Search results for: cell death
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4741

Search results for: cell death

3511 Expression of CASK Antibody in Non-Mucionus Colorectal Adenocarcinoma and Its Relation to Clinicopathological Prognostic Factors

Authors: Reham H. Soliman, Noha Noufal, Howayda AbdelAal

Abstract:

Calcium/calmodulin-dependent serine protein kinase (CASK) belongs to the membrane-associated guanylate kinase (MAGUK) family and has been proposed as a mediator of cell-cell adhesion and proliferation, which can contribute to tumorogenesis. CASK has been linked as a good prognostic factor with some tumor subtypes, while considered as a poor prognostic marker in others. To our knowledge, no sufficient evidence of CASK role in colorectal cancer is available. The aim of this study is to evaluate the expression of Calcium/calmodulin-dependent serine protein kinase (CASK) in non-mucinous colorectal adenocarcinoma and adenomatous polyps as precursor lesions and assess its prognostic significance. The study included 42 cases of conventional colorectal adenocarcinoma and 15 biopsies of adenomatous polyps with variable degrees of dysplasia. They were reviewed for clinicopathological prognostic factors and stained by CASK; mouse, monoclonal antibody using heat-induced antigen retrieval immunohistochemical techniques. The results showed that CASK protein was significantly overexpressed (p <0.05) in CRC compared with adenoma samples. The CASK protein was overexpressed in the majority of CRC samples with 85.7% of cases showing moderate to strong expression, while 46.7% of adenomas were positive. CASK overexpression was significantly correlated with both TNM stage and grade of differentiation (p <0.05). There was a significantly higher expression in tumor samples with early stages (I/II) rather than advanced stage (III/IV) and with low grade (59.5%) rather than high grade (40.5%). Another interesting finding was found among the adenomas group, where the stronger intensity of staining was observed in samples with high grade dysplasia (33.3%) than those of lower grades (13.3%). In conclusion, this study shows that there is significant overexpression of CASK protein in CRC as well as in adenomas with high grade dysplasia. This indicates that CASK is involved in the process of carcinogenesis and functions as a potential trigger of the adenoma-carcinoma cascade. CASK was significantly overexpressed in early stage and low-grade tumors rather than tumors with advanced stage and higher histological grades. This suggests that CASK protein is a good prognostic factor. We suggest that CASK affects CRC in two different ways derived from its physiology. CASK as part of MAGUK family can stimulate proliferation and through its cell membrane localization and as a mediator of cell-cell adhesion might contribute in tumor confinement and localization.

Keywords: CASK, colorectal cancer, overexpression, prognosis

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3510 Growth and Differentiation of Mesenchymal Stem Cells on Titanium Alloy Ti6Al4V and Novel Beta Titanium Alloy Ti36Nb6Ta

Authors: Eva Filová, Jana Daňková, Věra Sovková, Matej Daniel

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Titanium alloys are biocompatible metals that are widely used in clinical practice as load bearing implants. The chemical modification may influence cell adhesion, proliferation, and differentiation as well as stiffness of the material. The aim of the study was to evaluate the adhesion, growth and differentiation of pig mesenchymal stem cells on the novel beta titanium alloy Ti36Nb6Ta compared to standard medical titanium alloy Ti6Al4V. Discs of Ti36Nb6Ta and Ti6Al4V alloy were sterilized by ethanol, put in 48-well plates, and seeded by pig mesenchymal stem cells at the density of 60×103/cm2 and cultured in Minimum essential medium (Sigma) supplemented with 10% fetal bovine serum and penicillin/streptomycin. Cell viability was evaluated using MTS assay (CellTiter 96® AQueous One Solution Cell Proliferation Assay;Promega), cell proliferation using Quant-iT™ ds DNA Assay Kit (Life Technologies). Cells were stained immunohistochemically using monoclonal antibody beta-actin, and secondary antibody conjugated with AlexaFluor®488 and subsequently the spread area of cells was measured. Cell differentiation was evaluated by alkaline phosphatase assay using p-nitrophenyl phosphate (pNPP) as a substrate; the reaction was stopped by NaOH, and the absorbance was measured at 405 nm. Osteocalcin, specific bone marker was stained immunohistochemically and subsequently visualized using confocal microscopy; the fluorescence intensity was analyzed and quantified. Moreover, gene expression of osteogenic markers osteocalcin and type I collagen was evaluated by real-time reverse transcription-PCR (qRT-PCR). For statistical evaluation, One-way ANOVA followed by Student-Newman-Keuls Method was used. For qRT-PCR, the nonparametric Kruskal-Wallis Test and Dunn's Multiple Comparison Test were used. The absorbance in MTS assay was significantly higher on titanium alloy Ti6Al4V compared to beta titanium alloy Ti36Nb6Ta on days 7 and 14. Mesenchymal stem cells were well spread on both alloys, but no difference in spread area was found. No differences in alkaline phosphatase assay, fluorescence intensity of osteocalcin as well as the expression of type I collagen, and osteocalcin genes were observed. Higher expression of type I collagen compared to osteocalcin was observed for cells on both alloys. Both beta titanium alloy Ti36Nb6Ta and titanium alloy Ti6Al4V Ti36Nb6Ta supported mesenchymal stem cellsˈ adhesion, proliferation and osteogenic differentiation. Novel beta titanium alloys Ti36Nb6Ta is a promising material for bone implantation. The project was supported by the Czech Science Foundation: grant No. 16-14758S, the Grant Agency of the Charles University, grant No. 1246314 and by the Ministry of Education, Youth and Sports NPU I: LO1309.

Keywords: beta titanium, cell growth, mesenchymal stem cells, titanium alloy, implant

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3509 Rapid Green Synthesis of Silver Nanoparticles Using Solanum Nigrum Leaves Extract with Antimicrobial and Anticancer Properties

Authors: Anushaa A.

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In this work, silver nanoparticles (AgNP) were manufactured directly without harmful chemicals utilising methanol extract (SNLME) Solanum nigrume leaves. We are using nigrum leaf extract from Solanum, which converts silver nitrate to silver ions, for synthesization purposes. An examination of the AgNP produced was performed using ultraviolet (UV-VIS) spectroscopy, infrared spectroscopy (FTIR) transformed from Fourier and scanning electrons (SEM). Biological activity was also tested. UV-VIS has proven that biosynthesized AgNP exists (420-450 nm). The FTIR spectrum has been utilised to confirm the presence of different functional groups within the biomolecules, which are a nanoparticular capping agent and the spectroscopic and crystal nature of AgNP. The viability of the silver nanoparticles was evaluated using zeta potential calculations. Negative zeta potential of -33.4 mV demonstrated the stability of silver-nanoparticles. The morphology of AgNP was examined using a scanning electron microscope. Greenly generated AgNP showed significant anti-Staphylococcus aureus, Candida, and Escherichia coli action. The green AgNP demonstration indicated that the IC50 for the human teratocarcinoma cell line was 29.24 μg/ml during 24 hours of therapy (PA1 Ovarian cell line). The dose-dependent effects were reported in both antibacterial and cytotoxicity assays and as an effective agent. Finally, the findings of this research showed that silver nanoparticles generated might serve as a viable therapeutic agent to combat microorganisms killing and curing cancer.

Keywords: antimicrobial activity, PA1 ovarian cancer cell line, silver nanoparticles, Solanum nigrum

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3508 Synthesis and Characterization of Sulfonated Aromatic Hydrocarbon Polymers Containing Trifluoromethylphenyl Side Chain for Proton Exchange Membrane Fuel Cell

Authors: Yi-Chiang Huang, Hsu-Feng Lee, Yu-Chao Tseng, Wen-Yao Huang

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Proton exchange membranes as a key component in fuel cells have been widely studying over the past few decades. As proton exchange, membranes should have some main characteristics, such as good mechanical properties, low oxidative stability and high proton conductivity. In this work, trifluoromethyl groups had been introduced on polymer backbone and phenyl side chain which can provide densely located sulfonic acid group substitution and also promotes solubility, thermal and oxidative stability. Herein, a series of novel sulfonated aromatic hydrocarbon polyelectrolytes was synthesized by polycondensation of 4,4''''-difluoro-3,3''''- bis(trifluoromethyl)-2'',3''-bis(3-(trifluoromethyl)phenyl)-1,1':4',1'':4'',1''':4''',1''''-quinquephenyl with 2'',3''',5'',6''-tetraphenyl-[1,1':4',1'': 4'',1''':4''',1''''-quinquephenyl]-4,4''''-diol and post-sulfonated was through chlorosulfonic acid to given sulfonated polymers (SFC3-X) possessing ion exchange capacities ranging from 1.93, 1.91 and 2.53 mmol/g. ¹H NMR and FT-IR spectroscopy were applied to confirm the structure and composition of sulfonated polymers. The membranes exhibited considerably dimension stability (10-27.8% in length change; 24-56.5% in thickness change) and excellent oxidative stability (weight remain higher than 97%). The mechanical properties of membranes demonstrated good tensile strength on account of the high rigidity multi-phenylated backbone. Young's modulus were ranged 0.65-0.77GPa which is much larger than that of Nafion 211 (0.10GPa). Proton conductivities of membranes ranged from 130 to 240 mS/cm at 80 °C under fully humidified which were comparable or higher than that of Nafion 211 (150 mS/cm). The morphology of membranes was investigated by transmission electron microscopy which demonstrated a clear hydrophilic/hydrophobic phase separation with spherical ionic clusters in the size range of 5-20 nm. The SFC3-1.97 single fuel cell performance demonstrates the maximum power density at 1.08W/cm², and Nafion 211 was 1.24W/cm² as a reference in this work. The result indicated that SFC3-X are good candidates for proton exchange membranes in fuel cell applications. Fuel cell of other membranes is under testing.

Keywords: fuel cells, polyelectrolyte, proton exchange membrane, sulfonated polymers

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3507 Simulation Study on Spacecraft Surface Charging Induced by Jovian Plasma Environment with Particle in Cell Method

Authors: Meihua Fang, Yipan Guo, Tao Fei, Pengyu Tian

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Space plasma caused spacecraft surface charging is the major space environment hazard. Particle in cell (PIC) method can be used to simulate the interaction between space plasma and spacecraft. It was proved that surface charging level of spacecraft in Jupiter’s orbits was high for its’ electron-heavy plasma environment. In this paper, Jovian plasma environment is modeled and surface charging analysis is carried out by PIC based software Spacecraft Plasma Interaction System (SPIS). The results show that the spacecraft charging potentials exceed 1000V at 2Rj, 15Rj and 25Rj polar orbits in the dark side at worst case plasma model. Furthermore, the simulation results indicate that the large Jovian magnetic field increases the surface charging level for secondary electron gyration.

Keywords: Jupiter, PIC, space plasma, surface charging

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3506 The Effects of Continuous and Interval Aerobic Exercises with Moderate Intensity on Serum Levels of Glial Cell Line-Derived Neurotrophic Factor and Aerobic Capacity in Obese Children

Authors: Ali Golestani, Vahid Naseri, Hossein Taheri

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Recently, some of studies examined the effect of exercise on neurotrophic factors influencing the growth, protection, plasticity and function in central and peripheral nerve cells. The aim of this study was to investigate the effects of continuous and interval aerobic exercises with moderate intensity on serum levels of glial cell line-derived neurotrophic factor (GDNF) and aerobic capacity in obese children. 21 obese students with an average age of 13.6 ± 0.5 height 171 ± 5 and BMI 32 ± 1.2 were divided randomly to control, continuous aerobic and interval aerobic groups. Training protocol included continuous or interval aerobic exercises with moderate intensity 50-65%MHR, three times per week for 10 weeks. 48 hours before and after executing of protocol, blood samples were taken from the participants and their GDNF serum levels were measured by ELISA. Aerobic power was estimated using Shuttle-run test. T-test results indicated a small increase in their GDNF serum levels, which was not statistically significant (p =0.11). In addition, the results of ANOVA did not show any significant difference between continuous and interval aerobic training on the serum levels of their GDNF but their aerobic capacity significantly increased (p =0.012). Although continuous and interval aerobic exercise improves aerobic power in obese children, they had no significant effect on their serum levels of GDNF.

Keywords: aerobic power, continuous aerobic training, glial cell line-derived neurotrophic factor (GDNF), interval aerobic training, obese children

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3505 Real-Time Loop-Mediated Isothermal Amplification Assay for Rapid Detection of Human Papillomavirus 16 in Oral Squamous Cell Carcinoma

Authors: Suharni Mohamad Suharni Mohamad, Nurul Izzati Hamzan Nurul Izzati Hamzan, Norhayu Abdul Rahman Norhayu Abdul Rahman, Siti Suraiya Md Noor Siti Suraiya Md Noor

Abstract:

Human papillomavirus (HPV) is an important risk factor for development of oral cancer. HPV16 is the most common type found in HPV-positive squamous cell carcinoma. In the present study, we established a real-time loop-mediated isothermal amplification (real-time LAMP) for detection of HPV16. A set of six primers was specially designed to recognize eight distinct sequences of HPV16-E6. Detection and quantification was achieved by real-time monitoring using a real-time turbidimeter based on threshold time required for turbidity in the LAMP reaction. LAMP reagents (MgSO4, dNTPs, Bst polymerase concentrations) and various incubation times and temperatures were optimized. The sensitivity was determined using 10-fold serial dilutions of HPV16 standard strain. The specificity of was evaluated using other HPV genotypes. The optimized method was established with specifically designed primers by real-time detection in approximately 30 min at 65°C. The limit of detection of HPV16 using the LAMP assay was 10 pg/ml that could be detected in 30 min. The LAMP assay was 10 times more sensitive than the conventional PCR in detecting HPV16. No cross-reactivity with other HPV genotypes was observed. This quantitative real-time LAMP assay may improve diagnostic potential for the detection and quantification of HPV16 in clinical samples and epidemiological studies due to its rapidity, simplicity, high sensitivity and specificity. This assay will be further evaluated with HPV DNAs of saliva from patients with oral squamous cell carcinoma. Acknowledgement: This study was financially supported by the ScienceFund Grant, Ministry of Science, Technology and Innovation (305/PPSG/6113219).

Keywords: Oral Squamous Cell Carcinoma (OSCC), Human Papillomavirus 16 (HPV16), Loop-Mediated Isothermal Amplification (LAMP), rapid detection

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3504 Biochemical Effects of Low Dose Dimethyl Sulfoxide on HepG2 Liver Cancer Cell Line

Authors: Esra Sengul, R. G. Aktas, M. E. Sitar, H. Isan

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Hepatocellular carcinoma (HCC) is a hepatocellular tumor commonly found on the surface of the chronic liver. HepG2 is the most commonly used cell type in HCC studies. The main proteins remaining in the blood serum after separation of plasma fibrinogen are albumin and globulin. The fact that the albumin showed hepatocellular damage and reflect the synthesis capacity of the liver was the main reason for our use. Alpha-Fetoprotein (AFP) is an albumin-like structural embryonic globulin found in the embryonic cortex, cord blood, and fetal liver. It has been used as a marker in the follow-up of tumor growth in various malign tumors and in the efficacy of surgical-medical treatments, so it is a good protein to look at with albumins. We have seen the morphological changes of dimethyl sulfoxide (DMSO) on HepG2 and decided to investigate its biochemical effects. We examined the effects of DMSO, which is used in cell cultures, on albumin, AFP and total protein at low doses. Material Method: Cell Culture: Medium was prepared in cell culture using Dulbecco's Modified Eagle Media (DMEM), Fetal Bovine Serum Dulbecco's (FBS), Phosphate Buffered Saline and trypsin maintained at -20 ° C. Fixation of Cells: HepG2 cells, which have been appropriately developed at the end of the first week, were fixed with acetone. We stored our cells in PBS at + 4 ° C until the fixation was completed. Area Calculation: The areas of the cells are calculated in the ImageJ (IJ). Microscope examination: The examination was performed with a Zeiss Inverted Microscope. Daytime photographs were taken at 40x, 100x 200x and 400x. Biochemical Tests: Protein (Total): Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Albumin: Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Alpha-fetoprotein: Serum sample was analyzed by ECLIA method. Results: When liver cancer cells were cultured in medium with 1% DMSO for 4 weeks, a significant difference was observed when compared with the control group. As a result, we have seen that DMSO can be used as an important agent in the treatment of liver cancer. Cell areas were reduced in the DMSO group compared to the control group and the confluency ratio increased. The ability to form spheroids was also significantly higher in the DMSO group. Alpha-fetoprotein was lower than the values of an ordinary liver cancer patient and the total protein amount increased to the reference range of the normal individual. Because the albumin sample was below the specimen value, the numerical results could not be obtained on biochemical examinations. We interpret all these results as making DMSO a caretaking aid. Since each one was not enough alone we used 3 parameters and the results were positive when we refer to the values of a normal healthy individual in parallel. We hope to extend the study further by adding new parameters and genetic analyzes, by increasing the number of samples, and by using DMSO as an adjunct agent in the treatment of liver cancer.

Keywords: hepatocellular carcinoma, HepG2, dimethyl sulfoxide, cell culture, ELISA

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3503 Construction of Ovarian Cancer-on-Chip Model by 3D Bioprinting and Microfluidic Techniques

Authors: Zakaria Baka, Halima Alem

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Cancer is a major worldwide health problem that has caused around ten million deaths in 2020. In addition, efforts to develop new anti-cancer drugs still face a high failure rate. This is partly due to the lack of preclinical models that recapitulate in-vivo drug responses. Indeed conventional cell culture approach (known as 2D cell culture) is far from reproducing the complex, dynamic and three-dimensional environment of tumors. To set up more in-vivo-like cancer models, 3D bioprinting seems to be a promising technology due to its ability to achieve 3D scaffolds containing different cell types with controlled distribution and precise architecture. Moreover, the introduction of microfluidic technology makes it possible to simulate in-vivo dynamic conditions through the so-called “cancer-on-chip” platforms. Whereas several cancer types have been modeled through the cancer-on-chip approach, such as lung cancer and breast cancer, only a few works describing ovarian cancer models have been described. The aim of this work is to combine 3D bioprinting and microfluidic technics with setting up a 3D dynamic model of ovarian cancer. In the first phase, alginate-gelatin hydrogel containing SKOV3 cells was used to achieve tumor-like structures through an extrusion-based bioprinter. The desired form of the tumor-like mass was first designed on 3D CAD software. The hydrogel composition was then optimized for ensuring good and reproducible printability. Cell viability in the bioprinted structures was assessed using Live/Dead assay and WST1 assay. In the second phase, these bioprinted structures will be included in a microfluidic device that allows simultaneous testing of different drug concentrations. This microfluidic dispositive was first designed through computational fluid dynamics (CFD) simulations for fixing its precise dimensions. It was then be manufactured through a molding method based on a 3D printed template. To confirm the results of CFD simulations, doxorubicin (DOX) solutions were perfused through the dispositive and DOX concentration in each culture chamber was determined. Once completely characterized, this model will be used to assess the efficacy of anti-cancer nanoparticles developed in the Jean Lamour institute.

Keywords: 3D bioprinting, ovarian cancer, cancer-on-chip models, microfluidic techniques

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3502 Characterization of PRL-3 Oncogenic Phosphatase in Its Role in Mediating Acquired Resistance to Bortezomib in Multiple Myeloma

Authors: Shamill Amedot Udonwa, Phyllis S. Y. Chong, Lim S. L. Julia, Wee-Joo Chng

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In this paper, we investigated how PRL-3 expression in H929 and U266 cells affects the efficacy of drug treatment. H929 and U266 cells were treated with Bortezomib (BTZ) of different concentrations, and it was observed that H929 cells were resistant to BTZ, while U266 cells were not viable. Investigations into how BTZ targets these cells were conducted, and it was observed that BTZ affects the PARP-Caspase3 pathway as well as PRL-3-Leo1 pathways. These pathways regulate cell proliferation and cell cycle, respectively. Hence, we are able to show the mechanism of how BTZ affects cells and also the role PRL-3 plays on downstream oncogenes such as cyclin-D1 and c-MYC. More importantly, this investigation into PRL-3 in BTZ resistance will be highly applicable in the future as the first clinical trials of PRL-3 antibody (PRL3-zumab) are ongoing at the National University Hospital, Singapore (NUHS). This would mean that understanding the mechanism of resistance through PRL-3, which has yet to be studied, will demonstrate the potential of PRL-3 in developing novel strategies to improve the treatment of MM.

Keywords: drug resistance, hematology, multiple myeloma, oncogene

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3501 Capability of a Single Antigen to Induce Both Protective and Disease Enhancing Antibody: An Obstacle in the Creation of Vaccines and Passive Immunotherapies

Authors: Parul Kulshreshtha, Subrata Sinha, Rakesh Bhatnagar

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This study was conducted by taking B. anthracis as a model pathogen. On infecting a host, B. anthracis secretes three proteins, namely, protective antigen (PA, 83kDa), edema factor (EF, 89 kDa) and lethal factor (LF, 90 kDa). These three proteins are the components of two anthrax toxins. PA binds to the cell surface receptors, namely, tumor endothelial marker (TEM) 8 and capillary morphogenesis protein (CMG) 2. TEM8 and CMG2 interact with LDL-receptor related protein (LRP) 6 for endocytosis of EF and LF. On entering the cell, EF acts as a calmodulin-dependent adenylate cyclase that causes a prolonged increase of cytosolic cyclic adenosine monophosphate (cAMP). LF is a metalloprotease that cleaves most isoforms of mitogen-activated protein kinase kinases (MAPKK/MEK) close to their N-terminus. By secreting these two toxins, B.anthracis ascertains death of the host. Once the systemic levels of the toxins rise, antibiotics alone cannot save the host. Therefore, toxin-specific inhibitors have to be developed. In this wake, monoclonal antibodies have been developed for the neutralization of toxic effects of anthrax toxins. We created hybridomas by using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor of B. anthracis) to obtain anti-toxin antibodies. Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immunized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies from all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H8 and H10) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). The protective efficacy of H7, H8, H10 and H11 was investigated. H7, H8 and H10 were found to be protective. H11 was found to have disease enhancing characteristics in-vitro and in mouse model of challenge with B. anthracis. In this study the disease enhancing character of H11 monoclonal antibody and anti-rLFn polyclonal sera was investigated. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature both in-vitro and in-vivo. But combination of H11 with LETscFv (an scFv with VH and VL identical to H10 but lacking Fc region) could not abrogate the disease-enhancing character of H11 mAb. Therefore it was concluded that for suppression of disease enhancement, Fc portion was absolutely essential for interaction of H10 with H11. Our study indicates that the protective potential of an antibody depends equally on its idiotype/ antigen specificity and its isotype. A number of monoclonal and engineered antibodies are being explored as immunotherapeutics but it is absolutely essential to characterize each one for their individual and combined protective potential. Although new in the sphere of toxin-based diseases, it is extremely important to characterize the disease-enhancing nature of polyclonal as well as monoclonal antibodies. This is because several anti-viral therapeutics and vaccines have failed in the face of this phenomenon. The passive –immunotherapy thus needs to be well formulated to avoid any contraindications.

Keywords: immunotherapy, polyclonal, monoclonal, antibody-dependent disease enhancement

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3500 The Importance of Erythrocyte Parameters in Obese Children

Authors: Orkide Donma, M. Metin Donma, Burcin Nalbantoglu, Birol Topcu, Feti Tulubas, Murat Aydin, Tuba Gokkus, Ahmet Gurel

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Increasing prevalence of childhood obesity has increased the interest in early and late indicators of gaining weight. Cell blood counts may be indicators of proinflammatory states. The aim was to evaluate associations of hematological parameters, including Hematocrit (HTC), hemoglobin, blood cell counts, and their indices with the degree of obesity in pediatric population. A total of 249; -139 morbidly obese (MO), 82 healthy Normal Weight (NW) and 28 Overweight (OW) children were included into the scope of the study. WHO BMI-for age percentiles were used to form age- and sex-matched groups. Informed consent forms and the Ethics Committee approval were obtained. Anthropometric measurements were performed. Hematological parameters were determined. Statistical analyses were performed using SPSS. The degree for statistical significance was p≤0.05. Significant differences (p=0.000) between waist-to-hip ratios and head-to-neck ratios (hnrs) of MO and NW children were detected. A significant difference between hnrs of OW and MO children (p=0.000) was observed. Red cell Distribution Width (RDW) was higher in OW children than NW group (p=0.030). Such finding couldn’t be detected between MO and NW groups. Increased RDW was prominent in OW children. The decrease in Mean Corpuscular Hemoglobin Concentration (MCHC) values in MO children was sharper than the values in OW children (p=0.006 vs p=0.042) compared to those in NW group. Statistically higher HTC levels were observed between MO-NW (p=0.014), but none between OW-NW. Though the cause-effect relationship between obesity and erythrocyte indices still needs further investigation, alterations in RDW, HTC, MCHC during obesity may be of significance in the early life.

Keywords: anthropometry, children, erythrocytes, obesity

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3499 Bifunctional Electrospun Fibers Based on Poly(Lactic Acid)/Calcium Oxide Nanocomposites as a Potential Scaffold for Bone Tissue Engineering

Authors: Daniel Canales, Fabián Alvarez, Pablo Varela, Marcela Saavedra, Claudio García, Paula Zapata

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Calcium oxide nanoparticles (n-CaO) ca. 8 nm were obtained from eggshell waste. The n-CaO was incorporated into Poly(lactic acid) PLA matrix in 10 and 20 wt.% of filler content by electrospinning process to obtain PLA/n-CaO nanocomposite fibers as a potential use in scaffold for bone tissue regeneration. The fibers morphology and diameter were homogeneity, the PLA had a diameter of 2.2 ± 0.8 µm and, with the nanoparticles incorporation (20wt.%), reached ca. 2.9 ± 0.9 µm. The PLA/n-CaO nanocomposites fibers showed in vitro bioactivity, capable of inducing the precipitation of hydroxyapatite (HA) layer in the fiber surface after 7 days in Simulated Body Solution (SBF). The biocidal and biological properties of PLA/n-Cao with 20 wt.% were evaluated, showing a 30% reduction in bacterial viability against S. aureus and 11% for E. coli after 6 hours of bacterial suspensions exposure. Furthermore, the fibers did not show a cytotoxic effect on the bone marrow ST-2 cell line, permitting the cell adhesion and proliferation in Roswell Park Memorial Institute medium (RPMI). The PLA/n-CaO with 20 wt.% of nanoparticles showed a higher capacity to promote the osteogenic differentiation, significantly increasing the alkaline phosphatase (ALP) expression after 7 days compared to PLA and cell control. The in vivo analysis corroborated the biocompatibility of scaffolds prepared, the presence of n-CaO in PLA reduced the formation of fibrous encapsulation of the material improve the healing process.

Keywords: electrospun scaffolds, PLA based nanocomposites, calcium oxide nanoparticles, bioactive materials, tissue engineering

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3498 Formulation and in vitro Evaluation of Transdermal Delivery of Articaine

Authors: Dinakaran Venkatachalam, Paul Chambers, Kavitha Kongara, Preet Singh

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The objective of this study is to formulate different topical preparations containing articaine and to investigate their permeation through goat skin. Initially, articaine and its hydrochloride salt were compared for in vitro permeation using Franz cell model. Goat skin samples were collected after euthanizing male goat kids purchased from the dairy goat farmers. Subcutaneous fat was removed and the skin was mounted on the donor chamber (orifice area 1.00 cm²) and drugs were applied onto the epidermis. Phosphate buffer saline (pH 7.4) was used to maintain sink condition in the receptor chamber (8 ml) of the Franz cell. Samples (0.4 ml) were collected at various intervals over 24 hours after each sampling equal volume of PBS was replaced in the receptor chamber. Articaine in the collected samples were quantified using LC/MS. The results suggested that articaine free base permeates better than its hydrochloride salt through goat skin. This study results support the fact that local anesthetics in its base form are lipophilic and thus penetrates faster through cell membranes than their salts. Later, articaine free base was formulated either using ethanol and octyl salicylate or dimethyl sulfoxide (DMSO) as penetration enhancers and was compared for in vitro permeation. The transdermal flux of articaine in the formulation containing DMSO was approximately 3.8 times higher than that of the formulation containing ethanol and octyl salicylate. Further studies to evaluate the local anesthetic efficacy of the topical formulation containing articaine for dermal anesthesia in animals have been planned.

Keywords: articaine, dermal anesthesia, local anesthetic, transdermal

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3497 Novel Steviosides Analogs Induced Apoptosis in Breast Cancers

Authors: Ahmed Malki

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Breast cancer has been identified as the most lethal form of cancer today. In our study, we designed and screened 16 steviosides derivatives for their cytotoxic activities in MCF-7human breast cancer cells and normal MCF-12a cells. Our data indicated that steviosides derivatives 9 and 15 decreased cell proliferation and induced apoptosis in MCF-7 breast cancer cells more thannormal breast cells epithelial cells. Flow cytometric analysis showed that both steviosides, derivatives 9 and 15 arrested the MCF-7 cells in G1 phase, which is further confirmed by the increased expression level of p21. Moreover, both steviosides derivatives increased caspase-9 activity, and the induction of apoptosis was significantly reduced after treating cells with caspase-9 inhibitor LEHD-CHO. Both steviosides derivatives increased Caspase 3 activities and induced Parp-1 cleavage in H1299 cells. Based on previous results, we have identified two novel steviosides derivatives which provoked apoptosis in breast cancer cells by arresting cells in G1 phase and increasing caspase-9 and caspase-3 activities which merits further development and investigations.

Keywords: steviosides, breast cancer, p53, cell cycle

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3496 Effect of Oxidative Stress on Glutathione Reductase Activity of Escherichia coli Clinical Isolates from Patients with Urinary Tract Infection

Authors: Fariha Akhter Chowdhury, Sabrina Mahboob, Anamika Saha, Afrin Jahan, Mohammad Nurul Islam

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Urinary tract infection (UTI) is frequently experienced by the female population where the prevalence increases with aging. Escherichia coli, one of the most common UTI causing organisms, retains glutathione defense mechanism that aids the organism to withstand the harsh physiological environment of urinary tract, host oxidative immune response and even to affect antibiotic-mediated cell death and the emergence of resistance. In this study, we aimed to investigate the glutathione reductase activity of uropathogenic E. coli (UPEC) by observing the reduced glutathione (GSH) level alteration under stressful condition. Urine samples of 58 patients with UTI were collected. Upon isolation and identification, 88% of the samples presented E. coli as UTI causing organism among which randomly selected isolates (n=9), obtained from urine samples of female patients, were considered for this study. E. coli isolates were grown under normal and stressful conditions where H₂O₂ was used as the stress-inducing agent. GSH level estimation of the isolates in both conditions was carried out based on the colorimetric measurement of 5,5'-dithio-bis (2-nitrobenzoic acid) (DTNB) and GSH reaction product using microplate reader assay. The GSH level of isolated E. coli sampled from adult patients decreased under stress compared to normal condition (p = 0.011). On the other hand, GSH production increased markedly in samples that were collected from elderly subjects (p = 0.024). A significant partial correlation between age and change of GSH level was found as well (p = 0.007). This study may help to reveal ways for better understanding of E. coli pathogenesis of UTI prevalence in elderly patients.

Keywords: Escherichia coli, glutathione reductase activity, oxidative stress, reduced glutathione (GSH), urinary tract infection (UTI)

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3495 Implementation of Industrial Ecology Principles in the Production and Recycling of Solar Cells and Solar Modules

Authors: Julius Denafas, Irina Kliopova, Gintaras Denafas

Abstract:

Three opportunities for implementation of industrial ecology principles in the real industrial production of c-Si solar cells and modules are presented in this study. It includes: material flow dematerialisation, product modification and industrial symbiosis. Firstly, it is shown how the collaboration between R&D institutes and industry helps to achieve significant reduction of material consumption by a) refuse from phosphor silicate glass cleaning process and b) shortening of silicon nitride coating production step. Secondly, it was shown how the modification of solar module design can reduce the CO2 footprint for this product and enhance waste prevention. It was achieved by implementing a frameless glass/glass solar module design instead of glass/backsheet with aluminium frame. Such a design change is possible without purchasing new equipment and without loss of main product properties like efficiency, rigidity and longevity. Thirdly, industrial symbiosis in the solar cell production is possible in such case when manufacturing waste (silicon wafer and solar cell breakage) also used solar modules are collected, sorted and supplied as raw-materials to other companies involved in the production chain of c-Si solar cells. The obtained results showed that solar cells produced from recycled silicon can have a comparable electrical parameters like produced from standard, commercial silicon wafers. The above mentioned work was performed at solar cell producer Soli Tek R&D in the frame of H2020 projects CABRISS and Eco-Solar.

Keywords: manufacturing, process optimisation, recycling, solar cells, solar modules, waste prevention

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3494 Deciphering Electrochemical and Optical Properties of Folic Acid for the Applications of Tissue Engineering and Biofuel Cell

Authors: Sharda Nara, Bansi Dhar Malhotra

Abstract:

Investigation of the vitamins as an electron transfer mediator could significantly assist in merging the area of tissue engineering and electronics required for the implantable therapeutic devices. The present study report that the molecules of folic acid released by Providencia rettgeri via fermentation route under the anoxic condition of the microbial fuel cell (MFC) exhibit characteristic electrochemical and optical properties, as indicated by absorption spectroscopy, photoluminescence (PL), and cyclic voltammetry studies. The absorption spectroscopy has depicted an absorption peak at 263 nm with a small bulge around 293 nm on day two of bacterial culture, whereas an additional peak was observed at 365 nm on the twentieth day. Furthermore, the PL spectra has indicated that the maximum emission occurred at various wavelengths 420, 425, 440, and 445 nm when excited by 310, 325, 350, and 365 nm. The change of emission spectra with varying excitation wavelength might be indicating the presence of tunable optical bands in the folic acid molecules co-related with the redox activity of the molecules. The results of cyclic voltammetry studies revealed that the oxidation and reduction occurred at 0.25V and 0.12V, respectively, indicating the electrochemical behavior of the folic acid. This could be inferred that the released folic acid molecules in a MFC might undergo inter as well as intra molecular electron transfer forming different intermediate states while transferring electrons to the electrode surface. Synchronization of electrochemical and optical properties of folic acid molecules could be potentially promising for the designing of electroactive scaffold and biocompatible conductive surface for the applications of tissue engineering and biofuel cells, respectively.

Keywords: biofuel cell, electroactivity, folic acid, tissue engineering

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3493 Development and Characterization of Cathode Materials for Sodium-Metal Chloride Batteries

Authors: C. D’Urso, L. Frusteri, M. Samperi, G. Leonardi

Abstract:

Solid metal halides are used as active cathode ingredients in the case of Na-NiCl2 batteries that require a fused secondary electrolyte, sodium tetrachloraluminate (NaAlCl4), to facilitate the movement of the Na+ ion into the cathode. The sodium-nickel chloride (Na - NiCl2) battery has been extensively investigated as a promising system for large-scale energy storage applications. The growth of Ni and NaCl particles in the cathodes is one of the most important factors that degrade the performance of the Na-NiCl2 battery. The larger the particles of active ingredients contained in the cathode, the smaller the active surface available for the electrochemical reaction. Therefore, the growth of Ni and NaCl particles can lead to an increase in cell polarization resulting from the reduced active area. A higher current density, a higher state of charge (SOC) at the end of the charge (EOC) and a lower Ni / NaCl ratio are the main parameters that result in the rapid growth of Ni particles. In light of these problems, cathode and chemistry Nano-materials with recognized and well-documented electrochemical functions have been studied and manufactured to simultaneously improve battery performance and develop less expensive and more performing, sustainable and environmentally friendly materials. Starting from the well-known cathodic material (Na-NiCl2), the new electrolytic materials have been prepared on the replacement of nickel with iron (10-90%substitution of Nichel with Iron), to obtain a new material with potential advantages compared to current battery technologies; for example,, (1) lower cost of cathode material compared to state of the art as well as (2) choices of cheaper materials (stainless steels could be used for cell components, including cathode current collectors and cell housings). The study on the particle size of the cathode and the physicochemical characterization of the cathode was carried out in the test cell using, where possible, the GITT method (galvanostatic technique of intermittent titration). Furthermore, the impact of temperature on the different cathode compositions of the positive electrode was studied. Especially the optimum operating temperature is an important parameter of the active material.

Keywords: critical raw materials, energy storage, sodium metal halide, battery

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3492 Indenyl and Allyl Palladates: Synthesis, Bonding, and Anticancer Activity

Authors: T. Scattolin, E. Cavarzerani, F. Visentin, F. Rizzolio

Abstract:

Organopalladium compounds have recently attracted attention for their high stability even under physiological conditions and, above all, for their remarkable in vitro cytotoxicity towards cisplatin-resistant cell lines. Among the organopalladium derivatives, those bearing at least one N-heterocyclic carbene ligand (NHC) and the Pd(II)-η³-allyl fragment have exhibited IC₅₀ values in the micro and sub-micromolar range towards several cancer cell lines in vitro and in some cases selectivity towards cancerous vs. non-tumorigenic cells. Herein, a selection of allyl and indenyl palladates were synthesized using a solvent-free method consisting of grinding the corresponding palladium precursors with different saturated and unsaturated azolium salts. All compounds have been fully characterized by NMR, XRD and elemental analyses. The intramolecular H, Cl interaction has been elucidated and quantified using the Voronoi Deformation Density scheme. Most of the complexes showed excellent cytotoxicity towards ovarian cancer cell lines, with I₅₀ values comparable to or even lower than cisplatin. Interestingly, the potent anticancer activity was also confirmed in a high-serous ovarian cancer (HGSOC) patient-derived tumoroid, with a clear superiority of this class of compounds over classical platinum-based agents. Finally, preliminary enzyme inhibition studies of the synthesized palladate complexes against the model TrxR show that the compounds have high activity comparable to or even higher than auranofin and classical Au(I) NHC complexes. Based on such promising data, further in vitro and in vivo experiments and in-depth mechanistic studies are ongoing in our laboratories.

Keywords: anticancer activity, palladium complexes, organoids, indenyl and allyl ligands

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3491 Death Due to Ulnar Artery Injury by Glassdoor: A Case Report

Authors: Ashok Kumar Rastogi

Abstract:

Glass is a material commonly used for Glassdoor, glass bottles, cookware, and containers. It can be harmful, as it is a hard and blunt object. Glass has been associated with severe injury and is a common cause of injuries warranting hospital visits to the emergency department (ED). These injuries can be accidental or intentionally inflicted. Broken glass injuries can be severe, even deadly. If broken glass shards fall out on your arm, it may cause fatal injuries. Case history: A 20-year-old male dead body was found aside the road, police informed, and a video recording ceased during an investigation. In the video recording, the person was in a drunken state (unable to walk and disoriented), wandering in the residential area road. He saw a barber shop, the shop door made of Glass. Suddenly, he hit the Glassdoor with his right hand forcefully. The Glassdoor broke into multiple pieces, and multiple injuries were seen over the right hand. Observations: Multiple small and large lacerations were seen over the right anterior part of the elbow. The main injury looked like an incised wound caused by a hard and sharp object. The main injury was noted as a laceration of size 13 x 06 cm bone deep, placed obliquely over the anteromedial aspect of the right elbow joint, its medial end at medial end of elbow joint while its anterior end was 04 cm below the elbow joint with laceration of underline brachialis muscles and complete transaction of ulnar artery and vein, skin margins looking sharply cut with irregular margins with tiny cuts at the medial lower border of laceration. Injuries were antemortem and fresh in nature, caused by hard and blunt objects but looking like hard and sharp objects. All organs were found pale, and the cause of death was shock and hemorrhage because of ulnar vessel injury. Conclusion: The findings of this case report highlight the potentially lethal consequences of glass injuries, especially those involving Glassdoors. The study underscores the importance of accurate interpretation and identification of wounds caused by Glass, as they may resemble injuries caused by other objects. It emphasizes the challenges faced by autopsy surgeons when determining the cause and manner of death in cases where visual evidence of injury is absent or when the weapon is not recovered. Ultimately, this case report serves as a reminder of the potential dangers posed by Glass and the importance of comprehensive forensic examinations.

Keywords: glassdoor, incised, wound, laceration, autopsy

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3490 Characterization of Transmembrane Proteins with Five Alpha-Helical Regions

Authors: Misty Attwood, Helgi Schioth

Abstract:

Transmembrane proteins are important components in many essential cell processes such as signal transduction, cell-cell signalling, transport of solutes, structural adhesion activities, and protein trafficking. Due to their involvement in diverse critical activities, transmembrane proteins are implicated in different disease pathways and hence are the focus of intense interest in understanding functional activities, their pathogenesis in disease, and their potential as pharmaceutical targets. Further, as the structure and function of proteins are correlated, investigating a group of proteins with the same tertiary structure, i.e., the same number of transmembrane regions, may give understanding about their functional roles and potential as therapeutic targets. In this in silico bioinformatics analysis, we identify and comprehensively characterize the previously unstudied group of proteins with five transmembrane-spanning regions (5TM). We classify nearly 60 5TM proteins in which 31 are members of ten families that contain two or more family members and all members are predicted to contain the 5TM architecture. Furthermore, nine singlet proteins that contain the 5TM architecture without paralogues detected in humans were also identifying, indicating the evolution of single unique proteins with the 5TM structure. Interestingly, more than half of these proteins function in localization activities through movement or tethering of cell components and more than one-third are involved in transport activities, particularly in the mitochondria. Surprisingly, no receptor activity was identified within this family in sharp contrast with other TM families. Three major 5TM families were identified and include the Tweety family, which are pore-forming subunits of the swelling-dependent volume regulated anion channel in astrocytes; the sidoreflexin family that acts as mitochondrial amino acid transporters; and the Yip1 domain family engaged in vesicle budding and intra-Golgi transport. About 30% of the proteins have enhanced expression in the brain, liver, or testis. Importantly, 60% of these proteins are identified as cancer prognostic markers, where they are associated with clinical outcomes of various tumour types, indicating further investigation into the function and expression of these proteins is important. This study provides the first comprehensive analysis of proteins with 5TM regions and provides details of the unique characteristics and application in pharmaceutical development.

Keywords: 5TM, cancer prognostic marker, drug targets, transmembrane protein

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3489 Study of Mechanical Properties of Large Scale Flexible Silicon Solar Modules on the Various Substrates

Authors: M. Maleczek, Leszek Bogdan, Kazimierz Drabczyk, Agnieszka Iwan

Abstract:

Crystalline silicon (Si) solar cells are the main product in the market among the various photovoltaic technologies concerning such advantages as: material richness, high carrier mobilities, broad spectral absorption range and established technology. However, photovoltaic technology on the stiff substrates are heavier, more fragile and less cost-effective than devices on the flexible substrates to be applied in special applications. The main goal of our work was to incorporate silicon solar cells into various fabric, without any change of the electrical and mechanical parameters of devices. This work is realized for the GEKON project (No. GEKON2/O4/268473/23/2016) sponsored by The National Centre for Research and Development and The National Fund for Environmental Protection and Water Management. In our work, the polyamide or polyester fabrics were used as a flexible substrate in the created devices. Applied fabrics differ in tensile and tear strength. All investigated polyamide fabrics are resistant to weathering and UV, while polyester ones is resistant to ozone, water and ageing. The examined fabrics are tight at 100 cm water per 2 hours. In our work, commercial silicon solar cells with the size 156 × 156 mm were cut into nine parts (called single solar cells) by diamond saw and laser. Gap and edge after cutting of solar cells were checked by transmission electron microscope (TEM) to study morphology and quality of the prepared single solar cells. Modules with the size of 160 × 70 cm (containing about 80 single solar cells) were created and investigated by electrical and mechanical methods. Weight of constructed module is about 1.9 kg. Three types of solar cell architectures such as: -fabric/EVA/Si solar cell/EVA/film for lamination, -backsheet PET/EVA/Si solar cell/EVA/film for lamination, -fabric/EVA/Si solar cell/EVA/tempered glass, were investigated taking into consideration type of fabric and lamination process together with the size of solar cells. In investigated devices EVA, it is ethylene-vinyl acetate, while PET - polyethylene terephthalate. Depend on the lamination process and compatibility of textile with solar cell an efficiency of investigated flexible silicon solar cells was in the range of 9.44-16.64 %. Multi folding and unfolding of flexible module has no impact on its efficiency as was detected by Instron equipment. Power (P) of constructed solar module is 30 W, while voltage about 36 V. Finally, solar panel contains five modules with the polyamide fabric and tempered glass will be produced commercially for different applications (dual use).

Keywords: flexible devices, mechanical properties, silicon solar cells, textiles

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3488 Anti -proliferative and Apoptotic Effects of Selected Saudi Herbs from the Rhamnaceae, Polygonaceae, and Apocynaceae Families Against Various Cancer Cell Lines

Authors: Allulu Yousef Alturki, Raghad Abdullah Alshafi, Sara Abdulaziz Alghashem, Sahar Saleh Alghamdi, Rasha Saad Suliman, Zeyad Alehaideb, Rizwan Ali

Abstract:

Cancer is recognized as a worldwide public health concern. Therefore, there is a continuous quest to discover new effective medications with less side-effects. In recent years, researchers have shown an increased interest in medicinal plants as several plant species have shown promising biological activities. Thus, we seek to investigate three medicinal herbs that are commonly-found in the Middle Easternregion and yet have not been explored in depth, including plants belonging to the Rhamnaceae, Polygonaceae, and Apocynaceaeplant families. Initially, we investigated using three types of cancer cell lines for breast, colorectal, and liver cancers. We performed high Content Imaging (HCI)-Apoptosis Assay and ApoTox-Glo™ Triplex Assay on KAIMRC2 and HCT8 cell lines. The highest activity of HCI-Apoptosis Assay was with Calligonumcomosum and Ziziphusnummularia in ethanol, followed by Calotropis procera and Ziziphusnummularia in ethyl acetate. The IC50values for the families of Rhamnaceae, Polygonaceae, and Apocynaceae in HepG2 and HCT8 cell lines ranged from 0.089 to 9.84mg/mL and 0.080to 15.08mg/mL, respectively. Further screening was conducted on an additional two cell lines, namely the MDA-MB-231 and KAIMRC2, for selected seven extracts with the highest activity having IC50values ranged from 0.058 to0.51mg/mL and 0.029 to0.19mg/mL, respectively. Continuous scientific investigations to isolate and characterize the potent bioactive phytochemical(s) are warranted. Funding: The authors acknowledge financial support from King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia. Institutional Review Board Statement: The study was approved by the Institutional Review Board of the Institutional Review Board of King Abdullah International Medical Research Center (SP21R/463/12, 24 January 2022). Acknowledgments: The authors want to express their gratitude to the College of Pharmacy (COP) at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) and King Abdullah International Medical Research Center (KAIMRC) for their continued support.

Keywords: rhamnaceae, polygonaceae, apocynaceae, natural products

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3487 Culture of Primary Cortical Neurons on Hydrophobic Nanofibers Induces the Formation of Organoid-Like Structures

Authors: Nick Weir, Robert Stevens, Alan Hargreaves, Martin McGinnity, Chris Tinsley

Abstract:

Hydrophobic materials have previously demonstrated the ability to elevate cell-cell interactions and promote the formation of neural networks whilst aligned nanofibers demonstrate the ability to induce extensive neurite outgrowth in an aligned manner. Hydrophobic materials typically elicit an immune response upon implantation and thus materials used for implantation are typically hydrophilic. Poly-L-lactic acid (PLLA) is a hydrophobic, non-immunogenic, FDA approved material that can be electrospun to form aligned nanofibers. Primary rat cortical neurons cultured for 10 days on aligned PLLA nanofibers formed 3D cell clusters, approximately 800 microns in diameter. Neurites that extended from these clusters were highly aligned due to the alignment of the nanofibers they were cultured upon and fasciculation was also evident. Plasma treatment of the PLLA nanofibers prior to seeding of cells significantly reduced the hydrophobicity and abolished the cluster formation and neurite fasciculation, whilst reducing the extent and directionality of neurite outgrowth; it is proposed that hydrophobicity induces the changes to cellular behaviors. Aligned PLLA nanofibers induced the formation of a structure that mimics the grey-white matter compartmentalization that is observed in vivo and thus represents a step forward in generating organoids or biomaterial-based implants. Upon implantation into the brain, the biomaterial architectures described here may provide a useful platform for both brain repair and brain remodeling initiatives.

Keywords: hydrophobicity, nanofibers, neurite fasciculation, neurite outgrowth, PLLA

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3486 MAGE-A3 and PRAME Gene Expression and EGFR Mutation Status in Non-Small-Cell Lung Cancer

Authors: Renata Checiches, Thierry Coche, Nicolas F. Delahaye, Albert Linder, Fernando Ulloa Montoya, Olivier Gruselle, Karen Langfeld, An de Creus, Bart Spiessens, Vincent G. Brichard, Jamila Louahed, Frédéric F. Lehmann

Abstract:

Background: The RNA-expression levels of cancer-testis antigens MAGE A3 and PRAME were determined in resected tissue from patients with primary non-small-cell lung cancer (NSCLC) and related to clinical outcome. EGFR, KRAS and BRAF mutation status was determined in a subset to investigate associations with MAGE A3 and PRAME expression. Methods: We conducted a single-centre, uncontrolled, retrospective study of 1260 tissue-bank samples from stage IA-III resected NSCLC. The prognostic value of antigen expression (qRT-PCR) was determined by hazard-ratio and Kaplan-Meier curves. Results: Thirty-seven percent (314/844) of tumours expressed MAGE-A3, 66% (723/1092) expressed PRAME and 31% (239/839) expressed both. Respective frequencies in squamous-cell tumours and adenocarcinomas were 43%/30% for MAGE A3 and 80%/44% for PRAME. No correlation with stage, tumour size or patient age was found. Overall, no prognostic value was identified for either antigen. A trend to poorer overall survival was associated with MAGE-A3 in stage IIIB and with PRAME in stage IB. EGFR and KRAS mutations were found in 10.1% (28/311) and 33.8% (97/311) of tumours, respectively. EGFR (but not KRAS) mutation status was negatively associated with PRAME expression. Conclusion: No clear prognostic value for either PRAME or MAGE A3 was observed in the overall population, although some observed trends may warrant further investigation.

Keywords: MAGE A3, PRAME, cancer-testis gene, NSCLC, survival, EGFR

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3485 The Application of the Biopsychosocial-Spiritual Model to the Quality of Life of People Living with Sickle Cell Disease

Authors: Anita Paddy, Millicent Obodai, Lebbaeus Asamani

Abstract:

The management of sickle cell disease requires a multidisciplinary team for better outcomes. Thus, literature on the application of the biopsychosocial model for the management and explanation of chronic pain in sickle cell disease (SCD) and other chronic diseases abound. However, there is limited research on the use of the biopsychosocial model, together with a spiritual component (biopsychosocial-spiritual model). The study investigated the extent to which healthcare providers utilized the biopsychosocial-spiritual model in the management of chronic pain to improve the quality of life (QoL) of patients with SCD. This study employed the descriptive survey design involving a consecutive sampling of 261 patients with SCD who were between the ages of 18 to 79 years and were accessing hematological services at the Clinical Genetics Department of the Korle Bu Teaching Hospital. These patients willingly consented to participate in the study by appending their signatures. The theory of integrated quality of life, the gate control theory of pain and the biopsychosocial(spiritual) model were tested. An instrument for the biopsychosocial-spiritual model was developed, with a basis from the literature reviewed, while the World Health Organisation Quality of Life BREF (WHOQoLBref) and the spirituality rating scale were adapted and used for data collection. Data were analyzed using descriptive statistics (means, standard deviations, frequencies, and percentages) and partial least square structural equation modeling. The study revealed that healthcare providers had a great leaning toward the biological domain of the model compared to the other domains. Hence, participants’ QoL was not fully improved as suggested by the biopsychosocial(spiritual) model. Again, the QoL and spirituality of patients with SCD were quite high. A significant negative impact of spirituality on QoL was also found. Finally, the biosocial domain of the biopsychosocial-spiritual model was the most significant predictor of QoL. It was recommended that policymakers train healthcare providers to integrate the psychosocial-spiritual component in health services. Also, education on SCD and its resultant impact from the domains of the model should be intensified while health practitioners consider utilizing these components fully in the management of the condition.

Keywords: biopsychosocial (spritual), sickle cell disease, quality of life, healthcare, accra

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3484 Very First Synthesis of Carbazole Conjugates with Efflux Pump Inhibitor as Dual Action Hybrids

Authors: Ghazala Yaqub, Zubi Sadiq, Almas Hamid, Saira Iqbal

Abstract:

This paper is the very first report of three dual action hybrids synthesized by covalent linkage of carbazole based novel antibacterial compounds with efflux pump inhibitors i.e., indole acetic acid/gallic acid. Novel carbazole based antibacterial compounds were prepared first and then these were covalently linked with efflux pump inhibitors which leads to the successful formation of hybrids. All prepared compounds were evaluated for their bacterial cell killing capability against Escherichia coli, Staphylococcus aureus, Pasteurella multocida and Bacillus subtilis. Compound were effective against all tested bacterial strains at different concentrations. But when these compounds were linked with efflux pump inhibitors they showed dramatic enhancement in their bacterial cell killing potential and minimum inhibitory concentration of all hybrids ranges from 7.250 µg/mL to 0.0283 µg/mL.

Keywords: antimicrobial assay, carbazole, dual action hybrids, efflux pump inhibitors

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3483 Cytotoxic and Biocompatible Evaluation of Silica Coated Silver Nanoparticle Against Nih-3t3 Cells

Authors: Chen-En Lin, Lih-Rou Rau, Jiunn-Woei Liaw, Shiao-Wen Tsai

Abstract:

The unique optical properties of plasmon resonance metallic particles have attracted considerable applications in the fields of physics, chemistry and biology. Metal-Enhanced Fluorescence (MEF) effect is one of the useful applications. MEF effect stated that fluorescence intensity can be quenched or be enhanced depending on the distance between fluorophores and the metal nanoparticles. Silver nanoparticles have used widely in antibacterial studies. However, the major limitation for silver nanoparticles (AgNPs) in biomedical application is well-known cytotoxicity on cells. There were numerous literatures have been devoted to overcome the disadvantage. The aim of the study is to evaluate the cytotoxicity and biocompatibility of silica coated AgNPs against NIH-3T3 cells. The results were shown that NIH-3T3 cells started to detach, shrink, become rounded and finally be irregular in shape after 24 h of exposure at 10 µg/ml AgNPs. Besides, compared with untreated cells, the cell viability significantly decreased to 60% and 40% which were exposed to 10 µg/ml and 20 µg/ml AgNPs respectively. The result was consistent with previously reported findings that AgNPs induced cytotoxicity was concentration dependent. However, the morphology and cell viability of cells appeared similar to the control group when exposed to 20 µg/ml of silica coated AgNPs. We further utilized the dark-field hyperspectral imaging system to analysis the optical properties of the intracellular nanoparticles. The image displayed that the red shift of the surface plasmonic resonances band of the enclosed AgNPs further confirms the agglomerate of the AgNPs rather than their distribution in cytoplasm. In conclusion, the study demonstrated the silica coated of AgNPs showed well biocompatibility and significant lower cytotoxicity compared with bare AgNPs.

Keywords: silver nanoparticles, silica, cell viability, morphology

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3482 Freudian Psychoanalysis Towards an Ethics of Finitude

Authors: Katya E. Manalastas

Abstract:

This thesis is a dialogue with Freud about vulnerability and any forms of transience we encounter in life. This study argues that Freud’s Ethics of Finitude, which is framed within the psychoanalytic context, is a critical theory about how human beings fail to become what they are because of their attachment to their illusions—to their visions of perfection and immortality. Freud’s Ethics of Finitude positions itself between our detachment to ideals and recognition of our own death through our loved one. His texts portray the predicament of the finite individual who suffers from feelings of guilt and anxiety because of his failure to live up to the demands of his idealistic civilized society. The civilized society has overestimated men’s susceptibility to culture. It imposes excessive sublimation, conformity to rigid moral ideals, and instinctive repression to manage human aggression. However, by doing this, civilization becomes a main source of men’s suffering. The lack of instinctive freedom will result in a community of tamed but unhappy people. Civilization has also constructed theories and measures to rule out death and pain from the realities of life. Therefore, a man lives his life repressing his instincts and ignorant of his own mortality. For Freud, war and neurosis are just few of the consequences of a civilization that imprisons the individual from cultural hypocrisy instead of giving more play to truthfulness. The occurrence of Great War destroyed our pride in the attainments of civilization and let loose the hostile impulses within us which we thought had been totally eradicated by means of instinctive repression and sublimation. War destroyed most of the things that we had loved and showed us the impermanence of all the things that we had deemed perfect and everlasting. This chaotic event also revealed the damaging impact of our attachment to past values that no longer bind us; our futile attempts to escape suffering; and our refusal to confront the painfulness of loss and mourning. With this given backdrop, this study launches Freud’s Ethics of Finitude—which culminates not in the submission of an individual to the unquestioned authority nor in the blind optimism and love for illusory happiness but in the pedagogy of mourning which brings forth the authentic education of man towards the truth about himself. His Ethics of Finitude is a form of labor in and through which the individual steps out of the realm of illusions and ideals that hinder him to confront his imperfections and accept the difficulties of existence. Through his analysis of the Great War, Freud seeks to awaken in us our ability to evaluate the way we see ourselves and to live our lives with death in mind. His Ethics of Finitude leads us to the fulfillment of our first duty as a living being, which is to endure life. We can only endure life if we are prepared to die and let go.

Keywords: critical theory, ethics of finitude, psychoanalysis, Sigmund Freud

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