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Genomics Medicine

Wei Sun, Liang Leng, Qinggang Yin, MeiMei Xu, Mingkun Huang, Zhichao Xu, Yujun Zhang, Hui Yao, Caixia Wang, Chao Xiong, Sha Chen, Chunhong Jiang, Ning Xie, Xilong Zheng, Ying Wang, Chi Song, Reuben J Peters, Shilin Chen
Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asia countries. A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India and is still used for the treatment of infectious disease in China. A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide, neoandrographolide and their analogs; touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases...
November 16, 2018: Plant Journal: for Cell and Molecular Biology
Chen-Jun Hu, Ju He, Guo-Zheng Li, Pei-Pei Fang, Jia-Dong Xie, You-Wei Ding, Yu-Qing Mao, Kong-Fa Hu
BACKGROUND AND OBJECTIVE: Hedyotis diffusa is an herb used for anti-cancer, anti-oxidant, anti-inflammatory, and anti-fibroblast treatment in the clinical practice of Traditional Chinese Medicine. However, its pharmacological mechanisms have not been fully established and there is a lack of modern scientific verification. One of the best ways to further understand Hedyotis diffusa's mechanisms of action is to analyze it from the genomics perspective. METHODS: In this study, we used network pharmacology approaches to infer the herb-gene interactions, the herb-pathway interactions, and the gene families...
October 31, 2018: Computer Methods and Programs in Biomedicine
Li-Shiun Chen, Sarah M Hartz, Timothy B Baker, Yinjiao Ma, Nancy L Saccone, Laura J Bierut
AIM: This study tests whether polygenic risk scores (PRSs) for nicotine metabolism predict smoking behaviors in independent data. MATERIALS & METHODS: Linear regression, logistic regression and survival analyses were used to analyze nicotine metabolism PRSs and nicotine metabolism, smoking quantity and smoking cessation. RESULTS: Nicotine metabolism PRSs based on two genome wide association studies (GWAS) meta-analyses significantly predicted nicotine metabolism biomarkers (R2 range: 9...
November 16, 2018: Pharmacogenomics
Vladimír Bencko, Petr Šíma
Genetic information is transmitted among organisms through two pathways - vertically from generation to generation (from parents to progeny) and horizontally (laterally) by direct exchange of genetic material across species barriers. These are primarily prokaryotes, in which the exchange of genes or whole gene segments by horizontal transmission is quite common. They can dynamically and in a relatively short time generate highly diverse genomes, which does not allow the vertical transmission. As a result, prokaryotes can rapidly acquire new properties such as virulence and pathogenicity as well as resistance to toxins, including antibiotics, by which they increase their adaptability...
2018: Casopís Lékar̆ů C̆eských
Teck Yew Low, M Aiman Mohtar, Mia Yang Ang, Rahman Jamal
Understanding the relationship between genotypes and phenotypes is essential to disentangle biological mechanisms and to unravel the molecular basis of diseases. Genes and proteins are closely linked in biological systems. However, genomics and proteomics have developed separately into two distinct disciplines whereby crosstalk among scientists from the two domains has been limited and this constrains the integration of both fields into a single data modality of useful information. The emerging field of proteogenomics attempts to address this by building bridges between the two disciplines...
November 15, 2018: Proteomics
Qin Liang, Claudio Monetti, Maria V Shutova, Eric J Neely, Sabiha Hacibekiroglu, Huijuan Yang, Christopher Kim, Puzheng Zhang, Chengjin Li, Kristina Nagy, Maria Mileikovsky, Istvan Gyongy, Hoon-Ki Sung, Andras Nagy
Human pluripotent cell lines hold enormous promise for the development of cell-based therapies. Safety, however, is a crucial prerequisite condition for clinical applications. Numerous groups have attempted to eliminate potentially harmful cells through the use of suicide genes1 , but none has quantitatively defined the safety level of transplant therapies. Here, using genome-engineering strategies, we demonstrate the protection of a suicide system from inactivation in dividing cells. We created a transcriptional link between the suicide gene herpes simplex virus thymidine kinase (HSV-TK) and a cell-division gene (CDK1); this combination is designated the safe-cell system...
November 14, 2018: Nature
Ashleigh Parkin, Jennifer Man, Angela Chou, Adnan M Nagrial, Jaswinder Samra, Anthony J Gill, Paul Timpson, Marina Pajic
Pancreatic cancer is the third leading cause of cancer-related deaths, characterised by poor survival, marked molecular heterogeneity and high intrinsic and acquired chemoresistance. Only 10⁻20% of pancreatic cancer patients present with surgically resectable disease and even then, 80% die within 5 years. Our increasing understanding of the genomic heterogeneity of cancer suggests that the failure of definitive clinical trials to demonstrate efficacy in the majority of cases is likely due to the low proportion of responsive molecular subtypes...
November 13, 2018: Diseases (Basel)
Marina Gálvez-Peralta, Grazyna D Szklarz, Werner J Geldenhuys, Paul R Lockman
Objective. To develop an effective method in teaching pharmacogenomics as a part of a new course, Biopharmaceutics and Pharmacogenomics. Methods. Teaching effectiveness was measured by quizzes, retrospective pre- and post-surveys, team activities, and journal reflections. Four team activities were included in the course: genomic disease, patient case, genetic counselor and a debate about personalized medicine. Outcomes and course impact were evaluated at the end of the course. The evaluation methods included the assessment of knowledge, students' perceptions regarding the utility of team activities, the impact of the course on students' confidence to discuss pharmacogenomics with health care providers or patients, and long-term knowledge retention, measured in the following P2 semester...
October 2018: American Journal of Pharmaceutical Education
Anand N Malaviya, Narinder K Mehra
A young physician starting a fresh career in medicine in this millennium would hardly stop to think about the genesis of a particular biological drug that he/she will be prescribing for a patient evaluated in the morning outpatient department. For him/her, this is now routine, and the question of 'Who', 'How' and 'When' about these biologicals would be the last thing on their mind. However, for those who came to the medical profession in the 1950s, 1960s and 1970s, these targeted drugs are nothing short of 'miracles'...
September 2018: Indian Journal of Medical Research
Young Kwang Chae, Andrew A Davis, Kirtee Raparia, Sarita Agte, Alan Pan, Nisha Mohindra, Victoria Villaflor, Francis Giles
PURPOSE: To examine clinical predictors of tumor mutational burden (TMB), to explore the association between TMB and DNA repair mutations, and to analyze TMB as a biomarker for response to immune checkpoint blockade in non-small-cell lung cancer. PATIENTS AND METHODS: TMB scores were determined retrospectively for 72 consecutive patients at our institution with next-generation sequencing comprehensive genomic profiling testing by Foundation Medicine. TMB scores were correlated with a number of clinical variables and presence of DNA repair mutations...
September 25, 2018: Clinical Lung Cancer
Tommaso Giani, Samanta Sennati, Alberto Antonelli, Vincenzo Di Pilato, Tiziana di Maggio, Antonia Mantella, Claudia Niccolai, Michele Spinicci, Joaquín Monasterio, Paul Castellanos, Mirtha Martinez, Fausto Contreras, Dorian Balderrama Villaroel, Esther Damiani, Sdenka Maury, Rodolfo Rocabado, Lucia Pallecchi, Alessandro Bartoloni, Gian Maria Rossolini
BackgroundThe mcr-1 gene is a transferable resistance determinant against colistin, a last-resort antimicrobial for infections caused by multi-resistant Gram-negatives.AimTo study carriage of antibiotic-resistant bacteria in healthy school children as part of a helminth control and antimicrobial resistance survey in the Bolivian Chaco region.MethodsFrom September to October 2016 we collected faecal samples from healthy children in eight rural villages. Samples were screened for mcr-1 - and mcr-2 genes. Antimicrobial susceptibility testing was performed, and a subset of 18 isolates representative of individuals from different villages was analysed by whole genome sequencing (WGS)...
November 2018: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
Lejla Mahmutovic, Betul Akcesme, Camil Durakovic, Faruk Berat Akcesme, Aida Maric, Muhamed Adilovic, Nour Hamad, Matthias Wjst, Oliver Feeney, Sabina Semiz
BACKGROUND: Increasing evidence is demonstrating that a patient's unique genetic profile can be used to detect the disease's onset, prevent its progression, and optimize its treatment. This led to the increased global efforts to implement personalized medicine (PM) and pharmacogenomics (PG) in clinical practice. Here we investigated the perceptions of students from different universities in Bosnia and Herzegovina (BH) towards PG/PM as well as related ethical, legal, and social implications (ELSI)...
November 14, 2018: Human Genomics
Moyang Liu, Zhaotang Ma, Anhu Wang, Tianrun Zheng, Li Huang, Wenjun Sun, Yanjun Zhang, Weiqiong Jin, Junyi Zhan, Yuntao Cai, Yujia Tang, Qi Wu, Zizhong Tang, Tongliang Bu, Chenglei Li, Hui Chen
Auxin signaling plays an important role in plant growth and development. It responds to various developmental and environmental events, such as embryogenesis, organogenesis, shoot elongation, tropical growth, lateral root formation, flower and fruit development, tissue and organ architecture, and vascular differentiation. However, there has been little research on the Auxin Response Factor ( ARF ) genes of tartary buckwheat ( Fagopyrum tataricum ), an important edible and medicinal crop. The recent publication of the whole-genome sequence of tartary buckwheat enables us to study the tissue and expression profile of the FtARF gene on a genome-wide basis...
November 9, 2018: International Journal of Molecular Sciences
Adel Abuzenadah, Saad Al-Saedi, Sajjad Karim, Mohammed Al-Qahtani
Patau Syndrome (PS), characterized as a lethal disease, allows less than 15% survival over the first year of life. Most deaths owe to brain and heart disorders, more so due to septal defects because of altered gene regulations. We ascertained the cytogenetic basis of PS first, followed by molecular analysis and docking studies. Thirty-seven PS cases were referred from the Department of Pediatrics, King Abdulaziz University Hospital to the Center of Excellence in Genomic Medicine Research, Jeddah during 2008 to 2018...
November 10, 2018: International Journal of Molecular Sciences
Ares Pasipoularides
Morphology underlies subdivision of the primary/heritable sarcomeric cardiomyopathies (CMs) into hypertrophic (HCM) and dilated (DCM). Next-generation DNA-sequencing (NGS) has identified important disease-variants, improving CM diagnosis, management, genetic screening, and prognosis. Although monogenic (Mendelian) analyses directly point at downstream studies, they disregard coexisting genomic variations and gene-by-gene interactions molding detailed CM-phenotypes. In-place of polygenic models, in accounting for observed defective genotype-phenotype correlations, fuzzy concepts having gradations of significance and unsharp domain-boundaries are invoked, including pleiotropy, genetic-heterogeneity, incomplete penetrance, and variable expressivity...
November 10, 2018: Journal of Molecular and Cellular Cardiology
Takashi Mitamura, Peixin Dong, Kei Ihira, Masataka Kudo, Hidemichi Watari
The overall survival rate of patients with early-stage endometrial cancer is relatively high; however, there are few treatment options for patients with advanced or recurrent endometrial cancer, and the prognosis of such patients remains poor. Recent progress in molecular-targeted therapies demonstrated that they have the potential to improve the long-term survival of cancer patients with appropriate biomarkers. However, the median progression-free survival of patients who received single-agent molecular-targeted therapy was <5 months, and the development of molecular-targeted therapies for endometrial cancer patients is urgently needed...
November 13, 2018: Japanese Journal of Clinical Oncology
Hui Peng, Yi Zheng, Zhixun Zhao, Tao Liu, Jinyan Li
Motivation: CRISPR/Cas9 is driving a broad range of innovative applications from basic biology to biotechnology and medicine. One of its current issues is the effect of off-target editing that should be critically resolved and should be completely avoided in the ideal use of this system. Results: We developed an ensemble learning method to detect the off-target sites of a single guide RNA (sgRNA) from its thousands of genome-wide candidates. Nucleotide mismatches between on-target and off-target sites have been studied recently...
September 1, 2018: Bioinformatics
Melita Cirillo, Sarah Reinke, Wolfram Klapper, Sven Borchmann
Hodgkin Lymphoma (HL) is an unusual B-cell lymphoma because the malignant cells exist as a minority population in a densely cellular microenvironment. The microenvironment is comprised predominately of inflammatory and immune cells with fibrosis in some cases. There are multiple dysregulated signalling pathways that sustain HL within this microenvironment, such as the Nuclear factor-κB and Janus kinase/signal transducers and activators of transcription pathways. Advances in genomic medicine have enabled a better characterisation of the rare tumour cells and improved our understanding of the signalling mechanisms that exist between the malignant cell and its microenvironment...
November 12, 2018: British Journal of Haematology
Sameer H Halani, Safoora Yousefi, Jose Velazquez Vega, Michael R Rossi, Zheng Zhao, Fatemeh Amrollahi, Chad A Holder, Amelia Baxter-Stoltzfus, Jennifer Eschbacher, Brent Griffith, Jeffrey J Olson, Tao Jiang, Joseph R Yates, Charles G Eberhart, Laila M Poisson, Lee A D Cooper, Daniel J Brat
Oligodendrogliomas are diffusely infiltrative gliomas defined by IDH -mutation and co-deletion of 1p/19q. They have highly variable clinical courses, with survivals ranging from 6 months to over 20 years, but little is known regarding the pathways involved with their progression or optimal markers for stratifying risk. We utilized machine-learning approaches with genomic data from The Cancer Genome Atlas to objectively identify molecular factors associated with clinical outcomes of oligodendroglioma and extended these findings to study signaling pathways implicated in oncogenesis and clinical endpoints associated with glioma progression...
2018: NPJ Precision Oncology
Mahmut Cerkez Ergören, Gizem Söyler, Hüseyin Sah, Eda Becer
Obesity, as a global health issue, is a complex metabolic syndrome and its association with many chronic diseases. The pathology of obesity results from an interaction of psychological, environmental and variety of genetic factors. Etiologic determinants and molecular pathophysiology of obesity have not yet understood clearly. Previously shown that genetic markers have a significant role in the development of obesity, although results are divergent with populations. Turkish Cypriots have a unique mixture of allele distributions as being a small-islander population...
October 26, 2018: International Journal of Biological Macromolecules
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