8^th International Conference and Exhibition on Metabolomics & Systems Biology May 08-10, 2017 Singapore

Biography:

Takeshi Kimura is a Board Member and Corporate Vice President for Ajinomoto Co., Inc. and is currently In-Charge of Research and Development, Intellectual Property, Quality Assurance and Regulatory Affairs. He has studied Cell and Molecular Biology at University of London, Kings College and obtained his PhD in Biochemistry from University of London in 1984. He was a Visiting Fellow and Visiting Associate at the National Institutes of Health in the USA before joining Ajinomoto in 1989. He has worked in research, regulatory affairs and quality assurance since then, helping to establish the basis of AminoIndex Technology while in research. He became Corporate Executive Officer in 2009 and Board Member in 2013. He is also a Member of the Board of Trustees for International Life Sciences Institute and Research Foundation, International Advisory Council Member for Monell Chemical Senses Center and Japanese Private Sector Member for APEC Policy Partnership for Food Security. 

Abstract:

Early detection remains the most valuable tool in the fight against chronic diseases. Especially, the need for an early cancer screening method is evident as prognosis depends on how early treatment measures can be taken. Although various analytical platforms exist, currently there are only a few screening tests that have both high sensitivity and the ability for early detection, and also these tests must be taken for each individual cancer. Metabolomics have profound capacity in the search for such candidate markers in that we can obtain comprehensive knowledge and data of metabolisms under specific physiological states. From early observations indicating that amino acids were a convenient subset of the metabolome to investigate changes in metabolism associated with various physiological states, we have developed a technological package (AminoIndex technology) to generate biomarkers for various disease and physiological states using plasma free amino acid concentration data. Risk screening for various cancers with AminoIndex technology have been offered commercially in Japan since 2011. More recently, we have developed novel LC-MS platform that enables high-throughput metabolite profiling including over 40 amino acids, amines and their derivatives. Furthermore, we have constructed a large scale plasma biospecimen bank as well as database containing health and medical information of more than 50,000 Japanese in total concerning multiple diseases (e.g. cancers, metabolic syndrome etc.) and their metabolomic profiles. By variable selection and regression analysis, so far we have developed multivariate indices that enable the early detection of multiple cancers and predictive risk assessment for diabetes and inflammatory bowel disease from a single blood draw. In order to achieve commercialization, various issues ranging from sample handling, throughput to standardization have to be overcome and some of these issues, which may be relevant to other biomarker commercialization, will also be addressed.

Biography:

Yukio Fujiki and his colleagues investigate cellular homeostasis involving subcellular organelles such as peroxisome. His lab tackles the problems involving membrane assembly, matrix protein import, morphogenesis and homeostasis of peroxisomes. His group successfully identified and isolated more than a dozen PEX genes including the first Zellweger gene PEX2. He and his colleagues unveil the roles of peroxins in peroxisome biogenesis and the pathogenesis of PBDs from the viewpoint of dysregulation of peroxisome homeostasis.

Abstract:

Cellular homeostasis is regulated by orchestrating the functions of organelles in response to the extracellular stimuli and/or intracellular signals. To elucidate the highly organized functions of intracellular organelles, peroxisome, a single membrane-bounded essential organelle has been used as a model compartment in mammalian cells. Peroxisomes are present in a wide variety of eukaryotic cells and they function in various metabolic pathways, including β-oxidation of very long chain fatty acids and the synthesis of ether-lipids such as plasmalogens. The functional consequence of human peroxisomes is highlighted by fatal genetic peroxisome biogenesis disorders (PBD) such as Zellweger syndrome (ZS). We successfully isolated a dozen Chinese Hamster Ovary (CHO) cell mutants defective in peroxisome biogenesis and identified PEX genes encoding peroxisome biogenesis factors termed peroxins, including PEX2, PEX6, PEX12, PEX26, by means of the genetic phenotype-complementation of CHO cell mutants. We also unveiled the roles of peroxins in peroxisomal membrane assembly including targeting mechanism of nascent C-tailed anchored proteins, matrix protein import and division. We are now focusing on the peroxisomal membrane targeting mechanism of nascent C-tailed anchored proteins. Physiological consequence of plasmalogens is highlighted by PBDs. Ablation of plasmalogen homeostasis is reported in several neurological diseases including Alzheimer’s disease. In cells from PBD patents, plasmenylethanolamine is remarkably reduced and phosphatidylethanolamine is increased. We have shown that plasmalogen biosynthesis is regulated by modulating stability of fatty acyl-CoA reductase (Far1) and that plasmalogen homeostasis plays an important role in cholesterol synthesis. Moreover, plasmalogens located in the inner leaflet of plasma membrane are sensed for monitoring cellular plasmalogen level.

Biography:

Ng Sean Pin is the Deputy Director of Singapore Phenome Center. His interest is in the application of high-throughput technologies in advancing clinical and biological sciences. 

Abstract:

Phenomics is defined as the acquisition of high-dimensional phenotypic data on an organism-wide scale. In other words, phenomics is the study of the phenotypes of an organism and the response of the phenotypes to genetic and environmental changes.​ In recent years, -omics studies have become increasingly important due to their potential to increase our understanding of how environmental factors and diseases affect human health. This leads to improvement in the treatment or therapeutic strategies, ultimately resulting in improved healthcare and a higher standard of living. As such, the main research areas of the Singapore Phenome Centre (SPC) are in the clinical, biological and environmental sciences. These research studies are centered on the profiling of critical biomolecules such as metabolites, lipids and proteins through the use of the state-of-the-art ultra-performance liquid chromatography mass spectrometry (UPLC-MS), imaging mass spectrometry and NMR spectroscopy technologies available at the Singapore Phenome Centre at NTU. SPC aims to deliver a world-class competency in metabolic phenotyping research in association with local and international research institutions, hospitals and industry. The Centre, officially launched in 2015, is a member of the International Phenome Centre Network (IPCN) headed by Imperial College London’s (ICL) very own National Phenome Centre (NPC). This allows SPC to harmonize its research methods and technologies with centers that are part of the IPCN, which opens the path to building a global infrastructure around phenotyping. Currently the center houses 8 quadrupole time-of-flight hybrid tandem mass spectrometers, two triple quadrupole mass spectrometers and one 600 MHz nuclear magnetic resonance spectroscope. SPC has since been involved in collaborations with PIs from National Cancer Centre Singapore (SGH), IMB and IMCB (A*STAR), National Neuroscience Institute on Brain Cancer Imaging, National Institute of Education, and different schools in NTU (i.e. LKC Medicine, School of Biological Sciences, Singapore Centre on Environmental Life Sciences Engineering).

Biography:

Andrew M Chan is currently a Professor and Chief of the Cancer Biology & Experimental Therapeutics Thematic Research Program at the School of Biomedical Sciences of the Chinese University of Hong Kong. He has obtained his PhD degree from the Chester Beatty Laboratory of the Institute of Cancer Research in London. He was a Fogarty International Fellow at the US National Cancer Institute in the Laboratory of Cellular & Molecular Biology. He was a Faculty Member at the Mount Sinai School of Medicine and the Medical College of Wisconsin. His research interest is in the area of cancer cell signaling and mouse models of human cancers with focuses on the PI3-K and Ras-mediated signaling mechanisms in brain, breast and lung cancers.

Abstract:

Metastatic diseases in lung adenocarcinoma are often associated with poor prognosis. We have previously characterized a brain metastasis cell line of lung cancer origin, A1115, which possessed heightened glycolytic activity when compared with other lung adenocarcinoma cell lines such as, A549, derived from a primary site. A1115 has greater lactate production than A549. Conversely, A549 has a greater oxygen uptake rate that could be effectively blocked by oligomycin. Indeed, the proliferation of A549 was hypersensitive to oligomycin treatment while A1115 was greatly inhibited by glucose deprivation. Western blotting analysis revealed both hexokinase I (HK1) and phosphoenolpyruvate carboxykinase 1 (PCK1) were preferentially expressed in A1115. For energy sensing signaling, AMPKα, which senses cellular AMP level, was phosphorylated in A549 but not in A1115. Indeed, the proliferative capacity of A1115 was drastically reduced by an AMPK activator, AICAR, while A549 was not affected. Metabolite profiles under reduced 1 g/L revealed a 5- to 24-fold increase in metabolites that are linked to purine metabolism (e.g. hypoxanthine, GMP, and adenosine). Treatment with a XOD inhibitor, allopurinol under reduced glucose condition increased cell viability in A1115 at low doses while toxic at high doses. This data suggests that heightened hypoxanthine may be a prosurvival adaptive response in A1115 under nutrient stress conditions. We further selected A1115 sublines that could survive at a low glucose concentration (0.15 g/L). Western blotting analysis revealed a drastic overexpression of PCK1 and PKC2 when compared to parental cells. Transcriptomic analysis was also performed to reveal genes that could play a role in the survival of brain metastatic lung cancer cells under nutrient stresses. Taken together, these results identified multiple vulnerable points in metabolic signaling that could be therapeutic targets for treating metastatic lung cancers.

Biography:

Paul M Yen is a Professor at Duke-NUS Graduate Medical School in Singapore and Head of the Laboratory of Hormonal Regulation in the Cardiovascular and Metabolic Disorders Program. He has obtained his MD from Johns Hopkins, completed his Residency in Internal Medicine at University of Chicago and his Endocrinology Fellowship at NIH. Prior to Duke-NUS, he has served on the Faculty at Johns Hopkins, Harvard and as a Section Chief at NIDDK, NIH. He has served on the Editorial Boards of Endocrinology, Molecular Endocrinology and Thyroid. His current research interests are hormonal regulation of hepatic autophagy and lipid metabolism in non-alcoholic fatty liver disease as well as epigenetic regulation of metabolic genes by thyroid hormone

Abstract:

Statement of the Problem: Thyroid hormone (TH) plays a key role of metabolism and its dysfunction may be involved in non-alcoholic fatty liver disease (NAFLD). We previously showed that TH induces autophagy in the liver to promote the degradation and hydrolysis of triglycerides stored in fat droplets into free fatty acids (Lipophagy). Metabolomics analysis showed that TH also stimulated fatty acid β-oxidation.

Findings: TH increased mitophagy in hepatic cells in vivo that was associated with increased oxidative phosphorylation. This was evident from co-localization of autophagy/autolysosomal markers and mitochondria using confocal and electron microscopy. Furthermore, we found that T3 induced a concomitant increase in ROS that was crucial for TH-induced mitophagy through the AMPK/ULK1 pathway. Additionally, we showed that T3 is a potent inducer of mitochondrial biosynthesis and utilizes that activation of another nuclear hormone receptor ERRa to mediate many of its actions.

Conclusion & Significance: Our results describe a novel co-ordinated mechanism of TH-induced fatty acid β-oxidation that is dependent upon mitochondrial turnover. These findings suggest that low dose Levothyroxine or thyroid hormone analogs may be beneficial for patients with hepatosteatosis related to NAFLD and obesity.

Biography:

Eun Jin Yang has completed her PhD from Yonsei University and Postdoctoral Studies from the University of Pennsylvania, USA. She is a Principal Researcher at Korea Institute of Oriental Medicine, South Korea. She has published more than 25 papers in reputed journals and has been serving as an Editorial Board Member.

Abstract:

Vascular dementia (VaD) is caused by the reduction of blood supply by vessel occlusion and is characterized by progressive cognitive decline. VaD incidence has been growing due to the aging population, placing greater strain on social and economic resources. However, the pathological mechanisms underlying VaD remain unclear. Many studies have used the bilateral common carotid artery occlusion (BCCAO) animal model to investigate potential therapeutics for VaD. In this study, we investigated whether bee venom (BV) improves cognitive function and reduces neuroinflammation in the hippocampus of BCCAO animals. Animals were randomly divided into three groups: a sham group (n=15), BCCAO control group (n=15), and BV-treated BCCAO group (n=15). BCCAO animals were treated with 0.1 μg/g BV at ST36 (BJoksamli^ acupoint) four times every other day. In order to investigate the effect of BV treatment on cognitive function, we performed a Y-maze test. In order to uncover any potential relationship between these results and neuroinflammation, we also performed Western blotting in the BCCAO group. Animals that had been treated with BV, showed an improved cognitive function and a reduced expression of neuroinflammatory proteins in the hippocampus, including Iba-1, TLR4, CD14, and TNF-α. Furthermore, we demonstrated that BV treatment increased pERK and BDNF in the hippocampus. The present study thus underlines the neuroprotective effect of BV treatment against BCCAO induced cognitive impairment and neuroinflammation. Our findings suggest that BV may be an effective complementary treatment for VaD, as it may improve cognitive function and attenuate neuroinflammation associated with dementia.

Biography:

Mohamed A Elrayess has completed his PhD at University College London (UCL) in Cardiovascular Genetics in 2002. He has then studied the therapeutic utilization of hematopoietic stem cells in cardiovascular disease at the Department of Medicine in UCL. He has spent over 7 years working as a Stem Cell Scientist in Eisai Ltd, a major international pharmaceutical company, leading projects focusing on stem cell therapy in various neurodegenerative diseases. He currently occupies a Senior Scientist position at Anti-Doping Lab Qatar, where he leads projects focusing on the role of stem cells in diabetes and genetics and metabolomics of elite athletes.

Abstract:

Background & Aim: The elite performance of professional athletes is associated with alterations in their systemic metabolic profiling. The objectives of this study were to compare the metabolic profiling between low and high power and endurance elite athletes and to highlight the underlying metabolic pathways.

Methods: Sera from one 191 elite athletes who passed anti-doping laboratories’ tests were profiled using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid and gas. Differences in metabolic signatures were compared between low and high power and endurance groups by OPLS-DA and regression models.

Results & Conclusions: Data reveal that high performance athletes show a distinct metabolic profile that reflects steroid biosynthesis, fatty acid metabolism, oxidative stress and energy-related metabolites. Differences in performance-related metabolic profiles could shed light on the biochemical processes associated with their elite performance and potentially be utilized as biomarkers for endurance or power trainability in athletic candidates.

Biography:

Maximilian Zucker has studied Physics at the Technical University of Munich, Germany, Business Administration at the University of Hagen, Germany and received his PhD in Physics in 2000 at the University of Bonn, Germany. Prior to joining numares HEALTH AG, he was the Managing Director (COO) of Roche Multiplate and Management Consultant at various consulting companies.

Abstract:

Statement of the Problem: In recent years, metabolomics has become a powerful tool for discovering biomarkers for diagnostic purposes. Although numerous promising biomarker patterns have been reported for a broad range of disorders, only few have entered clinical routine. Our presentation aims at analyzing this paradox.

Theory & Practice: The detection of disease-specific biomarker patterns and their transfer from theory into clinical practice as diagnostic tools requires robust, accurate, reproducible and cost/time-efficient methods. Thus, numares has developed the AXINON System encompassing the Magnetic Group Signaling (MGS) technology allowing quantitative analyses of metabolites in body fluids by nuclear magnetic resonance (NMR) spectroscopy. This standardized NMR-analysis is combined with internal quality control algorithms and innovative biostatistics.

Clinical Application: By meeting all these above requirements, we present the in vitro discovery, implementation and validation of novel biomarkers in the fields of urological malignancies, atherosclerosis and kidney disease as application examples. The general workflow included NMR analysis of several hundred patient samples in three distinct cohorts per use-case. Spectra of a first use-case specific cohort (training sets) were evaluated to identify spectral regions discriminating patients from controls. Subsequently, metabolites within these regions were identified, validated and quantified by fitting algorithms. In order to increase diagnostic sensitivity and specificity, single marker candidates were combined into multi-marker patterns, which were selected by using the second cohorts (optimization cohort). The final patterns were validated in the third independent test cohorts.

Conclusion & Significance: In order to implement metabolomics-based diagnostic test into clinical routine, several technical and algorithmic hurdles have to be tackled. It will only be possible to overcome the above mentioned paradox if new skills and technologies are added to what is otherwise required in more classical diagnostic approaches.

Biography:

Zhi Yang Tam is a Computational Biologist with experience in applying supervised and unsupervised machine learning methodology on high throughput and imaging data, modeling biological processes using deterministic and stochastic models and applying other statistical tools to derive insights into biological process. 

Abstract:

Regulation of blood glucose in the body requires precise coordination between different endocrine organs. Diabetes mellitus arises from a dysregulated response to elevated glucose levels in the circulation. Globally, the prevalence of diabetes has increased dramatically in all age groups. Diabetes in older adults is associated with higher mortality and reduced functional status, leading to higher rate of institutionalization. Despite the potential healthcare challenges associated with the presence of diabetes in the older population, the pathogenesis and phenotype of late-onset diabetes is not well studied. Here we applied untargeted metabolite profiling of urine samples from people with and without late-onset diabetes using ultra-performance liquid-chromatography mass-spectrometry (UPLC-MS) to characterize the urine metabolic profile for the identification of urinary biomarkers for late-onset diabetes in older individuals. Statistical modeling of measurements and thorough validation of structural assignment using liquid chromatography tandem mass-spectrometry (LC-MS/MS) have led to the identification of metabolite biomarkers associated with late-onset diabetes mellitus. Lower levels of phenylalanine, acetylhistidine, and cyclic adenosine monophosphate (cAMP) were found in urine samples of diabetes subjects validated with commercial standards. Elevated level of 5'-methylthioadenosine (MTA) that previously has only been implicated in animal model of diabetes, was found in urine of older people with diabetes. 

Biography:

Abstract:

Statement of the Problem: About 15% couples are infertile. The “male factor” contributes to half of infertility. In spite of the development of treatment for infertile men, many questions regarding etiology of the male infertility remain to be answered. The use of high-throughput techniques brings hopes to treatment of male infertility. Especially, at present, metabolomics studies have been recognized as an outlook for the systematization of specific biomarkers in approval of a better identification of male infertility. Human semen is a biological fluid that consists of spermatozoa and seminal plasma. The seminal plasma can be used as an excellent source for noninvasive detection and diagnostic test of the male infertility. We have used the seminal plasma for metabolomics studies as a screening tool to diagnose male infertility and for biomarker discovery.

Methodology & Theoretical Orientation: There are different approaches that can be used in metabolomics study. We have used the easiest and cheapest approaches for clinical diagnosis, the pattern-recognition methods using Raman spectrometry. Additionally, we have applied GC-MS/MS for biomarker discovery.

Findings: Using metabolomics fingerprinting, we were able to classify idiopathic infertile men and asthenozoospermia men in the different groups compared to the fertile men. Additionally, it was observed at metabolome level that, there was oxidative imbalance in the seminal plasma of these patients. Via metabolomics profiling, we showed that metabolome of the seminal plasma of the non-obstructive azoospermia patients can be used for detection of spermatogenesis, as a noninvasive technique. Furthermore, we identified 38 metabolites which showed deregulation in these patients and can be used as potential biomarker for detection of spermatogenesis.

Conclusion & Significance: We have shown that metabolomics study of infertile men have come successfully out of discovery phase using the biological material seminal plasma. We now need to go to the test validation stage for further development of the technology.

Biography:

Binh Thang Tran is currently a Graduate student in the National Cancer Center Graduate School of Cancer Science and Policy, South Korea. He has also formerly worked for Hue University of Medicine and Pharmacy, Hue city, Vietnam, as a Research Associate for 5 years. His research interests focus on the health evaluation and cancer prevention.

Abstract:

Metabolic syndrome (MS) prevalence in Korea increased between the mid-1990s and mid-2000s; however, no data on the recent trends of MS prevalence are available. Furthermore, the Korean Government and the Korean National Assembly approved laws on health promotion and disease prevention, and one of the main targets of Health Plan 2020 is to reduce smoking, alcohol drinking and obesity. This policy includes lifestyle interventions, food safety and public education about healthy eating behaviors and physical activity. Therefore, a study is needed as a part of evaluation of the effectiveness of this intervention. We carried out the study using data from the Korean National Health and Nutrition Examination Survey from 2008 to 2013 to determine the prevalence trend of MS and risk factors. The revised National Cholesterol Education Program criteria were used for defining MS. A total of 34,587 men and women were included in the analysis. We found that MS prevalence in Korea is high, but did not follow a significant trend during 2008-2013. Several factors contributed to the stable MS prevalence: On the one hand, increased prevalence of high FPG, high BP, calorie intake and physical inactivity and on the other hand, decreased prevalence of abdominal obesity and smoking. Greater awareness of MS and its health consequences can help optimize the treatment of risk factors. Furthermore, risk factors such as smoking, alcohol drinking, obesity, diet and physical inactivity need to be considered in public health interventions. A multidimensional approach is vital to prevent future increases in MS.

Biography:

Amar Mohamed Ismail is head Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, Al-Neelain University – Sudan. Amar has his expertise in endocrinology and metabolism especially in breast cancer cells. In this work we aimed to investigate whether extra virgin olive oil and oleic acid could enhance the effects of aromatase inhibitors (letrozole and anastrozole) in estrogen receptor-positive MCF-7 cells, as well as to investigate its influence on cholesterol pathway.  

Abstract:

Background: Olive oil and cancer relationship has been proved by the support of many evidences. Present study aim to investigate whether EVOO and Oleic acid (OA) could enhance the effects of aromatase inhibitors (Letrozole and Anastrozole) in MCF-7 cells as well as to investigate its influence on aromatization.

Materials and Methods: The viability of the cells was assessed by MTT test. MCF-7 cells were divided into seven groups as flows: Letrozole treated, Anastrozole treated, Anastrozole combined with EVOO, Letrozole combined with EVOO, Anastrozole combined with OA, Letrozole combined with OA and control group. Estrone and cholesterol lysates were measured.

Results: MTT test results showed that for both Letrozole and Anastrozole combination with (EVOO or OA) significantly decreases the viability of the cells in comparison of standalone Anastrozol and Letrozol. Letrozole and Anastrozole treatments significantly increase the levels of cholesterol in comparison with the control, while combination treatments showed significant decreases in cholesterol levels. Standalone Letrozole or Anastrozole treatment significantly decreased estrone level while combination treatment highly significantly decreases the level of Estrone. Significance was determined according to p-value <0.05.

Conclusion: EVOO and OA potentiate aromatase inhibitors action lowering of Cholesterol, which acts as a precursor for estrogens hormones and cholesterol metabolites biosynthesis hence preventing MCF-7 cells proliferation.

Biography:

Sayan Chakraborty has obtained his PhD from the Chicago Medical School, USA in Molecular Virology, where he deciphered the mechanisms of entry and infection of Kaposi’s sarcoma herpesvirus in endothelial cell sarcoma. Subsequently, he moved to IMCB, Singapore to pursue research in hepatocellular carcinoma. Presently, he is working as a Senior Researcher in IMCB and he has identified Agrin as a promising therapeutic target for liver cancer.

Abstract:

Problem: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related deaths globally. The identity and role of cell surface molecules driving complex biological events leading to HCC progression are poorly understood, hence representing major lacunae in HCC therapies.

Approach: Combining quantitative proteomics and biochemical approaches, we uncover a critical oncogenic role of Agrin, which is frequently overexpressed and secreted in HCC. Our systematic cell biological analysis indicated a role of Agrin in maintaining focal adhesion integrity through stimulation of Focal Adhesion Kinase (FAK) that functions in cellular migration, invasion and tumor growth. However, the exact mechanisms by which Agrin’s mediates liver tumorigenesis remain unknown.

Findings: The present study dissects how Agrin mediated signals from the extracellular matrix are sensed by tumor cells. Agrin binds to its co-receptors Lrp4 and subsequently activates MuSK to mediate oncogenic effects through activating focal adhesions. Additionally, integrins and focal adhesions collaborate closely with Agrin in communicating ECM signals to intracellular components in HCC cell lines, thereby promoting their invasive, migratory and growth capabilities. More importantly, Lrp4-MuSK as well as integrin-FAK pathways are crucial downstream signaling axes of Agrin’s functions in liver tumorigenesis. Additional studies reveal that Agrin activates the Yes-Associated Protein (YAP) oncogenic program in liver by negatively regulating Hippo tumor suppressor pathway.

Conclusion & Significance: Our evidence suggests that function blocking antibodies against Agrin may inhibit integrin-FAK and YAP signaling, thereby reducing in vivo tumorigenesis. In addition to FAK and YAP inhibition in HCC, these novel insights shed significant weight on the possibility of targeting Agrin mediated oncogenesis in HCC.

Biography:

Jaleel K Ahmed has his expertise in Iron and Steel Industry. He has used chlorophyll as gamma ray absorber to protect Iraqi children from cancer and used red beet juice as scavenger for poisonous heavy metal ions and anticancer and detoxification of urea and uric acid from human body via urine system.

Abstract:

Anthocyanin from red beet juice, cherry and red rose which is extracted mechanically is water soluble due to the many hydroxyl groups and glucose molecule which is carried on the anthocyanin (position 3 on it). This juice is slightly sweet due to the free sugar present. The juice is very slightly acidic due to its exchangeable proton (Transmembrane proton with radius 1.5×10^-6 nm). The concentration of the proton in the juice is 10^-6.4 g proton/L. In spite of very low concentration of the exchangeable proton in the juice, it is very active to attack metal ions as soon as it comes in contact with it and as well as hetero atoms (like O, N, S) in organic molecules, such process is called protonation (exothermic process) in which this process pull the abnormal high energy molecules downhill and stabilize it. Proton is condensed in aqueous solution called hydrated proton PH₂O which moves to the whole human body and when become near high energy molecule with hetero atom leaving the water and attacks that molecule similar to the aircraft carrier when becomes near to the target, the aircraft leaves the carrier and attacks the target. In such process, proton saves the energy for the attack. Results show that solid anthocyanin from the evaporation of juice goes into condensation polymerization around 80 °C with liberation of water, as well as boiling concentrated juice (home-made) resulted in polymerization with very fine solid particles which reduce the ability of the exchangeable proton to precipitate heavy metal ions. Ultra violet-visible spectrum shows great difference between normal and filtered boiled juice .Thus it prefers to extract the juice mechanically not thermally and not any additional material added to the juice. Spectroscopic tests in addition to the visual one show that there is an interaction between anthocyanin and uric acid and urea in blood through hydrogen bonds and this help in detoxification process through urine system and this help kidney in its work.

Biography:

Junfang Zheng has accumulated rich experience in scientific research and formed rigorous research ideas after years of study. Her main research areas are regulation of tumor related signal transduction pathways and biomarker identification via MS-based proteomics and metabolomics. She has a passion for scientific research and has a deep knowledge of oncology. Her research contributes to the progress of oncology research.

Abstract:

Clear cell renal cell carcinoma (ccRCC) is the most lethal neoplasm of the urologic system. Clinical therapeutic effect varies greatly between individual ccRCC patients, so there is an urgent need to develop prognostic molecular biomarkers to help clinicians identify patients in need of early aggressive management. In this study, samples from primary ccRCC tumor and their corresponding non-tumor adjacent tissues (n=18) were analyzed by quantitative proteomic assay. Proteins downregulated in tumors were studied by GO and KEGG pathways enrichment analyses. Six proteins were found both downregulated and annotated with cell proliferation in ccRCC patients. Of these proteins, PDZK1 and FABP1 were also involved in the lipid metabolism pathway. The downregulation of PDZK1 was further validated in TCGA_KIRC dataset (n=532) and independent set (n=202). PDZK1 could discriminate recurrence, metastasis and prognosis between ccRCC patients. Low expressions of PDZK1 in both mRNA and protein were associated with reduced overall survival (OS) and disease–free survival (DFS) in two independent sets. In univariate and multivariate analyses, PDZK1 was defined as an independent prognostic factor for OS and DFS as well. These findings indicated that low level of PDZK1 could predict poor clinical outcome in patients with ccRCC.

Biography:

Dominika Maciejewska is currently a PhD Scholar at the Pomeranian Medical University, Poland. Her field of interest is the molecular mechanism of NAFLD development. Her PhD topic is “Changes in the fatty acid profile of NAFLD patients before and after 6 month dietary intervention", which focuses mainly on seeking lipid marker in NAFLD progression.

Abstract:

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions related to fat infiltration in this organ. The disease affects 20-30% of adults in developed countries and become important clinical entity. NAFLD, similarly to metabolic syndrome is associated with: Dyslipidemia, cardiovascular disease, obesity, type II diabetes and insulin resistance. There is a great need to find a noninvasive method which will be helpful in NAFLD evaluation. The study compared biochemical parameters and eicosanoid profile between first and second stage of hepatic steatosis and the effect of 6 months dietary intervention on various parameters. A group of 24 patients diagnosed with stage I and II of NAFLD according to Hamaguchi score were enrolled. Eicosanoids profiles were extracted from the 0.5 ml of plasma by using solid-phase extraction RP-18 SPE columns (Agilent Technologies, UK). The HPLC separations were performed on an Agilent Technologies 1260 liquid chromatography. We analyzed the following eicosanoids: Profiles 5(S), 6(R)-Lipoxin A₄, 5(S),6(R), 15(R)-Lipoxin A₄, 5(S)-HETE, 5(S)-oxoETE, 12(S)-HETE, 15(S)-HETE, 16(R)/16(S)-HETE, 9(S)-HODE and 13(S)-HODE. Patients, with stage I of NAFLD showed significantly higher level of HDL cholesterol (p<0.05), lower level of 5-HETE (p<0.05) and 9-HODE (p<0.05). After a six-month dietary intervention, all patients reported complete reduction of hepatic steatosis, which resulted in a significant decrease of the concentrations of all eicosanoids and key of biochemical parameters (ALT, AST, GGTP, HDL, insulin HOMA-IR, p<0.05). At the early stages of fatty liver the biochemical parameters may not be significantly impaired. In this case, the diagnosis was based on the non-invasive method, such as ultrasound, became more difficult. 9-HODE can be produced during non-enzymatic oxidation of linoleic acid, or by 5-lipoxygenase (5-LOX) conversion. 5-HETE is converted from AA by 5-LOX. It seems that 5-LOX activity is higher in patients with II degree of NAFLD than in patient with I degree of the disease. Furthermore, eicosanoid profile changes appear faster than changes in biochemical parameters. Our result shows that eicosanoids profile can be useful in NAFLD evaluation.

Biography:

Kieu Oanh T Nguyen has research interests on small molecule measurements and metabolomics in plants. She is also interested to apply metabolomics approach in natural product drug discovery (dereplication, chemotaxonomy, metabolic engineering). Her expertise is in the development of screening pipelines for small molecule extraction, isolation and derivatization where necessary, chromatographic separation (liquid and gas chromatography) and detection including mass spectrometry.

Abstract:

Isatis tinctoria is a plant species belonging to the Brassicaceae family that is known as an ancient source of indigo dye and as a medicinal plant with high industrial potential. Although a large comprehensive metabolite profiling of the bio-active dried leaf extracts has been reported, metabolite profiling of Isatis fresh leaves focused up to today on glucosinolates and flavonoids. We profiled here the methanol extracts of I. tinctoria fresh leaf extracts in an untargeted way and aimed especially to detect as yet unidentified compounds. Therefore, an algorithm was adopted in which liquid chromatography-mass spectrometry profiles are searched for pairs of peaks that have mass and retention time differences corresponding with those of substrates and products from well-known biochemical conversions. We then concatenated these peak pairs into a network where the nodes represent metabolites and edges represent biochemical conversions. Starting from known network nodes, following the edges of the network allowed the characterization of adjacent network nodes, leading to their structure. This high-throughput cheminformatics procedure allowed the characterization of the structures of a wide spectrum of hydroxycinnamic acid esters. Besides the sinapate esters of malate, glucose and gentiobiose, which are typical for brassicaceous plants, these conjugates comprised a large variety of glucaric acid esters which have not been reported in plants before. This untargeted approach suggests the existence of an as yet unknown acyltransferase activity in Isatis tinctoria rosette leaves.

Biography:

Abubaker M A Morgan has his expertise in extraction and isolation of secondary metabolites from plants and microbes using normal column chromatography, MPLC, preparative TLC, semiprep-HPLC, etc. and structure elucidation of isolated compounds using 1D and 2D NMR techniques as well as other spectral methods such as UV, FT-IR and X-ray crystallography. During his PhD degree, he has worked on three plant species from Sudanese native medicinal plants.

Abstract:

The genus Boscia (Capparaceae) contains more than 37 species distributed mainly in Africa, excluding one species found in southern Arabia. Boscia senegalensis (Pers.) Lam. ex. Poir. is an evergreen shrub reaching 7 meters in height. It is native to the Sahel and Sahara savannas stretching from Mauritania, Senegal, Mali, Niger and Nigeria to Cameroon and across Africa to Egypt, Sudan, Ethiopia, Somalia and Kenya. The importance of B. senegalensis for the rural agro-economy in Africa has been discussed in several reports, making it a plant of high value for both humans and animals. Previous phytochemical reports on B. senegalensis, which were conducted on the leaves and fruits, identified glucosinolate. Detailed chemical investigation of Boscia senegalensis (Per) Lam. ex Poir led to the isolation of one new flavonol glycoside, rhamnocitrin-3-O-β-D-(6''-O-E-feruloyl)-glucopyranoside named bosenegaloside A (1), with seven known compounds, rhamnocitrin- 3-O- β-D- (6''-O-E-p-coumaroyl)- glucopyranoside (2), rhamnocitrin- 3-O-β-D-glucopyranoside (3), 3,4,5-trimethoxyphenol-β-D-glucopyrinoside (4), lasianthionoside A (5), 3,7-dimethyl-1-octene-3,6,7-triol-6-O-β-D-glucopyranoside (6), syringin (7), and austroside B (8). The chemical structures of these compounds were elucidated from spectroscopic data (ESI-MS, HR-ESI-MS, 1D, 2D-NMR, UV and FT-IR) and by compared these data with previously published results. The inhibitory activity of the isolated compounds on soluble epoxide hydrolase (sEH) was assessed. Compounds 1-3 potently inhibited sEH activity with IC50 values of 12.8±0.5, 18.4±0.2 and 11.3±0.9 µM, respectively.

Biography:

Jian-Yong Li is a Leader of Research and Development program at Agricultural Science and Technology Innovative Program of CAAS. He has obtained his BSc degree in Pharmacy (1995) from Lanzhou University, MS degree in Clinic Veterinary Sciences (2000) from the Graduate School of CAAS and his PhD degree in Analytical Chemistry (2005) from the Graduate School of CAS. He was awarded the Research Medal of the nation government in 2009 and 2011 for his work on new animal drugs. Currently, his research is on research and development of novel animal drug, including chemistry, phamacokinetics, pharmacology and toxicology of pharmaceuticals.

Abstract:

The main objective of this study was to investigate the ameliorative effects of AEE in hyperlipidemic rat. After five-week oral administration of aspirin eugenol ester (AEE) in high fat diet (HFD)-induced hyperlipidemic rats, the impact of AEE on plasma and urine metabonomics was investigated to explore the underlying mechanism by UPLC-Q-TOF/MS analysis. Blood lipid levels and histopathological changes of liver, stomach and duodenum were also evaluated after AEE treatment. Without obvious gastrointestinal (GI) side effects, AEE significantly relieved fatty degeneration of liver and reduced triglyceride (TG), low density lipoprotein (LDL) and total cholesterol (TCH) (P<0.01). Clear separations of metabolic profiles were observed among control, model and AEE groups by using principal component analysis (PCA) and orthogonal partial least-squares-discriminate analysis (OPLS-DA). 16 endogenous metabolites in plasma and 18 endogenous metabolites in urine involved in glycerophospholipid metabolism, fatty acid metabolism, fatty acid betaoxidation, amino acid metabolism, TCA cycle, sphingolipid metabolism, gut microflora and pyrimidine metabolism were considered as potential biomarkers of hyperlipidemia and be regulated by AEE administration. It might be concluded that AEE was a promising candidate for hyperlipidemia treatment. These findings could contribute to the understanding of action mechanisms of AEE and provide evidence for further studies.

Biography:

Shi Shu did her PhD in the year 1986, and she is specialized in animal nutrition and metabolic diseases. Her research areas are proteomics, metabolomics, bioinformatics, molecular biology and so on.

Abstract:

The essential factor is follicular growth of dairy cows postpartum to ensure the reproductivity. If the initiation of follicular growth is suffocated, which is called inactive ovary, the reproductivity of dairy cows is hugely influenced. Glycometabolism is one of the main factors to effect on follicular development. There were few reports about metabolism profile of inactive ovary of dairy cows, but the effect of glycometabolism disorder on follicular growth is not clear. In this study, we explored this problem based on GC/MS between dairy cows with healthy and inactive ovary. Plasma samples from twenty-two dairy cows and 20 dairy cows with inactive ovary were selected at 60–90 days postpartum to screen for metabolic compounds using a gas chromatography/mass spectrometry (GC/MS) technique. The data were analyzed with multivariate statistical analysis (MSA) and pathway analysis. One hundred and nine compounds were screened and identified by GC/MS, and 16 compounds with decreased levels in the inactive ovary group were detected via analysis of variables important in projection values and the p values from MSA. Seven compounds are related with glycometabolism including Ribitol, Oxalate, Trehalose, D-Tagatose, methyl-beta-D-galactopyranoside, Hydroxylamine, 5-Aminoimidazole-4 -carboxamide ribotide. Meanwhile, 7 pathways involved the glycometabolism, such as pentose and glucuronate interconversions, glyoxylate and dicarboxylate metabolism, starch and sucrose metabolism, galactose metabolism, ABC transporters, nitrogen metabolism, biosynthesis of alkaloids derived from histidine and purine. In summary, it was speculated that glycometabolism disorder effect on the follicular growth induced the inactive ovary in dairy cows postpartum. 

Biography:

Jaleel K Ahmed has expertise in evaluation in iron and steel industry. He has registered 3 patents in USA, UK and Iraq, about using water in iron industry and wax for storage and transportation of DRI and using wax for carburizing of steel. He has also used chlorophyll as gamma ray absorber to protect Iraqi children from cancer and used red beet juice as scavenger for poisonous heavy metal ions and anticancer and detoxification of urea and uric acid from human body via urine system.

Abstract:

Oil rich countries are now using natural gas as a source for reducing gas production (H₂=75% and CO=14%) to produce Direct Reduced Iron (DRI) from iron oxide ore. In this research, a new source created which is pure hydrogen<99% obtained from electrolysis of water. The size of hydrogen atom is much smaller than that of carbon monoxide molecule, thus hydrogen could penetrate much deeper into the crystal structure of the iron oxide resulting in greater degree of metallization for the same time of reduction. After reduction, hydrogen returns to water, thus no material is consumed with hydrogen (closed circuit process). Since huge quantity of hydrogen is needed to reduce the iron oxide (e.g., to produce one million ton/year DRI), so prolonged electrolysis of alkaline aqueous solution is required; this will be accompanied by large quantity of oxygen gas liberated at the anode electrode (430000 tons/year) which is useful for industry and health purposes, as well as production of about 108 tons/year heavy water residue uses in nuclear industry. The world production of DRI is 75 million tons/year and continuously increases. In the present, DRI is comparatively new cargo that has already presented problems when shipped in bulk with its sponge-like structure is chemically reactive and easily oxidized with liberation of heat and hydrogen. The author has developed an efficient process for the treatment of DRI known as waxing process makes the DRI resistant to oxidation, corrosion, ignition and stop iron dust formation.

Biography:

Abstract:

Among historical nature remedies in Eastern Asia, Huaier (Trametes robiniophila Murr.) has long been reported for its significant efficacy on longevity and health maintenance, and more importantly, on cancer. The target cancers of Huaier overlap with those strongly influenced by the Hippo pathway, which is also well known as a tumor suppressor mechanism. Here we show a role of Hippo pathway as a main controlling mechanism of Huaier effect. The present study demonstrated that anti-cancer effect was a result of recovery of transcriptional dysregulation in Hippo pathway. We used Drosophila flies genetically disrupted transcriptional control in Hippo pathway with overexpressing non-phosphorylatable Yorkie (Yki:V5S168A) as an experimental model. The administration of Huaier clearly resulted in the recovery of rough eye formation caused by overabundant transcriptional signals in the mutants, indicating the modulation and the reconstruction of tumor suppressor mechanism. These improvements occurred in a dose-dependent manner, just as shown in clinical observations. The GC/MS-based metabolome analysis changed the metabolic profile to the early embryonic pattern. Judging from a broad spectrum of its efficacy, Huaier can provide a solution to a broad range of transcriptional dysregulation diseases, not only in cancer, but also many degenerative diseases via modulation of Hippo pathway control.