Biography:

Daniele Zink earned her PhD from the University of Heidelberg, Germany in 1995 and completed her Habilitation (2001) at the Ludwig Maximilian University of Munich. In 2001, she was awarded funding of a Junior Group from the Volkswagen-Foundation, which she led until she moved to the Institute of Bioengineering and Nanotechnology (IBN) in Singapore in 2007. Her work on predictive in vitro models has been awarded by Merck Millipore and the US Society of Toxicology. She has won the prestigious LUSH Prize (2016, Science Category). She holds 10 patents/patent applications, is Editorial Board Member of Scientific Reports, has more than 70 peer reviewed publications and is Co-Founder and Director of the spin-off company Cellbae.

Abstract:

Predictive in vitro methods are crucial for 21^st century toxicology. Currently, most in vitro methods are not predictive or their predictivity has not been determined. With respect to predictive assays there is often substantial confusion about the question what an assay actually predicts, and the way how results are presented is often not helpful. Crucial for developing predictive methods is pre-validation with a statistically robust set of compounds, and proper compound annotation and classification require careful consideration. Whereas most discussions focus on selection of proper cell and tissue models, little attention is paid to endpoint selection. Examples will be discussed how bioinformatics methods can be used for the identification of proper endpoints. In addition, the analysis of high-throughput data will be addressed.

Biography:

Jianwei Zhou has his expertise in research on DNA damage and repair, cancer initiation, metastasis and drug resistance. Based on the mechanistic discovery of JWA gene in anticancer and neuroprotection, he has developed anticancer polypeptides and small molecular compounds and these will can be potentially used as neurodegenerative protection and cancer metastasis therapeutic agents.

Abstract:

Cancer metastasis is still the biggest challenge to cancer patients worldwide. Melanoma is the most malignant tumor due to its rapid metastatic capacity and shorter survival rate. The JWA gene, also known as ARL6IP5, is initially cloned from a retinoid acid induced cell differentiation cell culture model in HBE (human bronchial epithelial) cells. JWA is also identified as an multi-functional protein in both normal and cancer cells. In normal cells, JWA works as an active ROS (reactive oxygen species) response gene and DNA repair protein; however, in cancer cells, JWA exerts a tumor suppressor role to inhibit cell migration, proliferation, angiogenesis and chemoresistance in some cancers including melanoma and gastric cancer. Here, we have developed a JWA gene based polypeptide (PJP1-RGD) which is able to specifically target overexpressed integrin αvβ3 on membrane of melanoma cells by its RGD linker. Our data showed 50 mg.kg/day of PJP1-RGD could effectively inhibit xenograft tumor growth of both B16H10 and A375 melanoma cells in mice, suppressed its metastasis and improved mice survival. The anticancer effect of PJP1-RGD is comparable to 80 mg.kg/day Dacarbazine, a first line drug for clinical melanoma chemotherapy. More importantly, a synergistic role was observed between PJP1-RGD and Dacarbazine in the treatment of melanoma. The combined use of PJP1-RGD (50 mg.kg/day) and Dacarbazine (40 mg.kg/day) indicated an enhanced inhibitory effects but less side effects of Dacarbazine. In conclusion, PJP1-RGD targeting peptide might be an useful anti-cancer metastasis candidate and with translational significance in drug development.

Biography:

Eva Novotna has her expertise in the preparation and purification of recombinant enzymes. She studies interactions of potential inhibitors with carbonyl reducing enzymes using human recombinant enzymes and cancer cell lines. Her research interest include: carbonyl reducing enzymes, inhibitors and cancer drug resistance.

Abstract:

Anthracyclines, in particular, doxorubicin (Dox) and daunorubicin (Dau), have been used as a key part of many cancer treatment regimes, but their usefulness is limited by intrinsic and/or acquired resistance. Pharmacokinetic anthracycline resistance is associated with the enzymatic detoxification and with changes in anthracycline absorption and retention. The major anthracycline metabolic pathway in humans is mediated by a group of cytosolic NADPH-dependent carbonyl reducing enzymes from AKR and SDR superfamilies that catalyze two-electron reduction of Dau and Dox to less active metabolites. Cyclin-dependent kinases (CDK) are key regulators of cell cycle progression, and defects in their regulation are associated with many human pathologies. The CDK inhibitors purvalanol A and roscovitine are purine analogs with different potencies and selectivities. Recent studies showed that roscovitine could effectively kill anthracycline-resistant cancer cells and increase the therapeutic activity of anthracyclines. Although beneficial effects of these combinations have been demonstrated, the molecular mechanisms have not been fully understood yet. In our study, we proved that both purvalanol A and roscovitine significantly inhibit recombinant AKR1C3 with IC50 values of 6.6 and 2.2 M, respectively. Kinetic measurements showed that the ARK1C3-mediated reduction of Dau is inhibited in a noncompetitive manner. Both the drugs were also active at the cellular level in the experiments with transiently transfected HCT116 cells. In the follow up combination experiments, we demonstrated that the inhibition of AKR1C3 by roscovitine and purvalanol A has a potential to overcome the Dau resistance mediated by this enzyme. The dose reduction indices suggest a potential of the examined combinations to increase the safety of the treatment with the involved drugs.

Biography:

Abstract:

The present study was addressed to gain better understanding of the intimate mechanisms of FA hepatotoxicity. Adult female Wistar rats were distributed into: (1) control, (2) FA; 10 ppm for 15 days, (3) FA; 10 ppm for 30 days, (4): FA; 20 ppm for 15 days and (5): FA; 20 ppm for 30 days. Histopathological description, immunohistochemical examination and molecular genetics analyses were carried out. Liver histopathological findings of liver tissue sections revealed sinusoidal congestion, liver necrosis and fibrosis due to FA exposure. Liver tissue sections immunostained with the antibody for PCNA or cytochrome c showed strong positive immunoreactivity within numerous nuclei and the cytoplasm of numerous cells respectively. Exposure of rat to FA for 15 days evoked downregulation in liver Cyp2c6 and BHMT genes expression level. Exposure of rat to FA for 30 days elicited upregulation in liver Cyp2c6 and BHMT genes expression level. Rats exposed to FA (20 ppm) for 15 or 30 days experienced downregulation in liver Mapk12 gene expression level. Liver HLA-A and GSTP1 genes expression of rats exposed to FA for 15 and 30 days showed upregulation except for 10 ppm of FA at 15 days. This study provides cellular and molecular evidences for FA–induced hepatotoxicity. Formaldehyde is reasonable to assume that apoptosis, oxidative stress and inflammation be involved in formaldehyde-induced hepatotoxicity.

Biography:

Semir Gül is a PhD student in the Department of Histology and Embryology, Faculty of Medicine, Inonu University, Turkey and obtained his Master’s Degree from the same university. He graduated from Molecular Biology and Genetics Department in 2010 from Izmir Institute of Technology, Turkey. His research interests are: toxicology, reproductive biology and developmental biology.         

Abstract:

Statement of the Problem: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic member of halogenated aromatic hydrocarbons. TCDD is able to pass from environment to humans through the food chain by absorption of the gastrointestinal system. TCDD has many biological effects such as carcinogenesis, immune system suppression, neuronal damage, liver damage, developmental defects and fertility problems. TCDD leads to lipid peroxidation resulting in molecular oxygen transport increase which causes formation of reactive oxygen species within the tissue. Thymoquinone (TQ) which is one of the active ingredients in Nigella sativa plant was reported to have anti-carcinogen, antitumor, antibacterial, anti-inflammatory, antioxidant and immune system supporter effects.

Aim: The aim of this study is to investigate the protective effects of TQ in liver tissues of rats exposed to TCDD.

Methodology & Theoretical Orientation: Fifty rats were randomly divided to 5 groups (n=10 for each group) as follows: control, corn oil, TCDD (1µg/kg/day), TQ (50 mg/kg/day), TCDD+TQ (1µg/kg/day TCDD and 50 mg/kg/day TQ). Biochemical, histopathological and electron microscopic analyses were performed for liver tissues obtained after the experiment.

Findings: TCDD significantly increased MDA, TOS, ALT, AST and ALP levels and reduced GSH, TAS, SOD and CAT levels (p≤0.05) when compared to all other groups. In the TCDD+TQ group, MDA, TOS, ALT, AST, ALP levels approached to the control group levels and GSH, TAS, SOD, CAT levels increased and approached to the control group levels and were significantly different from TCDD group (p≤0,05). In terms of histopathological evaluation, total damage score (TDS) findings demonstrated that TCDD group showed an increase in TDS when compared to all other groups. In contrast, TCDD+TQ group showed a statistically significant decrease in TDS compared to TCDD group (p≤0.05), Transmission electron microscopic analysis showed that ultrastructural changes seen in TCDD group were diminished in TCDD+TQ group.

Biography:

Catriona Kielty (BSc) is a Veterinary Nursing and Applied Bioscience Postgraduate student working in the field of lipid research with a particular focus on dietary linoleic acid and its impact on inflammation and coagulation. Her research interest include: Lipidomics and Cellular Toxicology.

Abstract:

Historical dietary recommendations have resulted in the substitution of saturated fatty acids with polyunsaturated fatty acids (PUFAs), with a subsequent increase in the intake of dietary linoleic acid. Some PUFAs, particularly, linoleic acid, have been associated in the past with a pro-inflammatory response. Linoleic acid, being a precursor for arachidonic acid, is associated with the production of pro-inflammatory eicosanoids such as prostaglandins, thromboxanes and leukotrienes, as well as independently affecting inflammation through its metabolism to biologically active oxidation products. The primary aim of this investigation is to delineate the mechanism of action of linoleic acid in its free fatty acid form, specifically cis-9, cis-12, unconjugated linoleic acid (ULA), in relation to cytotoxicity and inflammation. Experiments were performed using the epithelial cell line, HepG2, and the endothelial cell line, HUVEC (Human umbilical vein endothelial cells). Using the MTT assay as an endpoint, the potential cellular lipotoxicity of this essential fatty acid was investigated when cells were exposed to it at high concentrations (0 to 2.5 mM). The Oil Red O assay was also used to identify the intracellular accumulation of neutral lipids in treated cells. To date, results indicate that high concentrations of ULA inhibit cell proliferation (P=0.0001) which could indicate an inflammatory response. Intracellular lipid accumulation also declined as ULA concentrations increased. Future work will include the identification of inflammatory biomarkers, such as TNF-α, associated with inflammation, in order to further elucidate the mechanism of action of ULA. 

Biography:

Sarah Naughton has graduated with BSc in Biomedical Science, and with a BSc in Forensic Toxicology and the BSc (Hons) in Human and Animal Toxicology. Her work focuses on using microbiological techniques coupled with DNA and RNA informatics; on novel, non-chemical disinfection technologies such as pulsed ultraviolet light (PUV), as well as the rapid diagnosis and remediation of sudden changes in freshwater aquaculture.       

Abstract:

The lack of expansion in the freshwater aquaculture sector as a whole has become an alarming concern over the past 20 years in Ireland. This is in marked contrast with FoodWise 2025 which seeks to increase food exports by €19 bn by 2025. Impediments to the traditional flow-through production process encompassing fatal disease outbreaks, issues with uncertainty over discharge licensing and a lack of understanding of the overall culture-water dynamic have contributed to this stagnation. In order to address the intensive sustainability of Irelands’ freshwater aquaculture sector and to inform these bottleneck concerns, it is important to develop an in-depth understanding of the dynamic mix of biological and physico-chemical parameters governing desirable rearing water as a baseline for successful operation. This project focuses on development and testing of novel molecular diagnostic methods facilitating DNA profiling of predominant bacterial and algal communities in rearing water, with real-time detection of important fish pathogens. Gaining an understanding of target species that contribute to finfish disease outbreaks and poor water quality is essential for prevention and control of problematic species. Molecular-based techniques, such as real-time PCR, have many advantages over traditional plating methods in the identification of species present, as less than 1 % of environmental microorganisms are culturable. The use of species-specific probes enables detection of problematic pathogens and therefore aids future characterization of harmful bacteria and algae. Linking the biological profile with water quality parameters such as nitrates, nitrites and ammonia in a pill-pond farm when production is thriving will allow for the amendment of the process when production regresses or fails. It will also identify the potential to up-scale and replicate this type of fish farm in the culturing of a variety of freshwater species such as trout, therefore providing an opportunity to expand the industry.

Biography:

Semir Gül is a PhD student in the Department of Histology and Embryology, Faculty of Medicine, Inonu University, Turkey and obtained his Master’s Degree from the same university. He graduated from Molecular Biology and Genetics Department in 2010 from Izmir Institute of Technology, Turkey. His research interests are: toxicology, reproductive biology and developmental biology.

Abstract:

Statement of the Problem: Acetamiprid (ACMP) is an insecticide of the neonicotinoid class, widely used for combating insects in many areas of agricultural production. Neonicotinoids act as agonists of acetylcholine in the synaptic range and inhibit synaptic stimulation by binding to the nicotinic acetylcholine receptors in the central nervous system of insects. Since different nAChRs subspecies are expressed in human testes, prostate, mammalian nervous system, mouse testes and spermatozoa, these organs are the main targets of neonicotinoids and therefore acetamiprid. It has been reported that the insecticides cause structural and functional damage to spermatozoon, Sertoli cells and Leydig cells by oxidative stress in the testis. Vitamin-E is a cell membrane soluble vitamin and plays a protective role against harmful effects of free radicals in cells and tissues with antioxidant property. It is known that Vitamin-E is a potent lipophilic antioxidant that is vital for the protection of mammalian spermatogenesis and is present in high amounts in Sertoli and spermatogenic cells. We propose that the use of vitamin-E against acetamiprid testis toxicity may play protective role through oxidant-antioxidant mechanism.

Methodology & Theoretical Orientation: Thirty mice were divided into 5 groups (n=6 for each): water, corn oil, ACMP (25mg/kg/day), Vit-E (100mg/kg/day), ACMP+Vit-E (25mg/kg/day ACMP and 100mg/kg/day Vit-E). After 21 days, testis tissues were taken for histological, biochemical and intracellular ultrastructural evaluations.

Findings: In water, corn oil and Vit-E groups, testes tissues had normal testicular histomorphology, mature-healthy spermatogenic cells and seminiferous tubules. In ACMP group, degenerations in germ cells that accumulated in the lumen of the seminiferous tubule, seminiferous tubular atrophy and organization disorder of seminiferous tubule epithelium were observed. Histomorphological damage changes in the ACMP+Vit-E group were less than in ACMP group. However, histological scores showing the tissue improvement in ACMP+Vit-E were not very close to water, corn oil and Vit-E groups.