Search results for: clear cell renal cell carcinoma

Authors: Jiraporn Rojtinnakorn

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ICAM-2 (intercellular adhesion molecule 2) or CD102 (Cluster of Differentiation 102) is type I trans-membrane glycoproteins, composing 2-9 immunoglobulin-like C2-type domains. ICAM-2 plays the particular role in immune response and cell surveillance. It is concerned in innate and specific immunity, cell survival signal, apoptosis, and anticancer. EST clone of ICAM-2, from P. gigas blood cell EST libraries, showed high identity to human ICAM-2 (92%) with conserve region of ICAM N-terminal domain and part of Ig superfamily. Gene and protein of ICAM-2 has been founded in mammals. This is the first report of ICAM-2 in fish.

Keywords: ICAM-2, CD102, Pangasianodon gigas, antitumor

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Authors: Kevser Dincer, Basma Waisi, M. Ozan Ozdemir, Ugur Pasaogullari, Jeffrey McCutcheon

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Nanofibers are defined as fibers with diameters less than 100 nanometers. They can be produced by interfacial polymerization, electrospinning and electrostatic spinning. In this study, behaviours of activated carbon nano fiber (ACNF), carbon nano-fiber (CNF), Polyacrylonitrile/carbon nanotube (PAN/CNT), Polyvinyl alcohol/nano silver (PVA/Ag) in PEM fuel cells are investigated experimentally. This material was used as gas diffusion layer (GDL) in PEM fuel cells. When the performances of these cells are compared to each other at 5x5 cm2 cell, it is found that the PVA/Ag exhibits the best performance among all. In this work, nano fiber and nano fiber/nano particles electrical conductivities have been studied to understand their effects on PEM fuel cell performance. According to the experimental results, the maximum electrical conductivity performance of the fuel cell with nanofiber was found to be at PVA/Ag. The electrical conductivities of CNF, ACNF, PAN/CNT are lower for PEM. The resistance of cell with PVA/Ag is lower than the resistance of cell with PAN/CNT, ACNF, CNF.

Keywords: proton exchange membrane fuel cells, electrospinning, carbon nano fiber, activate carbon nano-fiber, PVA fiber, PAN fiber, carbon nanotube, nano particle nanocomposites

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Authors: Kamta P. Namdeo

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Novel thiazolidino-(3,2-b)-1, 2,4-triazole-5(6H)-one derivatives were synthesized, and anticancer activity was studied on human breast cancer cell line MFC7. It showed a significant decrease in cell viability with reference to the standard. The findings suggest that nitro-substituted compound showed best anticancer activity and activity was due to the triazole and thiazolidinone hetero nucleus present in the structure.

Keywords: anti-cancer, adriamycine, thiazolidinone, 1, 2, 4-triazole, thiazolidino-triazolone

Procedia PDF Downloads 348

Authors: Maria Borawska, Patryk Nowakowski, Sylwia K. Naliwajko, Renata Markiewicz-Zukowska, Anna Puscion-Jakubik, Krystyna Gromkowska-Kepka, Justyna Moskwa

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Coprinus comatus (O. F. Müll.) Pers.) should not be confused with the common Ink Cap, which contains coprine and can induce coprine poisoning. We study the possibility of applying coprinus mushroom (Coprinus comatus), available in Poland, as food product supporting the treatment of human glioblastoma cells. The U87MG and T98 glioblastoma cell lines were exposed to water (CW) or ethanol 95° (CE) Cantharellus extracts (50-500 μg/ml), with or without temozolomide (TMZ) during 24, 48 or 72 hours. The cell division was examined by the H³-thymidine incorporation. The statistical analysis was performed using Statistica v. 13.0 software. Significant differences were assumed for p < 0.05. We found that both, CW and CE, administrated alone, had inhibitory effect on cell lines growth, but the CE extract had a higher degree of growth inhibition. The anti-tumor effect of TMZ (50 μM) on U87MG was enhanced by mushroom extracts, and the effect was lower to the effect after using Coprinus comatus extracts (CW and CE) alone. A significant decrease (p < 0.05) in pro-MMP2 (82.61 ± 6.3% of control) secretion in U87MG cells was observed after treated with CE (250 μg/ml). We conclude that extracts of Coprinus comatus, edible mushroom, present cytotoxic properties on U87MG and T98 cell lines and may cooperate with TMZ synergistically enhancing its growth inhibiting activity against glioblastoma U87MG cell line.

Keywords: anticancer, glioma, mushroom, temozolomide

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Authors: Prajna Paramita Naik, Sujit Kumar Bhutia

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Background: Regardless of the development multimodal treatment strategies, oral squamous cell carcinoma (OSCC) is often associated with a high rate of recurrence, metastasis and chemo- and radio- resistance. The present study inspected the relevance of CD44, ABCB1 and ADAM17 expression as a putative stem cell compartment in oral squamous cell carcinoma (OSCC) and deciphered the role of autophagy in regulating the expression of aforementioned proteins, stemness and chemoresistance. Methods: A retrospective analysis of CD44, ABCB1 and ADAM17 expression with respect to the various clinicopathological factors of sixty OSCC patients were determined via immunohistochemistry. The correlation among CD44, ABCB1 and ADAM17 expression was established. Sphere formation assay, flow cytometry and fluorescence microscopy were conducted to elucidate the stemness and chemoresistance nature of established cisplatin-resistant oral cancer cells (FaDu). The pattern of expression of CD44, ABCB1 and ADAM17 in parental (FaDu-P) and resistant FaDu cells (FaDu-CDDP-R) were investigated through fluorescence microscopy. Western blot analysis of autophagy marker proteins was performed to compare the status of autophagy in parental and resistant FaDu cell. To investigate the role of autophagy in chemoresistance and stemness, sphere formation assay, immunofluorescence and Western blot analysis was performed post transfection with siATG14 and the level of expression of autophagic proteins, mitochondrial protein and stemness-associated proteins were analyzed. The statistical analysis was performed by GraphPad Prism 4.0 software. p-value was defined as follows: not significant (n.s.): p > 0.05;*: p ≤ 0.05; **: p ≤ 0.01; ***: p ≤ 0.001; ****: p ≤ 0.0001 were considered statistically significant. Results: In OSCC, high CD44, ABCB1 and ADAM17 expression were significantly correlated with higher tumor grades and poor differentiation. However, the expression of these proteins was not related to the age and sex of OSCC patients. Moreover, the expression of CD44, ABCB1 and ADAM17 were positively correlated with each other. In vitro and OSCC tissue double labeling experiment data showed that CD44+ cells were highly associated with ABCB1 and ADAM17 expression. Further, FaDu-CDDP-R cells showed higher sphere forming capacity along with increased fraction of the CD44+ population and β-catenin expression FaDu-CDDP-R cells also showed accelerated expression of CD44, ABCB1 and ADAM17. A comparatively higher autophagic flux was observed in FaDu-CDDP-R against FaDu-P cells. The expression of mitochondrial proteins was noticeably reduced in resistant cells as compared to parental cells indicating the occurrence of autophagy-mediated mitochondrial degradation in oral cancer. Moreover, inhibition of autophagy was coupled with the decreased formation of orospheres suggesting autophagy-mediated stemness in oral cancer. Blockade of autophagy was also found to induce the restoration of mitochondrial proteins in FaDu-CDDP-R cells indicating the involvement of mitophagy in chemoresistance. Furthermore, a reduced expression of CD44, ABCB1 and ADAM17 was also observed in ATG14 deficient cells FaDu-P and FaDu-CDDP-R cells. Conclusion: The CD44+ ⁄ABCB1+ ⁄ADAM17+ expression in OSCC might be associated with chemoresistance and a putative CSC compartment. Further, the present study highlights the contribution of mitophagy in chemoresistance and confirms the potential involvement of autophagic regulation in acquisition of stem-like characteristics in OSCC.

Keywords: ABCB1, ADAM17, autophagy, CD44, chemoresistance, mitophagy, OSCC, stemness

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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Authors: Jerman Madonsela, Wallace Matizamhuka, Akiko Yamamoto, Ronald Machaka, Brendon Shongwe

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In this study, biocompatibility evaluation of nanostructured near beta Ti-24Nb-4Zr-8Sn (Ti2448) alloy with non-toxic elements produced utilizing Spark plasma sintering (SPS) of very fine microsized powders attained through mechanical alloying was performed. The results were compared with pure titanium and Ti-6Al-4V (Ti64) alloy. Cell proliferation test was performed using murine osteoblastic cells, MC3T3-E1 at two cell densities; 400 and 4000 cells/mL for 7 days incubation. Pure titanium took a lead under both conditions suggesting that the presence of other oxide layers influence cell proliferation. No significant difference in cell proliferation was observed between Ti64 and Ti2448. Potentiodynamic measurement in Hanks, 0.9% NaCl and cell culture medium showed no distinct difference on the anodic polarization curves of the three alloys, indicating that the same anodic reaction occurred on their surface but with different rates. However, Ti2448 showed better corrosion resistance in cell culture medium with a slightly lower corrosion rate of 2.96 nA/cm2 compared to 4.86 nA/cm2 and 5.62 nA/cm2 of Ti and Ti64 respectively. Ti2448 adsorbed less protein as compared to Ti and Ti64 though no notable difference in surface wettability was observed.

Keywords: biocompatibility, osteoblast, corrosion, surface wettability, protein adsorption

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Authors: Kang-Hyun Leem, Myung-Gyou Kim, Hye Kyung Kim

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The prickly pear cactus (Opuntia ficus-indica) has a global distribution and have been used for medicinal benefits such as artherosclerosis, diabetes, gastritis, and hyperglycemia. However, very little information is currently available for their mechanism. The prikly pear variety Opuntia ficus-indica var. Saboten (OFS) is widely cultivated in Cheju Island, southwestern region of Korea, and used as a functional food. Present study investigated the effects of OFS on pancreatic β-cell function using pancreatic islet β cells (HIT cell). Alpha-glucosidase inhibition, glucose uptake, insulin secretion, insulin sensitivity, and pancreatic β cell proliferation were determined. The inhibitory effect of ethanol extract of OFS stem on α-glucosidase enzyme was measured in a cell free system. Glucose uptake was determined using fluorescent glucose analogue, 2-NBDG. Insulin secretion was measured by ELISA assay. Cell proliferation was measured by MTT assay. Ethanol extracts of OFS dose-dependently inhibited α-glucosidase activity as well as glucose uptake. Insulinotrophic effect of OFS extract was observed at high glucose media in pancreatic β-islet cells. Furthermore, pancreatic β cell regeneration was also observed.These results suggest that OFS mediates the antidiabetic activity mainly via α-glucosidase inhibition, glucose uptake, and improved insulin sensitivity.

Keywords: prickly pear cactus, Opuntia ficus-indica var. Saboten, pancreatic islet HIT cells, α-glucosidase, glucose uptake, insulinotrophic

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Authors: M. Dezvarei, S. Morovati

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In recent years, increasing usage of electrical energy provides a widespread field for investigating new methods to produce clean electricity with high reliability and cost management. Fuel cells are new clean generations to make electricity and thermal energy together with high performance and no environmental pollution. According to the expansion of fuel cell usage in different industrial networks, the identification and optimization of its parameters is really significant. This paper presents optimization of a proton exchange membrane fuel cell (PEMFC) parameters based on modified particle swarm optimization with real valued mutation (RVM) and clonal algorithms. Mathematical equations of this type of fuel cell are presented as the main model structure in the optimization process. Optimized parameters based on clonal and RVM algorithms are compared with the desired values in the presence and absence of measurement noise. This paper shows that these methods can improve the performance of traditional optimization methods. Simulation results are employed to analyze and compare the performance of these methodologies in order to optimize the proton exchange membrane fuel cell parameters.

Keywords: clonal algorithm, proton exchange membrane fuel cell (PEMFC), particle swarm optimization (PSO), real-valued mutation (RVM)

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Authors: Jung Park, Anca Mazare, Klaus Von Der Mark, Patrik Schmuki

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In clinical application of TiO2 implants on tooth and hip replacement, migration, adhesion and differentiation of neighboring mesenchymal stem cells onto implant surfaces are critical steps for successful bone regeneration. In a recent decade, accumulated attention has been paid on nanoscale electrochemical surface modifications on TiO2 layer for improving bone-TiO2 surface integration. We generated, on titanium surfaces, self-assembled layers of vertically oriented TiO2 nanotubes with defined diameters between 15 and 100 nm and here we show that mesenchymal stem cells finely sense TiO2 nanotubular geometry and quickly decide their cell fate either to differentiation into osteoblasts or to programmed cell death (apoptosis) on TiO2 nanotube layers. These cell fate decisions are critically dependent on nanotube size differences (15-100nm in diameters) of TiO2 nanotubes sensing by integrin clustering. We further demonstrate that nanoscale topography-sensing is feasible not only in mesenchymal stem cells but rather seems as generalized nanoscale microenvironment-cell interaction mechanism in several cell types composing bone tissue network including osteoblasts, osteoclast, endothelial cells and hematopoietic stem cells. Additionally we discuss the synergistic effect of simultaneous stimulation by nanotube-bound growth factor and nanoscale topographic cues on enhanced bone regeneration.

Keywords: TiO2 nanotube, stem cell fate decision, nano-scale microenvironment, bone regeneration

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Authors: Di Luo, Maria Buchberger, Anja Pickhard

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Objectives: The purpose of this study was to assess and compare the diagnostic accuracy of four common morphological approaches, including sonography, computed tomography (CT), positron emission tomography/computed tomography (PET/CT), and magnetic resonance imaging (MRI) for the evaluation of cervical lymph node metastases in head and neck squamous cell carcinoma (HNSCC) patients. Material and Methods: Included in this retrospective study were 26 patients diagnosed with HNSCC between 2010 and 2011 who all underwent sonography, CT, PET/CT, and MRI imaging before neck dissection. Morphological data were compared to the corresponding histopathological results. Statistical analysis was performed with SPSS statistic software (version 26.0), calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for detection of cervical lymph node metastases. Results: The 5-year survival rate of the patient collective was 55.5%.Risk factors for survival included initial primary tumor stage, initial lymph node stage, initial metastasis status, and therapeutic approaches. Cox regression showed initial metastasis status(HR 8.671, 95%CI 1.316-57.123, p=0.025) and therapeutic approaches(HR 6.699, 95%CI 1.746-25.700, p=0.006)to be independent predictive risk factors for survival. Sensitivity was highest for MRI (96% compared to 85% for sonography and 89% for CT and PET/CT). Specificity was comparable with 95 % for CT and 98 % for sonography and PET/CT, but only 68% for MRI. While the MRI showed the least PPV (34%) compared to all other methods (85% for sonography,75% for CT, and 86% for PET/CT), the NPV was comparable in all methods(98-99%). The overall accuracy of cervical lymph node metastases detection was comparable for sonography, CT, and PET/CT with 96%,97%,94%, respectively, while MRI had only 72% accuracy. Conclusion: Since the initial status of metastasis is an independent predictive risk factor for patients’ survival, efficient detection is crucial to plan adequate therapeutic approaches. Sonography, CT, and PET/CT have better diagnostic accuracy than MRI for the evaluation of cervical lymph node metastases in HNSCC patients.

Keywords: cervical lymph node metastases, diagnostic accuracy, head and neck squamous carcinoma, risk factors, survival

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Authors: David Chao, John Lai, Alvin Wu, Carl Wang

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For lithium-ion batteries with multiple cell configurations, some use scenarios can cause uneven aging effects to each cell within the battery because of uneven current distribution. Hence the focus of the study is to explore the aging effect(s) on batteries with different construction designs. In order to systematically study the influence of various factors in some key battery configurations, a detailed analysis of three key battery construction factors is conducted. And those key factors are (1) terminal position; (2) cell alignment matrix; and (3) interconnect resistance between cells. In this study, the 2S2P circuitry has been set as a model multi-cell battery to set up different battery samples, and the aging behavior is studied by a cycling test to analyze the current distribution and recoverable capacity. According to the outcome of aging tests, some key findings are: (I) different cells alignment matrices can have an impact on the cycle life of the battery; (II) symmetrical structure has been identified as a critical factor that can influence the battery cycle life, and unbalanced resistance can lead to inconsistent cell aging status; (III) the terminal position has been found to contribute to the uneven current distribution, that can cause an accelerated battery aging effect; and (IV) the internal connection resistance increase can actually result in cycle life increase; however, it is noteworthy that such increase in cycle life is accompanied by a decline in battery performance. In summary, the key findings from the study can help to identify the key aging factor of multi-cell batteries, and it can be useful to effectively improve the accuracy of battery capacity predictions.

Keywords: multiple cells battery, current distribution, battery aging, cell connection

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Authors: Ankita Gaur, Mouli Karmakar, Shyam

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In this study, a silicon solar cell has been modeled and analyzed to enhance its electrical performance by improving the optical properties using an antireflecting coating (ARC). The dynamic optical reflectance, transmittance along with the net transmissivity absorptivity product of each layer are assessed as per the diurnal variation of the angle of incidence using MATLAB 2019. The model is tested with various Anti-Reflective coatings and the performance has also been compared with uncoated cells. ARC improves the optical transmittance of the photon. Higher transmittance of ⁓96.57% with lowest reflectance of ⁓ 1.74% at 12.00 hours was obtained with MgF₂ coated silicon cells. The electrical efficiency of the configured solar cell was evaluated for a composite climate of New Delhi, India, for all weather conditions. The annual electricity generation for Anti-reflective coated and uncoated crystalline silicon PV Module was observed to be 103.14 KWh and 99.51 KWh, respectively.

Keywords: antireflecting coating, electrical efficiency, reflectance, solar cell, transmittance

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Authors: Fouad Berrabeh, Sabir Messalti

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The performances of the photovoltaic systems are very dependent on different conditions, such as solar irradiation, temperature, etc. Therefore, it is very important to provide detailed studies for different cases in order to provide continuously power, so the photovoltaic system must be properly sized. This paper presents the modelling and simulation of the photovoltaic cell using single diode model. I-V characteristics and P-V characteristics are presented and it verified at different conditions (irradiance effect, temperature effect, series resistance effect).

Keywords: photovoltaic cell, BP SX 150 BP solar photovoltaic module, irradiance effect, temperature effect, series resistance effect, I–V characteristics, P–V characteristics

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Authors: Hien Thi Thu Le, Nuno Rafael Candeias, Olli Yli-Harja, Meenakshisundaram Kandhavelu

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Purinergic receptor 1 (P2Y1R) is the potential therapeutic target for inducing prostate cancer (PCa) cell death. Recently, 1-indolinoalkyl 2-phenolic derivative, HIC, was identified as a P2Y1R agonist that increases apoptosis and inhibits cell proliferation of PCa. However, the biological effects of HIC have not been extensively studied at the molecular level. In the present study, we have investigated the anticancer effects of HIC and the molecular mechanisms underlying in PCa cells. Half maximal inhibitory concentration (IC₅₀) of HIC was measured as 15.98 μM and 15.64 μM for DU145 and PC3 cells, respectively. In addition, we found that HIC inhibited cell growth and metastasis of PC3 and DU145 cells colonies, spheroid areas, and migrated cells. RNA seq analysis revealed significant changes of over 3000 genes (p value < 0.05) upon HIC treatment in PC3 and DU145 cells. Genes involved in DNA damage, apoptosis, cell cycle arrest at G1/S phase were modulated by HIC treatment. MAPK and NF-κB protein array revealed the increased expression of ERK1/2, JNK1/2, p53 phosphorylation, and p53 protein. ERK1/2 and JNK1/2 activations are known to increase the stabilization of p53, a tumor suppressor protein, which is required to arrest the cell cycle at G1/S phase and cause cell death of PCa cells. Overall, our results suggest that HIC can serve as a multi-dimensional chemotherapeutic agent possessing strong cytotoxic, anti-cancer, and anti-metastasis against PCa growth.

Keywords: prostate cancer, P2Y1 receptor, apoptosis, metastasis

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Authors: Palak V. Patel, Jessica Pixley, Steven R. Feldman

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Introduction: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and requires substantial resources to treat. When choosing between indicated therapies, providers consider their associated adverse effects, efficacy, cosmesis, and function preservation. The patient’s tumor burden, infiltrative risk, and risk of tumor recurrence are also considered. Treatment cost is often left out of these discussions. This can lead to financial toxicity, which describes the harm and quality of life reductions inflicted by high care costs. Methods: We studied the guidelines set forth by the American Academy of Dermatology for the treatment of BCC. A PubMed literature search was conducted to identify the costs of each recommended therapy. We discuss costs alongside treatment efficacy and side-effect profile. Results: Surgical treatment for BCC can be cost-effective if the appropriate treatment is selected for the presenting tumor. Curettage and electrodesiccation can be used in low-grade, low-recurrence tumors in aesthetically unimportant areas. The benefits of cost-conscious care are not likely to be outweighed by the risks of poor cosmesis or tumor return ($471 BCC of the cheek). When tumor burden is limited, MMS offers better cure rates and lower recurrence rates than surgical excision, and with comparable costs (MMS $1263; SE $949). Surgical excision with permanent sections may be indicated when tumor burden is more extensive or if molecular testing is necessary. The utility of surgical excision with frozen sections, which costs substantially more than MMS without comparable outcomes, is less clear (SE with frozen sections $2334-$3085). Less data exists on non-surgical treatments for BCC. These techniques cost less, but recurrence-risk is high. Side-effects of nonsurgical treatment are limited to local skin reactions, and cosmesis is good. Cryotherapy, 5-FU, and MAL-PDT are all more affordable than surgery, but high recurrence rates increase risk of secondary financial and psychosocial burden (recurrence rates 21-39%; cost $100-270). Radiation therapy offers better clearance rates than other nonsurgical treatments but is associated with similar recurrence rates and a significantly larger financial burden ($2591-$3460 BCC of the cheek). Treatments for advanced or metastatic BCC are extremely costly, but few patients require their use, and the societal cost burden remains low. Vismodegib and sonidegib have good response rates but substantial side effects, and therapy should be combined with multidisciplinary care and palliative measures. Expert-review has found sonidegib to be the less expensive and more efficacious option (vismodegib $128,358; sonidegib $122,579). Platinum therapy, while not FDA-approved, is also effective but expensive (~91,435). Immunotherapy offers a new line of treatment in patients intolerant of hedgehog inhibitors ($683,061). Conclusion: Dermatologists working within resource-compressed practices and with resource-limited patients must prudently manage the healthcare dollar. Surgical therapies for BCC offer the lowest risk of recurrence at the most reasonable cost. Non-surgical therapies are more affordable, but high recurrence rates increase the risk of secondary financial and psychosocial burdens. Treatments for advanced BCC are incredibly costly, but the low incidence means the overall cost to the system is low.

Keywords: nonmelanoma skin cancer, basal cell skin cancer, squamous cell skin cancer, cost of care

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Authors: Han-Wei Shih, Yao-Nan Wang, Ko-Tung Chang, Lung-Ming Fu

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A multi-channel cell growth real-time monitor and evaluation system using charge-coupled device (CCD) sensors with 40X lens integrating a NI LabVIEW image processing program is proposed and demonstrated. The LED light source control of monitor system is utilizing 8051 microprocessor integrated with NI LabVIEW software. In this study, the same concentration RAW264.7 cells growth rate and morphology in four different culture conditions (DMEM, LPS, G1, G2) were demonstrated. The real-time cells growth image was captured and analyzed by NI Vision Assistant every 10 minutes in the incubator. The image binarization technique was applied for calculating cell doubling time and cell division index. The cells doubling time and cells division index of four group with DMEM, LPS, LPS+G1, LPS+G2 are 12.3 hr,10.8 hr,14.0 hr,15.2 hr and 74.20%, 78.63%, 69.53%, 66.49%. The image magnification of multi-channel CCDs cell real-time monitoring system is about 100X~200X which compares with the traditional microscope.

Keywords: charge-coupled device (CCD), RAW264.7, doubling time, division index

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Authors: Bohli Afef

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The fifth-generation (5G) wireless systems is featured by extreme densities of cell stations to overcome the higher future demand. Hence, interference management is a crucial challenge in 5G ultra-dense cellular networks. In contrast to the classical inter-cell interference coordination approach, which is no longer fit for the high density of cell-tiers, this paper proposes a novel virtual coordination based on the dynamic common cognitive monitor channel protocol to deal with the inter-cell interference issue. A tractable and flexible model for the coverage probability of a typical user is developed through the use of the stochastic geometry model. The analyses of the performance of the suggested protocol are illustrated both analytically and numerically in terms of coverage probability.

Keywords: ultra dense heterogeneous networks, dynamic common channel protocol, cognitive radio, stochastic geometry, coverage probability

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Authors: Fatma Keskin Arabul, Ibrahim Senol, Ahmet Yigit Arabul, Ali Rifat Boynuegri

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On account of the concern of the fossil fuel is depleting and its negative effects on the environment, interest in alternative energy sources is increasing day by day. However, considering the importance of transportation in human life, instead of oil and its derivatives fueled vehicles with internal combustion engines, electric vehicles which are sensitive to the environment and working with electrical energy has begun to develop. In this study, simulation was carried out for providing energy management and recovering regenerative braking in fuel cell-battery hybrid electric vehicle. The main power supply of the vehicle is fuel cell on the other hand not only instantaneous power is supplied by the battery but also the energy generated due to regenerative breaking is stored in the battery. Obtained results of the simulation is analyzed and discussed.

Keywords: electric vehicles, fuel cell, battery, regenerative braking, energy management

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Authors: Marcel Verwey, Anna M. Joubert, Elsie M. Nolte, Wolfgang Dohle, Barry V. L. Potter, Anne E. Theron

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A tetrahydroisoquinolinone (THIQ) core can be used to mimic the A,B-ring of colchicine site-binding microtubule disruptors such as 2-methoxyestradiol in the design of anti-cancer agents. Steroidomimeric microtubule disruptors were synthesized by introducing C'2 and C'3 of the steroidal A-ring to C'6 and C'7 of the THIQ core and by introducing a decorated hydrogen bond acceptor motif projecting from the steroidal D-ring to N'2. For this in vitro study, four non-steroidal THIQ-based analogues were investigated and comparative studies were done between the non-sulphamoylated compound STX 3450 and the sulphamoylated compounds STX 2895, STX 3329 and STX 3451. The objective of this study was to investigate the modes of cell death induced by these four THIQ-based analogues in A549 lung carcinoma epithelial cells and metastatic breast adenocarcinoma MDA-MB-231 cells. Cytotoxicity studies to determine the half maximal growth inhibitory concentrations were done using spectrophotometric quantification via crystal violet staining and lactate dehydrogenase (LDH) assays. Microtubule integrity and morphologic changes of exposed cells were investigated using polarization-optical transmitted light differential interference contrast microscopy, transmission electron microscopy and confocal microscopy. Flow cytometric quantification was used to determine apoptosis induction and the effect that THIQ-based analogues have on cell cycle progression. Signal transduction pathways were elucidated by quantification of the mitochondrial membrane integrity, cytochrome c release and caspase 3, -6 and -8 activation. Induction of autophagic cell death by the THIQ-based analogues was investigated by morphological assessment of fluorescent monodansylcadaverine (MDC) staining of acidic vacuoles and by quantifying aggresome formation via flow cytometry. Results revealed that these non-steroidal microtubule disrupting analogues inhibited 50% of cell growth at nanomolar concentrations. Immunofluorescence microscopy indicated microtubule depolarization and the resultant mitotic arrest was further confirmed through cell cycle analysis. Apoptosis induction via the intrinsic pathway was observed due to depolarization of the mitochondrial membrane, induction of cytochrome c release as well as, caspase 3 activation. Potential involvement of programmed cell death type II was observed due to the presence of acidic vacuoles and aggresome formation. Necrotic cell death did not contribute significantly, indicated by stable LDH levels. This in vitro study revealed the induction of the intrinsic apoptotic pathway as well as possible involvement of autophagy after exposure to these THIQ-based analogues in both MDA-MB-231- and A549 cells. Further investigation of this series of anticancer drugs still needs to be conducted to elucidate the temporal, mechanistic and functional crosstalk mechanisms between the two observed programmed cell deaths pathways.

Keywords: apoptosis, autophagy, cancer, microtubule disruptor

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Authors: Usha Kiran, M. Z. Abdin

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Osmotin is an abundant cationic multifunctional protein discovered in cells of tobacco (Nicotiana tabacum L. var Wisconsin 38) adapted to an environment of low osmotic potential. It provides plants protection from pathogens, hence placed in the PRP family of proteins. The osmotin induced proline accumulation has been reported in plants including transgenic tomato and strawberry conferring tolerance against both biotic and abiotic stresses. The exact mechanism of induction of proline by osmotin is however, not known till date. These observations have led us to hypothesize that osmotin induced proline accumulation could be due to its involvement as transcription factor and/or cell signal pathway modulator in proline biosynthesis. The present investigation was therefore, undertaken to analyze the osmotin protein as transcription factor /cell signalling modulator using bioinformatics tools. The results of available online DNA binding motif search programs revealed that osmotin does not contain DNA-binding motifs. The alignment results of osmotin protein with the protein sequence from DATF showed the homology in the range of 0-20%, suggesting that it might not contain a DNA binding motif. Further to find unique DNA-binding domain, the superimposition of osmotin 3D structure on modeled Arabidopsis transcription factors using Chimera also suggested absence of the same. We, however, found evidence implicating osmotin in cell signaling. With these results, we concluded that osmotin is not a transcription factor but regulating proline biosynthesis and accumulation through cell signaling during abiotic stresses.

Keywords: osmotin, cell signaling modulator, bioinformatic tools, protein

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Authors: Dean Robinson, Miriam Gublebank, Ella Sklan, Tali Tavor Re'em

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Alginate, a natural linear polysaccharide polymer extracted from brown seaweed, is extensively applied due to its biocompatibility, all- aqueous ease of handling, and relatively low costs. Alginate easily forms a hydrogel when crosslinked with a divalent ion, such as calcium. However, Alginate hydrogel holds low mechanical properties and is cell-inert. To overcome these drawbacks and to improve alginate as a bio-ink for bioprinting, we produced a new alginate matrix combined with spider silk, one of the most resilient, elastic, strong materials known to men. Recombinant spider silk biopolymer has a sponge-like structure and is known to be biocompatible and non-immunogenic. Our results indicated that combining synthetic spider-silk into bio-printed cell-seeded alginate hydrogels resulted in improved properties compared to alginate: improved mechanical properties of the matrix, achieving a tunable gel viscosity and high printability, alongside prolonged and higher cell viability in culture, probably due to the improved cell-matrix interactions. The new bio-ink was then used for bilayer bioprinting of epithelial and stromal endometrial cells. Such a co-culture model will be used for the formation of the complex endometrial tissue for studying the embryo implantation process.

Keywords: cell culture, tissue engineering, spider silk, alginate, bioprinting

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Authors: Evgeniya Y. Yuzbasheva, Tigran V. Yuzbashev, Natalia I. Perkovskaya, Elizaveta B. Mostova

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Cell-surface display of lipase is of great interest as it has many applications in the field of biotechnology owing to its unique advantages: simplified product purification, and cost-effective downstream processing. One promising area of application for whole-cell biocatalysts with surface displayed lipase is biodiesel synthesis. Biodiesel is biodegradable, renewable, and nontoxic alternative fuel for diesel engines. Although the alkaline catalysis method has been widely used for biodiesel production, it has a number of limitations, such as rigorous feedstock specifications, complicated downstream processes, including removal of inorganic salts from the product, recovery of the salt-containing by-product glycerol, and treatment of alkaline wastewater. Enzymatic synthesis of biodiesel can overcome these drawbacks. In this study, Lip2p lipase was displayed on Yarrowia lipolytica cells via C- and N-terminal fusion variant. The active site of lipase is located near the C-terminus, therefore to prevent the activity loosing the insertion of glycine-serine linker between Lip2p and C-domains was performed. The hydrolytic activity of the displayed lipase reached 12,000–18,000 U/g of dry weight. However, leakage of enzyme from the cell wall was observed. In case of C-terminal fusion variant, the leakage was occurred due to the proteolytic cleavage within the linker peptide. In case of N-terminal fusion variant, the leaking enzyme was presented as three proteins, one of which corresponded to the whole hybrid protein. The calculated number of recombinant enzyme displayed on the cell surface is approximately 6–9 × 105 molecules per cell, which is close to the theoretical maximum (2 × 106 molecules/cell). Thus, we attribute the enzyme leakage to the limited space available on the cell surface. Nevertheless, cell-bound lipase exhibited greater stability to short-term and long-term temperature treatment than the native enzyme. It retained 74% of original activity at 60°C for 5 min of incubation, and 83% of original activity after incubation at 50°C during 5 h. Cell-bound lipase had also higher stability in organic solvents and detergents. The developed whole-cell biocatalyst was used for recycling biodiesel synthesis. Two repeated cycles of methanolysis yielded 84.1–% and 71.0–% methyl esters after 33–h and 45–h reactions, respectively.

Keywords: biodiesel, cell-surface display, lipase, whole-cell biocatalyst

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Authors: He Yuhai, Ahmad Ziad Bin Sulaiman

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Tongkat Ali, or Eurycoma longifolia, is a traditional Malay and Orang Asli herb used as aphrodisiac, general tonic, anti-Malaria, and anti-Pyretic. It has been recognized as a cashcrop by Malaysia due to its high value for the pharmaceutical use. In Tongkat Ali, eurycomanone, a quassinoid is usually chosen as a marker phytochemical as it is the most abundant phytochemical. In this research, ultrasound and enzyme were used to enhance the extraction of Eurycomanone from Tongkat Ali. Ultrasonic assisted extraction (USE) enhances extraction by facilitating the swelling and hydration of the plant material, enlarging the plant pores, breaking the plant cell, reducing the plant particle size and creating cavitation bubbles that enhance mass transfer in both the washing and diffusion phase of extraction. Enzyme hydrolyses the cell wall of the plant, loosening the structure of the cell wall, releasing more phytochemicals from the plant cell, enhancing the productivity of the extraction. Possible effects of ultrasound on the activity of the enzyme during the hydrolysis of the cell wall is under the investigation by this research. The extracts was analysed by high performance liquid chromatography for the yields of Eurycomanone. In this whole process, the conventional water extraction was used as a control of comparing the performance of the ultrasound and enzyme assisted extraction.

Keywords: ultrasound, enzymatic, extraction, Eurycoma longifolia

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Authors: Dalwinder Singh, Amandeep Verma, Manpreet Kaur, Birmohan Singh

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The detection of pre-cancerous changes using a Pap smear test of cervical cell is the important step for the early diagnosis of cervical cancer. The Pap smear test consists of a sample of human cells taken from the cervix which are analysed to detect cancerous and pre-cancerous stage of the given subject. The manual analysis of these cells is labor intensive and time consuming process which relies on expert cytotechnologist. In this paper, a computer assisted system for the automated analysis of the cervical cells has been proposed. We propose a morphology based approach to the nucleus detection and segmentation of the cytoplasmic region of the given single or multiple overlapped cell. Further, various texture and region based features are calculated from these cells to classify these into normal and abnormal cell. Experimental results on public available dataset show that our system has achieved satisfactory success rate.

Keywords: cervical cancer, cervical tissue, mathematical morphology, texture features

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Authors: Patsorn Worawattananutai, Srisopa Ruangnoo, Arunporn Itharat

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Hibiscus sabdariffa (HS) leaves are vegetables which are extensively used as blood tonic and laxatives in Thai traditional medicine. They are popularly used as healthy sour soup for prevention of chronic diseases such as cancer. Therefore, the cytotoxic activity of different extracts of fresh and dried Hibiscus sabdariffa leaves were investigated via the sulforhodamine B (SRB) assay against three types of women’s cancer cell lines, namely the human cervical adenocarcinoma cell line (HeLa), the human ovarian adenocarcinoma cell line (SKOV-3), and the human breast adenocarcinoma cell line (MCF-7). Extraction methods were squeezing, boiling with water and maceration with 95% or 50% ethanol. The 95% ethanolic extracts of Hibiscus sabdariffa dry leaves (HSDE95) showed the highest cytotoxicity against all types of women’s cancer cell lines with the IC50 values in range 7.51±0.33 to 12.13±1.85 µg/ml. Its IC50 values against SKOV-3, HeLa and MCF-7 were 7.51±0.33, 9.44±1.41 and 12.13±1.85 µg/ml, respectively. In these results, this extract can be classified as “active” according to the NCI guideline which indicated that IC50 values of the active cytotoxic plant extracts have to be beneath 20 µg/ml. Thus, HSDE95 was concluded to be a potent cytotoxic drug for all women’s cancer cells. This extract should be further investigated to isolate active compounds against women’s cancer cells.

Keywords: breast adenocarcinoma, cervical adenocarcinoma, cytotoxic activity, Hibiscus sabdariffa, ovarian adenocarcinoma

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Authors: Bryan D. Llenarizas, Maria Carla F. Manzano

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The rapid growth of electricity demand has led to a pursuit of alternative energy sources with high power output and not harmful to the environment. The fuel cell is a device that generates electricity via chemical reactions between the fuel and oxidant. Fuel cells have been known for decades, but the development of high-power output and durability was still one of the drawbacks of this energy source. This study investigates the potential of layer-by-layer composite for fuel cell applications. A two-electrode electrochemical cell was used for the galvanostatic electrochemical deposition method to fabricate a Polypyrrole/rGO|Polypyrrole/ZnO layer-by-layer composite material for fuel cell applications. In the synthesis, the first layer comprised 0.1M pyrrole monomer and 1mg of rGO, while the second layer had 0.1M pyrrole monomer and variations of ZnO concentration ranging from 0.08M up to 0.12M. A constant current density of 8mA/cm² was applied for 1 hour in fabricating each layer. Scanning electron microscopy (SEM) for the fabricated LBL material shows a globular surface with white spots. These white spots are the ZnO particles confirmed by energy-dispersive X-ray spectroscopy, indicating a successful deposition of the second layer onto the first layer. The observed surface morphology was consistent for each variation of ZnO concentrations. AC measurements were conducted to obtain the AC resistance of the fabricated film. Results show a decrease in AC resistance as the concentration of ZnO increases.

Keywords: anode, composite material, electropolymerization, fuel cell, galvanostatic, polypyrrole

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Authors: Jiajia Peng, Jianqing Qiu, Jianjun Ren, Yu Zhao

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Background: We aimed to compare clinical and survival differences between B-cell (B-NHL) and NKT-cell non-Hodgkin lymphomas (NKT-NHL) located in the nasal cavity, nasopharynx and paranasal sinuses, which are always categorized as one sinonasal type. Methods: Patients diagnosed with primary B-NHL and NKT-NHL in the nasal cavity, nasopharynx, and paranasal sinuses from the SEER database were included. We identified these patients based on histological types and anatomical sites and subsequently conducted univariate and multivariate Cox regression and Kaplan–Meier analyses to examine cancer-special survival (CSS) outcomes. Results: Overall, most B-NHL cases originated from the nasopharynx, while the majority of NKT-NHL cases occurred in the nasal cavity. Notably, the CSS outcomes improved significantly in all sinonasal B-NHL cases over time, whereas no such improvement trend was observed in each sinonasal NKT-NHL type. Additionally, increasing age was linked with an elevated risk of death in B-NHL, particularly in the nasal cavity (HR:3.37), rather than in NKT-NHL. Compared with B-NHL, the adverse effect of the higher stage on CSS was more evident in NKT-NHL, particularly in its nasopharynx site (HR: 5.12). Furthermore, radiotherapy was beneficial for survival in patients with sinonasal B-NHL and NKT-NHL, except in those with NKT-NHL in the nasopharynx site. However, chemotherapy has only been beneficial for CSS in patients with B-NHL in paranasal sinuses (HR: 0.42) since 2010, rather than in other types of B-NHL or NKT-NHL. Conclusions: Although B-NHL and NKT-NHL in the nasal cavity, nasopharynx and paranasal sinuses have similar anatomical locations, their clinic demographics and prognoses are largely different and should be treated and studied as distinct diseases.

Keywords: B-cell non-Hodgkin lymphomas, NKT-cell non-Hodgkin lymphomas, nasal cavity lymphomas, nasal sinuses lymphomas, nasopharynx lymphomas

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Authors: Kyungbae Pi, Kibeom Lee, Yongil Kim, Eun-Jung Lee

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Abnormal adipocyte growth, in terms of increased cell numbers and increased cell differentiation, is considered to be a major pathological feature of obesity. Thus, the inhibition of preadipocyte mitogenesis and differentiation could help prevent and suppress obesity. The aim of this study was to assess whether extracts from Weissella koreensis 521 cells isolated from kimchi could exert anti-adipogenic effects in 3T3-L1 cells (fat cells). Differentiating 3T3-L1 cells were treated with W. koreensis 521 cell extracts (W. koreensis 521_CE), and cell viability was assessed by MTT assays. At concentrations below 0.2 mg/ml, W. koreensis 521_CE did not exert any cytotoxic effect in 3T3-L1 cells. However, treatment with W. koreensis 521_CE significantly inhibited adipocyte differentiation, as assessed by morphological analysis and Oil Red O staining of fat. W. koreensis 521_CE treatment (0.2 mg/ml) also reduced lipid accumulation by 24% in fully differentiated 3T3-L1 adipocytes. These findings collectively indicate that Weissella koreensis 521 may help prevent obesity.

Keywords: Weissella koreensis 521, 3T3-L1 cells, adipocyte differentiation, obesity

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Authors: Vijaya Madhuri Devraj, Swarnalatha Guditi, Kiran Kumar Bokara, Gangadhar Taduri

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Cell-based strategies may open therapeutic approaches that promote tolerance through manipulation of macrophages to increase long-term transplant survival rates and minimize side effects of the current immune suppressive regimens. The aim of the present study was, therefore, to test and compare the therapeutic potential of MSC and Tregs on macrophage polarization to develop an alternate cell-based treatment option in kidney transplantation. In the current protocol, macrophages from kidney transplant recipients with graft dysfunction were co-cultured with MSCs and Treg cells with and without cell-cell contact on transwell plates, further to quantitatively assess macrophage polarization in response to MSC and Treg treatment over time, M1 and M2 cell surface markers were used. Additionally, multiple soluble analytes were analyzed in cell supernatant by using bead-based immunoassays. Furthermore, to confirm our findings, gene expression analysis was done. MSCs induced the formation of M2 macrophages more than Tregs when macrophages M0 were cultured in transwell without cell contact. From this, we deduced the mechanism that soluble factors present in the MSCs condition media are involved in skewing of macrophages towards type 2 macrophages; similarly, in co-culture with cell-cell contact, MSCs resulted in more M2 type macrophages than Tregs. And an important finding of this study is the combination of both MSC-Treg showed significantly effective and consistent results in both with and without cell contact setups. Hence, it is suggestive to prefer MSCs over Tregs for secretome-based therapy and a combination of both for either therapy for effective transplantation outcomes. Our findings underline a key role of Tregs and MSCs in promoting macrophage polarization towards anti-inflammatory type. The study has great importance in prolongation of allograft and patient survival without any rejection by cell-based therapy, which induce self-tolerance and controlling infection.

Keywords: graft rejection, graft tolerance, macrophage polarization, mesenchymal stem cells, regulatory T cells, transplant immunology

Procedia PDF Downloads 93