scholarly journals A Systems Biology Approach for Personalized Medicine in Refractory Epilepsy

2019 ◽  
Vol 20 (15) ◽  
pp. 3717 ◽  
Author(s):  
Giuseppina Daniela Naimo ◽  
Maria Guarnaccia ◽  
Teresa Sprovieri ◽  
Carmine Ungaro ◽  
Francesca Luisa Conforti ◽  
...  
Keyword(s):  
Systems Biology ◽  
Personalized Medicine ◽  
Interindividual Variability ◽  
Refractory Epilepsy ◽  
Age Groups ◽  
Gene Mutations ◽  
Review Article ◽  
Specific Gene ◽  
Efficacy And Safety ◽  
Biological Mechanisms

Epilepsy refers to a common chronic neurological disorder that affects all age groups. Unfortunately, antiepileptic drugs are ineffective in about one-third of patients. The complex interindividual variability influences the response to drug treatment rendering the therapeutic failure one of the most relevant problems in clinical practice also for increased hospitalizations and healthcare costs. Recent advances in the genetics and neurobiology of epilepsies are laying the groundwork for a new personalized medicine, focused on the reversal or avoidance of the pathophysiological effects of specific gene mutations. This could lead to a significant improvement in the efficacy and safety of treatments for epilepsy, targeting the biological mechanisms responsible for epilepsy in each individual. In this review article, we focus on the mechanism of the epilepsy pharmacoresistance and highlight the use of a systems biology approach for personalized medicine in refractory epilepsy.

scholarly journals Recent drug approvals for acute myeloid leukemia

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Catherine Lai ◽  
Kimberley Doucette ◽  
Kelly Norsworthy
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Gene Mutations ◽  
Review Article ◽  
New Drugs ◽  
Specific Gene ◽  
New Agents ◽  
Survival Pathways ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults, with an incidence that increases with age, and a generally poor prognosis. The disease is clinically and genetically heterogeneous, and recent advances have improved our understanding of the cytogenetic abnormalities and molecular mutations, aiding in prognostication and risk stratification. Until recently, however, therapeutic options were mostly limited to cytotoxic chemotherapy. Since 2017, there has been an explosion of newly approved treatment options both nationally and internationally, with the majority of new drugs targeting specific gene mutations and/or pivotal cell survival pathways. In this review article, we will discuss these new agents approved for the treatment of AML within the last 2 years, and will outline the mechanistic features and clinical trials that led to their approvals.

scholarly journals The identification of novel gene mutations for degenerative lumbar spinal stenosis using whole-exome sequencing in a Chinese cohort

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xin Jiang ◽  
Dong Chen
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Spinal Stenosis ◽  
Lumbar Spinal Stenosis ◽  
Gene Mutations ◽  
Specific Gene ◽  
Single Nucleotide ◽  
Degenerative Lumbar Spinal Stenosis ◽  
Whole Exome ◽  
Lumbar Spinal

Abstract Background Degenerative lumbar spinal stenosis (DLSS) is a common lumbar disease that requires surgery. Previous studies have indicated that genetic mutations are implicated in DLSS. However, studies on specific gene mutations are scarce. Whole-exome sequencing (WES) is a valuable research tool that identifies disease-causing genes and could become an effective strategy to investigate DLSS pathogenesis. Methods From January 2016 to December 2017, we recruited 50 unrelated patients with symptoms consistent with DLSS and 25 unrelated healthy controls. We conducted WES and exome data analysis to identify susceptible genes. Allele mutations firstly identified potential DLSS variants in controls to the patients’ group. We conducted a site-based association analysis to identify pathogenic variants using PolyPhen2, SIFT, Mutation Taster, Combined Annotation Dependent Depletion, and Phenolyzer algorithms. Potential variants were further confirmed using manual curation and validated using Sanger sequencing. Results In this cohort, the major classification variant was missense_mutation, the major variant type was single nucleotide polymorphism (SNP), and the major single nucleotide variation was C > T. Multiple SNPs in 34 genes were identified when filtered allele mutations in controls to retain only patient mutations. Pathway enrichment analyses revealed that mutated genes were mainly enriched for immune response-related signaling pathways. Using the Novegene database, site-based associations revealed several novel variants, including HLA-DRB1, PARK2, ACTR8, AOAH, BCORL1, MKRN2, NRG4, NUP205 genes, etc., were DLSS related. Conclusions Our study revealed that deleterious mutations in several genes might contribute to DLSS etiology. By screening and confirming susceptibility genes using WES, we provided more information on disease pathogenesis. Further WES studies incorporating larger DLSS patient cohorts are required to comprehend the genetic landscape of DLSS pathophysiology fully.

scholarly journals Genome-wide analysis and expression profile of the bZIP gene family in poplar

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kai Zhao ◽  
Song Chen ◽  
Wenjing Yao ◽  
Zihan Cheng ◽  
Boru Zhou ◽  
...  
Keyword(s):  
Salt Stress ◽  
Systems Biology ◽  
Gene Family ◽  
Stress Responses ◽  
Metal Ion ◽  
Gene Networks ◽  
Expression Patterns ◽  
Gene Set Enrichment Analysis ◽  
Specific Gene ◽  
Biological Processes

Abstract Background The bZIP gene family, which is widely present in plants, participates in varied biological processes including growth and development and stress responses. How do the genes regulate such biological processes? Systems biology is powerful for mechanistic understanding of gene functions. However, such studies have not yet been reported in poplar. Results In this study, we identified 86 poplar bZIP transcription factors and described their conserved domains. According to the results of phylogenetic tree, we divided these members into 12 groups with specific gene structures and motif compositions. The corresponding genes that harbor a large number of segmental duplication events are unevenly distributed on the 17 poplar chromosomes. In addition, we further examined collinearity between these genes and the related genes from six other species. Evidence from transcriptomic data indicated that the bZIP genes in poplar displayed different expression patterns in roots, stems, and leaves. Furthermore, we identified 45 bZIP genes that respond to salt stress in the three tissues. We performed co-expression analysis on the representative genes, followed by gene set enrichment analysis. The results demonstrated that tissue differentially expressed genes, especially the co-expressing genes, are mainly involved in secondary metabolic and secondary metabolite biosynthetic processes. However, salt stress responsive genes and their co-expressing genes mainly participate in the regulation of metal ion transport, and methionine biosynthetic. Conclusions Using comparative genomics and systems biology approaches, we, for the first time, systematically explore the structures and functions of the bZIP gene family in poplar. It appears that the bZIP gene family plays significant roles in regulation of poplar development and growth and salt stress responses through differential gene networks or biological processes. These findings provide the foundation for genetic breeding by engineering target regulators and corresponding gene networks into poplar lines.

scholarly journals Efficacy and Safety of Teriflunomide in Multiple Sclerosis across Age Groups: Analysis from Pooled Pivotal and Real-world Studies

2021 ◽  
Vol 13 ◽  
pp. 117957352110287
Author(s):  
Jiwon Oh ◽  
Sandra Vukusic ◽  
Klaus Tiel-Wilck ◽  
Jihad Said Inshasi ◽  
David Rog ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Real World ◽  
Age Groups ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Additional Group ◽  
Disability Status ◽  
Scale Scores ◽  
Post Hoc ◽  
Phase Ii And Iii

Background: Evidence suggests that efficacy and safety of disease-modifying treatments for multiple sclerosis may differ with age. We evaluate efficacy and safety of teriflunomide across age subgroups of patients from pooled clinical trials and real-world studies. Methods: Post hoc analyses of patients who received teriflunomide 14 mg in the pooled phase II and III TEMSO, TOWER, TENERE, and TOPIC core and extension studies (n = 1978), and the real-world Teri-PRO (n = 928) and TAURUS-MS I (n = 1126) studies were conducted. Data were stratified by age at study entry: ⩽25, >25 to ⩽35, >35 to ⩽45, and >45 years. In Teri-PRO and TAURUS-MS I, an additional group, >55 years, was assessed. Results: In the pooled core studies, teriflunomide reduced annualized relapse rate (ARR) versus placebo across all ages. Unadjusted ARRs remained low across age groups in pooled extensions (0.18-0.30), Teri-PRO (0.10-0.35), and TAURUS-MS I (0.14-0.35). Baseline Expanded Disability Status Scale scores were higher with age, but stable through core and extension studies (mean increases over 7 years: ⩽25 years, +0.59; >25 to ⩽35 years, +0.46; >35 to ⩽45 years, +0.35; >45 years, +0.81). Across age groups, adverse event (AE) incidences were 78.4% to 90.7% in pooled core and extension studies and Teri-PRO, and 29.2% to 37.7% in TAURUS-MS I; serious AE incidences were ⩽21.3% in all studies. In pooled phase III and Teri-PRO studies, lymphocyte count decreases over 1 year after initiating teriflunomide, and proportions of patients developing lymphopenia, were small across age groups. Conclusions: Teriflunomide efficacy was demonstrated regardless of age. Safety was generally consistent across age groups.

scholarly journals Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC

2017 ◽  
Vol 114 (37) ◽  
pp. E7697-E7706 ◽  
Author(s):  
Kiyotoshi Satoh ◽  
Shinichi Yachida ◽  
Masahiro Sugimoto ◽  
Minoru Oshima ◽  
Toshitaka Nakagawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Gene Mutations ◽  
Metabolic Reprogramming ◽  
Colorectal Carcinogenesis ◽  
Specific Gene ◽  
Control Mechanisms ◽  
Pyrimidine Synthesis ◽  
Expression Of Genes

Cancer cells alter their metabolism for the production of precursors of macromolecules. However, the control mechanisms underlying this reprogramming are poorly understood. Here we show that metabolic reprogramming of colorectal cancer is caused chiefly by aberrant MYC expression. Multiomics-based analyses of paired normal and tumor tissues from 275 patients with colorectal cancer revealed that metabolic alterations occur at the adenoma stage of carcinogenesis, in a manner not associated with specific gene mutations involved in colorectal carcinogenesis. MYC expression induced at least 215 metabolic reactions by changing the expression levels of 121 metabolic genes and 39 transporter genes. Further, MYC negatively regulated the expression of genes involved in mitochondrial biogenesis and maintenance but positively regulated genes involved in DNA and histone methylation. Knockdown of MYC in colorectal cancer cells reset the altered metabolism and suppressed cell growth. Moreover, inhibition of MYC target pyrimidine synthesis genes such as CAD, UMPS, and CTPS blocked cell growth, and thus are potential targets for colorectal cancer therapy.

scholarly journals Diabetes, hyperglycemia and its role in fitness for work

2020 ◽  
Author(s):  
Mirsaeed Attarchi ◽  
Seyed Mohammad Seyedmehdi
Keyword(s):  
Decision Making ◽  
Scientific Evidence ◽  
Review Article ◽  
Diabetic Patients ◽  
Efficacy And Safety ◽  
Ability To Work ◽  
Personal Risk ◽  
Fitness For Work ◽  
The World ◽  
Prevalent Disease

Introduction: Diabetes is a prevalent disease in our country and in the world. Hyperglycemia complications can impact on ability to work. Decision making about fitness for work in diabetic patients is important and complicated. The aim of this study was assessment scientific evidence and present suitable approach for fitness for work in diabetic patients. Methods: In this review article the last evidence from Scopus, Science Direct, Pub Med, Google Scholar, SID and Magiran Data Base was evaluated and different aspects of fitness for work in hyperglycemia of diabetics of diabetic patients was analyzed. Results: Assessment of personal risk and diabetic patient abilities in comparison with inherent requirements of the job is important in decision making about fitness for work. Most of these patients can work and have acceptable efficacy and safety in most of the jobs. Conclusion: In most of job situations, with support of the employer and job environment modifications, diabetic patients can work with acceptable efficacy and safety.

scholarly journals Efficacy and safety of sodium valproate plus lamotrigine in children with refractory epilepsy

2020 ◽  
Author(s):  
Dongli Zhang ◽  
Li Qiu ◽  
Yuan Zhang ◽  
Yan Sang ◽  
Nuo Zheng ◽  
...  
Keyword(s):  
Sodium Valproate ◽  
Refractory Epilepsy ◽  
Efficacy And Safety
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