Network medicine is an emerging area of research dealing with molecular and genetic interactions, network biomarkers of disease, and therapeutic target discovery. Large-scale biomedical data ...generation offers a unique opportunity to assess the effect and impact of cellular heterogeneity and environmental perturbations on the observed phenotype. Marrying the two, network medicine with biomedical data provides a framework to build meaningful models and extract impactful results at a network level. In this review, we survey existing network types and biomedical data sources. More importantly, we delve into ways in which the network medicine approach, aided by phenotype-specific biomedical data, can be gainfully applied. We provide three paradigms, mainly dealing with three major biological network archetypes: protein-protein interaction, expression-based, and gene regulatory networks. For each of these paradigms, we discuss a broad overview of philosophies under which various network methods work. We also provide a few examples in each paradigm as a test case of its successful application. Finally, we delineate several opportunities and challenges in the field of network medicine. We hope this review provides a lexicon for researchers from biological sciences and network theory to come on the same page to work on research areas that require interdisciplinary expertise. Taken together, the understanding gained from combining biomedical data with networks can be useful for characterizing disease etiologies and identifying therapeutic targets, which, in turn, will lead to better preventive medicine with translational impact on personalized healthcare.
MicroRNAs (miRNAs) are a class of small, endogenous RNAs of 21–25 nucleotides (nts) in length. They play an important regulatory role in animals and plants by targeting specific mRNAs for degradation ...or translation repression. Recent scientific advances have revealed the synthesis pathways and the regulatory mechanisms of miRNAs in animals and plants. miRNA-based regulation is implicated in disease etiology and has been studied for treatment. Furthermore, several preclinical and clinical trials have been initiated for miRNA-based therapeutics. In this review, the existing knowledge about miRNAs synthesis, mechanisms for regulation of the genome, and their widespread functions in animals and plants is summarized. The current status of preclinical and clinical trials regarding miRNA therapeutics is also reviewed. The recent findings in miRNA studies, summarized in this review, may add new dimensions to small RNA biology and miRNA therapeutics.
The wide occurrence of microplastics (MPs) and nanoparticles resulted in their inevitable coexistence in environment. However, the joint effects of these two types of particulate emerging ...contaminants on denitrification have seldomly been investigated. Herein, non-biodegradable polyvinyl chloride, polypropylene, polyethylene and biodegradable polyhydroxyalkanoate (PHA) MPs were chosen to perform the co-occurrent effects with nano copper oxide (nano-CuO). Both the nano-CuO and MPs inhibited the denitrification process, and biodegradable PHA-MPs showed severer inhibition than non-biodegradable MPs. However, the presence of MPs significantly alleviated the inhibition of nano-CuO, suggesting an antagonistic effect. Other than MPs decreasing copper ion release from nano-CuO, MPs and nano-CuO formed agglomerations and induced lower levels of oxidative stress compared to individual exposure. Transcriptome analysis indicated that the co-occurrent MPs and nano-CuO induced different regulation on denitrifying genes (e. g. nar and nor) compared to individual ones. Also, the expressions of genes involved in denitrification-associated metabolic pathways, including glycolysis and NADH electron transfer, were down-regulated by nano-CuO or MPs, but exhibiting recovery under the co-occurrent conditions. This study firstly discloses the antagonistic effect of nano-CuO and MPs on environmental process, and these findings will benefit the systematic evaluation of MPs environmental behavior and co-occurrent risk with other pollutants.
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•Individual and joint effects of MPs and nano-CuO on denitrification were researched.•Biodegradable PHA-MPs showed severer inhibition compared to non-biodegradable MPs.•The presence of MPs significantly decreased inhibition effects of nano-CuO.•Co-occurrent MPs and nano-CuO induced lower ROS levels compared to nano-CuO.•MPs alleviated the inhibition of nano-CuO on glycolysis-related gene expressions.
The over-prescription of opioid analgesics is a growing problem in the field of addiction, which has reached epidemic-like proportions in North America. Over the past decade, oxycodone has gained ...attention as the leading opioid responsible for the North America opioid crisis. Oxycodone is the most incriminated drug in the early years of the epidemic of opioid use disorder in USA (roughly 1999-2016). The number of preclinical articles on oxycodone is rapidly increasing. Several publications have already compared oxycodone with other opioids, focusing mainly on their analgesic properties. The aim of this review is to focus on the genomic and epigenetic regulatory features of oxycodone compared with other opioid agonists. Our aim is to initiate a discussion of perceptible differences in the pharmacological response observed with these various opioids, particularly after repeated administration in preclinical models commonly used to study drug dependence potential.
In recent years, there has been significant progress toward understanding the transcriptional networks underlying mammalian immune responses, fueled by advances in regulatory genomic technologies. ...Epigenomic studies profiling immune cells have generated detailed genome‐wide maps of regulatory elements that will be key to deciphering the regulatory networks underlying cellular immune responses and autoimmune disorders. Unbiased analyses of these genomic maps have uncovered endogenous retroviruses as an unexpected ally in the regulation of human immune systems. Despite their parasitic origins, studies are finding an increasing number of examples of retroviral sequences having been co‐opted for beneficial immune function and regulation by the host cell. Here, we review how endogenous retroviruses have given rise to numerous regulatory elements that shape the epigenetic landscape of host immune responses. We will discuss the implications of these elements on the function, dysfunction, and evolution of innate immunity.
The crucial need for safe and healthy aquatic animals obligates researchers in aquaculture to investigate alternative and beneficial additives. Medicinal herbals and their extracts are compromised ...with diverse effects on the performances of aquatic animals. These compounds can affect growth performance and stimulate the immune system when used in fish diet. In addition, the use of medicinal herbs and their extracts can reduce oxidative stress induced by several stressors during fish culture. Correspondingly, aquatic animals could gain increased resistance against infectious pathogens and environmental stressors. Nevertheless, the exact mode of action where these additives can affect aquatic animals’ performances is still not well documented. Understanding the mechanistic role of herbal supplements and their derivatives is a vital tool to develop further the strategies and application of these additives for feasible and sustainable aquaculture. Gene-related studies have clarified the detailed information on the herbal supplements’ mode of action when administered orally in aquafeed. Several review articles have presented the potential roles of medicinal herbs on the performances of aquatic animals. However, this review article discusses the outputs of studies conducted on aquatic animals fed dietary, medicinal herbs, focusing on the gene expression related to growth and immune performances. Furthermore, a particular focus is directed to the expected influence of herbal supplements on the reproduction of aquatic animals.
In response to extracellular and intracellular stressors, the nucleus and nuclear compartments undergo distinct molecular changes to maintain cell homeostasis. In the context of Alzheimer's disease, ...misfolded proteins and various cellular stressors lead to profound structural and molecular changes at the nucleus. This review summarizes recent research on nuclear alterations in AD development, from the nuclear envelope changes to chromatin and epigenetic regulation and then to common nuclear stress responses. Finally, we provide our thoughts on the importance of understanding cell-type-specific changes and identifying upstream causal events in AD pathogenesis and highlight novel sequencing and gene perturbation technologies to address those challenges.
Phosphofructokinase-1 (PFK-1), a rate-determining enzyme of glycolysis, is an allosteric enzyme that regulates the oxidation of glucose in cellular respiration. Glycolysis phosphofructokinase ...platelet (PFKP) is the platelet isoform and works as an important mediator of cell metabolism. Considering that PFKP is a crucial player in many steps of cancer initiation and metastasis, we reviewed the specificities and complexities of PFKP and its biological roles in human diseases, especially malignant tumors. The possible use of PFKP as a diagnostic marker or a drug target in the prevention or treatment of cancer is also discussed.
Over the past few decades, regulatory RNAs, such as small RNAs (sRNAs), have received increasing attention in the context of host-microbe interactions due to their diverse roles in controlling ...various biological processes in eukaryotes. In addition, studies have identified an increasing number of sRNAs with novel functions across a wide range of bacteria. What is not well understood is why cells regulate gene expression through post-transcriptional mechanisms rather than at the initiation of transcription. The finding of a multitude of sRNAs and their identified associated targets has allowed further investigation into the role of sRNAs in mediating gene regulation. These foundational data allow for further development of hypotheses concerning how a precise control of gene activity is accomplished through the combination of transcriptional and post-transcriptional regulation. Recently, sRNAs have been reported to participate in interkingdom communication and signalling where sRNAs originating from one kingdom are able to target or control gene expression in another kingdom. For example, small RNAs of fungal pathogens that silence plant genes and vice-versa plant sRNAs that mediate bacterial gene expression. However, there is currently a lack of evidence regarding sRNA-based inter-kingdom signalling across more than two interacting organisms. A habitat that provides an excellent opportunity to investigate interconnectivity is the plant rhizosphere, a multifaceted ecosystem where plants and associated soil microbes are known to interact. In this paper, we discuss how the interconnectivity of bacteria, fungi, and plants within the rhizosphere may be mediated by bacterial sRNAs with a particular focus on disease suppressive and non-suppressive soils. We discuss the potential roles sRNAs may play in the below-ground world and identify potential areas of future research, particularly in reference to the regulation of plant immunity genes by bacterial and fungal communities in disease-suppressive and non-disease-suppressive soils.
Myocardial infarction has been the leading cause of morbidity and mortality in developed countries over the past few decades. The transplantation of cardiomyocytes offers a potential method of ...treatment. However, cardiomyocytes are in high demand and their supply is extremely limited. Embryonic stem cells (ESCs), which have been isolated from the inner cell mass of blastocysts, can self-renew and are pluripotent, meaning they have the ability to develop into any type of cell, including cardiomyocytes. This suggests that ESCs could be a good source of genuine cardiomyocytes for future therapeutic purposes. However, problems with the yield and purity of ESC-derived cardiomyocytes, among other hurdles for the therapeutic application of ESC-derived cardiomyocytes (e.g., potential immunorejection and tumor formation problems), need to be overcome before these cells can be used effectively for cell replacement therapy. ESC-derived cardiomyocytes consist of nodal, atrial, and ventricular cardiomyocytes. Specifically, for treatment of myocardial infarction, transplantation of a sufficient quantity of ventricular cardiomyocytes, rather than nodal or atrial cardiomyocytes, is preferred. Hence, it is important to find ways of increasing the yield and purity of specific types of cardiomyocytes. Atrial and ventricular cardiomyocytes have differential expression of genes (transcription factors, structural proteins, ion channels, etc.) and are functionally distinct. This paper presents a thorough review of differential gene expression in atrial and ventricular myocytes, their expression throughout development, and their regulation. An understanding of the molecular and functional differences between atrial and ventricular myocytes allows discussion of potential strategies for preferentially directing ESCs to differentiate into chamber-specific cells, or for fine tuning the ESC-derived cardiomyocytes into specific electrical and contractile phenotypes resembling chamber-specific cells.
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