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Frontiers in Genome Editing 2024With scientific progress and the development of new genomic techniques (NGTs), the spectrum of organisms modified for various purposes is rapidly expanding and includes...
Horizon scanning of potential environmental applications of terrestrial animals, fish, algae and microorganisms produced by genetic modification, including the use of new genomic techniques.
With scientific progress and the development of new genomic techniques (NGTs), the spectrum of organisms modified for various purposes is rapidly expanding and includes a wide range of taxonomic groups. An improved understanding of which newly developed products may be introduced into the market and released into the environment in the near and more distant future is of particular interest for policymakers, regulatory authorities, and risk assessors. To address this information need, we conducted a horizon scanning (HS) of potential environmental applications in four groups of organisms: terrestrial animals (excluding insects and applications with gene drives), fish, algae and microorganisms. We applied a formal scoping review methodology comprising a structured search of the scientific literature followed by eligibility screening, complemented by a survey of grey literature, and regulatory websites and databases. In all four groups of organisms we identified a broad range of potential applications in stages of basic as well as advanced research, and a limited number of applications which are on, or ready to be placed on, the market. Research on GM animals including fish is focused on farmed animals and primarily targets traits which increase performance, influence reproduction, or convey resistance against diseases. GM algae identified in the HS were all unicellular, with more than half of the articles concerning biofuel production. GM algae applications for use in the environment include biocontrol and bioremediation, which are also the main applications identified for GM microorganisms. From a risk assessor's perspective these potential applications entail a multitude of possible pathways to harm. The current limited level of experience and limited amount of available scientific information could constitute a significant challenge in the near future, for which risk assessors and competent authorities urgently need to prepare.
PubMed: 38938511
DOI: 10.3389/fgeed.2024.1376927 -
Brain Sciences May 2024The role of the extracellular matrix (ECM) in Parkinson's disease (PD) is not well understood, even though it is critical for neuronal structure and signaling. This... (Review)
Review
The role of the extracellular matrix (ECM) in Parkinson's disease (PD) is not well understood, even though it is critical for neuronal structure and signaling. This systematic review identified the top deregulated ECM-related pathways in studies that used gene set enrichment analyses (GSEA) to document transcriptomic, proteomic, or genomic alterations in PD. PubMed and Google scholar were searched for transcriptomics, proteomics, or genomics studies that employed GSEA on data from PD tissues or cells and reported ECM-related pathways among the top-10 most enriched versus controls. Twenty-seven studies were included, two of which used multiple omics analyses. Transcriptomics and proteomics studies were conducted on a variety of tissue and cell types. Of the 17 transcriptomics studies (16 data sets), 13 identified one or more adhesion pathways in the top-10 deregulated gene sets or pathways, primarily related to cell adhesion and focal adhesion. Among the 8 proteomics studies, 5 identified altered overarching ECM gene sets or pathways among the top 10. Among the 4 genomics studies, 3 identified focal adhesion pathways among the top 10. The findings summarized here suggest that ECM organization/structure and cell adhesion (particularly focal adhesion) are altered in PD and should be the focus of future studies.
PubMed: 38928523
DOI: 10.3390/brainsci14060522 -
International Journal of Nanomedicine 2024Due to their ability to replicate the in vivo microenvironment through cell interaction and induce cells to stimulate cell function, three-dimensional cell culture... (Review)
Review
Due to their ability to replicate the in vivo microenvironment through cell interaction and induce cells to stimulate cell function, three-dimensional cell culture models can overcome the limitations of two-dimensional models. Organoids are 3D models that demonstrate the ability to replicate the natural structure of an organ. In most organoid tissue cultures, matrigel made of a mouse tumor extracellular matrix protein mixture is an essential ingredient. However, its tumor-derived origin, batch-to-batch variation, high cost, and safety concerns have limited the usefulness of organoid drug development and regenerative medicine. Its clinical application has also been hindered by the fact that organoid generation is dependent on the use of poorly defined matrices. Therefore, matrix optimization is a crucial step in developing organoid culture that introduces alternatives as different materials. Recently, a variety of substitute materials has reportedly replaced matrigel. The purpose of this study is to review the significance of the latest advances in materials for cell culture applications and how they enhance build network systems by generating proper cell behavior. Excellence in cell behavior is evaluated from their cell characteristics, cell proliferation, cell differentiation, and even gene expression. As a result, graphene oxide as a matrix optimization demonstrated high potency in developing organoid models. Graphene oxide can promote good cell behavior and is well known for having good biocompatibility. Hence, advances in matrix optimization of graphene oxide provide opportunities for the future development of advanced organoid models.
Topics: Organoids; Animals; Graphite; Humans; Cell Proliferation; Cell Differentiation; Drug Combinations; Cell Culture Techniques; Cell Culture Techniques, Three Dimensional; Mice; Laminin; Collagen; Proteoglycans
PubMed: 38911499
DOI: 10.2147/IJN.S455940 -
Biomedicine & Pharmacotherapy =... Jul 2024The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation and acetylation offer new perspectives... (Review)
Review
The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation and acetylation offer new perspectives on the pathogenesis and treatment of kidney diseases. lncRNAs, a class of transcripts longer than 200 nucleotides with no protein-coding potential, are now recognized as key regulatory molecules influencing gene expression through diverse mechanisms. They modulate the epigenetic modifications by recruiting or blocking enzymes responsible for adding or removing methyl or acetyl groups, such as DNA, N6-methyladenosine (m6A) and histone methylation and acetylation, subsequently altering chromatin structure and accessibility. In kidney diseases such as acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy (DN), glomerulonephritis (GN), and renal cell carcinoma (RCC), aberrant patterns of DNA/RNA/histone methylation and acetylation have been associated with disease onset and progression, revealing a complex interplay with lncRNA dynamics. Recent studies have highlighted how lncRNAs can impact renal pathology by affecting the expression and function of key genes involved in cell cycle control, fibrosis, and inflammatory responses. This review will separately address the roles of lncRNAs and epigenetic modifications in renal diseases, with a particular emphasis on elucidating the bidirectional regulatory effects and underlying mechanisms of lncRNAs in conjunction with DNA/RNA/histone methylation and acetylation, in addition to the potential exacerbating or renoprotective effects in renal pathologies. Understanding the reciprocal relationships between lncRNAs and epigenetic modifications will not only shed light on the molecular underpinnings of renal pathologies but also present new avenues for therapeutic interventions and biomarker development, advancing precision medicine in nephrology.
Topics: RNA, Long Noncoding; Humans; Epigenesis, Genetic; Histones; Acetylation; DNA Methylation; Kidney Diseases; Chromatin; Animals
PubMed: 38870627
DOI: 10.1016/j.biopha.2024.116922 -
Osteoarthritis and Cartilage Jun 2024Understanding the mechanisms of hip disease, such as osteoarthritis (OA), is crucial to advance their treatment. Such hip diseases often involve specific morphological... (Review)
Review
OBJECTIVE
Understanding the mechanisms of hip disease, such as osteoarthritis (OA), is crucial to advance their treatment. Such hip diseases often involve specific morphological changes. Genetic variations, called single nucleotide polymorphisms (SNPs), influence various hip morphological parameters. This study investigated the biological relevance of SNPs correlated to hip morphology in genome-wide association studies (GWAS). The SNP-associated genes were compared to genes associated with OA in other joints, aiming to see if the same genes play a role in both hip development and the risk of OA in other lower limb joints.
METHODOLOGY
A systematic literature review was conducted to identify SNPs correlated with hip morphology, based on the Population, Intervention, Comparison, Outcome, and Study (PICOS) framework. Afterwards, Gene Ontology (GO) analysis was performed, using EnrichR, on the SNP-associated genes and compared with non-hip OA-associated genes, across different databases.
RESULTS
Reviewing 49 GWAS identified 436 SNPs associated with hip joint morphology, encompassing variance in bone size, structure and shape. Among the SNP-associated genes, SOX9 plays a pivotal role in size, GDF5 impacts bone structure, and BMP7 affects shape. Overall, skeletal system development, regulation of cell differentiation, and chondrocyte differentiation emerged as crucial processes influencing hip morphology. Eighteen percent of GWAS-identified genes related to hip morphology were also associated with non-hip OA.
CONCLUSION
Our findings indicate the existence of multiple shared genetic mechanisms across hip morphology and OA, highlighting the necessity for more extensive research in this area, as in contrast to the hip, the genetic background on knee or foot morphology remains largely understudied.
PubMed: 38852879
DOI: 10.1016/j.joca.2024.05.010 -
Heliyon Jun 2024Nanoparticles have recently become considered as a crucial player in contemporary medicine, with therapeutic uses ranging from contrast agents in imaging to carriers for... (Review)
Review
Nanoparticles have recently become considered as a crucial player in contemporary medicine, with therapeutic uses ranging from contrast agents in imaging to carriers for the transport of drugs and genes into a specific target. Nanoparticles have the ability to have more precise molecular interactions with the human body in order to target specific cells and tissues with minimal adverse effects and maximal therapeutic outcomes. With the least number of side effects and the greatest possible therapeutic benefit, nanoparticles can target particular cells and tissues through more precise molecular interactions with the human body. The majority of global public health problems are now treated with green synthesized silver nanoparticles (AgNPs), which substantially affect the fundamental structure of DNA and proteins and thus display their antimicrobial action. AgNPs can inhibit the proliferation of tumor cells and induce oxidative stress. By inhibiting vascular endothelial growth factor (HIF)-1, pro-inflammatory mediators generated by silver nanoparticles are reduced, mucin hypersecretion is lessened, and gene activity is subsequently regulated to prevent infections. The biogenic synthesis of silver nanoparticles (AgNPs) using various plants and their applications in antibacterial, antifungal, antioxidant, anticancer, anti-inflammatory, and antidiabetic activities have been extensively discussed in this article. Also, because only natural substances are utilized in the manufacturing process, the particles that are created naturally are coated, stabilized, and play a vital role in these biomedical actions. The characterization of AgNPs, possibility of preparing AgNPSs with different shapes using biological method and their impact on functions and toxicities, impact of size, shape and other properties on AgNPs functions and toxicity profiles, limitations, and future prospects of green-mediated AgNPs have also been reported in this study. The major goal of this study is to provide readers with a comprehensive, informed, and up-to-date summary of the various AgNPs production and characterization methods and their under-investigational antioxidant, antibacterial, and anticancer, antidiabetic, antifungal and anti-inflammatory properties. This review provides instructions and suggestions for additional studies based on AgNPs. This evaluation also pushes researchers to look into natural resources like plant parts in order to create useful nanobiotechnology.
PubMed: 38828360
DOI: 10.1016/j.heliyon.2024.e29766 -
Frontiers in Pharmacology 2024Traditional Chinese Medicine (TCM) has been used for thousands of years to treat human diseases. Recently, many databases have been devoted to studying TCM pharmacology....
Traditional Chinese Medicine (TCM) has been used for thousands of years to treat human diseases. Recently, many databases have been devoted to studying TCM pharmacology. Most of these databases include information about the active ingredients of TCM herbs and their disease indications. These databases enable researchers to interrogate the mechanisms of action of TCM systematically. However, there is a need for comparative studies of these databases, as they are derived from various resources with different data processing methods. In this review, we provide a comprehensive analysis of the existing TCM databases. We found that the information complements each other by comparing herbs, ingredients, and herb-ingredient pairs in these databases. Therefore, data harmonization is vital to use all the available information fully. Moreover, different TCM databases may contain various annotation types for herbs or ingredients, notably for the chemical structure of ingredients, making it challenging to integrate data from them. We also highlight the latest TCM databases on symptoms or gene expressions, suggesting that using multi-omics data and advanced bioinformatics approaches may provide new insights for drug discovery in TCM. In summary, such a comparative study would help improve the understanding of data complexity that may ultimately motivate more efficient and more standardized strategies towards the digitalization of TCM.
PubMed: 38738181
DOI: 10.3389/fphar.2024.1303693 -
International Journal of Molecular... Apr 2024Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive patterns of... (Review)
Review
Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive patterns of behavior. Family studies show that ASD is highly heritable, and hundreds of genes have previously been implicated in the disorder; however, the etiology is still not fully clear. Brain imaging and electroencephalography (EEG) are key techniques that study alterations in brain structure and function. Combined with genetic analysis, these techniques have the potential to help in the clarification of the neurobiological mechanisms contributing to ASD and help in defining novel therapeutic targets. To further understand what is known today regarding the impact of genetic variants in the brain alterations observed in individuals with ASD, a systematic review was carried out using Pubmed and EBSCO databases and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review shows that specific genetic variants and altered patterns of gene expression in individuals with ASD may have an effect on brain circuits associated with face processing and social cognition, and contribute to excitation-inhibition imbalances and to anomalies in brain volumes.
Topics: Humans; Autism Spectrum Disorder; Neuroimaging; Brain; Electroencephalography; Genetic Predisposition to Disease
PubMed: 38732157
DOI: 10.3390/ijms25094938 -
Molecular Genetics and Metabolism... Jun 2024Pompe disease is a rare genetic disorder characterized by a deficiency of acid α-glucosidase (GAA), leading to the accumulation of glycogen in various tissues,...
Pompe disease is a rare genetic disorder characterized by a deficiency of acid α-glucosidase (GAA), leading to the accumulation of glycogen in various tissues, especially in skeletal muscles. The disease manifests as a large spectrum of phenotypes from infantile-onset Pompe disease (IOPD) to late-onset Pompe disease (LOPD), depending on the age of symptoms onset. Quantifying GAA activity and glycogen content in skeletal muscle provides important information about the disease severity. However, the distribution of GAA and glycogen levels in skeletal muscles from healthy individuals and those impacted by Pompe disease remains poorly understood, and there is currently no universally accepted standard assay for GAA activity measurement. This systematic literature review aims to provide an overview of the available information on GAA activity and glycogen content levels in skeletal muscle biopsies from patients with Pompe disease. A structured review of PubMed and Google Scholar literature (with the latter used to check that no additional publications were identified) was conducted to identify peer-reviewed publications on glycogen storage disease type II [MeSH term] + GAA, protein human (supplementary concept), Pompe, muscle; and muscle, acid alpha-glucosidase. A limit of English language was applied. Results were grouped by methodologies used to quantify GAA activity and glycogen content in skeletal muscle. The search and selection strategy were devised and carried out in line with Preferred Reporting of Items in Systematic Reviews and Meta-Analysis guidelines and documented using a flowchart. Bibliographies of papers included in the analysis were reviewed and applicable publications not already identified in the search were included. Of the 158 articles retrieved, 24 (comprising >100 muscle biopsies from >100 patients) were included in the analysis, with four different assays. Analysis revealed that patients with IOPD exhibited markedly lower GAA activity in skeletal muscles than those with LOPD, regardless of the measurement method employed. Additionally, patients with IOPD had notably higher glycogen content levels in skeletal muscles than those with LOPD. In general, however, it was difficult to fully characterize GAA activity because of the different methods used. The findings underscore the challenges in the interpretation and comparison of the results across studies because of the substantial methodological variations. There is a need to establish standardized reference ranges of GAA activity and glycogen content in healthy individuals and in Pompe disease patients based on globally standardized methods to improve comparability and reliability in assessing this rare disease.
PubMed: 38698877
DOI: 10.1016/j.ymgmr.2024.101085 -
Journal of Integrative Neuroscience Apr 2024Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by motor impairment and non-motor symptoms. The involvement of the thalamus in...
BACKGROUND
Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by motor impairment and non-motor symptoms. The involvement of the thalamus in MNDs, especially in conditions such as amyotrophic lateral sclerosis (ALS), and its interaction with frontotemporal dementia (FTD), has garnered increasing research interest. This systematic review analyzed magnetic resonance imaging (MRI) studies that focused on thalamic alterations in MNDs to understand the significance of these changes and their correlation with clinical outcomes.
METHODS
Following PRISMA 2020 guidelines, the PubMed and Scopus databases were searched from inception to June 2023 for studies related to MRI findings in the thalamus of patients with MNDs. Eligible studies included adult patients diagnosed with ALS or other forms of MND who underwent brain MRI, with outcomes related to thalamic alterations. Studies were evaluated for risk of bias using the Newcastle-Ottawa scale.
RESULTS
A total of 52 studies (including 3009 MND patients and 2181 healthy controls) used various MRI techniques, including volumetric analysis, diffusion tensor imaging, and functional MRI, to measure thalamic volume, connectivity, and other alterations. This review confirmed significant thalamic changes in MNDs, such as atrophy and microstructural degradation, which are associated with disease severity, progression, and functional disability. Thalamic involvement varies across different MND subtypes and is influenced by the presence of cognitive impairment and mutations in genes including chromosome 9 open reading frame 72 (). The synthesis of findings across studies indicates that thalamic pathology is a prevalent early biomarker of MNDs that contributes to motor and cognitive deficits. The thalamus is a promising target for monitoring as its dysfunction underpins a variety of clinical symptoms in MNDs.
CONCLUSIONS
Thalamic alterations provide valuable insights into the pathophysiology and progression of MNDs. Multimodal MRI techniques are potent tools for detecting dynamic thalamic changes, indicating structural integrity, connectivity disruption, and metabolic activity.
Topics: Humans; Thalamus; Motor Neuron Disease; Magnetic Resonance Imaging; Amyotrophic Lateral Sclerosis
PubMed: 38682227
DOI: 10.31083/j.jin2304077