Human Genome Center
Human Genome Center
Sheikh S.A.,Universiti Sains Malaysia |
Roshan T.M.,Lady Davis Institute for Medical Research |
Khattak M.N.,Singapore Clinical Research Institute |
Baig A.A.,Human Genome Center |
And 2 more authors.
Menopause International | Year: 2011
Objectives. In healthy postmenopausal women (PMW) increased platelet activation has been associated with adverse cardiovascular events. There is much debate about the relationship between platelet function and serum estradiol level in PMW. This study assessed the effect of short-term oral estrogen replacement therapy (ERT) on platelet activation markers (CD62P and PAC-1) and its correlation with age and body mass index (BMI) among healthy PMW. Methods. A prospective intervention study was conducted at Hospital University Sains Malaysia, involving 48 healthy PMW who were evaluated for platelet activation marker levels as determined by flow cytometry, before and after two weeks of oral ERT with 0.625 mg of conjugated equine estrogen once daily. The pre- and post-ERT platelets activation markers difference was analysed by paired t-test. Results. The pre-ERT, mean ± SD percentage levels of CD62P and PAC-1 were significantly reduced from 7.00 ± 5.91 and 41.75 ± 26.85 to 3.05 ± 2.47 and 20.86 ± 19.02, respectively, after two weeks of ERT (P value < 0.001). The correlation of platelet activation markers was significant with estradiol but not with age and BMI. Conclusion. Short-term ERT leads to reduction in platelet activity, which might contribute to protection against cardiovascular diseases in healthy PMW.
News Article | December 5, 2016
Following a successful diet, many people are dismayed to find their weight rebounding - an all-too-common phenomenon termed "recurrent" or "yo-yo" obesity. Worse still, the vast majority of recurrently obese individuals not only rebound to their pre-dieting weight but also gain more weight with each dieting cycle. During each round of dieting-and-weight-regain, their proportion of body fat increases, and so does the risk of developing the manifestations of metabolic syndrome, including adult-onset diabetes, fatty liver and other obesity-related diseases. As reported today in Nature, researchers at the Weizmann Institute of Science have shown in mice that intestinal microbes - collectively termed the gut microbiome - play an unexpectedly important role in exacerbated post-dieting weight gain, and that this common phenomenon may in the future be prevented or treated by altering the composition or function of the microbiome. The study was performed by research teams headed by Dr. Eran Elinav of the Immunology Department and Prof. Eran Segal of the Computer Science and Applied Mathematics Department. The researchers found that after a cycle of gaining and losing weight, all the mice's body systems fully reverted to normal - except the microbiome. For about six months after losing weight, post-obese mice retained an abnormal "obese" microbiome. "We've shown in obese mice that following successful dieting and weight loss, the microbiome retains a 'memory' of previous obesity," says Elinav. "This persistent microbiome accelerated the regaining of weight when the mice were put back on a high-calorie diet or ate regular food in excessive amounts." Segal elaborates: "By conducting a detailed functional analysis of the microbiome, we've developed potential therapeutic approaches to alleviating its impact on weight regain." The study was led by Christoph Thaiss, a Ph.D. student in Elinav's lab. Thaiss collaborated with master's student Shlomik Itav of the Elinav lab, Daphna Rothschild, a Ph.D. student of Segal's lab, as well as with other scientists from Weizmann and elsewhere. In a series of experiments, the scientists demonstrated that the makeup of the "obese" microbiome was a major driver of accelerated post-dieting weight gain. For example, when the researchers depleted the intestinal microbes in mice by giving them broad-spectrum antibiotics, the exaggerated post-diet weight gain was eliminated. In another experiment, when intestinal microbes from mice with a history of obesity were introduced into germ-free mice (which, by definition, carry no microbiome of their own), their weight gain was accelerated upon feeding with a high-calorie diet, compared to germ-free mice that had received an implant of intestinal microbes from mice with no history of weight gain. Next, the scientists developed a machine-learning algorithm, based on hundreds of individualized microbiome parameters, which successfully and accurately predicted the rate of weight regain in each mouse, based on the characteristics of its microbiome after weight gain and successful dieting. Furthermore, by combining genomic and metabolic approaches, they then identified two molecules driving the impact of the microbiome on regaining weight. These molecules - belonging to the class of organic chemicals called flavonoids that are obtained through eating certain vegetables - are rapidly degraded by the "post-dieting" microbiome, so that the levels of these molecules in post-dieting mice are significantly lower than those in mice with no history of obesity. The researchers found that under normal circumstances, these two flavonoids promote energy expenditure during fat metabolism. Low levels of these flavonoids in weight cycling prevented this fat-derived energy release, causing the post-dieting mice to accumulate extra fat when they were returned to a high-calorie diet. Finally, the researchers used these insights to develop new proof-of-concept treatments for recurrent obesity. First, they implanted formerly obese mice with gut microbes from mice that had never been obese. This fecal microbiome transplantation erased the "memory" of obesity in these mice when they were re-exposed to a high-calorie diet, preventing excessive recurrent obesity. Next, the scientists used an approach that is likely to be more unobjectionable to humans: They supplemented post-dieting mice with flavonoids added to their drinking water. This brought their flavonoid levels, and thus their energy expenditure, back to normal levels. As a result, even on return to a high-calorie diet, the mice did not experience accelerated weight gain. Segal said: "We call this approach 'post-biotic' intervention. In contrast to probiotics, which introduce helpful microbes into the intestines, we are not introducing the microbes themselves but substances affected by the microbiome, which might prove to be more safe and effective." Recurrent obesity is an epidemic of massive proportions, in every meaning of the word. "Obesity affects nearly half of the world's adult population, and predisposes people to common life-risking complications such as adult-onset diabetes and heart disease," says Elinav. "If the results of our mouse studies are found to be applicable to humans, they may help diagnose and treat recurrent obesity, and this, in turn, may help alleviate the obesity epidemic." Also taking part in the study were Mariska Meijer, Maayan Levy, Claudia Moresi, Lenka Dohnalova, Sofia Braverman, Shachar Rozin, Dr. Mally Dori-Bachash and Staff Scientist Hagit Shapiro of the Immunology Department, Staff Scientists Drs. Yael Kuperman and Inbal Biton, and Prof. Alon Harmelin of the Veterinary Resources Department, and Dr. Sergey Malitsky and Prof. Asaph Aharoni of the Plant and Environmental Sciences Department - all of the Weizmann Institute of Science, as well as Prof. Arieh Gertler of the Hebrew University of Jerusalem and Prof. Zamir Halpern of the Tel-Aviv Sourasky Medical Center. Dr. Eran Elinav's research is supported by the Leona M. and Harry B. Helmsley Charitable Trust; the Adelis Foundation; the Else Kroener Fresenius Foundation; John L. and Vera Schwartz, Pacific Palisades, CA; the Rising Tide Foundation; Andrew and Cynthia Adelson, Canada; Yael and Rami Ungar, Israel; Donald L. Schwarz, Sherman Oaks, CA; Leesa Steinberg, Canada; Aaron Edelheit, Boca Raton, FL; Jack N. Halpern, New York, NY; and the Lawrence and Sandra Post Family. Dr. Elinav is the Incumbent of the Rina Gudinski Career Development Chair. Prof. Eran Segal's research is supported by the Crown Human Genome Center, which he heads; the Else Kroener Fresenius Foundation; Donald L. Schwarz, Sherman Oaks, CA; Jack N. Halpern, New York, NY; and Leesa Steinberg, Canada. The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.
Shahpudin S.N.M.,Human Genome Center |
Shahpudin S.N.M.,Universiti Sains Malaysia |
Mustapha M.A.,Human Genome Center |
Aziz A.A.A.,Human Genome Center |
And 7 more authors.
International Medical Journal | Year: 2011
Background: Colorectal cancer (CRC) is a multifactorial disease with factors including dietary and lifestyle habits and genetic predisposition contributing to its etiopathogenesis. Even though the genetic predisposing factors are still unclear, genetic polymorphisms of genes encoding enzymes involved in xenobiotic metabolic pathways that activate or inactivate dietary carcinogens have been proposed as candidate genes. Three members of the Gluthathione S-Transferase (GSTs) family GSTP1, GSTT1 and GSTM1 have been analyzed in Malaysian population for polymorphic variants, and to elucidate their role in colorectal carcinogenesis. Objective: To determine the frequencies of GSTPI, GSTTI and GSTMI genotypes in 111 histopathologically confirmed CRC patients and 128 healthy controls and to evaluate the association risk of GSTPI, GSTTI and GSTMI genotypes on CRC predisposition. Material and Methods: Peripheral blood from the study subjects were collected in EDTA tubes and genomic DNA extracted using QIAGEN kit. The GSTPI Ile105Val polymorphism was analyzed by PCR-RFLP technique using BsmA1 restriction enzyme. The presence or absence of GSTM1 and GSTT1, genes were determined using a multiplex PCR protocol with albumin as the housekeeping gene. The resulting PCR fragments were separated on 2.0% agarose gel for GSTP1 and 3.0% agarose gel electrophoresis for the GSTT1 and GSTM1. Results and Conclusion: On evaluating the CRC risk association with variant genotypes singly, GSTTI null genotype was associated significantly with an elevated risk (OR 1.804, 95%CI: 1.065-3.361, p=0.027). When the polymorphic genotypes were analyzed in combination, the combination genotypes of GSTPI Val/Val/GSTM+/GSTTI+ (OR 4.000), Val/Val/GSTMI-/GSTTI- (OR 3.000), and GSTPI Ile/Ile/GSTMI+/GSTTI- (OR 2.833) showed higher associated risk for CRC susceptibility, however the risk values were not statistically significant. Further studies involving larger sample size may help to identify the more specific risk groups and to determine factors of importance in CRC development. © 2011 Japan International Cultural Exchange Foundation & Japan Health Sciences University.
Mohd Shafi'i M.S.,Human Genome Center |
Mohd Shahpudin S.N.,Human Genome Center |
Mustapha M.A.,Human Genome Center |
Abdul Aziz A.A.,Human Genome Center |
And 5 more authors.
International Medical Journal | Year: 2012
Colorectal Cancer (CRC), represents a significant cause of morbidity and mortality worldwide. Its incidence is increasing in developed and developing countries including Malaysia. Multiple disease pathways including Nuclear Factor Kappa B (NFkB) signaling pathways, have been implicated in Colorectal carcinogenesis. Given the important role of NFkB pathway in Colorectal carcinogenesis, genes and genetic variations influencing NFkB signaling pathway could be candidate CRC predisposition factors. We hypothesized that an A to G variation in the 3' UTR of NFkB1A may be associated with CRC susceptibility risk in Malaysian population. Design: A Case - Control study was designed to investigate the genotype frequencies of A to G polymorphism at 3' UTR of NFkB1A in Malaysian CRC patients and normal Controls and to determine the genetic risk association of the variant genotype on CRC susceptibility. Objectives: To investigate the genotype frequencies of A to G polymorphism at 3' UTR of NFkB1A in Malaysian sporadic CRC patients and healthy controls and to determine the association risk of the variant genotype on CRC susceptibility. Materials and Methods: This study involved 510 subjects with 211 histopathologically confirmed CRC patients as Cases and 299 healthy individuals as Controls. Blood samples from study subjects were collected, DNA extracted and genotyped employing PCR-RFLP technique. Risk associations of specific genotypes with CRC susceptibility were determined by computing Odds Ratios (ORs) and 95% Confidence Intervals (CI). Results: The frequency of homozygous major (AA) genotype was significantly higher (p = 0.003) among Controls (44.8%) compared to CRC patients (31.8%) but heterozygous genotype (AG) showed no significant difference between cases and controls. However, the frequency of homozygous variant (GG) genotype was significantly higher in CRC cases (40.7%) compared to controls (24.4%). On investigating the risk, the variant genotype GG showed significant risk association with CRC susceptibility (OR = 2.356, CI: 1.536-3.615, p < 0.001). Conclusion: From the results, it is reasonable to suggest that the A to G variation in the 3' UTR of NFkB1A could be a predisposition risk factor in colorectal carcinogenesis, mediating through NFkB signaling pathway. © 2012 Japan International Cultural Exchange Foundation & Japan Health Sciences University.
Fang H.,University of Chicago |
Yamaguchi R.,Human Genome Center |
Liu X.,Section of Hematology Oncology |
Daigo Y.,Shiga University of Medical Science |
And 6 more authors.
OncoImmunology | Year: 2014
Immune responses play a critical role in various disease conditions including cancer and autoimmune diseases. However, to date, there has not been a rapid, sensitive, comprehensive, and quantitative analysis method to examine T-cell or B-cell immune responses. Here, we report a new approach to characterize T cell receptor (TCR) repertoire by sequencing millions of cDNA of TCR α and β chains in combination with a newly-developed algorithm. Using samples from lung cancer patients treated with cancer peptide vaccines as a model, we demonstrate that detailed information of the V-(D)-J combination along with complementary determining region 3 (CDR3) sequences can be determined. We identified extensive abnormal splicing of TCR transcripts in lung cancer samples, indicating the dysfunctional splicing machinery in T lymphocytes by prior chemotherapy. In addition, we found three potentially novel TCR exons that have not been described previously in the reference genome. This newly developed TCR NGS platform can be applied to better understand immune responses in many disease areas including immune disorders, allergies, and organ transplantations. © 2014 Taylor & Francis Group, LLC.
Yusoff N.H.,Basic science and Oral Biology Unit |
Alshehadat S.A.,Basic science and Oral Biology Unit |
Azlina A.,Basic science and Oral Biology Unit |
Azlina A.,Human Genome Center |
And 3 more authors.
Tropical Life Sciences Research | Year: 2015
In the past decade, the field of stem cell biology is of major interest among researchers due to its broad therapeutic potential. Stem cells are a class of undifferentiated cells that are able to differentiate into specialised cell types. Stem cells can be classified into two main types: adult stem cells (adult tissues) and embryonic stem cells (embryos formed during the blastocyst phase of embryological development). This review will discuss two types of adult mesenchymal stem cells, dental stem cells and amniotic stem cells, with respect to their differentiation lineages, passage numbers and animal model studies. Amniotic stem cells have a greater number of differentiation lineages than dental stem cells. On the contrary, dental stem cells showed the highest number of passages compared to amniotic stem cells. For tissue regeneration based on animal studies, amniotic stem cells showed the shortest time to regenerate in comparison with dental stem cells. © Penerbit Universiti Sains Malaysia, 2015.
Sasongko T.H.,Human Genome Center |
Salmi A.R.,Universiti Sains Malaysia |
Zilfalil B.A.,Human Genome Center |
Albar M.A.,Bioethics Center |
Mohd Hussin Z.A.,Universiti Sains Malaysia
Annals of Saudi Medicine | Year: 2010
Abortion has been largely avoided in Muslim communities. However, Islamic jurists have established rigorous parameters enabling abortion of fetuses with severe congenital abnormalities. This decision-making process has been hindered by an inability to predict the severity of such prenatally-diagnosed conditions, especially in genetic disorders with clinical heterogeneity, such as spinal muscular atrophy (SMA). Heterogeneous phenotypes of SMA range from extremely severe type 1 to very mild type 4. Advances in molecular genetics have made it possible to perform prenatal diagnosis and to predict the types of SMA with its potential subsequent severity. Such techniques will make it possible for clinicians working in predominantly Muslim countries to counsel their patients accurately and in harmony with their religious beliefs. In this paper, we discuss and postulate that with our current knowledge of determining SMA types and severity with great accuracy, abortion is legally applicable for type 1 SMA.
PubMed | Human Genome Center
Type: Journal Article | Journal: The Malaysian journal of medical sciences : MJMS | Year: 2012
The new millennium has been regarded as a genomic era. A lot of researchers and pathologists are beginning to understand the scientific basis of molecular genetics and relates with the progression of the diseases. Central nervous system (CNS) tumours are among the most rapidly fatal of all cancers. It has been proposed that the progression of malignant tumours may result from multi-step of genetic alterations, including activation of oncogenes, inactivation of tumour suppressor genes and also the presence of certain molecular marker such as telomerase activity. In this paper, we review some recent data from the literature, including our own studies, on the molecular genetics analysis in CNS tumours. Our studies have shown that two types of tumour suppressor genes, p53 and PTEN were involved in the development of these tumours but not in p16 gene among the patients from Hospital Universiti Sains Malaysia (HUSM). Telomerase activity also has been detected in various types of CNS tumours. Thus, it is important to assemble all data which related to this study and may provide as a vital information in a new approach to neuro-oncology studies in Malaysia.
PubMed | Human Genome Center
Type: Journal Article | Journal: The Southeast Asian journal of tropical medicine and public health | Year: 2011
The aim of the present study was to evaluate Malaysian dyslipidemic patient treatment practices and outcomes. Factors contributing to success in reaching treatment goal were determined. A retrospective review of the records of dyslipidemic patients who attended the Universiti Sains Malaysia Hospital in 2007 was conducted. All the patients were receiving standard recommended doses of statins. Records were analysed for 890 patients. Patients were divided into three categories: 384 patients (43.1%) had coronary heart disease or coronary heart disease risk equivalents, 216 patients (24.3%) had moderate risk for coronary heart disease and 290 patients (32.6%) had low risk. Statins were the most commonly prescribed drug group (92%), of which atorvastatin was the most commonly prescribed drug (50.6%). The overall success rate for reaching goal was 64.2%. The percentages of patients achieving low-density lipoprotein cholesterol targets in the coronary heart disease and coronary heart disease risk equivalents, moderate, and low-risk groups were 50.5, 66.7, and 80.3%, respectively (p < 0.001). Multiple logistic regression showed achievement of therapeutic goal declined with increasing risk group. The baseline low-density lipoprotein cholesterol value was inversely related to therapeutic goal attainment. An inadequate proportion of dyslipidemic patients achieved the National Cholesterol Education Program therapeutic goals for low-density lipoprotein cholesterol, especially those in the coronary heart disease and coronary heart disease risk equivalent group. The achievement of this goal was dependent on baseline low-density lipoprotein cholesterol levels.