Day 2 :
Keynote Forum
Anil K Saxena
CSIR-Central Drug Research Institute, India
Keynote: Design and synthesis of novel mycobacterial ATP synthase inhibitors against both replicating and non-replicating M. tuberculosis
Time : 09:50-10:30
Biography:
A K Saxena, is actively involved in the domain of Medicinal Chemistry & CADD, drug discovery and development research. He has 45 years of research experience with 200 research publications, 19 reviews/articles in books and/monographs, 72 patents and has delivered >180 invited lectures, chaired >45 sessions. He is Fellow of Royal Society of Chemistry, UK, Editorial Board Member of different prominent journals like, Medicinal Chemistry Research, SAR and QSAR in Environmental Research, online International journal ARKIVOC, and Patent Evaluator: Current Drugs, UK. He is also series Editor for book series “Topics in Medicinal Chemistry†published by Springer Verlag.
Abstract:
In recent years tuberculosis (TB) chemotherapy is dependent on drugs targeting bacterial metabolism with bactericidal action having no effect on dormant or latent or metabolically inactive bacilli that target cell division. The ATP synthase is a ubiquitous enzyme in energy metabolism due to its involvement in the generation of sufficient amount of ATP and/or in generating a proton motive force (PMF) in mycobacteria during adverse conditions of low oxygen environment and nutrient deficiency. This pivotal role of ATP synthase is targeted by the diarylquinoline TMC207 that kills Mycobacterium tuberculosis. Utilizing the state-of-the-art medicinal chemistry approach the quinoline class of aryl-sulfonamides has been identified as potent, orally bioavailable and selective mycobacterial ATP synthase inhibitors. Among a series of compounds synthesized which were effective in vitro on ATP synthase, the lead compound [N-(7-chloro-2-methylquinolin-4-yl)-N-(3-((diethylamino)methyl)-4-hydroxyphenyl)-2,3-dichlo-r obenzene sulfonamide] exhibited excellent selectivity (mycobacterium ATPase IC50 = 0.51 µM, mammalian ATPase IC50 >100 µM, and selectivity >200) and is also active in the hypoxic culture of non replicating M. tuberculosis at 100 µg/mL (32-fold of its MIC) as compared to positive control isoniazid [approximately 0.2 log10 reduction in CFU at 5 lg/mL (50-fold of its MIC)]. Docking of the best compound on homology modeled ATP synthase revealed the participation of the protonated tertiary amine and hydroxyl group to interact with the carboxylate oxygen of Glu61 that is similar to TMC207. The study provides a deep understanding about the structural requirements for ATP synthase inhibitors helpful in the discovery of novel chemical entities.
- Myeloid-specific deletion of SIRT1 impairs obesity and ageing-associated endothelial dysfunction
- Trends in Diabetes Complication
Session Introduction
Ping Gu
Nanjing General Hospital of Nanjing Military Command, Nanjing University, China
Title: Myeloid-specific deletion of SIRT1 impairs obesity and ageing-associated endothelial dysfunction
Biography:
Dr Ping Gu has completed her PhD from the Second Military Medicine University of China in 2007 and postdoctoral studies from the Hongkong University. She has published more than 20 papers in international journals and has been serving as associate chief physician in Jinling Hospital.
Abstract:
SIRT1 is a class III, NAD-dependent histone that plays a key role in curbing inflammatory responses in macrophages. However, whether SIRT1 controls macrophage polarization and its implication in vascular diseases is unclear. Aims. Here we aim to clarify whether SIRT1 deficiency biases macrophage polarization and contributed to endothelial dysfunction. Wild type (WT) and myeloid-specific SIRT1 knockout mice (MKO) were fed with standard chow or westernized diet for 12 weeks. Endothelium-dependent relaxation (EDR) in aortic rings was assessed by wire myograph. Macrophages were differentiated in vitro from bone marrow cells. Compared to WT mice, aortic EDR was significantly impaired in MKO mice under both obese and ageing conditions. In accompany, MKO mice were more susceptible to atherosclerosis in apoE-/- background. Macrophage were resistant to interleukin 4 (IL4)-induced polarization to M2 subtype. Moreover, endothelial cells co-cultured with MKO-derived macrophages exhibited higher inflammation and lower eNOS expression. SIRT1 plays a pivotal role in controlling macrophage polarization, which in turn causes impaired endothelial function.
Dipak Mall
National Academy of Medical Science, Nepal
Title: Role Of A Doctor In Management And Educating Patients With Diabetes Mellitus In Nepal
Time : 11:00-11:30
Biography:
I Dr. Dipak Mall have completed my MBBS Degree from Peoples friendship university of Russia in year 2004 and MD from Yangze University of China in year 2015.After my graduation I have been working in the department of endocrinology in one of the tertiary center in Kathmandu, Nepal. We as a team have been working to promote and encourage our patients to have early detection of diabetes mellitus and to prevent the complications.
Abstract:
After 10 years of Maoist insurgency in Nepal and political instability lots of people have moved from their home in village to big cities like Kathmandu. With this urbanization and change in life style Diabetes mellitus is one of the high burden disease in Nepal. With changing political situations and unstable government, ministry of health and population in Nepal is not being able to address and priorities diabetes on public health case agenda in Nepal through the promotion of preventive measures such as dietary pattern, exercise and periodic checkup. Several studies conducted in Nepal shows that the increasing trend of prevalence of diabetes mellitus with increasing age in Nepal is may be due to lack of public awareness regarding the problem and poor medical service in Nepal. As a Doctor in Nepal, we have loads of challenges to detect and prevent the complications of Diabetes mellitus who visit us for initial management. For most of the patients living in villages of Nepal to visit a diabetic specialty center in Nepal he or she has to travel for at least 24 hours on various modes of transport. In our center, which is the only tertiary and endocrine specialty hospital, every day we have few patients with severe complications like diabetic retinopathy, nephropathy and diabetic foot as an initial presentation. We doctors have a great responsibility to take care of our patients suffering from Diabetes mellitus and we must educate them to make our society healthy. At the same time we must encourage the government of Nepal to give more diabetic awareness program in Nepal.
Ensieh Shahvazian
Shahid Sadoughi University of Medical Sciences, Iran
Title: Resequencing of KLF14 gene in population based family study with type two diabetes
Time : 12:00-12:30
Biography:
Ensieh Shahvazian has completed her MSc at the age of 25 years from Shahid Sadoughi University of Medical Sciences, Iran. She has accomplished several organized and valuable projects on Diabetes and Diabetic retinopathy. She is also a Genetic R&D researcher at ROJETechnologies.
Abstract:
KLF14 belongs to Krȕppel-like transcription factor family. It has been reported as main transcription factor of adipose tissue, which regulates ten genes. KLF14 is an intronless gene with high CG content (around 74%), which is hot spot for mutations. Since 2010, many GWAs report SNPs near KLF14 gene as a susceptible loci related to T2D, it was reasonable to resequence this locus to find out important associated SNP with T2D. To accomplish this purpose, we selected 50 nuclear families with individuals older than 35 years, included probands, who were registered in Yazd Diabetes Research Center with at least one of their parents and their available siblings. DNA was isolated from peripheral blood. KLF14 gene was amplified by CG-Rich PCR in two overlapping parts. The gene parts were sequenced by Sanger method. Among 220 SNPs of the gene, Rs76603546 with OR=2.15, (CI: 1.08-4.30) and Pvalue= 0.02 was associated with type two diabetes. To our knowledge, it is the first time that the association of Rs76603546 SNP with T2D is reported. As Rs76603546 is located in CG Island at KLF14 gene, it is probable that it have significant influence on methylation of KLF14, which may effect on the expression of KLF14. That is the subjects of our ongoing studies, although the association of Rs76603546 should be confirmed in future studies with higher power, which is in progress.
Dipak Mall
National Academy of Medical Science, Nepal
Title: Financial burden and outreach of Diabetes clinics for patients in Nepal
Biography:
I Dr. Dipak Mall have completed my MBBS Degree from Peoples friendship university of Russia in year 2004 and MD from Yangze University of China in year 2015.After my graduation I have been working in the department of endocrinology in one of the tertiary center in Kathmandu, Nepal. We as a team have been working to promote and encourage our patients to have early detection of diabetes mellitus and to prevent the complications.
Abstract:
Financial burden and outreach of diabetes clinics for patients in Nepal: In the capital city of Nepal,there are only two hospital based endocrinology referal centers,which is run 6 days a week with loads of around 120 patients a day with 2-3 doctors handling the burden. Most of the patients visiting higher centers are from remote areas of Nepal who travel for around half a day or whole day o reach doctors clinics. As per trend from 2006 to 2014 the per capita income of Nepal is increased by $327 to $ 426.48 according to world bank.Now we can see how much is a burden for patients who need oral hypoglycemic agents and insulin therapy everyday to fight with diabetes. Only few studies are being studies carried out in Nepal which states that the cost of intial visit to doctor with laboratory investigations and treatment cost around Nepalese Rupee 3000 to 4500($20 and $35) which patiens have to bear on self, which dosent include personal and travel cost. Though the tertiary centers are located in centers of the capital,most of the patients visiting government hospitals are from remote and nearby villages,who visit tertiery centers not as a initial presentation but with complications.Which states that the financial burden to the patients are increased more with screening for Diabetes retinopathy,Nephropathy,peripheral vascular diease,diabetes foot examination and use of insulin therapy.
Niru Khatiwada
Kathmandu University, Nepal
Title: Treatment adherence among patients undergoing hemodialysis
Time : 14:10-14:40
Biography:
Niru Khatiwada has completed her Master of Nursing in 2015 from Maharajgunj Nursing Campus and this theses has been completed as a partial requirement of the degree and is currently working as a lecturer in Kathmandu University affiliated Nepal Medical College, Attarkhel, Jorpati, Kathmandu.
Abstract:
Treatment adherence with four domains: hemodialysis schedule, diet restriction, fluid restriction and medicine adherence, is a crucial factor that influences morbidity and mortality of hemodialysis patients. The aim of the study was to assess treatment adherence among patients undergoing hemodialysis and the associated factors in the year 2014. Methods: A total of 166 patients undergoing hemodialysis for at least 3 months in National Kidney Center, Kathmandu were interviewed. Patients with communication problems and those who were too sick for interview were excluded. Relationship between four domains and various factors were identified using inferential statistics. Results: The self-reported treatment adherence was found to be 73.5%, 32.5%, 39.8% and 78.9% in hemodialysis schedule, diet restriction, fluid restriction and medicine adherence respectively. Adherence to hemodialysis schedule was significantly associated with duration of hemodialysis (p=0.050), companion to reach the center (p=0.038), time to reach the center (p=0.020) and type of transportation (p=0.004). Fluid restriction had significant association with marital status (p=0.034), adequacy of treatment expenditure (p=0.015) and Interdialytic Weight Gain (IDWG) (p=0.012). Adherence to diet restriction had significant association with counseling on the same (p=0.013). Medicine adherence was significantly associated with age (p=0.017) and duration of hemodialysis (p=0.049). It also showed association of age (p=0.001), Hepatitis C infection (p=0.013), Diabetes mellitus (p=0.012), duration of hemodialysis (p=0.010) with IDWG. Conclusion: There is an immediate need for strategies to promote the treatment adherence of the patients under hemodialysis with focus on diet and fluid restriction adherence.
Ensieh Shahvazian
Shahid Sadoughi University of Medical Sciences, Iran
Title: Heritability and familiality of Type 2 Diabetes in Yazd population, Iran
Time : 14:40-15:10
Biography:
Ensieh Shahvazian has completed her MSc at the age of 25 years from Shahid Sadoughi University of Medical Sciences, Iran. She has accomplished several organized and valuable projects on Diabetes and Diabetic Retinopathy. She is also a Genetic R&D researcher at ROJETechnologies.
Abstract:
Type2 diabetes (T2D) is the growing health problem in Yazd population, having a prevalence of 16.3% among adolescent. The level of consanguineous marriage is high (46%), hence a high level of homozygosity is predictable. Besides, this population have special predisposing life style of low relocation rates, a relatively high standard of living, large family sizes. To direct association and linkage studies in Yazd, we decided to calculate the heritability of type2 diabetes in a population based family study. 2065 individuals were participated in The Yazd Diabetes family Study (YDS). The study was conducted among diabetic probands between 35-80 years, whose disease were confirmed in Yazd Diabetes Research Center, and their expanded families. Heritability was calculated for type2 diabetes in SOLAR software package and was adjusted for common covariates (age, sex, age × sex, age2 and BMI). The strongest heritability for type two diabetes (h2 = 0.56±0.28, Pvalue= 0.016) was seen in age group 40-60 years. However, in age group 20-60 years, heritability reduced to 0.22±0.2. The heritability for 40-75 years was 0.28±0.11. λR = 2.4 and λR (nuclear family) = 3.42 and λS= 3.14 was seen in age group of 35 to 80 years. As a conclusion, for detecting high influenced genetic risk factor with OR≥2, it is recommended to conduct studies on individuals between 40 to 60 years. To cover all genetic risk factor either with less OR, it is better to limit the sample study on individuals with onset 40 to 75 years.
Rasha Mosa
University of Queensland, Australia
Title: Effects of growth hormone secretagogue receptor agonist and antagonist in non-obese Type 2 Diabetes MKR mice
Time : 15:10-15:40
Biography:
Rasha Mosa, a third year PhD student at University of Queensland, School of Biomedical Sciences, Australia supported by competitive Egypt Government International Scholarship and UQ International Scholarship. She was an assistant lecturer of Medical Physiology at Sohag University, Faculty of Medicine, Egypt since 2009. She was awarded Master degree in Physiology from Sohag Faculty of Medicine in 2009 and a Bachelor of Medicine and Surgery from Sohag Faculty of Medicine in 2004. She is interested in studying the pathophysiology of type 2 diabetes and its potential therapy. Recently, she published a review in endocrine: “Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases”.
Abstract:
Ectopic lipid deposition is a high risk factor for insulin resistance and its associated diseases such as type 2 diabetes (T2D). Peroxisome proliferator-activated receptor gamma (PPARγ) plays a key role in adipocyte differentiation, lipid metabolism and is a therapeutic target for the treatment of insulin resistance. Recent evidence suggests that Hexarelin, a ghrelin synthetic analogue that acts through GH secretagogue receptor (GHS-R), promotes PPARγ activation in macrophages and adipocytes. However, whether Hexarelin impacts the fat and glucose metabolism in diabetes remains unclear. By using the MKR diabetic mouse model, which is characterized by hyperinsulinaemia, hypertriglyceridaemia and ectopic fat deposition, we assessed the effects of Hexarelin and the GHS-R antagonist, D-Lys GHRP-6, on glucose homeostasis, energy balance, hormonal and metabolic profiles in MKR diabetic mice. Our data demonstrated that chronic treatment with Hexarelin for 2 weeks improved glucose and insulin tolerance in diabetic mice. This effect is likely through activation of fatty acid metabolism and adipocyte proliferation, as well as increased insulin sensitivity. In conclusion, our results suggest that long-term treatment of Hexarelin benefits glucose and fat metabolism via reducing ectopic lipid deposition.
- Cheminformatics Tools For Drug Discovery
Session Introduction
Achintya Saha
University of Calcutta, India
Title: Development of QAAR models to explore the selectivity profile of PPAR α, δ, and γ modulators
Biography:
Achintya Saha, Professor and Head, Department of Chemical Technology, University of Calcutta, India has 20 years teaching and research experience in Pharmaceutical fields, especially in Drug Design through Cheminformatics techniques. He completed his PhD in Pharmaceutical Technology from Jadavpur University, India and did Post-doctoral research in University of North Carolina, USA. He has published more than 100 papers in peer reviewed journals.
Abstract:
Disease related to metabolic syndrome is an interesting topic to the researchers throughout the world. The peroxisome proliferator-activated receptors (PPARα, δ, and γ) are the members of the nuclear receptor family, which play important roles in regulation of metabolism, inflammation, and cell differentiation, it is seemed to be very much related with metabolic syndrome. These receptor subtypes are very much interrelated on the basis of their homology and the active catalytic sides. In the present approach, quantitative activity-activity relationship (QAAR) has been performed to develop the relationship between selectivity of modulators of each subtypes over others. It is observed that there is a positive influence of γ and δ subtypes modulators, whereas α and δ subtypes modulators have a negative influence on each other. Similarly, it is also seen that the descriptor contribution is different for each subtypes. For the γ and δ selectivity, the descriptors- electrotopological state keys (JX), atom type indices (Atype_O_59), jurs (Jurs-RPCG) and atom pairs indices T(S..F) have opposite contribution to develop the QAAR model. But for the α subtype modulation, different type descriptors, such as ETA descriptor (ETA_Shape_X), constitutional indices (nAB), functional group counts (nCONHRPh and nHDon), and atom type indices (Atype_F_84, Atype_N_71 and Atype_C_34) show the importance of selectivity contribution.
Biography:
Prof. Mridula Saxena, Head of Department of Chemistry, Amity University, Lucknow, India is dynamically involved in teaching and drug discovery research. She worked for her PhD degree at Central Drug Research Institute, Lucknow and received her degree from the Meerut University in 1986. She had worked on different positions like Research Associate ships of ICMR/CSIR and Research Pool Scientist till 1999. There after she got herself associated with both teaching and research and got DST sponsored project in 2004 as well as faculty position at Amity University, Lucknow. All through her 39 years of teaching and research experience she has >30 papers and review/book articles in national and international journals, >30 conference papers and has 4 patents in her credit. She has visited many countries like, Germany, Hong Kong, China, Turkey, Slovenia, Russia, Greece, Egypt, South Korea and Montenegro for presenting her work.
Abstract:
Drug discovery and development is highly challenging, expensive and time consuming process. for the identification of drug candidates having potential role in human therapeutics. It involves two major steps; viz the identification of the lead in terms of both target and the design of novel prototypes and the second rate limiting step for finding the candidate drug for development through optimization of the lead molecule. The chemoinformatics including ligand based and structure based approaches help in accelerating the drug discovery and design process through better understanding of the structure and activity relationships. The 2-substituted octahydropyrazinopyridoindoles have shown potent histamine H1 receptor antagonism and the ligand based 2D & 3D QSARs explained well the SARs except for some outliers. The absence of human H1 crystal structure at that time prompted us to construct a homology model of H1 using the bovine rhodopsin as template which also could not explain the outlier behavior of these compounds. The structure based studies carried out on the crystal structure of human H1 receptor have been used to explain the behavior of these outliers.
Biography:
Minqian Shen has completed her Medicine Master Degree from Shanghai Medicine College, Fudan University. Since 2007, she has been working as an ophthalmologist in Zhongshan Hospital, Fudan University. She has published 2 Sci papers.
Abstract:
Corneal neovascularization (CNV) was induced in Balb/c mice by alkali burns in the central area of the cornea with a diameter of 2.5mm. After 14 days, some eyeballs were enucleated to histological staining to examine CNV, and the corneas from other eyes were harvested to perform label-free proteomics analysis. The label-free quantitative proteomic approach was applied to analyze five normal corneal tissues (normal group mice n=5) and five corresponding neovascularized corneal tissues (model group mice n=5). The protein data were subject to statistical analysis using Maxquant Software. A total of 2124 proteins were identified and 1682 proteins were quantified from these corneal tissues. Among these quantified proteins, 290 proteins were changed significantly. Of these significantly changed proteins, 35 were reported or predicted as angiogenesis-related proteins. Then, these 35 proteins were analyzed using Ingenuity Pathway Analysis Software, resulting in 26 proteins enriched and connected to each other in the protein-protein interaction network, such as LCN-2, αB-crystalline, and PEDF. These three angiogenesis-related proteins were verified by western blotting test. Consistent with the quantitative proteomic results, Western blotting showed that LCN-2 and αB-crystalline were significantly up-regulated in CNV model, while PEDF was down-regulated. This study provided increased understanding of angiogenesis-related proteins involved in corneal vascular development, which will be useful in the ophthalmic clinic of specifically target angiogenesis.
Ahmed Haroun
National University of Singapore
Title: Micro vibration energy harvesters for low frequency operation
Biography:
Ahmed Haroun has completed his PhD from University of Tokyo in Mechanical Engineering. He is currently a Post-doctoral research fellow at National University of Singapore (NUS) and holding the position of Lecturer Assistant at Cairo University. His research interests include energy harvesting for implantable and wearable devices; MEMS-based energy harvesting; MEMS sensors and actuators, Implantable bio-MEMS; Vibration energy harvesting and Dynamics of multi-body systems.
Abstract:
Self-powering of wireless sensors and wireless micro devices attract the attention of many researches nowadays. Problems associated with chemical batteries such as limited life time and minimization restrictions can be solved using the approach of energy harvesting. Various ambient energy sources such as vibration, thermal, light, wind, etc. could be harvested and converted into electrical energy. However, vibration energy harvesting is more convenient for important kinds of applications such as machine condition monitoring, where sensors are placed in a deep dark place and human body-powered devices whether they are wearable or implantable. Some problems arise when dealing with human motion energy harvesting. Human body provides a kind of unsteady low frequency vibrations which are difficult to match by most common resonant harvesters. Instead, a way of non-resonant low frequency energy harvesting should be used. In this speech, a micro electromagnetic non-resonant energy harvester based on free/impact motion will be presented. Free relative motion is allowed between tube-carrying an electrical coil directly connected to the vibration source and a permanent magnet inside. Impacts appear between the magnet and two hard end stops. Free motion enhances power harvesting at low frequency, while combined free/impact motion results in a non-resonant behavior in which the output power increases with input amplitude and/or frequency. In addition, the harvester has a simple construction which allows fabrication with small sizes. Hence, the harvester can be well suited for small size applications encountered variable large amplitude – low frequency vibrations such as human powered devices.
Huda Abdulaziz Shaheen
King Abdulaziz University, Saudi Arabia
Title: Selective adsorption of gold ions from complex system using oxidized multi-walled carbon nanotubes
Biography:
Huda Abdulaziz Shaheen obtained her Bachelor's degree in General Chemistry in 2008 at King Abdulaziz University. In 2013, she completed her Master’s degree in analytical chemistry at King Abdelaziz University. The focus of her research is nanotechnology and specifically studied the use of carbon nanotubes as adsorbent and demonstrated several methods to improve this material and use it to estimate the elements negligible concentrations of different water samples. Currently, she is PhD student in the second year of analytical chemistry PhD program. She has published an article in September 2015 in the Journal of Molecular Liquids and work is underway to publish other articles.
Abstract:
The selective adsorption and removal of Au(III) ions using oxidized multi-walled carbon nanotubes from aqueous solutions containing different metal ions were studied. Characterization studies showed that MWCNTs were oxidized by the concentrated nitric acid under normal laboratory conditions. The adsorption study results showed that only Au(III) ions could be adsorbed completely from the complex system containing other metal ions at pH 2.0, and within a few minutes at ambient temperature. Also, the interfering effect of other ions that may co-exist with the Au(III) ions in aqueous solutions was explored, and the results showed no sign of interference with the Au(III) ions for the adsorption at the oxidized multi-walled carbon nanotube surface. The adsorption was studied at equilibrium and was found to follow the Langmuir adsorption model, and kinetically obey the pseudo second order kinetic model. The adsorption capacity obtained using oxidized multi-walled carbon nanotubes was 62.3 mg g−1, which is higher than any reported value. Finally, the selective removal and adsorption of Au(III) ions from real environmental water samples were studied and the results showed that oxidized multi-walled carbon nanotubes had high affinity and selectivity for Au(III) ions and could be used successfully for the removal of Au(III) ions from aqueous solutions.