Search results for: clear cell renal cell carcinoma

Authors: Dhruv J. Limaye, Hanga Galfalvy, Cheick A. Sissoko, Yung-yu Huang, Chunanning Tang, Ying Liu, Shu-Chi Hsiung, Andrew J. Dwork, Gorazd B. Rosoklija, Victoria Arango, Lewis Brown, J. John Mann, Maura Boldrini

Abstract:

Memory and emotion require hippocampal cell viability and connectivity and are disrupted in major depressive disorder (MDD). Applying shotgun proteomics and stereological quantification of neural progenitor cells (NPCs), intermediate neural progenitors (INPs), and mature granule neurons (GNs), to postmortem human hippocampus, identified differentially expressed proteins (DEPs), and fewer NPCs, INPs and GNs, in untreated MDD (uMDD) compared with non-psychiatric controls (CTRL) and antidepressant-treated MDD (MDDT). DEPs lower in uMDD vs. CTRL promote mitosis, differentiation, and prevent apoptosis. DEPs higher in uMDD vs. CTRL inhibit the cell cycle, and regulate cell adhesion, neurite outgrowth, and DNA repair. DEPs lower in MDDT vs. uMDD block cell proliferation. We observe group-specific correlations between numbers of NPCs, INPs, and GNs and an abundance of proteins regulating mitosis, differentiation, and apoptosis. Altered protein expression underlies hippocampus cellular and volume loss in uMDD, supports a trophic effect of antidepressants, and offers new treatment targets.

Keywords: proteomics, hippocampus, depression, mitosis, migration, differentiation, mitochondria, apoptosis, antidepressants, human brain

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Authors: Darya O. Prima, Elena V. Vorontsova, Yuri G. Slizhov, Andrey V. Zibarev

Abstract:

A broad family of carbocycle-fluorinated aza-heterocycles including 1,3-benzodiazoles (benzimidazoles), 1,2,3-benzotriazoles, 2,1,3-benzothia/selenadiazoles and 1,4-benzodiazines (quinoxalines) was synthesized in the unified way and assessed for cytotoxicity towards the Hep2 (laryngeal epidermoid carcinoma, a kind of oral cancer) cells. The diazoles, triazoles and selenadiazoles revealed low medium inhibitory concentrations IC50 = 2.2-26.4 µМ and induced the cells’ apoptosis at low concentrations C = 1-25 µМ. For selenadiazoles, cell death dynamics was observed already in the first hours after the treatment. Replacement of one atom F by group Me2N in some cases enlarged apoptotic activity of the compounds towards the Hep2 cells. In contrast, the archetypal (i.e. non-fluorinated) 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole were low toxic (IC50 > 100 µM) and induced apoptosis only at high concentrations. The chlorinated congeners of the heterocycles under discussion were highly toxic towards the Hep2 cells but revealed insignificant ability to induce their apoptosis. Overall, the findings above suggest that fluorinated 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole derivatives can be considered as potential anticancer drugs. For the laryngeal epidermoid carcinoma (for which, according to available statistics, the five-year survival rate remained ~50% during the past 30 years), it is especially important since surgical treatment is seriously complicated here thus encouraging medicament one.

Keywords: Apoptosis, aza-heterocycles, cytotoxicity, fluorinated, Hep2 cells, synthesis

Procedia PDF Downloads 336

Authors: Daruliza Kernain, Shaharum Shamsuddin, See Too Wei Cun

Abstract:

CTCF is a unique, highly conserved and ubiquitously expressed 11 zinc finger (ZF) transcriptional factor with multiple target sites. It is able to bind to various target sequences to perform different regulatory roles including promoter activation or repression, creating hormone-responsive gene silencing element, and functional block of enhancer-promoter interactions. The binding of CTCF to the essential binding site is through the combination of different ZF domain. On the other hand, BORIS for brother of the regulator of imprinted sites, which expressed only in the testis and certain cancer cell line is homology to CTCF 11 ZF domains. Since both transcriptional factors share the same ZF domains hence there is a possibility for both to bind to the same target sequences. In this study, the interaction of these two proteins to multi-functional Y-box DNA/RNA-binding factor, YB-1 was determined. The protein-protein interaction between CTCF/YB-1 and BORIS/YB-1 were discovered by Co-immuno-precipitation (CO-IP) technique through reciprocal experiment from RGBM total cell lysate. The results showed that both CTCF and BORIS were able to interact with YB-1 in Glioma RGBM cell line. To the best of our knowledge, this is the first findings demonstrating the ability of BORIS and YB-1 to form a complex in vivo.

Keywords: immunoprecipitation, CTCF/BORIS/YB-1, transcription factor, molecular medicine

Procedia PDF Downloads 257

Authors: Vladimir Ryabov, Mikhail Baryshevs, Mikhail Voskresenskey, Boris Popov

Abstract:

The human prostate gland (PG) samples were obtained from patients who had undergone radical prostatectomy for prostate cancer (PC) and used to extract total RNA and prepare the prostate stromal cell cultures (PSCC) and patients-derived organoids (PDO). Growth of the cell cultures was accessed under microscopic evaluation in transmitted light and the marker expression by reverse polymerase chain reaction (RT-PCR), immunofluorescence, and immunoblotting. Some PCR products from prostate tissue, PSCC, and PDO were cloned and sequenced. We found that the cells of early and late passages of PSCC and corresponding PDO expressed luminal (androgen receptor, AR; cytokeratin 18, CK18) and basal (CK5, p63) epithelial markers, the production of which decreased or disappeared in late PSCC and PDO. The PSCC and PDO of early passages from cancer tissue additionally produced cancer markers AMACR, TMPRSS2-ERG, and Ezh2. The expression of TMPRSS2-ERG fusion transcripts was verified by cloning and sequencing the PCR products. The results obtained suggest that early passages of PSCC might be used as a pre-clinical model for the evaluation of early markers of prostate cancer.

Keywords: localized prostate cancer, prostate epithelial markers, prostate cancer markers, AMACR, TMPRSS2-ERG, prostate stromal cell cultures, PDO

Procedia PDF Downloads 102

Authors: Su-Hyun Jung, Chang-Bin Ha, Hyoung-Kyu Song

Abstract:

Recently, increasing the quality of experience (QoE) is an important issue. Since performance degradation at cell edge extremely reduces the QoE, several techniques are defined at LTE/LTE-A standard to remove inter-cell interference (ICI). However, the conventional techniques have disadvantage because there is a trade-off between resource allocation and reliable communication. The proposed scheme reduces the ICI more efficiently by using channel state information (CSI) smartly. It is shown that the proposed scheme can reduce the ICI with less resources.

Keywords: adaptive beamforming, CoMP, LTE-A, ICI reduction

Procedia PDF Downloads 463

Authors: Surajbhan Sevda

Abstract:

Metal containing wastewater is generated in large quintiles due to rapid industrialization. Generally, the metal present in wastewater is not biodegradable and can be accumulated in living animals, humans and plant tissue, causing disorder and diseases. The conventional metal recovery methods include chemical, physical and biological methods, but these are chemical and energy intensive. The recent development in microbial fuel cell (MFC) technology provides a new approach for metal recovery; this technology offers a flexible platform for both reduction and oxidation reaction oriented process. The use of MFCs will be a new platform for more efficient and low energy approach for metal recovery from the wastewater. So far metal recover was extensively studied using chemical, physical and biological methods. The MFCs present a new and efficient approach for removing and recovering metals from different wastewater, suggesting the use of different electrode for metal recovery can be a new efficient and effective approach.

Keywords: metal recovery, microbial fuel cell, wastewater, bioelectricity

Procedia PDF Downloads 210

Authors: Sharareh Sharifi, Pargol Ghavam Mostafavi, Ali Mashinchian Moradi, Mohammad Hadi Givianrad, Hassan Niknejad

Abstract:

Marine organisms such as soft coral, sponge, ascidians, and tunicate containing rich source of natural compound have been studied in last decades because of their special chemical compounds with anticancer properties. The aim of this study was to investigate anti-cancer property of ethyl acetate extracted from marine sea pen Virgularia gustaviana found from Persian Gulf coastal (Bandar Abbas). The extraction processes were carried out with ethyl acetate for five days. Thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) were used for qualitative identification of crude extract. The viability of HeLa and MDA-Mb-231 cancer cells was investigated using MTT assay at the concentration of 25, 50, and a 100 µl/ml of ethyl acetate is extracted. The crude extract of Virgularia gustaviana demonstrated ten fractions with different Retention factor (Rf) by TLC and Retention time (Rt) evaluated by HPLC. The crude extract dose-dependently decreased cancer cell viability compared to control group. According to the results, the ethyl acetate extracted from Virgularia gustaviana inhibits the growth of cancer cells, an effect which needs to be further investigated in the future studies.

Keywords: anti-cancer, Hela cancer cell, MDA-Md-231 cancer cell, Virgularia gustavina

Procedia PDF Downloads 429

Authors: Nigus Maregu Demewoz, Shu-Kai Yeh

Abstract:

Low-density nanocellular foam is a fascinating new-generation advanced material due to its mechanical strength and thermal insulation properties. In nanocellular foam, reducing the density increases the insulation ability. However, producing a nanocellular foam of densities less than 0.3 with a cell size of less than 100 nm is very challenging. In this study, poly (methyl methacrylate) (PMMA) was blended with Polyether block amide (PEBAX) to study the effects of PEBAX on the nanocellular foam structure of the PMMA matrix. We added 2 wt% of PEBAX in the PMMA matrix, and the PEBAX nanostructured domain size of 45 nm was well dispersed in the PMMA matrix. The foaming result produced a new generation special bouquet-like nanocellular foam of cell size less than 50 nm with a relative density of 0.24. Also, we were able to produce a nanocellular foam of a relative density of about 0.17. In addition to thermal insulation applications, bouquet-like nanocellular foam may be expected for filtration applications.

Keywords: nanocellular foam, low-density, cell size, relative density, PMMA/PEBAX

Procedia PDF Downloads 73

Authors: Yasaman Tabari-Saadi, Kaiwen Sun, Jialiang Huang, Martin Green, Xiaojing Hao

Abstract:

Optical and electrical properties of p-type AgBiS₂ absorber material have been improved by copper doping on silver sites. X-Ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analysis suggest that complete solid solutions of Ag₁₋ₓCuₓBiS₂ thin film have been formed. The carrier concentration of pure AgBiS₂ thin film deposited by the chemical process is 4.5*E+14 cm⁻³, and copper doping leads to the improved carrier concentration despite the semiconductor AgBiS₂ remains p-type semiconductor. Copper doping directly changed the absorption coefficient and increased the optical band gap (~1.5eV), which makes it a promising absorber for thin-film solar cell applications.

Keywords: copper doped, AgBiS₂, thin-film solar cell, carrier concentration, p-type semiconductor

Procedia PDF Downloads 118

Authors: Liangliang Tang, Chang Xu, Xingying Chen

Abstract:

GaInAsSb cells probably show better performance than GaSb cells in low-temperature thermophotovoltaic systems due to lower bandgap; however, few experiments proved this phenomenon so far. In this paper, numerical simulation is used to evaluate GaInAsSb and GaSb cells with similar structures under different radiation temperatures. We found that GaInAsSb cells with n-type emitters show slightly higher output power densities compared with that of GaSb cells with n-type emitters below 1,550 K-blackbody radiation, and the power density of the later cells will suppress the formers above this temperature point. During the temperature range of 1,000~2,000 K, the efficiencies of GaSb cells are about twice of GaInAsSb cells if perfect filters are used to prevent the emission of the non-absorbed long wavelength photons. Several parameters that affect the GaInAsSb cell were analyzed, such as doping profiles, thicknesses of GaInAsSb epitaxial layer and surface recombination velocity. The non-p junctions, i.e., n-type emitters are better for GaInAsSb cell fabrication, which is similar to that of GaSb cells.

Keywords: thermophotovoltaic cell, GaSb, GaInAsSb, diffused emitters

Procedia PDF Downloads 275

Authors: E. Shahsavari, R. Ghasemi, A. Akramizadeh

Abstract:

This paper presents a new method to design nonlinear feedback linearization controller for polymer electrolyte membrane fuel cells (PEMFCs). A nonlinear controller is designed based on nonlinear model to prolong the stack life of PEM fuel cells. Since it is known that large deviations between hydrogen and oxygen partial pressures can cause severe membrane damage in the fuel cell, feedback linearization is applied to the PEM fuel cell system so that the deviation can be kept as small as possible during disturbances or load variations. To obtain an accurate feedback linearization controller, tuning the linear parameters are always important. So in proposed study NSGA_II method was used to tune the designed controller in aim to decrease the controller tracking error. The simulation result showed that the proposed method tuned the controller efficiently.

Keywords: nonlinear dynamic model, polymer electrolyte membrane fuel cells, feedback linearization, optimal control, NSGA_II

Procedia PDF Downloads 511

Authors: Nigus Maregu Demewoz, Shu-Kai Yeh

Abstract:

Low-density nanocellular foam is a fascinating new-generation advanced material due to its mechanical strength and thermal insulation properties. In nanocellular foam, reducing the density increases the insulation ability. However, producing a nanocellular foam of densities less than 0.3 with a cell size of less than 100 nm is very challenging. In this study, poly (methyl methacrylate) (PMMA) was blended with Polyether block amide (PEBAX) to study the effects of PEBAX on the nanocellular foam structure of the PMMA matrix. We added 2 wt% of PEBAX in the PMMA matrix, and the PEBAX nanostructured domain size of 45 nm was well dispersed in the PMMA matrix. The foaming result produced a new generation special bouquet-like nanocellular foam of cell size less than 50 nm with a relative density of 0.24. Also, we were able to produce a nanocellular foam of a relative density of about 0.17. In addition to thermal insulation applications, bouquet-like nanocellular foam may be expected for filtration applications.

Keywords: nanocellular foam, low-density, cell size, relative density, PMMA/PEBAX blend

Procedia PDF Downloads 84

Authors: Laila Seada, Hanan Oreiby, Fawaz Al Rashid, Ashraf Negm

Abstract:

Background and Objective: In most areas of the world, the incidence of thyroid cancer has been increasing over the last decade, mostly due to a combination of early detection of the neoplasm resulting from sensitive procedures and increased population exposure to radiation and unrecognized carcinogens. Methods: Cases of thyroid cancer have been retrieved from the cancer registry at King Khalid Hospital during the period from August 2012 to April 2016. Age, gender and histopathologic types have been recorded. Results: Thyroid carcinoma ranked as the second most common malignancy in females (25%) after breast cancer (31%). It constituted 20.8% of all newly diagnosed cancer cases. As for males, it ranked the 4^th type of malignancy after gastrointestinal cancer, lymphomas and soft tissue sarcomas. Mean age for females and males was 38.7 +/- 13.2 and 60.25 +/- 11.5 years, respectively, and the difference between the two groups was statistically significant (p value = 0.0001). Fifty-five (82%) were papillary carcinomas including 10 follicular variant of papillary (FVPC), and eight papillary micro carcinomas (PMC) and two tall cell/oncocytic variants. Follicular carcinomas constituted two (3.1%), while two (3.1%) were anaplastic, and two (3.1%) were medullary. Conclusion: Thyroid cancer incidence in Hail is ranking as the 2^nd most common female malignancy similar to other regions in the Kingdom. However, this high incidence contrasts with much lower rates worldwide.

Keywords: thyroid, hail, papillary, microcarcinoma

Procedia PDF Downloads 304

Authors: Kenichi Yamahara, Makiko Ohshima, Shunsuke Ohnishi, Hidetoshi Tsuda, Akihiko Taguchi, Toshihiro Soma, Hiroyasu Ogawa, Jun Yoshimatsu, Tomoaki Ikeda

Abstract:

We have previously reported the therapeutic potential of rat fetal membrane(FM)-derived mesenchymal stem cells (MSCs) using various rat models including hindlimb ischemia, autoimmune myocarditis, glomerulonephritis, renal ischemia-reperfusion injury, and myocardial infarction. In this study, 1) we isolated and characterized MSCs from human amnion and chorion; 2) we examined their differences in the expression profile of growth factors and cytokines; and 3) we investigated the therapeutic potential and difference of these MSCs using murine hindlimb ischemia and acute graft-versus-host disease (GVHD) models. Isolated MSCs from both amnion and chorion layers of FM showed similar morphological appearance, multipotency, and cell-surface antigen expression. Conditioned media obtained from amnion- and chorion-derived MSCs inhibited cell death caused by serum starvation or hypoxia in endothelial cells and cardiomyocytes. Amnion and chorion MSCs secreted significant amounts of angiogenic factors including HGF, IGF-1, VEGF, and bFGF, although differences in the cellular expression profile of these soluble factors were observed. Transplantation of human amnion or chorion MSCs significantly increased blood flow and capillary density in a murine hindlimb ischemia model. In addition, compared to human chorion MSCs, human amnion MSCs markedly reduced T-lymphocyte proliferation with the enhanced secretion of PGE2, and improved the pathological situation of a mouse model of GVHD disease. Our results highlight that human amnionand chorion-derived MSCs, which showed differences in their soluble factor secretion and angiogenic/immuno-suppressive function, could be ideal cell sources for regenerative medicine.

Keywords: amnion, chorion, fetal membrane, mesenchymal stem cells

Procedia PDF Downloads 410

Authors: Yao Song, Danni Cheng, Jianjun Ren

Abstract:

Objectives: We aimed to explore the prognostic effects of absolute values and dynamic changes of common hematological indices on oropharynx squamous cell carcinoma (OPSCC) patients treated with radiation. Methods and materials: The absolute values of white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), hemoglobin (Hb), platelet (Plt), albumin (Alb), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline (within 45 days before radiation), 1-, 3-, 6- and 12-months after the start of radiotherapy were retrospectively collected. Locally-estimated smoothing scatterplots were used to describe the smooth trajectory of each index. A mixed-effect model with a random slope was fitted to describe the changing rate and trend of indices over time. Cox proportional hazard analysis was conducted to assess the correlation between hematological indices and treatment outcomes. Results: Of the enrolled 85 OPSCC patients, inflammatory indices, such as WBC and ALC, dropped rapidly during acute treatment and gradually recovered, while NLR and PLR increased at first three months and subsequently declined within 3-12 months. Higher absolute value or increasing trend of nutritional indices (Alb and Hb) was associated with better prognosis (all p<0.05). In contrast, patients with higher absolute value or upward trend of inflammatory indices (WBC, ANC, Plt, PLR and NLR) had worse survival (all p<0.05). Conclusions: The absolute values and dynamic changes of hematological indices were valuable prognostic factors for OPSCC patients who underwent radiotherapy.

Keywords: hematological indices, oropharyngeal cancer, radiotherapy, NLR, PLR

Procedia PDF Downloads 174

Authors: Jae-Hyeon Kim, Michael Lee

Abstract:

Intrinsic and acquired resistance limits the therapeutic benefits of oncogenic BRAF inhibitors in melanoma. MicroRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation. Thus, we investigated miRNA expression patterns in melanoma cell lines to identify candidate biomarkers for acquired resistance to BRAF inhibitor. Here, we used Affymetrix miRNA V3.0 microarray profiling platform to compare miRNA expression levels in three cell lines containing BRAF inhibitor-sensitive A375P BRAF V600E cells, their BRAF inhibitor-resistant counterparts (A375P/Mdr), and SK-MEL-2 BRAF-WT cells with intrinsic resistance to BRAF inhibitor. The miRNAs with at least a two-fold change in expression between BRAF inhibitor-sensitive and –resistant cell lines, were identified as differentially expressed. Averaged intensity measurements identified 138 and 217 miRNAs that were differentially expressed by 2 fold or more between: 1) A375P and A375P/Mdr; 2) A375P and SK-MEL-2, respectively. The hierarchical clustering revealed differences in miRNA expression profiles between BRAF inhibitor-sensitive and –resistant cell lines for miRNAs involved in intrinsic and acquired resistance to BRAF inhibitor. In particular, 43 miRNAs were identified whose expression was consistently altered in two BRAF inhibitor-resistant cell lines, regardless of intrinsic and acquired resistance. Twenty five miRNAs were consistently upregulated and 18 downregulated more than 2-fold. Although some discrepancies were detected when miRNA microarray data were compared with qPCR-measured expression levels, qRT-PCR for five miRNAs (miR-3617, miR-92a1, miR-1246, miR-1936-3p, and miR-17-3p) results showed excellent agreement with microarray experiments. To further investigate cellular functions of miRNAs, we examined effects on cell proliferation. Synthetic oligonucleotide miRNA mimics were transfected into three cell lines, and proliferation was quantified using a colorimetric assay. Of the 5 miRNAs tested, only miR-1246 altered cell proliferation of A375P/Mdr cells. The transfection of miR-1246 mimic strongly conferred PLX-4720 resistance to A375P/Mdr cells, implying that miR-1246 upregulation confers acquired resistance to BRAF inhibition. We also found that PLX-4720 caused much greater G2/M arrest in A375P/Mdr cells transfected with miR-1246mimic than that seen in scrambled RNA-transfected cells. Additionally, miR-1246 mimic partially caused a resistance to autophagy induction by PLX-4720. These results indicate that autophagy does play an essential death-promoting role inPLX-4720-induced cell death. Taken together, these results suggest that miRNA expression profiling in melanoma cells can provide valuable information for a network of BRAF inhibitor resistance-associated miRNAs.

Keywords: microRNA, BRAF inhibitor, drug resistance, autophagy

Procedia PDF Downloads 323

Authors: Siminfar Samakoush Galougah

Abstract:

In this paper, we study two power allocation problems for an uplink user-centric (UC) cell-free massive multiple-input multiple-output (CF-mMIMO) system. Besides, we assume each access point (AP) is connected to a central processing unit (CPU) via a fronthaul link with limited capacity. To efficiently use the fronthaul capacity, two strategies for transmitting signals from APs to the CPU are employed, namely, compress-forward estimate (CFE), estimate-compress-forward (ECF). The capacity of the aforementioned strategies in user-centric CF-mMIMO is drived. Then, we solved the two power allocation problems with minimum Spectral Efficiency (SE) and sum-SE maximization objectives for ECF and CFE strategies.

Keywords: cell-free massive MIMO, limited capacity fronthaul, spectral efficiency

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Authors: S. Saadi, S. Benissaad, S. Poncet, Y. Kabar

Abstract:

In photovoltaic (PV) cells, most of the absorbed solar radiation cannot be converted into electricity. A large amount of solar radiation is converted to heat, which should be dissipated by any cooling techniques. In the present study, the cooling is achieved by inserting triangular ribs in the duct. A comprehensive two-dimensional thermo-fluid model for the effective cooling of PV cells has been developed. It has been first carefully validated against experimental and numerical results available in the literature. A parametric analysis was then carried out about the influence of the number and size of the ribs, wind speed, solar irradiance and inlet fluid velocity on the average solar cell and outlet air temperatures as well as the thermal and electrical efficiencies of the module. Results indicated that the use of triangular ribbed channels is a very effective cooling technique, which significantly reduces the average temperature of the PV cell, especially when increasing the number of ribs.

Keywords: effective cooling, numerical modeling, photovoltaic cell, triangular ribs

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Authors: Bernard L. Middleton, Susan P. Cosgrove

Abstract:

There is an immediate need for alternative anti-herpetic treatment options effective for both primary infections and reoccurring reactivations of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Alternatives currently approved for the purposes of clinical administration includes antivirals and a reduced set of nucleoside analogues. The present article tests a treatment based on a systemic understanding of how the herpes virus affects cell inhibition and breakdown and targets different phases of the viral cycle, including the entry stage, reproductive cross mutation, and cell-to-cell infection. The treatment consisted of five immunotherapeutic core compounds (5CC), which were hypothesized to be capable of neutralizing human monoclonal antibodies. The tested 5CC were noted as being functional in the application of eliminating the DNA synthesis of herpes viral interferon (IFN) - induced cellular antiviral response. They were here found to neutralize antiviral reproduction by blocking cell-to-cell infection. The activity of the 5CC was tested on RC-37 in vitro using an assay plaque reduction and in vivo against HSV-1 and HSV-2. The 50% inhibitory concentration (IC50) of 5CC was 0.0009% for HSV-1 plaque formation and 0.0008% for HSV-2 plaque formation. Further tests were performed to evaluate the susceptibility of HSV-1 and HSV-2 to anti-herpetic drugs in Vero cells after virus entry. There were high-level markers of the 5CC virucidal activity in the viral suspension of HSV-1 and HSV-2. These concentrations of the 5CC are nontoxic and reduced plaque formation by 98.2% for HSV-1 and 93.0% for HSV-2. Virus HSV-1 and HSV-2 titers were reduced significantly by 5CC to the point of being negative, ranging 0.01–0.09 in 72%. The results concluded the 5CC as being an effective treatment option for the herpes simplex virus.

Keywords: synergy pharmaceuticals, herpes treatment, herpes cure, synergy pharmaceuticals treatment

Procedia PDF Downloads 238

Authors: Ana M. Lara, Manuela Llano, Felipe Gaitán, Rosa H. Bustos, Ana Maria Perdomo-Arciniegas, Ximena Bonilla

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Umbilical cord blood is used as a source of progenitor and stem cells for the regeneration of the hematopoietic and immune system to treat patients with different hematological or non-hematological diseases. This stem cell source represents an advantage over the use of bone marrow or mobilized peripheral blood because it has a lower incidence rate of graft-versus-host disease, probably due to fewer immunological compatibility restrictions. However, its low cellular dose limits its use in pediatric patients. This work proposes the standardization of a cell expansion technique to compensate for the dose of infused cells through the ex-vivo manipulation of hematopoietic progenitor cells from umbilical cord blood before transplantation. The expansion model is carried out through co-cultures with mesenchymal stem cells (MSC) from bone marrow (BM) and less explored fetal tissues such as Wharton's jelly (WJ) and umbilical cord blood (UCB). Initially, a master cell bank of primary mesenchymal stem cells isolated from different sources was established and characterized following International Society of Cell Therapies (ISCT) indications. Additionally, we assessed the effect of a short 25 Gy cycle of gamma irradiation on cell cycle arrest of mesenchymal cells over the support capacity for the expansion of hematopoietic stem cells from umbilical cord blood was evaluated. The results show that co-cultures with MSC from WJ and UCB allow the cellular dose of HSPC to be maximized between 5 and 16 times having a similar support capacity as BM. In addition, was evaluated the hematopoietic stem progenitor cell's HSPC functionality through the evaluation of migration capacity, their differentiation capacity during culture time by flow cytometry to evaluate the expression of membrane markers associated with lineage-committed progenitors, their clonogenic potential, and the evaluation of secretome profile in the expansion process was evaluated. So far, the treatment with gamma irradiation maintains the hematopoietic support capacity of mesenchymal stem cells from the three sources studied compared to treatments without irradiation, favoring the use of fetal tissues that are generally waste to obtain mesenchymal cell lines for ex-vivo expansion systems. With the results obtained, a standardized protocol that will contribute to the development of ex-vivo expansion with MSC on a larger scale will be achieved, enabling its clinical use and expanding its application in adults.

Keywords: ex-vivo expansion, hematopoietic stem cells, hematopoietic stem cell transplantation, mesenchymal stem cells, umbilical cord blood

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Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

Abstract:

Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

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Authors: Hamza Assiry, Gamal A. Mohamed, Sabrin R. M. Ibrahim, Hossam M. Abdallah

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Chemical investigation of the aerial parts of Barleria trispinosa(Forssk.) Vahl. resulted in isolation of four major iridoids that were identified as 6,8-O,O-diacetylshanhiside methyl ester (acetyl barlerin) (1), 8-O-acetylshanzhiside methyl ester (barlerin) (2), shanzhiside methyl ester (3), and 6- ⍺ -L-rhamnopyranosyl-8-O-acetylshanzihiside methyl ester (4). The isolated compounds were confirmed by detailed one and two-dimensional NMR. Isolated compounds were tested for their cytotoxic activity on breast cancer (MCF-7, MDA-MB-231) and colon cancer (LS174T) cell linesusing sulphorhodamine B (SRB) assay. It is noteworthy that compound 1 demonstrated a significant cytotoxic potential towards MDA-MB-231 cell line with IC5016.7 ± 2.7µg / mL compared to doxorubicin whereas compounds 2, showed moderate cytotoxic potential with IC5021.2 ± 1.9µg / mL on MCF-7. The other compounds showed moderate activity on the tested cell lines.

Keywords: acanthaceae, cytotoxicity, metabolites, barleria trispinosa

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Authors: Francis Gyapong, Denis Yar

Abstract:

The use of cell phones has become an indispensable tool in the hospital's settings. Cell phones are used in hospitals without restrictions regardless of their unknown microbial load. However, the indiscriminate use of mobile devices, especially at health facilities, can act as a vehicle for transmitting pathogenic bacteria and other microorganisms. These potential pathogens become exogenous sources of infection for the patients and are also a potential health hazard for self and as well as family members. These are a growing problem in many health care institutions. Innovations in mobile communication have led to better patient care in diabetes, asthma, and increased in vaccine uptake via SMS. Notwithstanding, the use of cell phones can be a great potential source for nosocomial infections. Many studies reported heavy microbial contamination of cell phones among healthcare workers and communities. However, limited studies have been reported in our region on bacterial contamination on cell phones among healthcare workers. This study assessed microbial contamination of cell phones of health care workers (HCWs) at the Mampong Municipal Government Hospital (MMGH), Ghana. A cross-sectional design was used to characterize bacterial microflora on cell phones of HCWs at the MMGH. A total of thirty-five (35) swab samples of cell phones of HCWs at the Laboratory, Dental Unit, Children’s Ward, Theater and Male ward were randomly collected for laboratory examinations. A suspension of the swab samples was each streak on blood and MacConkey agar and incubated at 37℃ for 48 hours. Bacterial isolates were identified using appropriate laboratory and biochemical tests. Kirby-Bauer disc diffusion method was used to determine the antimicrobial sensitivity tests of the isolates. Data analysis was performed using SPSS version 16. All mobile phones sampled were contaminated with one or more bacterial isolates. Cell phones from the Male ward, Dental Unit, Laboratory, Theatre and Children’s ward had at least three different bacterial isolates; 85.7%, 71.4%, 57.1% and 28.6% for both Theater and Children’s ward respectively. Bacterial contaminants identified were Staphylococcus epidermidis (37%), Staphylococcus aureus (26%), E. coli (20%), Bacillus spp. (11%) and Klebsiella spp. (6 %). Except for the Children ward, E. coli was isolated at all study sites and predominant (42.9%) at the Dental Unit while Klebsiella spp. (28.6%) was only isolated at the Children’s ward. Antibiotic sensitivity testing of Staphylococcus aureus indicated that they were highly sensitive to cephalexin (89%) tetracycline (80%), gentamycin (75%), lincomycin (70%), ciprofloxacin (67%) and highly resistant to ampicillin (75%). Some of these bacteria isolated are potential pathogens and their presence on cell phones of HCWs could be transmitted to patients and their families. Hence strict hand washing before and after every contact with patient and phone be enforced to reduce the risk of nosocomial infections.

Keywords: mobile phones, bacterial contamination, patients, MMGH

Procedia PDF Downloads 95

Authors: Elif Gencturk, Ekin Yurdakul, Ahmet Y. Celik, Senol Mutlu, Kutlu O. Ulgen

Abstract:

Yeast cells are generally used as a model system of eukaryotes due to their complex genetic structure, rapid growth ability in optimum conditions, easy replication and well-defined genetic system properties. Thus, yeast cells increased the knowledge of the principal pathways in humans. During fermentation, carbohydrates (hexoses and pentoses) degrade into some toxic by-products such as 5-hydroxymethylfurfural (5-HMF or HMF) and furfural. HMF influences the ethanol yield, and ethanol productivity; it interferes with microbial growth and is considered as a potent inhibitor of bioethanol production. In this study, yeast single cell behavior under HMF application was monitored by using a continuous flow single phase microfluidic platform. Microfluidic device in operation is fabricated by hot embossing and thermo-compression techniques from cyclo-olefin polymer (COP). COP is biocompatible, transparent and rigid material and it is suitable for observing fluorescence of cells considering its low auto-fluorescence characteristic. The response of yeast cells was recorded through Red Fluorescent Protein (RFP) tagged Nop56 gene product, which is an essential evolutionary-conserved nucleolar protein, and also a member of the box C/D snoRNP complexes. With the application of HMF, yeast cell proliferation continued but HMF slowed down the cell growth, and after HMF treatment the cell proliferation stopped. By the addition of fresh nutrient medium, the yeast cells recovered after 6 hours of HMF exposure. Thus, HMF application suppresses normal functioning of cell cycle but it does not cause cells to die. The monitoring of Nop56 expression phases of the individual cells shed light on the protein and ribosome synthesis cycles along with their link to growth. Further computational study revealed that the mechanisms underlying the inhibitory or inductive effects of HMF on growth are enriched in functional categories of protein degradation, protein processing, DNA repair and multidrug resistance. The present microfluidic device can successfully be used for studying the effects of inhibitory agents on growth by single cell tracking, thus capturing cell to cell variations. By metabolic engineering techniques, engineered strains can be developed, and the metabolic network of the microorganism can thus be manipulated such that chemical overproduction of target metabolite is achieved along with the maximum growth/biomass yield.  

Keywords: COP, HMF, ribosome biogenesis, thermoplastic microbioreactor, yeast

Procedia PDF Downloads 167

Authors: Amina Farooq, Nauman Zafar Butt

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This paper is about methods and tools for counting particles of interest, such as cells. A microfluidic system with interconnected electronics on a flexible substrate, inlet-outlet ports and interface schemes, sensitive and selective detection of cells specificity, and processing of cell counting at polymer interfaces in a microscale biosensor for use in the detection of target biological and non-biological cells. The development of fluidic channels, planar fluidic contact ports, integrated metal electrodes on a flexible substrate for impedance measurements, and a surface modification plasma treatment as an intermediate bonding layer are all part of the fabrication process. Magnetron DC sputtering is used to deposit a double metal layer (Ti/Pt) over the polypropylene film. Using a photoresist layer, specified and etched zones are established. Small fluid volumes, a reduced detection region, and electrical impedance measurements over a range of frequencies for cell counts improve detection sensitivity and specificity. The procedure involves continuous flow of fluid samples that contain particles of interest through the microfluidic channels, counting all types of particles in a portion of the sample using the electrical differential counter to generate a bipolar pulse for each passing cell—calculating the total number of particles of interest originally in the fluid sample by using MATLAB program and signal processing. It's indeed potential to develop a robust and economical kit for cell counting in whole-blood samples using these methods and similar devices.

Keywords: impedance, biochip, cell counting, microfluidics

Procedia PDF Downloads 158

Authors: Arindam Pramanik, Parimal Karmakar

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We have explored the synergistic anti-cancer activity of copper ion and acetylacetone complex containing 1,3 diketone group (like curcumin) in metallorganic compound “Copper acetylacetonate” (CuAA). The cytotoxicity mechanism of CuAA complex was evaluated on various cancer cell lines in vitro. Among these, reactive oxygen species (ROS), glutathione level (GSH) in the cell was found to increase. Further mitochondrial membrane damage was observed. The fate of cell death was found to be induced by apoptosis. For application purpose, we have developed a novel biodegradable, non-toxic polymer-based nanoparticle which has hydrophobically modified core for loading of the CuAA. Folic acid is conjugated on the surface of the polymer (chitosan) nanoparticle for targeting to cancer cells for minimizing toxicity to normal cells in-vivo. Thus, this novel drug CuAA has an efficient anticancer activity which has been targeted specifically to cancer cells through polymer nanoparticle.

Keywords: anticancer, apoptosis, copper nanoparticle, targeted drug delivery

Procedia PDF Downloads 478

Authors: Muñiz-Lino Marcos Agustín, Vazquez Borbolla Jessica, Licéaga-Escalera Carlos

Abstract:

The ectomesenchymal tissues involved in tooth development and their remnants are the origin of different odontogenic lesions, including tumors and cysts of the jaws, with a wide range of clinical behaviors. Dentigerous cyst (DC) represents approximately 20% of all cases of odontogenic cysts, and it has been demonstrated that it can develop benign and malignant odontogenic tumors. DC is characterized by bone destruction of the area surrounding the crown of a tooth which has not erupted and it contain is liquid. The treatment of odontogenic tumors and cysts usually are partial or total removal of the jaw, causing important secondary co-morbidities. However, molecules implicated in DC pathogenesis as well in its development to odontogenic tumors remains unknown. A cellular model may be useful to study these molecules, but that model has not been established yet. Here, we reported the establishment of a cell culture derived from a dentigerous cyst. This cell line was named DeCy-1. In spite of its ectomesenchymal morphology, DeCy-1 cells express epithelial markers such as cytokeratins 5, 6, and 8. Furthermore, these cells express the ODAM protein, which is present in odontogenesis and in dental follicle, indicating that DeCy-1 cells derived from odontogenic epithelium. Analysis by electron microscopy of this cell line showed that it has a high vesicular activity, suggesting that DeCy-1 could secrete molecules that may be involved in DC pathogenesis. Thus, secreted proteins were analyzed by PAGE-SDS, where we observed approximately 11 bands. In addition, the capacity of these secretions to degrade proteins was analyzed by gelatin substrate zymography. A degradation band of about 62 kDa was found in these assays. Western blot assays suggested that the matrix metalloproteinase 2 (MMP-2) is responsible of this protease activity. Thus, our results indicate that the establishment of a cell line derived from DC is a useful in vitro model to study the biology of this odontogenic lesion and its participation in the development of odontogenic tumors.

Keywords: dentigerous cyst, MMP20, cancer, cell culture

Procedia PDF Downloads 131

Authors: Sweta Agrawal, Sachin Chaugule, Gargi Rane, Shashank More, Madhavi Indap

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Angiogenesis and metastasis are two of the most important hallmarks of cancer. Hence, most of the cancer therapies nowadays are multi-targeted so as to reduce resistance and have better efficacy. As synthetic molecules arise with a burden of their toxicities and side-effects, more and more research is being focussed on exploiting the vast natural resources of drugs, in the form of plants and animals. Although, the idea of using marine organisms as a source of pharmaceuticals is not new, the pace at which marine drugs are being discovered, has definitely up surged! In the present study, we have assessed the anti-angiogenic and in vitro anti-metastatic activity of aqueous fraction from the extract of marine gastropod Euchelus asper. The soft body of Euchelus Asper was extracted with methanol and named EAME. Partition chromatography of EAME gave three fractions EAME I, II and III. Biochemical analysis revealed the presence of proteins in EAME III. Preliminary analysis had revealed the anti-angiogenic activity was exhibited by EAME III out of the three fractions. Hereafter, EAME III (concentration 25µg/ml-400µg/ml) was tested on chick chorioallantoic membrane (CAM) model for the detailed analysis of its potential anti-angiogenic effect. In vitro testing of the fraction (concentration 0.25µg/ml - 1µg/ml), involved cytotoxicity by SRB assay, cell cycle analysis by flow cytometry and anti-proliferative effect by scratch wound healing assay on A549 lung carcinoma cells. Apart from this, a portion of treated CAM as well as conditioned medium from treated A549 were subjected to gelatin zymography for assessment of matrix metalloproteinases MMP-2 and MMP-9 levels. Our results revealed that EAME III exhibited significant anti-angiogenic activity on CAM which was also supported by histological observations. During histological studies of CAM, it was found that EAME III caused reduction in angiogenesis by altering the extracellular matrix of the CAM membrane. In vitro analysis disclosed that EAME III exhibited moderate cytotoxic effect on A549 cells and its effect was not dose-dependent. The results of flow cytometry confirmed that EAME III caused cell cycle arrest in A549 cell line as almost all of the treated cells were found in G1 phase. Further, the migration and proliferation of A549 was significantly reduced by EAME III as observed from the scratch wound assay. Moreover, Gelatin zymography analysis revealed that EAME III caused suppression of MMP-2 in CAM membrane and reduced MMP-9 and MMP-2 expression in A549 cells. This verified that the anti-angiogenic and anti-metastatic effects of EAME III were correlated with the suppression of MMP-2 and -9. To conclude, EAME III shows dual anti-tumour action by reducing angiogenesis and exerting anti-metastatic effect on lung cancer cells, thus it has the potential to be used as an anti-cancer agent against lung carcinoma.

Keywords: angiogenesis, anti-cancer, marine drugs, matrix metalloproteinases

Procedia PDF Downloads 227

Authors: A. Bouloufa, F. Khaled, K. Djessas

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This paper presents a new structure of solar cell based on p-type microcrystalline silicon as an absorber and n-type aluminum doped zinc oxide (ZnO:Al) transparent conductive oxide as an optical window. The ZnO:Al layer deposited by rf-magnetron sputtering at room temperature yields a low resistivity about 7,64.10-2Ω.cm and more than 85% mean optical transmittance in the VIS–NIR range, with an optical band gap of 3.3 eV. These excellent optical properties of this layer in combination with an optimal contact at the front surface result in a superior light trapping yielding to efficiencies about 20%. In order to improve efficiency, we have used a p+-µc-Si thin layer highly doped as a back surface field which minimizes significantly the impact of rear surface recombination velocity on voltage and current leading to a high efficiency of 24%. Optoelectronic parameters were determined using the current density-voltage (J-V) curve by means of a numerical simulation with Analysis of Microelectronic and Photonic Structures (AMPS-1D) device simulator.

Keywords: optical window, thin film, solar cell, efficiency

Procedia PDF Downloads 285

Authors: Tianjiao Chu, Carla Rios Luci, Christy Maksoudian, Ara Sargsian, Bella B. Manshian, Stefaan J. Soenen

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Nanomaterials have gained high interest in their use as potent anticancer agents. Apart from delivering chemotherapeutic agents in order to reduce off-target effects, molecular agents have also been widely explored. The advances in our understanding of cell biology and cell death mechanisms1 has generated a broad library of potential therapeutic targets by siRNA, mRNA, or pDNA complexes. In the present study, we explore the ability of pDNA-polyplexes to induce tumor-specific necroptosis. This results in a cascade of effects, where immunogenic cell death potentiates anti-tumor immune responses and results in an influx of dendritic cells and cytotoxic T cells, rendering the tumor more amenable to immune checkpoint inhibition. This study aims to explore whether the induction of necroptosis in a subpopulation of tumor cells can be used to potentiate immune checkpoint inhibition studies.

Keywords: nanoparticle, MLKL, necroptosis, immunotherapy

Procedia PDF Downloads 133