Rizwan Mughal

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Many universities around the world are working on modular and low budget architecture of small spacecraft to reduce the development cost of the overall system. This paper focuses on the design of a modular solar power harvesting system for a hexagonal-shaped small satellite. The designed solar power harvesting systems are composed of solar panels and power converter subsystems. The solar panel is composed of solar cells mounted on the external face of the printed circuit board (PCB), while the electronic components of power conversion are mounted on the interior side of the same PCB. The solar panel with dimensions 16.5cm × 99cm is composed of 36 solar cells (each solar cell is 4cm × 7cm) divided into four parallel banks where each bank consists of 9 solar cells. The output voltage of a single solar cell is 2.14V, and the combined output voltage of 9 series connected solar cells is around 19.3V. The output voltage of the solar panel is boosted to the satellite power distribution bus voltage level (28V) by a boost converter working on a constant voltage maximum power point tracking (MPPT) technique. The solar panel module is an eight-layer PCB having embedded coil in 4 internal layers. This coil is used to control the attitude of the spacecraft, which consumes power to generate a magnetic field and rotate the spacecraft. As power converter and distribution subsystem components are mounted on the PCB internal layer, therefore it is mandatory to do thermal analysis in order to ensure that the overall module temperature is within thermal safety limits. The main focus of the overall design is on compactness, miniaturization, and efficiency enhancement.

Keywords: small satellites, power subsystem, efficiency, MPPT

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Authors: Amir Seyfoori, Ehsan Samiei, Mohsen Akbari

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The use of microtechnology for detection and high yield isolation of circulating tumor cells (CTCs) has shown enormous promise as an indication of clinical metastasis prognosis and cancer treatment monitoring. The Immunomagnetic assay has been also coupled to microtechnology to improve the selectivity and efficiency of the current methods of cancer biomarker isolation. In this way, generation and configuration of the local high gradient magnetic field play essential roles in such assay. Additionally, considering the intrinsic heterogeneity of cancer cells, real-time analysis of isolated cells is necessary to characterize their responses to therapy. Totally, on-chip isolation and monitoring of the specific tumor cells is considered as a pressing need in the way of modified cancer therapy. To address these challenges, we have developed a bi-layer magnetic-based microfluidic chip for enhanced CTC detection and capturing. Micromagnet arrays at the bottom layer of the chip were fabricated using a new method of magnetic nanoparticle paste deposition so that they were arranged at the center of the chain microchannel with the lowest fluid velocity zone. Breast cancer cells labelled with EPCAM-conjugated smart microgels were immobilized on the tip of the micromagnets with greater localized magnetic field and stronger cell-micromagnet interaction. Considering different magnetic nano-powder usage (MnFe2O4 & gamma-Fe2O3) and micromagnet shapes (ellipsoidal & arrow), the capture efficiency of the systems was adjusted while the higher CTC capture efficiency was acquired for MnFe2O4 arrow micromagnet as around 95.5%. As a proof of concept of on-chip tumor cell monitoring, magnetic smart microgels made of thermo-responsive poly N-isopropylacrylamide-co-acrylic acid (PNIPAM-AA) composition were used for both purposes of targeted cell capturing as well as cell monitoring using antibody conjugation and fluorescent dye loading at the same time. In this regard, magnetic microgels were successfully used as cell tracker after isolation process so that by raising the temperature up to 37⁰ C, they released the contained dye and stained the targeted cell just after capturing. This microfluidic device was able to provide a platform for detection, isolation and efficient real-time analysis of specific CTCs in the liquid biopsy of breast cancer patients.

Keywords: circulating tumor cells, microfluidic, immunomagnetic, cell isolation

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Authors: Salma Loukman, Reda Benmrid, Najat Bouchmaa, Hicham Hboub, Rachid El Fatimy, Rachid Benhida

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In this study, it use integrated transcriptomic datasets from the GEO repository with the purpose of investigating immune dysregulation in COVID-19. Thus, in this context, we decided to be focused on NK cells and CD14+ monocytes gene expression, considering datasets GSE165461 and GSE198256, respectively. Other datasets with PBMCs, lung, olfactory, and sensory epithelium and lymph were used to provide robust validation for our results. This approach gave an integrated view of the immune responses in COVID-19, pointing out a set of potential biomarkers and therapeutic targets with special regard to standards of physiological conditions. IFI27, MKI67, CENPF, MBP, HBA2, TMEM158, THBD, HBA1, LHFPL2, SLA, and AC104564.3 were identified as key genes from our analysis that have critical biological processes related to inflammation, immune regulation, oxidative stress, and metabolic processes. Consequently, such processes are important in understanding the heterogeneous clinical manifestations of COVID-19—from acute to long-term effects now known as 'long COVID'. Subsequent validation with additional datasets consolidated these genes as robust biomarkers with an important role in the diagnosis of COVID-19 and the prediction of its severity. Moreover, their enrichment in key pathophysiological pathways presented them as potential targets for therapeutic intervention.The results provide insight into the molecular dynamics of COVID-19 caused by cells such as NK cells and other monocytes. Thus, this study constitutes a solid basis for targeted diagnostic and therapeutic development and makes relevant contributions to ongoing research efforts toward better management and mitigation of the pandemic.

Keywords: SARS-COV-2, RNA-seq, biomarkers, severity, long COVID-19, bio analysis

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Authors: Gintarė Sauliutė, Gintaras Svecevičius

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Landfill leachates contain a number of persistent pollutants, including heavy metals. They have the ability to spread in ecosystems and accumulate in fish which most of them are classified as top-consumers of trophic chains. Fish are freely swimming organisms; but perhaps, due to their species-specific ecological and behavioral properties, they often prefer the most suitable biotopes and therefore, did not avoid harmful substances or environments. That is why it is necessary to evaluate the persistent pollutant dispersion in hydroecosystem using fish tissue metal concentration. In hydroecosystems of hybrid type (e.g. river-pond-river) the distance from the pollution source could be a perfect indicator of such a kind of metal distribution. The studies were carried out in the Kairiai landfill neighboring hybrid-type ecosystem which is located 5 km east of the Šiauliai City. Fish tissue (gills, liver, and muscle) metal concentration measurements were performed on two types of ecologically-different fishes according to their feeding characteristics: benthophagous (Gibel carp, roach) and predatory (Northern pike, perch). A number of mathematical models (linear, non-linear, using log and other transformations) have been applied in order to identify the most satisfactorily description of the interdependence between fish tissue metal concentration and the distance from the pollution source. However, the only one log-multiple regression model revealed the pattern that the distance from the pollution source is closely and positively correlated with metal concentration in all predatory fish tissues studied (gills, liver, and muscle).

Keywords: bioaccumulation in fish, heavy metals, hydroecosystem, landfill leachate, mathematical model

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Authors: Gonzalo Ortiz de Elguea-Culebras, Raúl Sánchez-Vioquea, Adela Mena-Morales, Manuel Alaiz, Enrique Melero-Bravo, Esteban García-Romero, Javier Vioque, Lourdes Marchante-Cuevas, Julio Girón-Calle

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Saffron (Crocus sativus L.) is a highly valued crop for the manufacture of spice that consists of the dried stigma of the flowers. This is in contrast to other underutilized parts of the saffron plant as leaves, which represent abundant biomass whose use might help to enhance the sustainability of the saffron crop. Saffron leaves contain significant amounts of phenolic compounds, 7.8 equivalent grams of gallic acid per 100g of extract, and are very promising compounds in terms of exploring novel uses of saffron leaves. Given that phenolic compounds have numerous effects on cancer-related biological pathways, we have investigated the in vitro antiproliferative effect of saffron leaf polyphenols against human colon adenocarcinoma cells (Caco-2). Polyphenols were extracted from leaves with 70% ethanol, defatted with hexane, and purified by solid phase extraction using C18 silica gel and then silica gel 60. Analysis of polyphenols was performed by HPLC-ESI-MS. Di-, tri-, and tetrahexosides of quercetin, kaempferol, and isorhamnetin, as well as C-hexosides like isoorientin and vitexin, were tentatively identified. Polyphenols strongly inhibited the proliferation of Caco-2 cells, which is consistent with model studies in which several of the polyphenols identified in saffron leaves have demonstrated their potential as chemopreventive agents in cancer. Due to the low profitability that saffron leaf currently represents, we consider these results very encouraging and that this by-product deserves further investigation as a potential source of active molecules against colorectal cancer.

Keywords: saffron leaves, agricultural by-products, polyphenols, antiproliferative effect, human colon adenocarcinoma cells

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Authors: Samantha Meyr, Eman Mirdamadi, Martha Wang, Tao Lowe, Ryan Smith, Quinn Burke

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Critical-sized bone defects (CSD) treatment options remain a major clinical orthopedic challenge. They are uniquely contoured diseased or damaged bones and can be defined as those that will not heal spontaneously and require surgical intervention. Autografts are the current gold standard CSD treatment, which are histocompatible and provoke a minimal immunogenic response; however, they can cause donor site morbidity and will not suffice for the size required for replacement. As an alternative to traditional surgical methods, bone tissue engineering will be implemented via 3D printing methods. A freeze-dried bone matrix (FDBM) is a type of graft material available but will only function as desired when in the presence of bone growth factors. Polycaprolactone (PCL) is a known biodegradable material with good biocompatibility that has been proven manageable in 3D printing as a medical device. A 3D-extrusion printing strategy is introduced to print these materials into scaffolds for bone grafting purposes, which could be more accessible and rapid than the current standard. Mechanical, thermal, cytotoxic, and physical properties were investigated throughout a degradation period of 6 months using fibroblasts and dental pulp stem cells. PCL-FDBM scaffolds were successfully printed with high print fidelity in their respective pore sizes and allograft content. Additionally, we have created a method for evaluating PCL using differential scanning calorimetry (DSC) and have evaluated PCL degradation over roughly 6 months.

Keywords: 3D printing, bone tissue engineering, cytotoxicity, degradation, scaffolds

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Authors: Adel A. Ghoneim

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Air conditioning devices are substantially utilized in the summer months, as a result maximum loads in Kuwait take place in these intervals. Peak energy consumption are usually more expensive to satisfy compared to other standard power sources. The primary objective of the current work is to enhance the performance of high concentrated photovoltaic (HCPV) systems in an attempt to minimize peak power usage in Kuwait using HCPV modules. High concentrated PV multi-junction solar cells provide a promising method towards accomplishing lowest pricing per kilowatt-hour. Nevertheless, these cells have various features that should be resolved to be feasible for extensive power production. A single diode equivalent circuit model is formulated to analyze multi-junction solar cells efficiency in Kuwait weather circumstances taking into account the effects of both the temperature and the concentration ratio. The diode shunt resistance that is commonly ignored in the established models is considered in the present numerical model. The current model results are successfully validated versus measurements from published data to within 1.8% accuracy. Present calculations reveal that the single diode model considering the shunt resistance provides accurate and dependable results. The electrical efficiency (η) is observed to increase with concentration to a specific concentration level after which it reduces. Implementing grid systems is noticed to increase with concentration to a certain concentration degree after which it decreases. Employing grid connected HCPV systems results in significant peak load reduction.

Keywords: grid connected, high concentrated photovoltaic systems, peak load, solar cells

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Authors: A. R. Diniz, P. Borrego, I. Bártolo, N. Taveira

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Cell-to-cell transmission plays a critical role in the spread of HIV-1 infection in vitro and in vivo. Inhibition of HIV-1 cell-associated infection by antiretroviral drugs and neutralizing antibodies (NAbs) is more difficult compared to cell-free infection. Limited data exists on cell-associated infection by HIV-2 and its inhibition. In this work, we determined the ability of entry inhibitors to inhibit HIV-1 and HIV-2 cell-to cell fusion as a proxy to cell-associated infection. We developed a method in which Hela-CD4-cells are first transfected with a Tat expressing plasmid (pcDNA3.1+/Tat101) and infected with recombinant vaccinia viruses expressing either the HIV-1 (vPE16: from isolate HTLV-IIIB, clone BH8, X4 tropism) or HIV-2 (vSC50: from HIV-2SBL/ISY, R5 and X4 tropism) envelope glycoproteins (M.O.I.=1 PFU/cell).These cells are added to TZM-bl cells. When cell-to-cell fusion (syncytia) occurs the Tat protein diffuses to the TZM-bl cells activating the expression of a reporter gene (luciferase). We tested several entry inhibitors including the fusion inhibitors T1249, T20 and P3, the CCR5 antagonists MVC and TAK-779, the CXCR4 antagonist AMD3100 and several HIV-2 neutralizing antibodies (Nabs). All compounds inhibited HIV-1 and HIV-2 cell fusion albeit to different levels. Maximum percentage of HIV-2 inhibition (MPI) was higher for fusion inhibitors (T1249- 99.8%; P3- 95%, T20-90%) followed by co-receptor antagonists (MVC- 63%; TAK-779- 55%; AMD3100- 45%). NAbs from HIV-2 infected patients did not prevent cell fusion up to the tested concentration of 4μg/ml. As for HIV-1, MPI reached 100% with TAK-779 and T1249. For the other antivirals, MPIs were: P3-79%; T20-75%; AMD3100-61%; MVC-65%.These results are consistent with published data. Maraviroc had the lowest IC50 both for HIV-2 and HIV-1 (IC50 HIV-2= 0.06 μM; HIV-1=0.0076μM). Highest IC50 were observed with T20 for HIV-2 (3.86μM) and with TAK-779 for HIV-1 (12.64μM). Overall, our results show that entry inhibitors in clinical use are less effective at preventing Env mediated cell-to-cell-fusion in HIV-2 than in HIV-1 which suggests that cell-associated HIV-2 infection will be more difficult to inhibit compared to HIV-1. The method described here will be useful to screen for new HIV entry inhibitors.

Keywords: cell-to-cell fusion, entry inhibitors, HIV, NAbs, vaccinia virus

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Authors: Elham Ahmadi, Mehrdad Ravanshad, Joyce Fingeroth, Mazyar Ziyaeyan, Rajesh Panigrahi, Jun Xie, Gao Guangping

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B-cell proliferative disorders often occur among persons that are T-cell compromised. These disorders are primarily EBV+ and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy and immunotherapy by reducing systemic toxicity, to which the immunocompromised host is most vulnerable. Widely studied as a vehicle for gene therapy, AAV has only rarely been applied to treat cancer. As a prelude to development of a therapeutic vehicle, we assessed the ability of 15 distinct recombinant AAV serotypes (rAAV1, rAAV2, rAAV3b, rAAV4, rAAV5, rAAV6, rAAV6.2, rAAV6TM, rAAV7, rAAV8, rAAVrh8, rAAV9, rAAVrh10, rAAV39, rAAV43) bearing eGFP to infect human B-cell tumor lines compared with primary B-cells in vitro. Enhanced infection of tumor lines by AAV 6.2 was demonstrated by flow cytometry. EBV superinfection of EBV negative B-cell tumor lines increased susceptibility to AAV6.2 infection. As proof of concept, AAV6.2 bearing HSV-1 thymidine kinase in place of eGFP eliminated tumor cells upon exposure to ganciclovir.

Keywords: AAV, gene therapy, lymphoma, malignancy, tropism

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Authors: Tery Nehemia Nugraha Joseph, J. D. P. Wisnubroto

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Thyroid cancer is a healthcare problem with high morbidity and mortality. Follicular adenoma and follicular carcinoma are thyroid tumors from the thyroid follicular cells differentiation with a microfollicular pattern that consists of follicular cuboidal cells. vascular endothelial growth factor (VEGF) is a potent and powerful mitogen for endothelial cells and increases vascular permeability. Therefore, due to an increase in thyroid-stimulating hormone (TSH), VEGF production is activated in the thyroid that leads to the end of mitogenic TSH stimulation and initiation of angiogenesis. The differences in VEGF levels in the follicular carcinoma of thyroid tissue with follicular adenoma thyroid can be used as a basis in differentiating the two types of neoplasms. This study aims to analyze VEGF in the serum so that it can be used to differentiate the types of thyroid carcinoma before surgery. This study uses a cross-sectional research design. Samples were carried out by taking serum samples, and the VEGF levels were calculated. Data were analyzed using the Mann-Whitney test. The results found a significant difference between VEGF levels in the follicular carcinoma thyroid group and VEGF levels in the follicular adenoma thyroid group with a value of p = 0.007 (p < 0.05). The results obtained are 560,427 ± 160,506 ng/mL in the type of follicular carcinoma thyroid and 320.943 ± 134.573 ng/mL in the type of follicular adenoma thyroid. VEGF levels between follicular adenoma and follicular carcinoma are different. VEGF levels are higher in follicular carcinoma thyroid than follicular adenoma thyroid.

Keywords: follicular adenoma thyroid, follicular carcinoma thyroid, thyroid, VEGF

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Authors: Ahmed Zahran

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Bifidobacterium breve ATCC 15700, Bifidobacterium adolescents ATCC 15704 and Bifidobacterium longum ATCC 15707 were tested for their growth, acid production, bile tolerance, antibiotic resistance and adherence to columnar epithelial cells of the small intestine of goat. The growth of all studied species was determined in the MRSL medium. B.longum 15707 was the most active species in comparison with the other two species; it was also more resistant to bile acids. The adhesion of the studied species to the columnar epithelial cells was studied. All the studied species showed some degree of adhesion; however, B.longum adhered more than the other two species. This species was resistant to four types of antibiotics and was sensitive to chloramphenicol 30 µg. The activity of Bifidobacterium species in soymilk was evaluated by measuring the development of titratalle acidity. B.longum 15707 was the most active species in terms of growth and activity of soymilk. So, soymilk containing bifidobacteria could be added to goat milk to produce acceptable functional soy yogurt, using the ratio of (1:4) soy milk to goat milk. This product could be of unique health benefits, especially in the case of high cholesterol levels and replenishment of intestinal flora after antibiotic therapy.

Keywords: bifidobacteria physiological properties, soy milk, goat milk, attachment epithelial cells, columnar tissues, probiotic food

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Authors: Dimitra Sygkridou, Andreas Rapsomanikis, Elias Stathatos, Polycarpos Falaras, Evangelos Vitoratos

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At the present work highly transparent strip type quasi-solid state dye-sensitized solar cells (DSSCs) were fabricated through inkjet printing using nanocomposite TiO2 inks as raw materials and tested under outdoor illumination conditions. The cells, which can be considered as the structural units of large area modules, were fully characterized electrically and electrochemically and after the evaluation of the received results a large area DSSC module was manufactured. The module design was a sandwich Z-interconnection where the working electrode is deposited on one conductive glass and the counter electrode on a second glass. Silver current collective fingers were printed on the conductive glasses to make the internal electrical connections and the adjacent cells were connected in series and finally insulated using a UV curing resin to protect them from the corrosive (I-/I3-) redox couple of the electrolyte. Finally, outdoor tests were carried out to the fabricated dye-sensitized solar module and its performance data were collected and assessed.

Keywords: dye-sensitized solar devices, inkjet printing, quasi-solid state electrolyte, transparency, up-scaling

Procedia PDF Downloads 339

Authors: Mahsa Jalili, Trude Johansen, Signe Dille Lovmo, Turid Rustad, Rolf Erik Olsen, Atle M. Bones

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The quality of fish muscle is a key factor in fish industry, and dietary ingredients can influence fish quality. The aim of this study was to examine the impact of krill meal, soybean meal, Bactocell® and butyrate fortified feeds and control diet on characteristics of salmon fillet. Thirty Atlantic salmon (6 per each group) were farmed for 12 weeks. All the fish were killed and frozen immediately. The white muscle from top posterior part of dorsal fin was dissected to analyze fat content, carotenoid content, content of water-soluble and salt-soluble proteins, cathepsin B and cathepsin B-L activities. ANOVA test was used to analyze mean and standard error of mean values at 0.05 significance level. There were significant difference in cathepsin B activity, water-soluble proteins and salt-soluble proteins (p-value= 0.005, 0.009 and 0.002). The mean values of other factors were not significantly different among the groups. Cathepsin B activity was higher in soymeal group. Water-soluble proteins were reported higher in soy meal and krill groups and salt-soluble proteins were significantly higher in soy meal and butyrate rich diets. Although soy meal has proven effect on enteritis, it results in higher percentage of protein in fillets. On the other hand, this feeding may have role in textural deterioration of fillets owing to higher values of endogenous cathepsin B in soymeal group.

Keywords: aquaculture, food quality, Krill protein extract, prebiotics, probiotics, Salmo salar, soy

Procedia PDF Downloads 210

Authors: Aravella Flores, Jose Rafael E. Sotelo, Luis Romulus Phillippe R. Javier, Josh Christian V. Nunez

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This study focuses on analyzing the performance of Grade 12 STEM students of De La Salle University - Integrated School that has completed the Disaster Readiness and Risk Reduction course in handling fire hazards through Minecraft Java Edition. This platform is suitable because fire DRRR is challenging to learn in a practical setting as well as questionable with regard to supplementing the successful implementation of textbook knowledge into actual practice. The purpose of this study is to acknowledge whether Minecraft can be a suitable environment to familiarize oneself to fire DRRR. The objectives are achieved through utilizing Minecraft in simulating fire scenarios which allows the participants to freely act upon and practice fire DRRR. The experiment was divided into the grounding and validation phase, where researchers observed the performance of the participants in the simulation. A pre-simulation and post-simulation survey was given to acknowledge the change in participants’ perception of being able to utilize fire DRRR procedures and their vulnerabilities. The paired t-test was utilized, showing significant differences in the pre-simulation and post-simulation survey scores, thus, insinuating improved judgment of DRRR, lessening their vulnerabilities in the possibility of encountering a fire hazard. This research poses a model for future research which can gather more participants and dwell on more complex codes outside just command blocks and into the code lines of Minecraft itself.

Keywords: minecraft, DRRR, fire, disaster, simulation

Procedia PDF Downloads 140

Authors: Venkatesan Annadurai, Kannan Ethirajalu, Anu Roshini Ramakrishnan

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Copper oxide (CuO) and zinc oxide (ZnO) based coaxial (CuO-ZnO nanorods) heterojunction has been the interest of various research communities for solar cells, light emitting diodes (LEDs) and photodetectors applications. Copper oxide (CuO) is a p-type material with the band gap of 1.5 eV and it is considered to be an attractive absorber material in solar cells applications due to its high absorption coefficient and long minority carrier diffusion length. Similarly, n-type ZnO nanorods possess many attractive advantages over thin films such as, the light trapping ability and photosensitivity owing to the presence of oxygen related hole-traps at the surface. Moreover, the abundant availability, non-toxicity, and inexpensiveness of these materials make them suitable for potentially cheap, large area, and stable photovoltaic applications. However, the efficiency of the CuO-ZnO nanorods heterojunction based devices is greatly affected by interface defects which generally lead to the poor performance. In spite of having much potential, not much work has been carried out to understand the interface quality and transport mechanism involved across the CuO-ZnO nanorods heterojunction. Therefore, a detailed investigation of CuO-ZnO heterojunction is needed to understand the interface which affects its photovoltaic performance. Herein, we have fabricated the CuO-ZnO nanorods based heterojunction by simple hydrothermal and electrodeposition technique and investigated its interface quality by carrying out temperature (300 –10 K) dependent current-voltage (I-V) measurements under dark and illumination of visible light. Activation energies extracted from the temperature dependent I-V characteristics reveals that recombination and tunneling mechanism across the interfacial barrier plays a significant role in the current flow.

Keywords: heterojunction, electrical transport, nanorods, solar cells

Procedia PDF Downloads 224

Authors: Anupama Sahoo, Bongyong Lee, Katia Boniface, Julien Seneschal, Sanjaya K. Sahoo, Tatsuya Seki, Chunyan Wang, Soumen Das, Xianlin Han, Michael Steppie, Sudipta Seal, Alain Taieb, Ranjan J. Perera

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Vitiligo is a common, chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has a complex immune, genetic, environmental, and biochemical etiology, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. Here we characterized the human vitiligo cell line PIG3V and the normal human melanocytes, HEM-l by RNA-sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched miR-211, a known metabolic switch in non-pigmented melanoma cells, was severely downregulated in vitiligo cell line PIG3V and skin biopsies from vitiligo patients, while its novel predicted targets transcriptional co-activator PGC1-α (PPARGC1A), ribonucleotide reductase regulatory subunit M2 (RRM2), and serine-threonine protein kinase TAO1 (TAOK1) were reciprocally upregulated. miR-211 binds to PGC1-α 3’UTR locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated miR-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of miR-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo.

Keywords: metabolism, microRNA, mitochondria, vitiligo

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Authors: Mahmoodreza Tahamtan

Abstract:

Malignant surface epithelial ovarian tumors(SEOT) account for approximately 90% of primary ovarian cancer. We evaluate the immunohistochemical expression of WT1 protein among different histologic subtypes of SEOT. Immunohistochemistry for WT1 was done on 35 serous cystadenocarcinomas, 9 borderline serous tumors. A tumor was considered negative if < 1% of tumor cells were stained.Positive reactions were graded as follows:1+,1%-24%; 2+,25%-49%; 3+,50%-74%; 4+,75%-100%. Of the 35 cases of ovarian serous cystadenocarcinoma 30(85.7%)were diffusely positive(3+,4+),4 showed reactivity of < 50% of the tumor cells(1+,2+) and one were negative. All 9 borderline serous tumors showed immunoreactivity with WT1. WT1 is a good marker to distinguish primary ovarian serous carcinomas from other surface epithelial tumors.

Keywords: WT1, ovary, malignant, epithelial tumors

Procedia PDF Downloads 103

Authors: Maria Barbano Acevedo-Gomez, Elena Sonsoles Rodriguez-Lopez, Sofia Olivia Calvo-Moreno, Angel Basas-Garcia, Cristophe Ramirez

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Introduction: Urinary incontinence (UI) is defined as the involuntary leakage of urine. In persons who practice sport, its prevalence is 36.1% (95% CI 26.5%-46.8%) and varies as it seems to depend on the intensity of exercise, movements, and impact on the ground. Such high impact sports are likely to generate higher intra-abdominal pressures and leading to pelvic floor muscle weakness. Even though the emphasis of this research is on female athletes, all women should perform pelvic floor muscle exercises as a part of their general physical exercise. Pelvic floor exercises are generally considered the first treatment against urinary incontinence. Objective: The main objective of the present study was to determine the knowledge of the pelvic floor and of the UI in elite athletes and know if they incorporate pelvic floor strengthening in their training. Methods: This was an observational study conducted on 754 elite athletes. After collecting questions about the pelvic floor, UI, and sport-related data, participants completed the questionnaire International Consultation on Incontinence Questionnaire-UI Short-Form (ICIQ-SF). Results: 57.3% of the athletes reflect not having knowledge of their pelvic floor, 48.3% do not know what strengthening exercises are, and around 90% have never practiced them. 78.1% (n=589) of all elite athletes do not include pelvic floor exercises in their training. Of the elite athletes surveyed, 33% had UI according to ICIQ-SF (mean age 23.75 ± 7.74 years). In response to the question 'Do you think you have or have had UI?', Only 9% of the 754 elite athletes admitted they presently had UI, and 13.3% indicated they had had UI at some time. However, 22.7% (n=171) reported they had experienced urine leakage while training. Of the athletes who indicated they did not have UI in the ICIQ-SF, 25.7% stated they did experience urine leakage during training (χ² [1] = 265.56; p < 0.001). Further, 12.3% of the athletes who considered they did not have UI and 60% of those who admitted they had had UI on some occasion stated they had suffered some urine leakage in the past 3 months (χ² [1] = 287.59; p < 0.001). Conclusions: There is a lack of knowledge about UI in sport. Through the use of validated questionnaires, we observed a UI prevalence of 33%, and 22.7% reported they experienced urine leakage while training. These figures contrast with only 9% of athletes who reported they had or had in the past had UI. This discrepancy could reflect the great lack of knowledge about UI in sports and that sometimes an athlete may consider that urine leakage is normal and a consequence of the demands of training. These data support the idea that coaches, physiotherapists, and other professionals involved in maximizing the performance of athletes should include pelvic floor muscle exercises in their training programs. Measures such as this could help to prevent UI during training and could be a starting point for future studies designed to develop adequate prevention and treatment strategies for this embarrassing problem affecting young athletes, both male and female.

Keywords: athletes, pelvic floor, performance, prevalence, sport, training, urinary incontinence

Procedia PDF Downloads 127

Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

Procedia PDF Downloads 282