Search results for: renal cell carcinoma

Authors: Hassane Ben Slimane, Benmoussa Dennai, Abderrahman Hemmani, Abderrachid Helmaoui

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During the past few years a great variety of multi-junction solar cells has been developed with the aim of a further increase in efficiency beyond the limits of single junction devices. This paper analyzes the GaAs/CIGS based tandem solar cell performance by AMPS-1D numerical modeling. Various factors which affect the solar cell’s performance are investigated, carefully referring to practical cells, to obtain the optimum parameters for the GaAs and CIGS top and bottom solar cells. Among the factors studied are thickness and band gap energy of dual junction cells.

Keywords: multijunction solar cell, GaAs, CIGS, AMPS-1D

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

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

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

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Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

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Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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Authors: Ismail Celik, Gulgun Ayhan Kilcigil, Berna Guven, Zumra Kara, Arzu Onay-Besikci

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Epidermal Growth Factor Receptor is the cell-surface receptor of the ErbB (erythroblastic leukemia viral oncogene homologue receptors) family of tyrosine kinases. It plays a vital role in regulating the proliferation and differentiation of cells. However, a variety of mechanisms, such as EGFR expression, mutation, and ligand-dependent receptor dimerization, are associated with the development of various activated EGFR tumors. EGFR is highly expressed in most solid tumors, including breast, head and neck cancer, non-small cell lung cancer (NSCLC), renal, ovarian, and colon cancers. Thus, specific EGFR inhibition plays one of the key roles in cancer treatment. The compounds used in the treatment as tyrosine kinase inhibitors are known to contain the benzimidazole isosterium indole, pazopanib, and axitinibin indazole rings. In addition, benzimidazoles have been shown to exhibit protein kinase inhibitory activity in addition to their different biological activities.Based on these data, it was planned and synthesized of some oxadiazole bearing benzimidazole derivatives [N-cyclohexyl-5-((2-phenyl/substitutedphenyl-1H-benzo[d]imidazole-1-yl) methyl)-1,3,4-oxadiazole-2-amine]. EGFR kinase inhibitory efficiency of the synthesized compounds was determined by comparing them with a known kinase inhibitor erlotinib in vitro, and two of the compounds bearing phenyl (19a) and 3,4-dibenzyloxyphenyl (21a) ring exhibited significant activities.

Keywords: benzimidazole, EGFR kinase inhibitory, oxadiazole, synthesis

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Authors: Ayesha Waqar Khan, Mariam Altaf, Jamil Ahmad, Shaheen Shahzad

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Kidney fibrosis is an anticipated outcome of possibly all types of progressive chronic kidney disease (CKD). Epithelial-mesenchymal transition (EMT) signaling pathway is responsible for production of matrix-producing fibroblasts and myofibroblasts in diseased kidney. In this study, a discrete model of TGF-beta (transforming growth factor) and CTGF (connective tissue growth factor) was constructed using Rene Thomas formalism to investigate renal fibrosis turn over. The kinetic logic proposed by Rene Thomas is a renowned approach for modeling of Biological Regulatory Networks (BRNs). This modeling approach uses a set of constraints which represents the dynamics of the BRN thus analyzing the pathway and predicting critical trajectories that lead to a normal or diseased state. The molecular connection between TGF-beta, Smad 2/3 (transcription factor) phosphorylation and CTGF is modeled using GenoTech. The order of BRN is CTGF, TGF-B, and SMAD3 respectively. The predicted cycle depicts activation of TGF-B (TGF-β) via cleavage of its own pro-domain (0,1,0) and presentation to TGFR-II receptor phosphorylating SMAD3 (Smad2/3) in the state (0,1,1). Later TGF-B is turned off (0,0,1) thereby activating SMAD3 that further stimulates the expression of CTGF in the state (1,0,1) and itself turns off in (1,0,0). Elevated CTGF expression reactivates TGF-B (1,1,0) and the cycle continues. The predicted model has generated one cycle and two steady states. Cyclic behavior in this study represents the diseased state in which all three proteins contribute to renal fibrosis. The proposed model is in accordance with the experimental findings of the existing diseased state. Extended cycle results in enhanced CTGF expression through Smad2/3 and Smad4 translocation in the nucleus. The results suggest that the system converges towards organ fibrogenesis if CTGF remains constructively active along with Smad2/3 and Smad 4 that plays an important role in kidney fibrosis. Therefore, modeling regulatory pathways of kidney fibrosis will escort to the progress of therapeutic tools and real-world useful applications such as predictive and preventive medicine.

Keywords: CTGF, renal fibrosis signaling pathway, system biology, qualitative modeling

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Authors: Mahmoodreza Tahamtan

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Background: Malignant surface epithelial ovarian tumors (SEOT) account for approximately 90% of primary ovarian cancer. Wilms tumor gene (WT1) product was defined as a tumor suppressor gene, but today it is considered capable of performing oncogenic functions. There seems to be differences in WT1 expression patterns among SEOT subtypes. We evaluate the immunohistochemical expression of WT1 protein among different histologic subtypes of SEOT. Materials and Methods: Immunohistochemistry for WT1 was done on 35 serous cystadenocarcinomas, 9 borderline serous tumors, 3 mucinous cystadenocarcinomas, 10 borderline mucinous tumors, 7 endometrioid ovarian carcinomas, 3 clear cell carcinomas, 1 malignant Brenner tumor, 2 metastatic adenocarcinomas, and 6 endometrial adenocarcinomas. A tumor was considered negative if < 1% of tumor cells were stained.Positive reactions were graded as follows:1+,1%-24%; 2+,25%-49%; 3+,50%-74%; 4+,75%-100%. Results: Of the 35 cases of ovarian serous cystadenocarcinoma, 30(85.7%) were diffusely positive (3+,4+),4 showed reactivity of < 50% of the tumor cells (1+,2+), and one were negative. All 9 borderline serous tumors showed immunoreactivity with WT1. All the mucinous tumors(n:13), endometrioid carcinomas (n: 7), clear cell carcinomas (n: 3), metastatic adenocarcinomas (n: 2) and primary endometrial carcinomas (n:6) were negative. The single malignant Brenner tumor showed a positive reaction for WT1(4+) Conclusion: WT1 is a good marker to distinguish primary ovarian serous carcinomas from other surface epithelial tumors (especially endometrioid subtype) and metastatic carcinomas (especially endometrial serous carcinoma), other than malignant mesothelioma. We cannot rely to the degree of expression inorder to separate high grade borderline serous tumors from low grade ones.

Keywords: WT1, ovary, epithelial tumors, malignant

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Authors: Doaa Hashad, Amany Elyamany, Perihan Salem

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Introduction: Hepatitis C virus infection (HCV) constitutes a serious dilemma that has an impact on the health of millions of Egyptians. Hepatitis C virus related hepatocellular carcinoma (HCV-HCC) is a crucial consequence of HCV that represents the third cause of cancer-related deaths worldwide. Aim of the study: assess the use of mitochondrial DNA (mtDNA) content as a non-invasive molecular biomarker in hepatitis c virus related hepatocellular carcinoma (HCV-HCC). Methods: A total of 135 participants were enrolled in the study. Volunteers were assigned to one of three groups equally; a group of HCV related cirrhosis (HCV-cirrhosis), a group of HCV-HCC and a control group of age- and sex- matched healthy volunteers with no evidence of liver disease. mtDNA was determined using a quantitative real-time PCR technique. Results: mtDNA content was lowest in HCV-HCC cases. No statistically significant difference was observed between the group of HCV-cirrhosis and the control group as regards mtDNA level. HCC patients with multi-centric hepatic lesions had significantly lower mtDNA content. On using receiver operating characteristic curve analysis, a cutoff of 34 was assigned for mtDNA content to distinguish between HCV-HCC and HCV-cirrhosis patients who are not yet complicated by malignancy. Lower mtDNA was associated with greater HCC risk on using healthy controls, HCV-cirrhosis, or combining both groups as a reference group. Conclusions: mtDNA content might constitute a non-invasive molecular biomarker that reflects tumor burden in HCV-HCC cases and could be used as a predictor of HCC risk in patients of HCV-cirrhosis. In addition, the non significant difference of mtDNA level between HCV-cirrhosis patients and healthy controls could eliminate the grey zone created by the use of AFP in some cirrhotic patients.

Keywords: DNA copy number, HCC, HCV, mitochondrial

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Authors: Olga Tkacheva, Pavel Arkhipov, Alexey Rudenko, Yurii Zaikov

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The aluminum electrolysis process in the conventional cryolite-alumina electrolyte with cryolite ratio of 2.7 was carried out at an initial temperature of 970 °C and the anode current density of 0.5 A/cm² in a 15A lab-scale cell in order to study the formation of the side ledge during electrolysis and the alumina distribution between electrolyte and side ledge. The alumina contained 35.97% α-phase and 64.03% γ-phase with the particles size in the range of 10-120 μm. The cryolite ratio and the alumina concentration were determined in molten electrolyte during electrolysis and in frozen bath after electrolysis. The side ledge in the electrolysis cell was formed only by the 13^th hour of electrolysis. With a slight temperature decrease a significant increase in the side ledge thickness was observed. The basic components of the side ledge obtained by the XRD phase analysis were Na₃AlF₆, Na₅Al₃F₁₄, Al₂O₃, and NaF^.5CaF₂^.AlF₃. As in the industrial cell, the increased alumina concentration in the side ledge formed on the cell walls and at the ledge-electrolyte-aluminum three-phase boundary during aluminum electrolysis in the lab cell was found (FTP No 05.604.21.0239, IN RFMEFI60419X0239).

Keywords: alumina distribution, aluminum electrolyzer, cryolie-alumina electrolyte, side ledge

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Authors: Fenni Sim

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Background: The application of systemic family therapy approaches to community health cases have not gathered traction. In National Kidney Foundation, Singapore, the belief is that community support has great potential in helping End Stage Renal Failure (ESRF) patients manage the demands of their treatment regime, whether Hemodialysis (HD) or Peritoneal Dialysis(PD) and sustain them on the treatment. However, the current community support does not include family interventions and is largely nursing based. Although nursing support is well provided to patients, and their family members in issues related to treatment and compliance, complex family issues and dynamics arising from caregiver strain or pre-dialysis relationship strain might deter efforts in managing the challenges of the treatment. Objective: The objective of the study is to understand the potential scope of work provided by a social worker who is trained in systemic family therapy and the effects of these interventions. Methodology: 3 families on HD and 3 families on PD who have been receiving family intervention for the past 6 months would be chosen for the study. A qualitative interview would be conducted to review the effectiveness for the family. Scales such as SCORE-15, PHQ-9, and Zarit Burden were used to measure family functioning, depression, and caregiver’s burden for the families. Results: The research is still in preliminary phase. Conclusion: The study highlights the importance of family intervention for families with multiple stressors on different treatment modalities who might have different needs and challenges. Nursing support needs to be complemented with family-based support to manage complex family issues in order to achieve better health outcomes and improved family coping.

Keywords: complementing nursing support, end stage renal failure, healthcare, systemic approaches

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Authors: Shanshan Guo, Xiaoying Zhu, Dominik Jańczewski, Koon Gee Neoh

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Surface charge and wettability are two prominent physical factors governing cell adhesion and have been extensively studied in the literature. However, a comparison between the two driving forces in terms of their independent and cooperative effects in affecting cell adhesion is rarely explored on a systematic and quantitative level. Herein, we formulate a protocol which allows two-dimensional and independent control over both surface charge and wettability. This protocol enables the unambiguous comparison of the effects of these two properties on cell adhesion. This strategy is implemented by controlling both the relative thickness of polyion layers in the layer-by-layer assembly and the polyion side chain chemical structures. The 2D property matrix spans surface isoelectric point ranging from 5 to 9 and water contact angle from 35º to 70º, with other interferential factors (e.g. roughness) eliminated. The interplay between these two surface variables influences 3T3 fibroblast cell adhesion. The results show that both surface charge and wettability have an effect on its adhesion. The combined effects of positive charge and hydrophilicity led to the highest cell adhesion whereas negative charge and hydrophobicity led to the lowest cell adhesion. Our design strategy can potentially form the basis for studying the distinct behaviors of electrostatic force or wettability driven interfacial phenomena and serving as a reference in future studies assessing cell adhesion to surfaces with known charge and wettability within the property range studied here.

Keywords: cell adhesion, layer-by-layer, surface charge, surface wettability

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Authors: Masood Sattari

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Using fuel cell technology to generate electricity for large commercial and industrial sites is a growing segment in the fuel cell industry. The installation of these systems involves design, permitting, procurement of long-lead electrical equipment, and construction involving multiple utilities. The installation of each fuel cell system requires the same amount of coordination as the construction of a new structure requiring a foundation, gas, water, and electricity. Each of these components provide variables that can delay and possibly eliminate a new project. As the manufacturing process and efficiency of fuel cell systems improves, so must the installation methods to prevent a ‘bottle-neck’ in the installation phase of the deployment. Installation methodologies to install the systems vary among companies and this paper will examine the methodologies, describe the benefits and drawbacks for each, and provide guideline for the industry to improve overall installation efficiency.

Keywords: construction, installation, methodology, procurement

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Authors: M. M. Rahman, A. Liu, A. Frostegard, J. Frostegard

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The human immune system plays an essential role in cardiovascular disease (CVD) and atherosclerosis. Our earlier studies showed that major immunocompetent cells including T cells are activated by phosphorylcholine epitope. Further, we have determined for the first time in a clinical cohort that antibodies against phosphorylcholine (anti-PC) are negatively and independently associated with the development of atherosclerosis and thus a low risk of cardiovascular diseases. It is still unknown whether activated T cells play a role in anti-PC production. Here we aim to clarify the role of T cells in anti-PC production. B cell alone, or with CD3 T, CD4 T or with CD8 T cells were cultured in polystyrene plates to examine anti-PC IgM production. In addition to mixed B cell with CD3 T cell culture, B cells with CD3 T cells were also cultured in transwell co-culture plates. Further, B cells alone and mixed B cell with CD3 T cell cultures with or without anti-HLA 2 antibody were cultured for 6 days. Anti-PC IgM was detected by ELISA in independent experiments. More than 8 fold higher levels of anti-PC IgM were detected by ELISA in mixed B cell with CD3 T cell cultures in comparison to B cells alone. After the co-culture of B and CD3 T cells in transwell plates, there were no increased antibody levels indicating that B and T cells need to interact to augment anti-PC IgM production. Furthermore, anti-PC IgM was abolished by anti-HLA 2 blocking antibody in mixed B and CD3 T cells culture. In addition, the lack of increased anti-PC IgM in mixed B with CD8 T cells culture and the increased levels of anti-PC in mixed B with CD4 T cells culture support the role of helper T cell for the anti-PC IgM production. Atherosclerosis is a major cause of cardiovascular diseases, but anti-PC IgM is a protection marker for atherosclerosis development. Understanding the mechanism involved in the anti-PC IgM regulation could play an important role in strategies to raise anti-PC IgM. Studies suggest that anti-PC is T-cell independent antibody, but our study shows the major role of T cell in anti-PC IgM production. Activation of helper T cells by immunization could be a possible mechanism for raising anti-PC levels.

Keywords: anti-PC, atherosclerosis, aardiovascular diseases, phosphorylcholine

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Authors: Chijioke Okafor, Malik Maaza, Touhami Mokrani

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Proton exchange membrane, PEM was developed and tested for potential application in fuel cell. Nafion was electrospun to nanofiber network with the aid of poly(ethylene oxide), PEO, as a carrier polymer. The matrix polymer was crosslinked with Norland Optical Adhesive 63 under UV after compacting and annealing. The welded nanofiber mat was characterized for morphology, proton conductivity, and methanol permeability, then tested in a single cell test station. The results of the fabricated nanofiber membrane showed a proton conductivity of 0.1 S/cm at 25 oC and higher fiber volume fraction; methanol permeability of 3.6x10^-6 cm2/s and power density of 96.1 and 81.2 mW/cm2 for 5M and 1M methanol concentration respectively.

Keywords: fuel cell, nafion, nanofiber, permeability

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Authors: Djaafar F., Hadri B., Bachir G.

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We studied mainly the influence of temperature, thickness, molar fraction and the doping of the various layers (emitter, base, BSF and window) on the performances of a photovoltaic solar cell. In a first stage, we optimized the performances of the InGaP/GaAs dual-junction solar cell while varying its operation temperature from 275°K to 375 °K with an increment of 25°C using a virtual wafer fabrication TCAD Silvaco. The optimization at 300°K led to the following result Icc =14.22 mA/cm2, Voc =2.42V, FF =91.32 %, η = 22.76 % which is close with those found in the literature. In a second stage ,we have varied the molar fraction of different layers as well their thickness and the doping of both emitters and bases and we have registered the result of each variation until obtaining an optimal efficiency of the proposed solar cell at 300°K which was of Icc=14.35mA/cm2,Voc=2.47V,FF=91.34,and η =23.33% for In(1-x)Ga(x)P molar fraction( x=0.5).The elimination of a layer BSF on the back face of our cell, enabled us to make a remarkable improvement of the short-circuit current (Icc=14.70 mA/cm2) and a decrease in open circuit voltage Voc and output η which reached 1.46V and 11.97% respectively. Therefore, we could determine the critical parameters of the cell and optimize its various technological parameters to obtain the best performance for a dual junction solar cell. This work opens the way with new prospects in the field of the photovoltaic one. Such structures will thus simplify the manufacturing processes of the cells; will thus reduce the costs while producing high outputs of photovoltaic conversion.

Keywords: modeling, simulation, multijunction, optimization, silvaco ATLAS

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Authors: Atefeh Esmailnejad, Gholamreza Nikbakht Brujeni

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Major histocompatibility complex (MHC) is one of the best characterized genetic regions associated with immune responses and controlling disease resistance in chicken. Association of the MHC with a wide range of immune responses makes it a valuable predictive factor for the disease pathogenesis and outcome. In this study, the association of MHC with cell-mediated immune responses was analyzed in commercial broiler chicken. The tandem repeat LEI0258 was applied to investigate the MHC polymorphism. Cell-mediated immune response was evaluated by peripheral blood lymphocyte proliferation assay using MTT method. Association study revealed a significant influence of MHC alleles on cellular immune responses in this population. Alleles 385 and 448 bp were associated with elevated cell-mediated immunity. Haplotypes associated with improved immune responses could be considered as candidate markers for disease resistance and applied to breeding strategies.

Keywords: MHC, cell-mediated immunity, broiler, chicken

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Authors: Maedeh Rahimnejad, Bahman Vahidi, Bahman Ebrahimi Hoseinzadeh, Fatemeh Yazdian, Puria Motamed Fath, Roghieh Jamjah

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Introduction: The intensive labor and high cost of developing new vehicles for controlled drug delivery highlights the need for a change in their discovery process. Computational models can be used to accelerate experimental steps and control the high cost of experiments. Methods: In this work, to better understand the interaction of anti-cancer drug and the nanocarrier with the cell membrane, we have done molecular dynamics simulation using NAMD. We have chosen paclitaxel for the drug molecule and dipalmitoylphosphatidylcholine (DPPC) as a natural phospholipid nanocarrier. Results: Next, center of mass (COM) between molecules and the van der Waals interaction energy close to the cell membrane has been analyzed. Furthermore, the simulation results of the paclitaxel interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane have been compared. Discussion: Analysis by molecular dynamics (MD) showed that not only the energy between the nanocarrier and the cell membrane is low, but also the center of mass amount decreases in the nanocarrier and the cell membrane system during the interaction; therefore they show significantly better interaction in comparison to the individual drug with the cell membrane.

Keywords: anti-cancer drug, center of mass, interaction energy, molecular dynamics simulation, nanocarrier

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Authors: Yu-Chen Hu

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Gene editing by CRISPR and gene regulation by microRNA or CRISPR activation have dramatically changed the way to manipulate cellular gene expression and cell fate. In recent years, various gene editing and gene manipulation technologies have been applied to control stem cell differentiation to enhance tissue regeneration. This research will focus on how to develop CRISPR, CRISPR activation (CRISPRa), CRISPR inhibition (CRISPRi), as well as bi-directional CRISPR-AI gene regulation technologies to control cell differentiation and bone regeneration. Moreover, in this study, CRISPR/Cas13d-mediated RNA editng for miRNA editing and bone regeneration will be discussed.

Keywords: gene therapy, bone regeneration, stem cell, CRISPR, gene regulation

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Authors: Isaac Quiros-Fernandez, Angel Cid-Arregui

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Tumor-reactive T cell receptors (TCRs) are being subject of intense investigation since they offer great potential in adoptive cell therapies against cancer. However, the identification of tumor-specific TCRs has proven challenging, for instance, due to the limited expansion capacity of tumor-infiltrating T cells (TILs) and the extremely low frequencies of tumor-reactive T cells in the repertoire of patients and healthy donors. We have developed an approach for rapid identification and characterization of neoepitope-reactive TCRs from the T cell repertoire of healthy donors. CD8 T cells isolated from multiple donors are subjected to a first sorting step after staining with HLA multimers carrying the peptide of interest. The isolated cells are expanded for two weeks, after which a second sorting is performed using the same peptide-HLA multimers. The cells isolated in this way are then processed for single-cell sequencing of their TCR alpha and beta chains. Newly identified TCRs are cloned in appropriate expression vectors for functional analysis on Jurkat, NK92, and primary CD8 T cells and tumor cells expressing the appropriate antigen. We have identified TCRs specifically binding HLA-A2 presenting epitopes of tumor antigens, which are capable of inducing TCR-mediated cell activation and cytotoxicity in target cancer cell lines. This method allows the identification of tumor-reactive TCRs in about two to three weeks, starting from peripheral blood samples of readily available healthy donors.

Keywords: cancer, TCR, tumor antigens, immunotherapy

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Authors: Magdalena Barbara Kaziuk, Waldemar Kosiba, Marek Jan Kuzniewski

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Introduction: Vitamin D3 has a proven pleiotropic effect, not only responsible for calcium and phosphate management, but also influencing normal functioning of the whole body. Aim: Evaluation of vitamin D3 resources and its effect on a nutritional status, obesity type and glomerular filtration in kidney transplant recipients. Methods: Group of 152 (81 women and 71 men, average age 47.8 ± 11.6 years) patients with a functioning renal transplant their body composition was assessed using the bioimpendance method (BIA) and anthropometric measurements more than 3 months after the transplant. The nutritional status and the obesity type were determined with the Waist to Height Ratio (WHtR) and the Waist to Hip Ratio (WHR). 25- Hydroxyvitamin D3 (25 (OH)D3) was determined, together with its correlation with the obesity type and the glomerular filtration rate (eGFR) calculated with the MDRD formula. Results: The mean 25 (OH)D3 level was 20.4 ng/ml. 30ng/ml was considered as a minimum correct level 22,7% of patients from the study group were classified to be a correct body weight, 56,7% of participants had an android type and 20,6% had a gynoid type. Significant correlation was observed between 25 (OH)D3 deficiency and abdominal obesity (p < 0.005) in patients. Furthermore, a statistically significant relationship was demonstrated between the 25 (OH)D3 levels and eGFR in patients after a kidney transplant. Patients with an android body type had lower eGFR versus those with the gynoid body type (p=0.004). Conclusions: Correct diet in patients after a kidney transplant determines minimum recommended serum levels of vitamin D3. Excessive fatty tissue, low levels of 25 (OH)D3), may be a predictor for android obesity and renal injury; therefore, correct diet and pharmacological management together with physical activities adapted to the physical fitness level of a patient are necessary.

Keywords: kidney transplantation, glomerular filtration rate, obesity, vitamin D3

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Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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Authors: S. AliReza Mirghasemi, Zameer Hussain, Mohammad Saleh Sadeghi, Narges Rahimi Gabaran, Mohamadreza Baghaban Eslaminejad

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Background: Despite promising results have shown by osteogenic cell-based demineralized bone matrix composites, they need to be optimized for grafts that act as structural frameworks in load-bearing defects. The purpose of this experiment is to determine the effect of bone-marrow-mesenchymal-stem-cells seeding on partially demineralized laser-perforated structural allografts that have been implanted in critical femoral defects. Materials and Methods: P3 stem cells were used for graft seeding. Laser perforation in four rows of three holes was achieved. Cell-seeded grafts were incubated for one hour until they were planted into the defect. We used four types of grafts: partially demineralized only (Donly), partially demineralized stem cell seeded (DST), partially demineralized laser-perforated (DLP), and partially demineralized laser-perforated stem cell seeded (DLPST). histologic and histomorphometric analysis were performed at 12 weeks. Results: Partially demineralized laser-perforated had the highest woven bone formation within graft limits, stem cell seeded demineralized laser-perforated remained intact, and the difference between partially demineralized only and partially demineralized stem cell seeded was insignificant. At interface, partially demineralized laser-perforated and partially demineralized only had comparable osteogenesis, but partially demineralized stem cell seeded was inferior. The interface in stem cell seeded demineralized laser-perforated was almost replaced by distinct endochondral osteogenesis with higher angiogenesis in the vicinity. Partially demineralized stem cell seeded and stem cell seeded demineralized laser-perforated graft surfaces had extra vessel-ingrowth-like porosities, a sign of delayed resorption. Conclusion: This demonstrates that simple cell-based composites are not optimal and necessitates the supplementation of synergistic stipulations and surface changes.

Keywords: structural bone allograft, partial demineralization, laser perforation, mesenchymal stem cell

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Authors: Karthikeyan M., Paul M. J.

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This case report discusses a 54-year-old woman from Salem, Tamilnadu, who presented with a rare case of papillary thyroid carcinoma (PTC), manifesting as a hypervascular mass in the left carotid sheath. The patient had a two-and-a-half-month history of non-progressive neck swelling, with symptoms including dysphagia and a choking sensation. Clinical examination and investigations such as FNAC and CECT revealed a large vascular mass in the left neck region, initially perplexing the diagnosis. The patient underwent total thyroidectomy and excision of the left carotid sheath mass. Histopathology confirmed PTC. Postoperatively, the patient received Iodine-131 ablation and showed good recovery with no recurrence. This case highlights the diagnostic challenge and atypical presentation of PTC as a vascular neck mass, emphasizing the importance of a comprehensive approach in evaluating thyroid and neck lesions.

Keywords: lateral neck vascular mass, lateral aberrant thyroid, thyroid vascular swelling, smooth post op recovery

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Authors: Stephen Adeniyi Adefegha, Vitor Mostardeiro, Vera Maria Morsch, Ademir F. Morel, Ivana Beatrice Manica Da Cruz, Sabrina Somacal Maria Rosa Chitolina Schetinger

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Moringa stenopetala is often consumed as food and used in folkloric medicine for the management of several diseases. Purpose: This study was set up in order to assess the effect of aqueous extract of Moringa stenopetala on cell viability and oxidative stress biomarkers in BV-2 microglial cells. Aqueous extracts of M. stenopetala were prepared, lyophilized and reconstituted in 0.5% dimethylsulphoxide (DMSO). Cells were treated with M. stenopetala extracts (0.1 - 100 µg/ml) for cell viability and nitric oxide (NO) production tests. However, M. stenopetala extract (50 µg/ml) was used in the treatment of cells for the determination of protein carbonyl content and reactive oxygen species (ROS) level. Incubation of BV-2 microglia cell with M. stenopetala extract maintained cell viability, diminished NO and ROS levels, and reduced protein carbonyl contents Chlorogenic acid, rutin, kaempferol and quercetin derivatives were the main phenolic compounds identified in M. stenopetala leaf extract. These phenolic compounds present in M. stenopetala may be responsible for the mitigation of oxidative stress in BV-2 microglial cells.

Keywords: oxidative stress, BV-2 microglial cell, Moringa stenopetala, cell viability, antioxidant

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Authors: Robert P. Dufresne, Hamid Arabzadeh

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The current study investigates the effectiveness of a new form of permanent baseboard insulators with an umbrella action, hereinafter referred to as Coronary Insulator, in supporting and protecting the assembly of electrodes immersed in an electrolytic cell and in increasing the lifespan of the lateral sides of the electrolytic cell, in both electro-winning and electro-refinery method. The advantages of using a coronary insulator in addition to the top capping board (equipotential insulator) were studied compared to the conventional assembly of an electrolytic cell. Then, a thermal imaging technique was utilized during high-temperature thermal (heat transfer) tests for sample cell walls with and without coronary insulators in their assembly to show the effectiveness of coronary insulators in protecting the cell wall under extreme conditions. It was shown that, unlike the conventional assembly, which is highly prone to damages to the cell wall under thermal shocks, the presence of coronary insulator can significantly increase the level of protection of the cell due to their ultra-high thermal and chemical resistance, as well as decreasing the replacement frequency of insulators to almost zero. Besides, the results of the study showed that the test assembly with the coronary insulator provides better consistency in positioning and, subsequently, better contact, compared to the conventional method, which reduces the chance of electric short-circuit in the system.

Keywords: capping board, coronary insulator, electrolytic cell, thermal shock.

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Authors: Yasmin M. Attia, Hanan S. El-Abhar, Mahmoud M. Al Marzabani, Samia A. Shouman

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Background: Tamoxifen (TAM) is the most commonly used hormone therapy for the treatment of early and metastatic breast cancer. Although it significantly decreases the tumor recurrence rate and provides an overall benefit, as much as 20–30% of women still relapse during or after long-term therapy. 3-Bromopyruvate (3-BP) is a promising agent with impressive antitumor effects in several models of animal tumors and cell lines. Aim: This study was designed to investigate the combined effect of (TAM) and (3-BP) in breast cancer cells and to explore their molecular interaction via assessment of apoptotic, angiogenic, and metastatic markers. Methods: In vitro cytotoxicity study was carried out for both compounds to determine the combination regimen producing a synergistic effect and mechanistic pathways were studied using RT-PCR and western techniques. Moreover, the anti-oncolytic and anti-angiogenic potentials were assessed in mice bearing solid Ehrlich carcinoma (SEC). Results: The combined treatment significantly increased the expressions and protein levels of caspase 7, 9, and 3 and decreased of angiogenic markers VEGF, HIF-1α, and HK2 compared to cells treated with either drug individually. However, there were no significant changes in MMP-2 and MMP-9 protein levels. Interestingly, the in vivo results supported the in vitro findings; there was a decrease in the tumor volume and VEFG using immunohistochemistry in the combination-treated groups compared to either TAM or 3-BP treated one. Conclusion: 3-BP synergizes the cytotoxic effect of TAM by increasing apoptosis and decreasing angiogenesis which makes this combination a promising regimen to be applied clinically.

Keywords: tamoxifen, 3-bromopyruvate, breast cancer, cytotoxicity, angiogenesis

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Authors: Djaafar Fatiha, Ghalem Bachir, Hadri Bagdad

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We studied mainly the influence of temperature, thickness, molar fraction and the doping of the various layers (emitter, base, BSF and window) on the performances of a photovoltaic solar cell. In a first stage, we optimized the performances of the InGaP/GaAs dual-junction solar cell while varying its operation temperature from 275°K to 375 °K with an increment of 25°C using a virtual wafer fabrication TCAD Silvaco. The optimization at 300 °K led to the following result: Icc =14.22 mA/cm2, Voc =2.42V, FF=91.32 %, η= 22.76 % which is close with those found in the literature. In a second stage ,we have varied the molar fraction of different layers as well their thickness and the doping of both emitters and bases and we have registered the result of each variation until obtaining an optimal efficiency of the proposed solar cell at 300°K which was of Icc=14.35mA/cm2,Voc=2.47V,FF=91.34,and η=23.33% for In(1-x)Ga(x)P molar fraction( x=0.5).The elimination of a layer BSF on the back face of our cell, enabled us to make a remarkable improvement of the short-circuit current (Icc=14.70 mA/cm2) and a decrease in open circuit voltage Voc and output η which reached 1.46V and 11.97% respectively. Therefore, we could determine the critical parameters of the cell and optimize its various technological parameters to obtain the best performance for a dual junction solar cell .This work opens the way with new prospects in the field of the photovoltaic one. Such structures will thus simplify the manufacturing processes of the cells; will thus reduce the costs while producing high outputs of photovoltaic conversion.

Keywords: modeling, simulation, multijunction, optimization, Silvaco ATLAS

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Authors: Magdalena Rusady Goey, Gordon Strathdee, Neil Perkins

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Background: Acute lymphoblastic leukaemia (ALL) is the most frequent type of childhood malignancy, accounting for 25% of all cases. TWIST2, a basic helix-loop-helix transcription factor, has been implicated in ALL development. Prior studies found that TWIST2 undergoes epigenetic silencing in more than 50% cases of ALL through promoter hypermethylation and suggested that re-expression of TWIST2 may inhibit cell growth/survival of leukaemia cell lines. TWIST2 has also been implicated as a regulator of NF-kappaB activity, which is constitutively active in leukaemia. Here, we use a lentiviral transductions system to confirm the importance of TWIST2 in controlling leukaemia cell growth and to investigate whether this is achieved through altered regulation of NF-kappaB activity. Method: Re-expression of TWIST2 in leukaemia cell lines was achieved using lentiviral-based transduction. The lentiviral vector also expresses enhanced green fluorescent protein (eGFP), allowing transduced cells to be tracked using flow cytometry. Analysis of apoptosis and cell proliferation were done using annexinV and VPD450 staining, respectively. Result and Discussion: TWIST2-expressing cells were rapidly depleted from a mixed population in ALL cell lines (NALM6 and Reh), indicating that TWIST2 inhibited cell growth/survival of ALL cells. In contrast, myeloid cell lines (HL60 and K562) were comparatively insensitive to TWIST2 re-expression. Analysis of apoptosis and cell proliferation found no significant induction of apoptosis, but did find a rapid induction of proliferation arrest in TWIST2-expressing Reh and NALM6 cells. Initial experiment with NF-kappaB inhibitor demonstrated that inhibition of NF-kappaB has similar impact on cell proliferation in the ALL cell lines, suggesting that TWITST2 may induce cell proliferation arrest through inhibition of NF-kappaB. Conclusion: The results of this study suggest that epigenetic inactivation of TWIST2 in primary ALL leads to increased proliferation, potentially by altering the regulation of NF-kappaB.

Keywords: leukaemia, acute lymphoblastic leukaemia, NF-kappaB, TWIST2, lentivirus

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Authors: Debajit Kalita, Macmillan Nongkhlaw, S. R. Joshi

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Mercury (Hg) is a highly toxic heavy metal released both from naturally occurring volcanoes and anthropogenic activities like alkali and mining industries as well as biomedical wastes. Exposure to mercury is known to affect the nervous, gastrointestinal and renal systems. In the present study, a bacterial isolate identified using 16S rRNA marker as Paenibacillus jamilae PKR1 isolated from India’s largest sandstone-type uranium deposits, containing an average of 0.1% U3O8, was found to be resistance to Hg contamination under culture conditions. It showed strong hydrophobicity as revealed by SAT, MATH, PAT, SAA adherence assays. The Fourier Transform Infrared (FTIR) spectra showed the presence of hydroxyl, amino and carboxylic functional groups on the cell surface EPS which are known to contribute in the binding of metals. It is proposed that the characterized isolate tolerating up to 4.0mM of mercury provides scope for its application in bioremediation of mercury from contaminated sites.

Keywords: mercury, Domiasiat, uranium, paenibacillus jamilae, hydrophobicity, FTIR

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Authors: Daniel Thompson, Muhammad Peerbux, Sophie Cerutti, Hansraj Bookun

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Introduction: Dialysis access is a key component of the care of patients with end stage renal failure. In our institution, a combined service of vascular surgeons and nephrologists are responsible for the creation and maintenance of arteriovenous fisultas (AVF), tenckhoff cathethers and Hickman/permcath lines. This poster investigates the last 10 years of dialysis access surgery conducted at St. Vincent’s Hospital Melbourne. Method: A cross-sectional retrospective analysis was conducted of patients of St. Vincent’s Hospital Melbourne (Victoria, Australia) utilising data collection from the Australasian Vascular Audit (Australian and New Zealand Society for Vascular Surgery). Descriptive demographic analysis was carried out as well as operation type, length of hospital stays, postoperative deaths and need for reoperation. Results: 2085 patients with renal failure were operated on between the years of 2011 and 2020. 1315 were male (63.1%) and 770 were female (36.9%). The mean age was 58 (SD 13.8). 92% of patients scored three or greater on the American Society of Anesthiologiests classification system. Almost half had a history of ischaemic heart disease (48.4%), more than half had a history of diabetes (64%), and a majority had hypertension (88.4%). 1784 patients had a creatinine over 150mmol/L (85.6%), the rest were on dialysis (14.4%). The most common access procedure was AVF creation, with 474 autologous AVFs and 64 prosthetic AVFs. There were 263 Tenckhoff insertions. We performed 160 cadeveric renal transplants. The most common location for AVF formation was brachiocephalic (43.88%) followed by radiocephalic (36.7%) and brachiobasilic (16.67%). Fistulas that required re-intervention were most commonly angioplastied (n=163), followed by thrombectomy (n=136). There were 107 local fistula repairs. Average length of stay was 7.6 days, (SD 12). There were 106 unplanned returns to theatre, most commonly for fistula creation, insertion of tenckhoff or permacath removal (71.7%). There were 8 deaths in the immediately postoperative period. Discussion: Access to dialysis is vital for patients with end stage kidney disease, and requires a multidisciplinary approach from both nephrologists, vascular surgeons, and allied health practitioners. Our service provides a variety of dialysis access methods, predominately fistula creation and tenckhoff insertion. Patients with renal failure are heavily comorbid, and prolonged hospital admission following surgery is a source of significant healthcare expenditure. AVFs require careful monitoring and maintenance for ongoing utility, and our data reflects a multitude of operations required to maintain usable access. The requirement for dialysis is growing worldwide and our data demonstrates a local experience in access, with preferred methods, common complications and the associated surgical interventions.

Keywords: dialysis, fistula, nephrology, vascular surgery

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Authors: Mohd Farooq Naqshbandi

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The four fractions of aqueous extract of Sesame Seeds (Sesamum indicum L.) were studied for invitro DNA fragmentation, cell migration, and cellular apoptosis on SW480 and HTC116 human colorectal cancer cell lines. The seeds of Sesamum indicum were extracted with six solvents, including Methanol, Ethanol, Aqueous, Chloroform, Acetonitrile, and Hexane. The aqueous extract (IC₅₀ value 154 µg/ml) was found to be the most active in terms of cytotoxicity with SW480 human colorectal cancer cell lines. Further fractionation of this aqueous extract on flash chromatography gave four fractions. These four fractions were studied for anticancer and DNA binding studies. Cell viability was assessed by colorimetric assay (MTT). IC₅₀ values for all these four fractions ranged from 137 to 548 µg/mL for the HTC116 cancer cell line and 141 to 402 µg/mL for the SW480 cancer cell line. The four fractions showed good anticancer and DNA binding properties. The DNA binding constants ranged from 10.4 ×10⁴ 5 to 28.7 ×10⁴, showing good interactions with DNA. The DNA binding interactions were due to intercalative and π-π electron forces. The results indicate that aqueous extract fractions of sesame showed inhibition of cell migration of SW480 and HTC116 human colorectal cancer cell lines and induced DNA fragmentation and apoptosis. This was demonstrated by calculating the low wound closure percentage in cells treated with these fractions as compared to the control (80%). Morphological features of nuclei of cells treated with fractions revealed chromatin compression, nuclear shrinkage, and apoptotic body formation, which indicate cell death by apoptosis. The flow cytometer of fraction-treated cells of SW480 and HTC116 human colorectal cancer cell lines revealed death due to apoptosis. The results of the study indicate that aqueous extract of sesame seeds may be used to treat colorectal cancer.

Keywords: Sesamum indicum, cell migration inhibition, apoptosis induction, anticancer activity, colorectal cancer

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