Day 2 :
Keynote Forum
Irina Kurnikova
RUDN-University, Russia
Keynote: Heart rate variability at the stages of carbohydrate metabolism disturbance and the phenomenon of early aging of regulatory system in diabetes type-2
Time : 10:00-10:35
Biography:
Irina Kurnikova - MD, PhD, Professor of Medicine, RUDN University, Moscow, Russia She has become Doctor of Medical Sciences (PhD) in 2010, the first academic degree (MD) received at the age of 28 years. Dealing with Problems of Endocrinology for over 20 years. She had led a course of Endocrinology at the Medical Academy (Izhevsk, Russia), was the Head of Endocrinology department at the Russian Scientific Center of Medical Rehabilitation and Health Resort (Moscow, Russia). Currently she teaches at Peoples' Friendship University of Russia, curator of the Scientific Direction Endocrinology. She has published more than 30 articles in well-known journals, the author of 25 books and tutorials in Russian language. Author of 10 patents for inventions.
Abstract:
Statement of the Problem: Study of heart rate variability indices allows not only to identify already existing disorders with the system of regulation and adaptation, but also to predict the risk of developing diseases by measuring the overall stress of regulatory mechanisms, neurohumoral regulation of the heart and the relationship between sympathetic and parasympathetic parts of the autonomic nervous system.
Purpose: Is to assess the impact of diabetes mellitus on mechanisms of autonomic regulatory at the different stages of carbohydrate metabolism disturbance.
Methodology & Theoretical Orientation: At the first stage of this study, patients were divided into several groups. The group of patients without metabolic disorders as the primary cause of the disease - group 1 (n=27); patients with abdominal obesity, hypertension, dyslipidemia - metabolic syndrome - group 2 (n=33); group with symptomatic of DT 2 - group 3b (n=62) at the stage of clinically expressed disorders. Group 3a (n=39) - patients with DT 2 and HTN with normal body weight (endogenous insulin at the lower limit of the norm or below). At the second stage patients with DT 2 (101 people) were divided in four age group: 20-30 years, 31-40 years, 41-50 years,51-60 years of age. All patients were evaluated autonomic regulation by the method of spectral analysis of daily variability of the heart rhythm power spectrum of oscillation in three frequency bands: 0,004-0,08 Hz (very low frequency – VLF), 0,09-0,16 Hz (low frequency – LF), 0,17-0,5 Hz (high frequency – HF). The selection of three frequency ranges is due to differences in their formation. The low frequency range reflects the activity of the sympathetic system on the segmental level, the high-frequency range, the activity of parasympathetic nervous system at the segmental level.
Findings: Simultaneous progressive increase in the power spectra of low-frequency and high-frequency waves at the stages of the progression of metabolic disturbances indicates the transition of the mechanisms of vegetative regulation to a higher energy-consuming level, and the decrease in VLF is about the centralization of regulation and depletion of body resources. Evaluation of spectral analysis revealed a significant increase in the power of ULF% waves in patients with type 2 diabetes, which indicates disruption in adaptation and violation of autonomic regulation of heart rhythm. The revealed significant difference in the analysis of the centralization index in groups with metabolic syndrome and type 2 diabetes with obesity and hypertension emphasizes the importance of the stages of carbohydrate metabolism disorders. Changing the IC towards the increase at the stages of the progression of the violations of the carbohydrate metabolism testifies to the activation of the central contour of regulation and the gradual transition of systemic vegetative regulation from the control level to the management level. Patients with diabetes at the age of 30-40 years we have seen a decrease in parasympathetic activity, which is more typical for patients the next decade of life. Since the age of 41, there was considerable centralization on mechanism of regulation (increase VLF), which usually starts 10-15 years later. The decrease in the total power spectrum on the background of inadequate compensator of diabetes showed decrease of reserve opportunities of the organism.
Keynote Forum
Sarah H Elsea
Baylor College of Medicine, USA
Keynote: A multi-omics precision medicine approach to diagnosis of inborn errors of metabolism
Time : 11:00-11:35
Biography:
Sarah H Elsea is a Professor of Molecular and Human Genetics at Baylor College of Medicine and the Senior Director of Biochemical Genetics at Baylor Genetics. She has received her BS in Chemistry with a minor in Biology from Missouri State University and a PhD in Biochemistry from Vanderbilt University. She has completed her Postdoctoral Fellowships in Molecular and Biochemical Genetics at the Baylor College of Medicine and is a Board-Certified Geneticist through the American Board of Medical Genetics and Genomics. She held Faculty appointments at Michigan State University and the Medical College of Virginia at Virginia Commonwealth University prior to returning to Baylor College of Medicine. Her research is focused on the discovery, pathomechanisms, diagnosis, and treatment of rare disease, particularly neurodevelopmental and neurometabolic disorders. She is a Member of several professional societies and has authored more than 90 scientific and lay articles.
Abstract:
Metabolomics is the study of the distinctive chemical fingerprint produced by specific cellular processes. Untargeted mass spectrometry-based metabolomic profiling for small molecules in body fluids is an emerging technique used to produce and analyze this chemical fingerprint. This technology holds the promise of providing new insights into human disease states and serving as a primary diagnostic tool for novel and previously characterized inborn errors of metabolism (IEM), as well as for the identification of biomarkers of disease and treatment. Clinical metabolomic profiling allows for parallel screening of hundreds of metabolites in a single biological specimen. On average, ~900 small molecules are detected in a given plasma sample with a core group of ~350 analytes found in all specimens tested to date. The analytes detected encompass numerous classes of small molecule biomarkers including acylcarnitine’s, amino acids, bile acids, carbohydrates, lipids, and nucleotides. In addition, metabolomic data in many cases affords a much richer view of a patient's metabolic disturbance by identifying: (1) elevated metabolites located far upstream of the genetic defect, (2) treatment related compounds, including commonly tested therapeutic drug monitoring analytes, and (3) spectrally unique analytes that are not yet associated with a biochemical phenotype. In our clinical experience, the integration of whole exome sequencing data with the metabolomics profile has improved the interpretation of genetic variants, including ruling out the diagnosis of IEMs, as well as supporting a specific diagnosis, and for the identification of new disease and/or treatment biomarkers. For undifferentiated clinical phenotypes such as intellectual disability, hypotonia, autism, or seizures, many different tests involving different sample types are often needed for diagnosis. This can lead to prohibitive costs and ongoing diagnostic odysseys. Data will be presented on genomic and metabolomic profiling of previously non-diagnostic cases which pointed to genetic disorders such as aromatic amino acid decarboxylase deficiency, GABA transaminase deficiency, adenylosuccinate lyase deficiency, and peroxisome biogenesisdisorders, illustrating the powerful synergy of genomic and metabolomic analysis in determining the pathogenicity of variants of uncertain significance. Ultimately, a clinical systems biology approach to the integration clinical data with genomic, transcriptomic, epigenomic, proteomic, and metabolomics data will provide a comprehensive precision medicine approach to improve understanding of natural biological variation and to improve diagnosis and management of disease.
Keynote Forum
Hui Feng
Boston University School of Medicine, USA
Keynote: Differential dependence of the TCA cycle in triple-negative breast cancer cells
Time : 11:35-12:10
Biography:
Hui Feng has her expertise in Zebrafish Genetics and Cancer Therapeutics. Her application of innovative Zebrafish model system led to uncovery of novel metabolic pathways important for survival and proliferation of MYC-dependent leukemic cells. She has expanded her studies of this metabolic pathway into multiple MYC-driven cancers, including triple-negative breast cancer.
Abstract:
Statement: Despite the demonstrated role of glutamine in the growth and survival of Triple-Negative Breast Cancer (TNBC) cells, how glutamine is utilized in TNBC cells remains unclear. The tricarboxylic acid (TCA) cycle is a central route for oxidative phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and redox balance requirements. Our research aims to understand whether TNBC cells metabolize glutamine via the TCA cycle (i.e., glutamine anaplerosis). The key cycle intermediate α-ketoglutarate (α-KG) serves as the entry point for glutamine anaplerosis. α-KG can then be converted to succinyl-CoA by the α-KG dehydrogenase complex (KGDHC) through oxidative phosphorylation, or to isocitrate by isocitrate dehydrogenase (IDH2) through reductive carboxylation pathways.
Findings: Here, we show that glutamine anaplerosis is critical for survival and growth of human TNBC cells. However, the dependence of human TNBC cells on KGDHC and IDH2 varies. In our presentation, we will discuss the potential mechanisms underlying the differential dependence of glutamine anaplerosis in human TNBC cells.
Conclusion & Significance: Overall, our studies provide compelling evidence to support metabolic dependence of TNBC cells on the TCA cycle, and also reveal the various pathways they may utilize in the TCA cycle.
- Therapeutic Metabolomics | Metabolomics in Precision Medicine | Cellular and Molecular Endocrinology
Session Introduction
Maria E Peña
Icahn School of Medicine, USA
Title: Diabetes and nutritional screening in post-bariatric patients
Biography:
Maria E Peña is an Assistant Professor at the Icahn School of Medicine and Director of Endocrine Services at Mount Sinai Doctors Forest Hills. She is board certified in Internal Medicine, Endocrinology, and Obesity Medicine. She proceeded to finish the last two years of her clinical training at their affiliate school, New York Medical College, where she obtained her MD degree in 2008. Dr. Peña completed her residency and fellowship training at North Shore University Hospital/LIJ. Dr. Peña is a member of numerous Medical Societies including: The Endocrine Society, the American Association of Clinical Endocrinologists, the American Diabetes Association and the Obesity Society. She also served as a member of the American Board of Obesity Medicine exam questions writing committee. She has given presentations at medical grand rounds, published in medical journals, including a chapter in Current Diabetes Reviews and has presented her work at National Conferences. Furthermore, Dr. Peña is actively involved in coordinating medical missions in Latin America, volunteering in mentoring programs for minority students interested in health care and health education in the community.
Abstract:
With the rise of obesity there has been a concomitant increase in the incidence of type 2 diabetes (T2DM). As a result, the term “diabesity” has become a popular disease entity in the past several years. When lifestyle modification and pharmacotherapy fail to achieve successful weight loss and diabetes control, bariatric surgery is a recommended treatment option. Bariatric surgery has been shown to promote sustained T2DM remission in 30–63% of patients and improve other components of metabolic syndrome; thus a preferred term has been “metabolic surgery”. As the practice of bariatric surgery for the treatment of T2DM increases, so will the number of patients with T2DM not achieving remission or with T2DM recurrence. There are currently no clear evidence-based guidelines delineating the proper management of T2DM in post-bariatric surgery patients. The focus of this review is to discuss current data on the efficacy of bariatric surgery in promoting T2DM remission, factors that predict T2DM remission and recurrence, and current treatment options for persistent hyperglycemia in postbariatric surgery patients. To increase long-term T2DM remission and prevent or delay recurrence, post-bariatric surgery patients need close follow up to encourage adherence to healthy nutrition and lifestyle practices that will lead to sustained weight loss. In addition to this, patients need adequate nutritional supplementation and periodic screening for vitamin, mineral and protein deficiencies. Therefore, we will conclude with a brief review of current recommendations for nutritional deficiency screening and supplementation.
Keti Zeka
The University of Cambridge, UK
Title: Use of natural products in prevention and management of type 2 diabetes
Biography:
Keti Zeka has completed her MSc from The University of L’Aquila, Italy in Medical Biotechnology and finished her PhD degree in Chemical Engineering and Biotechnology Innovation in 2015. She has been serving as a Lecturer and Tutor at the School of Medicine in L’Aquila and at the Faculty of Pharmacy in Leicester (UK). She is now a Postdoc at the University of Cambridge (UK) with an AIRC Fellowship. Her areas of expertise include the Chemistry of Medicinal Natural Products and their role in diseases prevention. Her current research interests cover the performance of diet and natural products in the revention of degenerative diseases, focusing in optimization of metabolomics and proteomics tools in cancer and development of novel druggable agents.
Abstract:
Metabolic syndrome is an umbrella term for a group of disorders related to imbalance of energy utilization and storage. It includes obesity, hypertension, increased triglyceride levels, aberrant cholesterol levels, insulin resistance with the resulting elevated fasting blood glucose levels. Metabolic syndrome is associated with chronic low-grade local tissue inflammation and increased susceptibility to a variety of degenerative diseases. Lifestyle changes, e.g. more physical exercise, a diet rich in fruit and vegetables, can help prevent or delay metabolic syndrome related problems. In addition, certain food supplements or herbal extracts are commonly believed to make an important contribution to a healthy life style. Whereas, there is a consensus that a vegetable-rich diet contributes to a lower occurrence of metabolic syndrome related disorders, the exact nature of the compounds in the diet that contribute to prevention of degenerative diseases is still a matter of debate. Our work sets out to evaluate several models that are currently considered to play a role in the prevention or management of type 2 diabetes. Phytochemicals with antioxidant activity were long believed to be a major contributing factor in the suppression of chronic inflammation. However, all antioxidant compounds do not always have anti-inflammatory properties. Further, the peroxisome proliferator-activated receptor gamma (PPARγ)-activating potential of a wide range of natural products has been explored in great detail and resulted in a credible model. A third model considers the potential role of phytoestrogens on human physiology. These compounds are known to interact with oestrogen receptors and can modulate a range of cell signaling pathways, either as agonists or as antagonists. The efficacy of several of the identified pharmaceutically active compounds and plant extracts, either as supplements or as dietary factors as part of a healthy life style, may be underpinned by laboratory results. However, caution is justified when considering food supplements in doses that greatly exceed the amounts that would be obtained through a regular diet.
Kashif Rizvi
New Mowasat Hospital Diabetes & Medical Centre, Kuwait
Title: Diabetes current perspectives and lessons learnt from the epicenter, the Persian Gulf
Biography:
Kashif Rizvi is a Consultant Endocrinologist at Mazaya Clover Centre, Jabriya, Kuwai, Director of New Mowasat Hospital Diabetes & Medical Centre, Kuwait and Former Head of Department of Endocrinology and Diabetes - Kettering, UK. He earned Certificate of Completion of Specialist Training UK and served as Accredited Physician, Endocrinologist & Diabetologist and Teaching Faculty at University of Leicester/Wales, UK. He is the Editor of Journal of Endocrinology & Human metabolism, California USA. He is a Member of Royal College of Physicians (London - UK), British Diabetes Association, British Endocrine Society and Association of British Clinical Diabetologists, author of several peer reviewed research papers and Tutor of Royal College of Physicians.
Abstract:
Given the upsurge in type 2 diabetes of epidemic proportions especially within the Persian Gulf region, it is of utmost importance to realize that no health care system in the world could deal with it just through therapeutic interventions or management of its complications. Given its myriad affects type 2 diabetes has the potential to pass the threshold of sustainable spending in the health care sector of even the wealthiest economies of the world. This talk aims to run through lifestyle habits of a sedentary obesogenic society as the root cause of the epidemic and addresses the current dearth of knowledge
amongst health care providers and their ‘glucocentric’ approach which often results in missed diagnosis of warning signs of this syndrome or suboptimal care once diagnosed. In the industrial and automation age there has been a paradigm shift in the metabolic syndrome’s prevalence and unless a holistic, multifaceted and multifactorial approach is adopted we run the risk of not only cutting short the productive years of life but also add to the enormous burden of morbidity and mortality spanning virtually all age groups . Kuwait features amongst the top countries of the world in this regard and has a unique cohort where an indigenous population compares expats in the disease prevalence indicating a strong environmental factor. This talk runs through type 2 diabetes in a holistic manner covering all aspects of it within Kuwaiti society and sets guidelines for the rest of the affluent world.
Saeed Akhter
Pak Diabetes Center, Pakistan
Title: Beat the diabetes with novel and future therapies for T1DM
Biography:
Completed MBBS from Pakistan at the age of 26 years. And MSc applied Envi. Sci. from University of Punjab, Pakistan and MSc Diabetes Care and Management from the Glasgow Caledonian University, Scotland United Kingdom. Presently working as Director PAK DIABETES CENTER in Pakistan
Abstract:
Type 1 diabetes (T1D) still remains a big mystery disease of the 21st century. It has posed a big challenge for all the stakeholders in its management. As the incidence and prevalence of diabetes is increasing worldwide so the complications and cost related to diabetes are increasing. Researchers are still unable to completely understand the aetiopathological nature of this disease. Treatment of T1D was revolutionized after the discovery of Insulin. Exogenous insulin replacement therapy is being used effectively since then, but it does not provide a cure. There are many other treatment options, which are being investigated extensively all over the world in an effort to find a cure. Limitations of insulin therapy have led to search for strategies targeting beta cell replacement therapies. Plasticity towards beta cells has been revealed in clinical trials. Stem cells (SC) are colonogenic cells and have been found capable of both self-renewal and multilineage differentiation. SCs are unspecialized cell but has a potential to differentiate into specialized cells. In SC engineering, exploring the potential of embryonic and adult stem cells or induced pluripotent stem cells to differentiate into insulin producing beta cells, if given the specific growth factors, signaling molecules and transcription factors has demonstrated encouraging results in rodent models. Reprogramming or genetic modification of other cell types such as gut and liver cells in the production of insulin producing beta cells are one of the possibility which could be utilized in human beings after the encouraging results obtained in rodent models These properties now offer a great scope and potential for their clinical use and are being explored further. Vaccine for T1D based on the rationale that reestablishment of immune tolerance to diabetes specific self-antigens has been seen as a step forward in finding the cure. Artificial pancreas which will work just like a normal functioning pancreas by using automatic techniques is another option and is seen as a mechanical cure by many researchers is being tested in many research centers and is in its final stages of developments. Studies on diabetic animals have proved useful and have helped to understand the molecular and pathophysiological events leading to the underlying causes of the T1D, with an emphasis on the current, novel and future techniques and their potential for clinical use in future.
Biography:
Zelalem Kiros Bitsue has completed his PhD in Immunology, MBBS Degree in Medicine and Surgery, a Bachelor’s degree in Nursing and Health Administration, a Bachelor’s degree in Theology and Leadership and a Diploma in advanced research proposal writing, research report writing, methods and grant proposal writing. He is an Assistant Professor at the Addis Ababa Institute of Technology. He is the Owner, Founder and General Director of the African Health Organization “USAHO”. He has made 120+ publications, is corresponding/first author of 112+ Publications as well as over 44,000 citations.
Abstract:
Hypothesis: Estrogen and leptin independently regulate neuroendocrine, leukocytes, and mitochondrial, along with cytokine function. I hypothesis that depending on the concentration of estrogen and leptin has synergetic effect in regulating hormonal signaling, and transcription factors and maintaining metabolic disorders.
Objective: The objective of this study was to determine the effective potential of estrogen in combination with leptin in T4, NADPH dependent cytochrome P450 monooxygenase (mixed function oxidases, MFO), glutathione-S-transferase, epoxide hydrolase, APCs (gilial, DC, Mθ), CD4 T cell subsets (Th1, Th17, Treg), CD8+ Sub sets (CD25+ (for Treg cells) response in animal models of lipoprotein disorders.
Methods: After encephalomyocarditis virus induction was done using 40 C57BL/6 mice; for experimental animal models of lipoprotein disorders in the presence of estrogen in combination with leptin on the 10 weeks old female mice, we analyzed the culture supernatant or serum levels to determining the level of NADPH dependent cytochrome P450 monooxygenase (mixed function oxidases, MFO), glutathione-S-transferase, epoxide hydrolase, IFN-γ, IL-6, IL-1β, IL-10, IL-17 and TGFβ. ELISA method is performed according to the manufacturer's instructions. Tbet, RORÒ¯t, FOXP3, IFN γ, IL-17, IL-10, IL-1β, TGFβ, TNFα, IL-12, IL-6 and HPRT1, gene expressions analysis was done using Real time PCR method and perform according to the protocol of the manufacturer ERα and ERβ, Ca++ influx, ATP, cytochromeoxidase subunits I, II, III, techniques such as immunohistochemistry, immunocytochemistry, and immunoblots using a wide range of antibodies
Result/Conclusions: Estrogen in combination with leptin exerts a dual effect (inhibition versus enhancement) in regulation and prevention of lipoprotein disorders; moreover, maintaining tolerance and balance modifying in B cells, APCs, CD4+T cell subsets (Th1, Th17 and Treg), and CD8+ Sub sets. Which are implicated in the immune-pathogenesis, molecular mechanism, and cytokine pathways, suggest that Estrogen in combination with leptin both prevention and therapeutically relevant in lipoprotein disorders and autoimmunity. However, while exciting discoveries have been made, further work is required to understand the diverse effect of Estrogen in combination with leptin in in regulation and prevention of lipoprotein disorders; moreover, maintaining tolerance and balance modifying in B cells, APCs, CD4+T cell subsets (Th1, Th17 and Treg), and CD8+ Sub sets.
Kenneth K Wu
China Medical University, Taiwan
Title: Cell-specific 5-hydroxytryptophan (5-HTP) metabolism and its relevance to cell function
Biography:
Kenneth K Wu is Professor Emeritus at University of Texas Health Science Center in Houston, Distinguished Investigator and President emeritus at National Health Research Institutes (NHRI) in Taiwan. He is currently a Distinguished Professor and the Director in the Metabolomics Medicine Research Center at China Medical University (CMU) in Taichung, Taiwan. He also holds Hou Jindui Chair at National Tsing-Hua University in Hsin-Chu, Taiwan and Distinguished Chair Professorship at National Taiwan University in Taipei, Taiwan. His research experiences and expertise are in the areas of hematology, vascular biology and prostaglandin cellular and molecular biology.
Abstract:
5-HTP is derived from L-tryptophan via the catalysis by tryptophan hydroxylase (TPH). It is a common precursor of several bioactive molecules including serotonin (5-hydroxytryptamine), melatonin (N-acetyl- 5-methoxytryptamine) and cytoguardin (5-methoxytryptophan). Enzymes catalyzing serotonin and melatonin synthesis are well characterized. In serotonergic neurons, 5-HTP is converted to serotonin by aromatic amino acid decarboxylase (AADC) while its conversion to melatonin in pineal cells is catalyzed sequentially by AADC, alkylamine N-acetyltransferase (AANAT) and N-acetylserotonin methyltransferase (ASMT also known as hydroxyindole O-methyltransferase or HIOMT). 5-HTP catabolism in non-neuron, non-pineal cells are less clear. We have shown that human fibroblasts and endothelial cells (EC) possess enzymatic machinery to convert 5-HTP to 5-methoxytryptophan (5-MTP). Neither cell type expresses AADC and hence is unable to synthesize serotonin or melatonin. 5-MTP suppresses pro-inflammatory mediator-induced COX-2 and cytokine expressions and plays a
fundamental role in defending against inflammatory tissue damage and tumorigenesis. Thus, there is cell-specific utilization of 5-HTP to generate distinct bioactive metabolites to carry out anti-inflammatory, neurotransmission and circadian rhythm regulatory functions. Our preliminary results show that A549 cancer cells express AADC to convert 5-HTP to serotonin. Metabolomic analysis detected miniscule quantities of 5-MTP or melatonin which is correlated with low level of HIOMT. Stable transfection of HIOMT reprogrammed 5-HTP catabolism resulting in a switch from serotonin to 5-MTP synthesis. HIOMT overexpressed A549 cells had slow growth and low metastasis when compared to vector controls. In contrast with production of CNS bioactive metabolites, i.e. serotonin and melatonin by neurons and pineal cells, peripheral cells such as fibroblasts, EC and epithelial cells convert 5-HTP to 5-MTP to defend against inflammation. Cancer cells have an aberrant transcription program which can be corrected by HIOMT gene transfer.
Biography:
Zelalem Kiros Bitsue has completed his PhD in Immunology, MBBS Degree in Medicine and Surgery, a Bachelor’s degree in Nursing and Health Administration, a Bachelor’s degree in Theology and Leadership and a Diploma in advanced research proposal writing, research report writing, methods and grant proposal writing. He is an Assistant Professor at the Addis Ababa Institute of Technology. He is the Owner, Founder and General Director of the African Health Organization “USAHO”. He has made 120+ publications, is corresponding/first author of 112+ Publications as well as over 44,000 citations.
Abstract:
Background: Modern biomedical, space science research and health care are provided by multidisciplinary teams in which biomedical engineers contribute to the advancement of knowledge equally as medical professions. Biomedical engineering represents one of the most rapidly growing branches of industry in the developed world.
Objective: The objective of this study was to develop software, hardware, and bioelectronics devices (machine) and identify and determine the effective potential in biomedical and space science researches.
Methods: The software development methods to be use formal, informal, approaches, and various forms of prototyping methods, are of interest in this work.
Result & Discussion: Having a cross-disciplinary approach, the project will have the potential to discover whole new softwares, hard wares, and bioelectronics devices openings in the area of the biomedical and space science research. This research project enhances the prospects of the economy as a whole as it improves the capabilities and competitive advantage of the soft wares, hard wares, and bioelectronics devices development at university.