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BMC Ophthalmology Jul 2016Beta-thalassemia is a severe genetic blood disorder caused by a mutation in the gene encoding for the beta chains of hemoglobin. Individuals with beta-thalassemia major... (Review)
Review
BACKGROUND
Beta-thalassemia is a severe genetic blood disorder caused by a mutation in the gene encoding for the beta chains of hemoglobin. Individuals with beta-thalassemia major require regular lifelong Red Blood Cell transfusions to survive. Ocular involvement is quite common and may have serious implications.
METHODS
Extensive review of observational studies on beta-thalassemia, to determine the prevalence and spectrum of ocular abnormalities, by clinical examination and multimodal imaging, and to investigate risk factors for their development.
RESULTS
Frequency of ocular involvement differs among various studies (41.3-85 %, three studies). Ocular findings in beta-thalassemia may correlate to the disease itself, iron overload or the chelating agents used. Beta-thalassemia ocular manifestations include ocular surface disease, as demonstrated by tear function parameters (two studies). Lens opacities are present in 9.3-44 % (five studies). Lenticular opacities and RPE degeneration correlated positively with use of desferrioxamine and deferriprone respectively (two studies). Ocular fundus abnormalities characteristic of pseudoxanthoma elasticum (PXE), including peau d'orange, angioid streaks, pattern dystrophy-like changes, and optic disc drusen are a consistent finding in seven studies. Patients with PXE-like fundus changes were older than patients without these fundus changes (two studies). Age (two studies) and splenectomy (one study) had the strongest association with presence of PXE-like fundus changes. Increased retinal vascular tortuosity independently of the PXE-like fundus changes was found in 11-17.9 % (three studies), which was associated with aspartate amino transferase, hemoglobin and ferritin levels (two studies). Fundus autofluorescence and electrophysiological testing (ERG and EOG) may indicate initial stages or more widespread injury than is suggested by fundus examination (two studies).
CONCLUSIONS
Beta-thalassemia may present with various signs, both structural and functional. Pseudoxanthoma elasticum like fundus changes are a frequent finding in patients with b-thalassemia. These changes increase with duration or severity of the disease. Retinal vascular tortuosity may be an additional disease manifestation related to the severity and duration of anemia and independent of the PXE-like syndrome. Patients with long-standing disease need regular ophthalmic checkups because they are at risk of developing PXE-like fundus changes and potentially of subsequent choroidal neovascularization.
Topics: Chelating Agents; Humans; Iron Overload; Observational Studies as Topic; Retinal Diseases; Vision Disorders; beta-Thalassemia
PubMed: 27390837
DOI: 10.1186/s12886-016-0285-2 -
Survey of Ophthalmology 2023Myopic choroidal neovascularization (CNV) is a vision-threatening complication of high myopia. Here, we systematically review cohort, case-control, and cross-sectional... (Meta-Analysis)
Meta-Analysis Review
Myopic choroidal neovascularization (CNV) is a vision-threatening complication of high myopia. Here, we systematically review cohort, case-control, and cross-sectional studies in PubMed, Embase, and Web of Science, and summarize the associated factors of myopic CNV using meta-analysis where applicable. Among 1,333 records assessed, 50 were found eligible, all having a low-to-moderate risk of bias. Highly myopic eyes with CNV had a higher risk of lacquer cracks (odds ratio = 2.88) and patchy chorioretinal atrophy (odds ratio = 3.43) than those without. The mean posterior staphyloma height (µm) was greater in myopic CNV eyes than in highly myopic eyes without CNV (mean difference = 82.03). The thinning of choroidal thickness (µm) between myopic eyes with and without CNV differed significantly (mean difference = -47.76). The level of vascular endothelial growth factor (pg/ml) in the aqueous humor of myopic CNV eyes was significantly higher than in highly myopic eyes without CNV (mean difference = 24.98), the same as interleukin-8 (IL-8) (pg/ml, mean difference = 7.73). Single-nucleotide polymorphisms in the vascular endothelial growth factor, complement factor I, and collagen type VIII alpha 1 genes were associated with myopic CNV. We found that myopic CNV eyes have a higher ratio of lacquer cracks and patchy chorioretinal atrophy, thinner choroid, greater posterior staphyloma height, and a higher level of vascular endothelial growth factor and IL-8 in aqueous. Structural predisposing lesions, hemodynamic, genetic, and systemic factors are also associated with myopic CNV.
Topics: Humans; Interleukin-8; Vascular Endothelial Growth Factor A; Cross-Sectional Studies; Visual Acuity; Retrospective Studies; Myopia; Choroidal Neovascularization; Atrophy; Myopia, Degenerative; Fluorescein Angiography
PubMed: 37517683
DOI: 10.1016/j.survophthal.2023.07.006 -
Pancreatology : Official Journal of the... Jan 2018Extracellular matrix (ECM) plays a fundamental role in tissue architecture and homeostasis and modulates cell functions through a complex interaction between cell... (Review)
Review
Extracellular matrix (ECM) plays a fundamental role in tissue architecture and homeostasis and modulates cell functions through a complex interaction between cell surface receptors, hormones, several bioeffector molecules, and structural proteins like collagen. These components are secreted into ECM and all together contribute to regulate several cellular activities including differentiation, apoptosis, proliferation, and migration. The so-called "matricellular" proteins (MPs) have recently emerged as important regulators of ECM functions. The aim of our review is to consider all different types of MPs family assessing the potential relationship between MPs and survival in patients with pancreatic ductal adenocarcinoma (PDAC). A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement issued in 2009 was conducted through Ovid interface, and literature review was performed in May 2017. The search text words were identified by means of controlled vocabulary, such as the National Library of Medicine's MESH (Medical Subject Headings) and Keywords. Collected data showed an important role of MPs in carcinogenesis and in PDAC prognosis even though the underlying mechanisms are still largely unknown and data are not univocal. Therefore, a better understanding of MPs role in regulation of ECM homeostasis and remodeling of specific organ niches may suggest potential novel extracellular targets for the development of efficacious therapeutic strategies.
Topics: Extracellular Matrix; Gene Expression Regulation, Neoplastic; Humans; Pancreatic Neoplasms; Survival Analysis
PubMed: 29137857
DOI: 10.1016/j.pan.2017.11.001 -
Frontiers in Cell and Developmental... 2023Circular RNA (circRNA) molecules are noncoding RNAs with ring-like structures formed by covalent bonds and are characterized by no 5caps or polyadenylated tails.... (Review)
Review
Circular RNA (circRNA) molecules are noncoding RNAs with ring-like structures formed by covalent bonds and are characterized by no 5caps or polyadenylated tails. Increasing evidence shows that circRNAs may play an important role in tumorigenesis and cancer metastasis. Circ-SHPRH originates from exons 26-29 of the gene, and it is closely associated with human cancers. We searched PubMed, Web of Science, and Embase databases for relevant literatures until 24 December 2022. Eighteen research papers were included in this review, and 11 papers were selected for meta-analysis after screening. Three eligible published studies about circ-SHPRH were enrolled based on their tumor diagnosis aspect, 7 eligible published studies were related to overall survival (OS), and 3 eligible published studies were related to tumor grade. Many studies have shown that circ-SHPRH acts as a miRNA sponge or encodes a protein to regulate downstream genes or signal pathways, and exerts specific biological functions that affect the proliferation, invasion, and apoptosis of cancer cells. Meta-analysis showed that patients with high expression of circ-SHPRH had better OS (HR = 0.53, 95% CI 0.38-0.74, -value <0.05) and lower TNM stage (HR = 0.33, 95% CI 0.18-0.62, -value = 0.001). In addition, circ-SHPRH has potential diagnostic value (AUC = 0.8357). This review will help enrich our understanding of the role and mechanism of circ-SHPRH in human cancers. Circ-SHPRH has the potential to be a novel diagnostic and prognostic biomarker for various solid cancers.
PubMed: 37305675
DOI: 10.3389/fcell.2023.1182900 -
International Journal of Molecular... Nov 2023The objective was to evaluate the current evidence regarding the etiology of medication-related osteonecrosis of the jaw (MRONJ). This study systematically reviewed the... (Review)
Review
The objective was to evaluate the current evidence regarding the etiology of medication-related osteonecrosis of the jaw (MRONJ). This study systematically reviewed the literature by searching PubMed, Web of Science, and ProQuest databases for genes, proteins, and microRNAs associated with MRONJ from the earliest records through April 2023. Conference abstracts, letters, review articles, non-human studies, and non-English publications were excluded. Twelve studies meeting the inclusion criteria involving exposure of human oral mucosa, blood, serum, saliva, or adjacent bone or periodontium to anti-resorptive or anti-angiogenic agents were analyzed. The Cochrane Collaboration risk assessment tool was used to assess the quality of the studies. A total of 824 differentially expressed genes/proteins (DEGs) and 22 microRNAs were extracted for further bioinformatic analysis using Cytoscape, STRING, BiNGO, cytoHubba, MCODE, and ReactomeFI software packages and web-based platforms: DIANA mirPath, OmicsNet, and miRNet tools. The analysis yielded an interactome consisting of 17 hub genes and hsa-mir-16-1, hsa-mir-21, hsa-mir-23a, hsa-mir-145, hsa-mir-186, hsa-mir-221, and hsa-mir-424. A dominance of cytokine pathways was observed in both the cluster of hub DEGs and the interactome of hub genes with dysregulated miRNAs. In conclusion, a panel of genes, miRNAs, and related pathways were found, which is a step toward understanding the complexity of the disease.
Topics: Humans; MicroRNAs; Osteonecrosis; Computational Biology; Gene Regulatory Networks
PubMed: 38069068
DOI: 10.3390/ijms242316745 -
Molecular Cancer Research : MCR Jun 2021Mucosal melanoma is a rare subtype of melanoma. To date, there has been no comprehensive systematic collation and statistical analysis of the aberrations and aggregated... (Meta-Analysis)
Meta-Analysis
Mucosal melanoma is a rare subtype of melanoma. To date, there has been no comprehensive systematic collation and statistical analysis of the aberrations and aggregated frequency of driver events across multiple studies. Published studies using whole genome, whole exome, targeted gene panel, or individual gene sequencing were identified. Datasets from these studies were collated to summarize mutations, structural variants, and regions of copy-number alteration. Studies using next-generation sequencing were divided into the "main" cohort ( = 173; fresh-frozen samples), "validation" cohort ( = 48; formalin-fixed, paraffin-embedded samples) and a second "validation" cohort comprised 104 tumors sequenced using a targeted panel. Studies assessing mutations in , and were summarized to assess hotspot mutations. Statistical analysis of the main cohort variant data revealed , and as significantly mutated genes. and mutations occurred more commonly in lower anatomy melanomas and in the upper anatomy. , and were commonly affected by chromosomal copy loss, while , and were commonly amplified. Further notable genomic alterations occurring at lower frequencies indicated commonality of signaling networks in tumorigenesis, including MAPK, PI3K, Notch, Wnt/β-catenin, cell cycle, DNA repair, and telomere maintenance pathways. This analysis identified genomic aberrations that provide some insight to the way in which specific pathways may be disrupted. IMPLICATIONS: Our analysis has shown that mucosal melanomas have a diverse range of genomic alterations in several biological pathways. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/6/991/F1.large.jpg.
Topics: Biomarkers, Tumor; DNA Copy Number Variations; Genetic Predisposition to Disease; Genomics; Humans; Melanoma; Mutation; Signal Transduction; Skin Neoplasms; Whole Genome Sequencing
PubMed: 33707307
DOI: 10.1158/1541-7786.MCR-20-0839 -
Horticulture Research 2020Members of the genus , which consists of globally renowned ornamentals and traditional medicinal plants with a rich history spanning over 1500 years, are widely... (Review)
Review
Members of the genus , which consists of globally renowned ornamentals and traditional medicinal plants with a rich history spanning over 1500 years, are widely distributed throughout the Northern Hemisphere. Since 1900, over 2200 new horticultural cultivars have been created by the discovery and breeding of wild species. However, information pertaining to breeding is considerably fragmented, with fundamental gaps in knowledge, creating a bottleneck in effective breeding strategies. This review systematically introduces germplasm resources, including wild species and cultivars, summarizes the breeding strategy and results of each cultivar group, and focuses on recent progress in the isolation and functional characterization of structural and regulatory genes related to important horticultural traits. Perspectives pertaining to the resource protection and utilization, breeding and industrialization of in the future are also briefly discussed.
PubMed: 32637135
DOI: 10.1038/s41438-020-0332-2 -
Bone Feb 2022Fibrous dysplasia (FD) is a rare genetic bone disorder resulting in an overproduction of cAMP leading to a structurally unsound tissue, caused by a genetic mutation in...
BACKGROUND
Fibrous dysplasia (FD) is a rare genetic bone disorder resulting in an overproduction of cAMP leading to a structurally unsound tissue, caused by a genetic mutation in the guanine nucleotide-binding protein gene (GNAS). In order to better understand this disease, several animal models have been developed with different strategies and features.
OBJECTIVE
Conduct a systematic review to analyze and compare animal models with the causative mutation and features of FD.
METHODS
A PRISMA search was conducted in Scopus, PubMed, and Web of Science. Studies reporting an in vivo model of FD that expressed the causative mutation were included for analysis. Models without the causative mutation, but developed an FD phenotype and models of FD cell implantation were included for subanalysis.
RESULTS
Seven unique models were identified. The models were assessed and compared for their face validity, construct validity, mosaicism, and induction methods. This was based on the features of clinical FD that were reported within the categories of: macroscopic features, imaging, histology and histomorphometry, histochemical and cellular markers, and blood/urine markers.
LIMITATIONS
None of the models reported all features of FD and some features were only reported in one model. This made comparing models a challenge, but indicates areas where further research is necessary.
CONCLUSION
The benefits and disadvantages of every model were assessed from a practical and scientific standpoint. While all published reports lacked complete data, the models have nonetheless informed our understanding of FD and provided meaningful information to guide researchers in bench and clinical research.
Topics: Animals; Bone and Bones; Fibrous Dysplasia of Bone; GTP-Binding Protein alpha Subunits, Gs; GTP-Binding Proteins; Mutation
PubMed: 34875396
DOI: 10.1016/j.bone.2021.116270 -
Cardiovascular Drugs and Therapy Jun 2017Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with pronounced morbidity and mortality. Its prevalence, expected to further increase... (Review)
Review
Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with pronounced morbidity and mortality. Its prevalence, expected to further increase for the forthcoming years, and associated frequent hospitalizations turn AF into a major health problem. Structural and electrical atrial remodelling underlie the substrate for AF, but the exact mechanisms driving this remodelling remain incompletely understood. Recent studies have shown that microRNAs (miRNA), short non-coding RNAs that regulate gene expression, may be involved in the pathophysiology of AF. MiRNAs have been implicated in AF-induced ion channel remodelling and fibrosis. MiRNAs could therefore provide insight into AF pathophysiology or become novel targets for therapy with miRNA mimics or anti-miRNAs. Moreover, circulating miRNAs have been suggested as a new class of diagnostic and prognostic biomarkers of AF. However, the origin and function of miRNAs in tissue and plasma frequently remain unknown and studies investigating the role of miRNAs in AF vary in design and focus and even present contradicting results. Here, we provide a systematic review of the available clinical and functional studies investigating the tissue and plasma miRNAs in AF and will thereafter discuss the potential of miRNAs as biomarkers or novel therapeutic targets in AF.
Topics: Animals; Atrial Fibrillation; Biomarkers; Gene Expression; Humans; MicroRNAs
PubMed: 28752208
DOI: 10.1007/s10557-017-6736-z -
Frontiers in Allergy 2023Epigenetics facilitates insights on the impact of host environment on the genesis of chronic rhinosinusitis (CRS) through modulations of host gene expression and... (Review)
Review
BACKGROUND
Epigenetics facilitates insights on the impact of host environment on the genesis of chronic rhinosinusitis (CRS) through modulations of host gene expression and activity. Epigenetic mechanisms such as DNA methylation cause reversible but heritable changes in gene expression over generations of progeny, without altering the DNA base-pair sequences. These studies offer a critical understanding of the environment-induced changes that result in host predisposition to disease and may help in developing novel biomarkers and therapeutics. The goal of this systematic review is to summarize the current evidence on epigenetics of CRS with a focus on chronic rhinosinusitis with nasal polyps (CRSwNP) and highlight gaps that merit further research.
METHODS
A systematic review of the English language literature was performed to identify investigations related to epigenetic studies in subjects with CRS.
RESULTS
The review identified 65 studies. These have focused on DNA methylation and non-coding RNAs, with only a few on histone deacetylation, alternative polyadenylation, and chromatin accessibility. Studies include those investigating and changes or both. Studies also include animal models of CRS. Almost all have been conducted in Asia. The genome-wide studies of DNA methylation found differences in global methylation between CRSwNP and controls, while others specifically found significant differences in methylation of the CpG sites of the thymic stromal lymphopoietin (), , and . In addition, DNA methyltransferase inhibitors and histone deacetylase inhibitors were studied as potential therapeutic agents. Majority of the studies investigating non-coding RNAs focused on micro-RNAs (miRNA) and found differences in global expression of miRNA levels. These studies also revealed some previously known as well as novel targets and pathways such as tumor necrosis factor alpha, TGF beta-1, IL-10, , aryl hydrocarbon receptor, PI3K/AKT pathway, mucin secretion, and vascular permeability. Overall, the studies have found a dysregulation in pathways/genes involving inflammation, immune regulation, tissue remodeling, structural proteins, mucin secretion, arachidonic acid metabolism, and transcription.
CONCLUSIONS
Epigenetic studies in CRS subjects suggest that there is likely a major impact of the environment. However, these are association studies and do not directly imply pathogenesis. Longitudinal studies in geographically and racially diverse population cohorts are necessary to quantify genetic vs. environmental risks for CRSwNP and CRS without nasal polyps and assess heritability risk, as well as develop novel biomarkers and therapeutic agents.
PubMed: 37284022
DOI: 10.3389/falgy.2023.1165271