scholarly journals Emerging Insights into the Metabolic Alterations in Aging Using Metabolomics

Metabolites ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 301 ◽  
Author(s):  
Sarika Srivastava
Keyword(s):  
Biomarker Discovery ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Cellular Tissue ◽  
Model Organisms ◽  
Biological Mechanisms ◽  
Comprehensive Overview ◽  
Biomarkers Of Aging ◽  
Complex Biological Process ◽  
Novel Biomarkers

Metabolomics is the latest ‘omics’ technology and systems biology science that allows for comprehensive profiling of small-molecule metabolites in biological systems at a specific time and condition. Metabolites are cellular intermediate products of metabolic reactions, which reflect the ultimate response to genomic, transcriptomic, proteomic, or environmental changes in a biological system. Aging is a complex biological process that is characterized by a gradual and progressive decline in molecular, cellular, tissue, organ, and organismal functions, and it is influenced by a combination of genetic, environmental, diet, and lifestyle factors. The precise biological mechanisms of aging remain unknown. Metabolomics has emerged as a powerful tool to characterize the organism phenotypes, identify altered metabolites, pathways, novel biomarkers in aging and disease, and offers wide clinical applications. Here, I will provide a comprehensive overview of our current knowledge on metabolomics led studies in aging with particular emphasis on studies leading to biomarker discovery. Based on the data obtained from model organisms and humans, it is evident that metabolites associated with amino acids, lipids, carbohydrate, and redox metabolism may serve as biomarkers of aging and/or longevity. Current challenges and key questions that should be addressed in the future to advance our understanding of the biological mechanisms of aging are discussed.

scholarly journals In control of biology: of mice, men and Foxes

2006 ◽  
Vol 397 (2) ◽  
pp. 233-246 ◽  
Author(s):  
Patrick J. E. C. Wijchers ◽  
J. Peter H. Burbach ◽  
Marten P. Smidt
Keyword(s):  
Transcription Factors ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Model Organisms ◽  
Functional Protein ◽  
Comprehensive Overview ◽  
Developmental Defects ◽  
Forkhead Transcription Factors ◽  
Human Pathology ◽  
Forkhead Gene

Forkhead proteins comprise a highly conserved family of transcription factors, named after the original forkhead gene in Drosophila. To date, over 100 forkhead genes have been identified in a large variety of species, all sharing the evolutionary conserved ‘forkhead’ DNA-binding domain, and the cloning and characterization of forkhead genes have continued in recent years. Forkhead transcription factors regulate the expression of countless genes downstream of important signalling pathways in most, if not all, tissues and cell types. Recent work has provided novel insights into the mechanisms that contribute to their functional diversity, including functional protein domains and interactions of forkheads with other transcription factors. Studies using loss- and gain-of-function models have elucidated the role of forkhead factors in developmental biology and cellular functions such as metabolism, cell division and cell survival. The importance of forkhead transcription factors is underlined by the developmental defects observed in mutant model organisms, and multiple human disorders and cancers which can be attributed to mutations within members of the forkhead gene family. This review provides a comprehensive overview of current knowledge on forkhead transcription factors, from structural organization and regulatory mechanisms to cellular and developmental functions in mice and humans. Finally, we will discuss how novel insights gained from involvement of ‘Foxes’ in the mechanisms underlying human pathology may create new opportunities for treatment strategies.

scholarly journals Drosophila Short stop as a paradigm for the role and regulation of spectraplakins

2017 ◽  
Author(s):  
Andre Voelzmann ◽  
Yu-Ting Liew ◽  
Yue Qu ◽  
Ines Hahn ◽  
Cristina Melero ◽  
...  
Keyword(s):  
Genetic Model ◽  
Current Knowledge ◽  
Fruit Fly ◽  
Model Organisms ◽  
Functional Domains ◽  
Cellular Functions ◽  
Comprehensive Overview ◽  
Characteristic Functional ◽  
Intracellular Organelles ◽  
Linker Molecules

AbstractSpectraplakins are evolutionarily well conserved cytoskeletal linker molecules that are true members of three protein families: plakins, spectrins and Gas2-like proteins. Spectraplakin genes encode at least 7 characteristic functional domains which are combined in a modular fashion into multiple isoforms, and which are responsible for an enormous breadth of cellular functions. These functions are related to the regulation of actin, microtubules, intermediate filaments, intracellular organelles, cell adhesions and signalling processes during the development and maintenance of a wide variety of tissues. To gain a deeper understanding of this enormous functional diversity, invertebrate genetic model organisms, such as the fruit fly Drosophila, can be used to develop concepts and mechanistic paradigms that can inform the investigation in higher animals or humans. Here we provide a comprehensive overview of our current knowledge of the Drosophila spectraplakin Short stop (Shot). We describe its functional domains and isoforms and compare them with those of the mammalian spectraplakins dystonin and MACF1. We then summarise its roles during the development and maintenance of the nervous system, epithelia, oocytes and muscles, taking care to compare and contrast mechanistic insights across these functions in the fly, but especially also with related functions of dystonin and MACF1 in mostly mammalian contexts. We hope that this review will improve the wider appreciation of how work on Drosophila Shot can be used as an efficient strategy to promote the fundamental concepts and mechanisms that underpin spectraplakin functions, with important implications for biomedical research into human disease.

The glycomes of Caenorhabditis elegans and other model organisms

2002 ◽  
Vol 69 ◽  
pp. 117-134 ◽  
Author(s):  
Stuart M. Haslam ◽  
David Gems ◽  
Howard R. Morris ◽  
Anne Dell
Keyword(s):  
Caenorhabditis Elegans ◽  
Current Knowledge ◽  
Structural Data ◽  
Model Organisms ◽  
Entire Genome ◽  
C Elegans ◽  
The Face ◽  
Area Of Concern ◽  
Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

Role of Regulatory Oncogenic or Tumor Suppressor miRNAs of PI3K/AKT Signaling Axis in the Pathogenesis of Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4605-4610 ◽  
Author(s):  
Atena Soleimani ◽  
Farzad Rahmani ◽  
Gordon A. Ferns ◽  
Mikhail Ryzhikov ◽  
Amir Avan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Current Knowledge ◽  
Akt Signaling ◽  
Tumor Tissues ◽  
Radio Therapy ◽  
Signaling Axis ◽  
Cancer Tumor ◽  
Novel Biomarkers

Colorectal cancer (CRC) is the leading cause of cancer death worldwide and its incidence is increasing. In most patients with CRC, the PI3K/AKT signaling axis is over-activated. Regulatory oncogenic or tumor suppressor microRNAs (miRNAs) for PI3K/AKT signaling regulate cell proliferation, migration, invasion, angiogenesis, as well as resistance to chemo-/radio-therapy in colorectal cancer tumor tissues. Thus, regulatory miRNAs of PI3K/AKT/mTOR signaling represent novel biomarkers for new patient diagnosis and obtaining clinically invaluable information from post-treatment CRC patients for improving therapeutic strategies. This review summarizes the current knowledge of miRNAs’ regulatory roles of PI3K/AKT signaling in CRC pathogenesis.

Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

2020 ◽  
Vol 19 (2) ◽  
pp. 176-192
Author(s):  
Samantha Bedell ◽  
Janine Hutson ◽  
Barbra de Vrijer ◽  
Genevieve Eastabrook
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Maternal Obesity ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Placental Development ◽  
Exchange Site ◽  
And Function

: Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

Disparities in Health Between Black and White Americans: Current Knowledge and Directions for Future Research

2018 ◽  
pp. 456-478
Author(s):  
Thomas E. Fuller-Rowell ◽  
David S. Curtis ◽  
Adrienne M. Duke
Keyword(s):  
Health Disparities ◽  
Current Knowledge ◽  
Public Investment ◽  
The United States ◽  
Future Research ◽  
Sociocultural Factors ◽  
White Americans ◽  
Biological Mechanisms ◽  
Black And White ◽  
Racial Ethnic

Conceptual frameworks for racial/ethnic health disparities are abundant, but many have received insufficient empirical attention. As a result, there are substantial gaps in scientific knowledge and a range of untested hypotheses. Particularly lacking is specificity in behavioral and biological mechanisms for such disparities and their underlying social determinants. Alongside lack of political will and public investment, insufficient clarity in mechanisms has stymied efforts to address racial health disparities. Capitalizing on emergent findings from the Midlife in the United States (MIDUS) study and other longitudinal studies of aging, this chapter evaluates research on health disparities between black and white US adults. Attention is given to candidate behavioral and biological mechanisms as precursors to group differences in morbidity and mortality and to environmental and sociocultural factors that may underlie these mechanisms. Future research topics are discussed, emphasizing those that offer promise with respect to illuminating practical solutions to racial/ethnic health disparities.

scholarly journals Significance of indeterminate pulmonary nodules in resectable pancreatic adenocarcinoma—a review

2021 ◽  
Author(s):  
Li Lian Kuan ◽  
Ashley R. Dennison ◽  
Giuseppe Garcea
Keyword(s):  
Overall Survival ◽  
Pancreatic Adenocarcinoma ◽  
Median Overall Survival ◽  
Current Knowledge ◽  
Pulmonary Nodules ◽  
Preoperative Imaging ◽  
Significant Finding ◽  
Comprehensive Overview ◽  
Significant Difference ◽  
Clinical Dilemma

Abstract Background The clinical significance of indeterminate pulmonary nodules (IPN) in patients with resectable pancreatic adenocarcinoma (PDAC) is unknown. The rate of detection on IPN has risen due to enhanced staging investigations to determine resectability. IPNs detected on preoperative imaging represent a clinical dilemma and complicate decision-making. Currently, there are no recommendations on the management of IPN. This review provides a comprehensive overview of the current knowledge on the natural history of IPN detected among patients with resectable PDAC. Methods A systematic review based on a search in Medline and Embase databases was performed. All clinical studies evaluating the significance of IPN in patients with resectable PDAC were included. PRISMA guidelines were followed. Results Five studies met the inclusion criteria. The total patient population was 761. The prevalence of IPN reported ranged from 18 to 71%. The median follow-up duration was 17 months. The median overall survival was 19 months. Patients with pre-operative IPN which subsequently progressed to clinically recognizable pulmonary metastases, ranged from 1.5 to 16%. Four studies found that there was no significant difference in median overall survival in patients with or without IPNs. Conclusion This is a first review on the significance of IPN in patients with resectable PDAC. The preoperative presence of IPN does not demonstrate an association with overall survival after surgery. The identification of IPN is a significant finding however it should not preclude patients with resectable PDAC from undergoing curative resection.

scholarly journals Mining the plasma-proteome associated genes in patients with gastro-esophageal cancers for biomarker discovery

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Frederick S. Vizeacoumar ◽  
Hongyu Guo ◽  
Lynn Dwernychuk ◽  
Adnan Zaidi ◽  
Andrew Freywald ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
Predictive Accuracy ◽  
Area Under The Curve ◽  
Cancer Recurrence ◽  
The Cancer Genome Atlas ◽  
Svm Classifier ◽  
Plasma Proteome ◽  
Cancer Genome Atlas ◽  
Novel Biomarkers ◽  
Evaluation Metric

AbstractGastro-esophageal (GE) cancers are one of the major causes of cancer-related death in the world. There is a need for novel biomarkers in the management of GE cancers, to yield predictive response to the available therapies. Our study aims to identify leading genes that are differentially regulated in patients with these cancers. We explored the expression data for those genes whose protein products can be detected in the plasma using the Cancer Genome Atlas to identify leading genes that are differentially regulated in patients with GE cancers. Our work predicted several candidates as potential biomarkers for distinct stages of GE cancers, including previously identified CST1, INHBA, STMN1, whose expression correlated with cancer recurrence, or resistance to adjuvant therapies or surgery. To define the predictive accuracy of these genes as possible biomarkers, we constructed a co-expression network and performed complex network analysis to measure the importance of the genes in terms of a ratio of closeness centrality (RCC). Furthermore, to measure the significance of these differentially regulated genes, we constructed an SVM classifier using machine learning approach and verified these genes by using receiver operator characteristic (ROC) curve as an evaluation metric. The area under the curve measure was > 0.9 for both the overexpressed and downregulated genes suggesting the potential use and reliability of these candidates as biomarkers. In summary, we identified leading differentially expressed genes in GE cancers that can be detected in the plasma proteome. These genes have potential to become diagnostic and therapeutic biomarkers for early detection of cancer, recurrence following surgery and for development of targeted treatment.

scholarly journals Research on Plants for the Understanding of Diseases of Nuclear and Mitochondrial Origin

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Claudia P. Spampinato ◽  
Diego F. Gomez-Casati
Keyword(s):  
Current Knowledge ◽  
Model System ◽  
Human Diseases ◽  
Model Organisms ◽  
Human Cell Lines ◽  
Molecular Defects ◽  
Human Genes ◽  
Clinical Disorders ◽  
Mitochondrial Origin ◽  
Experimental Findings

Different model organisms, such asEscherichia coli,Saccharomyces cerevisiae,Caenorhabditis elegans,Drosophila melanogaster, mouse, cultured human cell lines, among others, were used to study the mechanisms of several human diseases. Since human genes and proteins have been structurally and functionally conserved in plant organisms, the use of plants, especiallyArabidopsis thaliana, as a model system to relate molecular defects to clinical disorders has recently increased. Here, we briefly review our current knowledge of human diseases of nuclear and mitochondrial origin and summarize the experimental findings of plant homologs implicated in each process.

scholarly journals A Comprehensive Review on Eryptosis

2016 ◽  
Vol 39 (5) ◽  
pp. 1977-2000 ◽  
Author(s):  
Etheresia Pretorius ◽  
Jeanette N. du Plooy ◽  
Janette Bester
Keyword(s):  
Current Knowledge ◽  
Cell Model ◽  
Health Indicators ◽  
Comprehensive Overview ◽  
Ultrastructural Studies ◽  
Important Health ◽  
Membrane Changes ◽  
Cell Model System ◽  
Cell Changes

Erythrocytes (RBCs) are extremely sensitive cells, and although they do not have nuclei and mitochondria, are important health indicators. This is particularly true because, during inflammation, whether it is systemic or chronic, the haematological system is constantly exposed to circulating inflammatory mediators. RBCs have a highly specialized and organized membrane structure, which interacts and reacts to inflammatory molecule insults, and undergo programmed cell death, similar to apoptosis, known as eryptosis. Over the past years, eryptosis studies have focussed on determining if membrane changes have occurred, particularly whether a phosphatidylserine (PS) flip, Ca2+ leakage into the cell, changes to ceramide and cell shrinkage have occurred. Mostly, flow cytometry is used, but confocal microscopy and ultrastructural studies also confirm eryptosis. Here, we provide a comprehensive overview of eryptosis, where we revisit the biochemical process of the process, review all literature in PUBMED, that is shown under the search word, “eryptosis”, and also discuss current methodologies to determine the presence of eryptosis; included in the discussion of the methodologies, we discuss a pitfalls section for each method. This paper is therefore a comprehensive synopsis of current knowledge of eryptosis and discusses how RBCs may provide an essential in vivo cell model system to study not only inflammation in disease, but also track disease progression and treatment regimes.

Sign in / Sign up

Export Citation Format

Share Document