AdoMet analog synthesis and utilization: current state of the art.
Ontology highlight
ABSTRACT:
SUBMITTER: Huber TD
PROVIDER: S-EPMC5138144 | biostudies-literature | 2016 Dec
REPOSITORIES: biostudies-literature
Publications
AdoMet analog synthesis and utilization: current state of the art.
Huber Tyler D TD Johnson Brooke R BR Zhang Jianjun J Thorson Jon S JS
Current opinion in biotechnology 20160806
S-Adenosyl-l-methionine (AdoMet) is an essential enzyme cosubstrate in fundamental biology with an expanding range of biocatalytic and therapeutic applications. In recent years, technologies enabling the synthesis and utilization of novel functional AdoMet surrogates have rapidly advanced. Developments highlighted within this brief review include improved syntheses of AdoMet analogs, unique S-adenosyl-l-methionine isosteres with enhanced stability, and corresponding applications in epigenetics, ...[more]
Similar Datasets
Project description:The completion of the human genome project 10 years ago was met with great optimism for improving drug therapy through personalized medicine approaches, with the anticipation that an era of genotype-guided patient prescribing was imminent. To some extent this has come to pass and a number of key pharmacogenomics markers of inter-individual drug response, for both safety and efficacy, have been identified and subsequently been adopted in clinical practice as pre-treatment genetic tests. However, the universal application of genetics in treatment guidance is still a long way off. This review will highlight important pharmacogenomic discoveries which have been facilitated by the human genome project and other milestone projects such as the International HapMap and 1000 genomes, and by the continued development of genotyping and sequencing technologies, including rapid point of care pre-treatment genetic testing. However, there are still many challenges to implementation for the many other reported biomarkers which continue to languish within the discovery phase. As technology advances over the next 10 years, and the costs fall, the field will see larger genetic data sets, including affordable whole genome sequences, which will, it is hoped, improve patient outcomes through better diagnostic, prognostic and predictive biomarkers.
| S-EPMC4094941 | biostudies-literature
Project description:Microglia are the tissue macrophages of the central nervous system (CNS) and the first to respond to CNS dysfunction and disease. Gene expression profiling of microglia during development, under homeostatic conditions and in the diseased CNS provided insight in microglia functions and changes thereof. Single cell sequencing studies further contributed to our understanding of microglia heterogeneity in relation to age, sex and CNS disease. Recently, single nucleus gene expression profiling was performed on (frozen) CNS tissue. Transcriptomic profiling of CNS tissues by (single) nucleus RNA-sequencing has the advantage that it can be applied to archived and well stratified frozen specimens. Here, we give an overview of the significant advances recently made in microglia transcriptional profiling. In addition, we present matched cellular and nuclear microglia RNA-seq datasets we generated from mouse and human CNS tissue to compare cellular versus nuclear transcriptomes from fresh and frozen samples. We demonstrate that microglia can be similarly profiled with cell and nucleus profiling, and importantly also with nuclei isolated from frozen tissue. Nuclear microglia transcriptomes are a reliable proxy for cellular transcriptomes. Interestingly, lipopolysaccharide- (LPS)-induced changes in gene expression were even more pronounced in the nuclear transcriptome. In addition, heterogeneity in microglia observed in fresh samples is similarly detected in frozen nuclei of the same donor. Together, these results show that microglia nuclear RNAs obtained from frozen CNS tissue are a reliable proxy for microglia gene expression and cellular heterogeneity and may prove an effective strategy to study of the role of microglia in neuropathology.
2019-08-10 | GSE135618 | GEO
Project description:Histamine intolerance, also referred to as enteral histaminosis or sensitivity to dietary histamine, is a disorder associated with an impaired ability to metabolize ingested histamine that was described at the beginning of the 21st century. Although interest in histamine intolerance has considerably grown in recent years, more scientific evidence is still required to help define, diagnose and clinically manage this condition. This article will provide an updated review on histamine intolerance, mainly focusing on its etiology and the existing diagnostic and treatment strategies. In this work, a glance on histamine intoxication will also be provided, as well as the analysis of some uncertainties historically associated to histamine intoxication outbreaks that may be better explained by the existence of interindividual susceptibility to ingested histamine.
| S-EPMC7463562 | biostudies-literature
Project description:Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy that generally conveys a poor prognosis. Currently, surgical resection is considered the lone curative treatment modality. In addition, the low prevalence of ACC has limited effective clinical trial design to develop evidence-based approaches to ACC therapy. The proper role of radio- and chemotherapy treatment for ACC is still being defined. Similarly, the molecular pathogenesis of ACC remains to be fully characterized. Despite these challenges, progress has been made in several areas. After years of refinement, an internationally accepted staging system has been defined. International collaborations have facilitated increasingly robust clinical trials, especially regarding agent choice and patient selection for chemotherapeutics. Genetic array data and molecular profiling have identified new potential targets for rational drug design as well as potential tumor markers and predictors of therapeutic response. However, these advances have not yet been translated into a large outcomes benefit for ACC patients. In this paper, we summarize established therapy for ACC and highlight recent findings in the field that are impacting clinical practice.
| S-EPMC3483813 | biostudies-literature
Project description:After decades of efforts, we have recently made progress into targeting KRAS mutations in several malignancies. Known as the 'holy grail' of targeted cancer therapies, KRAS is the most frequently mutated oncogene in human malignancies. Under normal conditions, KRAS shuttles between the GDP-bound 'off' state and the GTP-bound 'on' state. Mutant KRAS is constitutively activated and leads to persistent downstream signaling and oncogenesis. In 2013, improved understanding of KRAS biology and newer drug designing technologies led to the crucial discovery of a cysteine drug-binding pocket in GDP-bound mutant KRAS G12C protein. Covalent inhibitors that block mutant KRAS G12C were successfully developed and sotorasib was the first KRAS G12C inhibitor to be approved, with several more in the pipeline. Simultaneously, effects of KRAS mutations on tumour microenvironment were also discovered, partly owing to the universal use of immune checkpoint inhibitors. In this review, we discuss the discovery, biology, and function of KRAS in human malignancies. We also discuss the relationship between KRAS mutations and the tumour microenvironment, and therapeutic strategies to target KRAS. Finally, we review the current clinical evidence and ongoing clinical trials of novel agents targeting KRAS and shine light on resistance pathways known so far.
| S-EPMC9597994 | biostudies-literature
Project description:Breast cancer is the most commonly occurring invasive cancer among women and its estimated incidence rate worldwide is approximately 1 million cases annually. Although several breast cancer susceptibility genes have been identified over the past two decades, it is likely that many genes with modest effects are yet to be found. In this review, we discuss the progress that has been recently made with the emergence of empirical genome-wide association studies for breast cancer and the identification of several common, low-penetrance disease alleles at loci that had not been previously implicated as candidates for breast cancer susceptibility. We also discuss the implications of these recent findings for risk prediction, targeted screening and public health interventions, and conclude by discussing the strengths and weaknesses of these studies, and the strategies required to identify additional risk factors for breast cancer.
| S-EPMC4931895 | biostudies-literature
Project description:Many skin conditions are associated with an imbalance in the skin microbiome. In recent years, the skin microbiome has become a hot topic, for both therapeutic and cosmetic purposes. The possibility of manipulating the human skin microbiome to address skin conditions has opened exciting new paths for therapy. Here we review the skin microbiome manipulation strategies, ranging from skin microbiome transplantation, over skin bacteriotherapy to the use of prebiotics, probiotics and postbiotics. We summarize all efforts undertaken to exchange, manipulate, transplant or selectively apply the skin microbiome to date. Multiple microbial groups have been targeted, since they have been proven to be beneficial for skin health. We focus on the most common skin disorders and their associated skin microbiome dysbiosis and we review the existing scientific data and clinical trials undertaken to combat these skin conditions. The skin microbiome represents a novel platform for therapy. Transplantation of a complete microbiome or application of single strains has demonstrated beneficial therapeutic application.
| S-EPMC7806958 | biostudies-literature
Project description:Fabry disease (FD) is a lysosomal storage disorder caused by mutations of the GLA gene that lead to a deficiency of the enzymatic activity of α-galactosidase A. Available therapies for FD include enzyme replacement therapy (ERT) (agalsidase alfa and agalsidase beta) and the chaperone migalastat. Despite the large body of literature published about ERT over the years, many issues remain unresolved, such as the optimal dose, the best timing to start therapy, and the clinical impact of anti-drug antibodies. Migalastat was recently approved for FD patients with amenable GLA mutations; however, recent studies have raised concerns that "in vitro" amenability may not always reflect "in vivo" amenability, and some findings on real-life studies have contrasted with the results of the pivotal clinical trials. Moreover, both FD specific therapies present limitations, and the attempt to correct the enzymatic deficiency, either by enzyme exogenous administration or enzyme stabilization with a chaperone, has not shown to be able to fully revert FD pathology and clinical manifestations. Therefore, several new therapies are under research, including new forms of ERT, substrate reduction therapy, mRNA therapy, and gene therapy. In this review, we provide an overview of the state-of-the-art on the currently approved and emerging new therapies for adult patients with FD.
| S-EPMC7794923 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a malignancy that requires multidisciplinary evaluation to develop individualized and tailored treatment concepts. While liver resection and transplantation represent the mainstay of curative treatment in patients with early-stage HCC, disease recurrence remains an important burden. Immune checkpoint inhibitors (ICI) have become standard of care in the palliative setting, achieving promising response rates with overall good tolerability. Accordingly, ICIs are being evaluated in (neo)adjuvant concepts in order to improve survival. Nevertheless, neoadjuvant therapies are not recommended by current guidelines as they have not been proven to improve the outcome in large Phase III trials yet. Especially in the context of liver transplantation (LT), perioperative ICI usage is in need of a particularly critical risk-benefit assessment, as the immunotherapy may significantly increase the risk of rejection. In this review, we summarize available data on ICI-based perioperative treatment strategies in HCC. We discuss current drawbacks and challenges of this treatment concept and specifically highlight the risk of allograft rejection when ICI are given in patients (subsequently) considered for liver transplantation.
| S-EPMC9922501 | biostudies-literature
Project description:Cancer kills 8 million annually worldwide. Although survival rates in prevalent cancers continue to increase, many cancers have no effective treatment, prompting the search for new and improved protocols. Immunotherapy is a new and exciting addition to the anti-cancer arsenal. The successful and accurate identification of aberrant host proteins acting as antigens for vaccination and immunotherapy is a key aspiration for both experimental and computational research. Here we describe key elements of in silico prediction, including databases of cancer antigens and bleeding-edge methodology for their prediction. We also highlight the role dendritic cell vaccines can play and how they can act as delivery mechanisms for epitope ensemble vaccines. Immunoinformatics can help streamline the discovery and utility of Cancer Immunogens.
| S-EPMC5856276 | biostudies-literature