Investigating G-quadruplex structures in gene: Implications for understanding X-linked retinal degeneration.

Aims: This pilot study investigates the potential pathogenic role of G-quadruplex (G4) structures in -associated retinal degeneration, starting from a case of suspected X-linked form affected family. We hypothesize that the stabilization of these structures might alter DNA replication and transcription, inducing genetic instability and influencing gene expression.

Main Methods: We conducted whole genome amplification experiments and next-generation sequencing to detect the blockade of polymerase activity by G4 structures.

From powerhouse to regulator: The role of mitoepigenetics in mitochondrion-related cellular functions and human diseases.

Beyond their crucial role in energy production, mitochondria harbor a distinct genome subject to epigenetic regulation akin to that of nuclear DNA. This paper delves into the nascent but rapidly evolving fields of mitoepigenetics and mitoepigenomics, exploring the sophisticated regulatory mechanisms governing mitochondrial DNA (mtDNA). These mechanisms encompass mtDNA methylation, the influence of non-coding RNAs (ncRNAs), and post-translational modifications of mitochondrial proteins.

Efficacy of an experimental gaseous ozone-based sterilization method for clear aligners.

Objectives: To assess effectiveness of an experimental sterilization method based on the exposure of an O3/O2 gas mixture directly inside the packaging for clear aligners.

Materials And Methods: Fifty samples consisting of pieces of polyethylene terephthalate glycol (PET-G) aligners were contaminated by manual handling and subsequently divided into different groups (n = 30 for exposure to O3/O2 gas at different times, n = 10 for positive control with 2% chlorhexidine digluconate, n = 10 for negative control). The measurement of optical densities (OD) of the initial and final microbial cultures was recorded for all groups.

Human retinal secretome: A cross-link between mesenchymal and retinal cells.

In recent years, mesenchymal stem cells (MSC) have been considered the most effective source for regenerative medicine, especially due to released soluble paracrine bioactive components and extracellular vesicles. These factors, collectively called the secretome, play crucial roles in immunomodulation and in improving survival and regeneration capabilities of injured tissue. Recently, there has been a growing interest in the secretome released by retinal cytotypes, especially retinal pigment epithelium and Müller glia cells.

The impact of modifier genes on cone-rod dystrophy heterogeneity: An explorative familial pilot study and a hypothesis on neurotransmission impairment.

Cone-rod dystrophies (CORDs) are a heterogeneous group of inherited retinopathies (IRDs) with more than 30 already known disease-causing genes. Uncertain phenotypes and extended range of intra- and interfamilial heterogenicity make still difficult to determine a precise genotype-phenotype correlation. Here, we used a next-generation sequencing approach to study a Sicilian family with a suspected form of CORD.

Epitranscriptome Analysis of Oxidative Stressed Retinal Epithelial Cells Depicted a Possible RNA Editing Landscape of Retinal Degeneration.

Oxidative stress represents one of the principal causes of inherited retinal dystrophies, with many related molecular mechanisms still unknown. We investigated the posttranscriptional RNA editing landscape of human retinal pigment epithelium cells (RPE) exposed to the oxidant agent N-retinylidene-N-retinyl ethanolamine (A2E) for 1 h, 2 h, 3 h and 6 h. Using a transcriptomic approach, refined with a specific multialgorithm pipeline, 62,880 already annotated and de novo RNA editing sites within about 3000 genes were identified among all samples.

Deciphering impact of single nucleotide polymorphisms on cotranscriptional modification in CCM gene mRNAs.

Novel insights on regulation of gene expression mechanisms highlight the pivotal role of epitranscriptomic modifications on decision about transcript fate. These modifications include methylation of adenosine and cytosine in RNA molecules. Impairment of the normal epitranscriptome profile was observed in several pathological conditions, such as cancer and neurodegeneration.

Editome landscape of CCM-derived endothelial cells.

By regulating several phases of gene expression, RNA editing modifications contribute to maintaining physiological RNA expression levels. RNA editing dysregulation can affect RNA molecule half-life, coding/noncoding RNA interaction, alternative splicing, and circular RNA biogenesis. Impaired RNA editing has been observed in several pathological conditions, including cancer and Alzheimer's disease.

Raman Spectroscopic Study of Amyloid Deposits in Gelatinous Drop-like Corneal Dystrophy.

The genetic and histopathological features of the cornea of a Polish patient with Gelatinous Drop-like Corneal Dystrophy (GDCD) and the molecular composition with Raman spectroscopy of corneal deposits were examined. A 62 year-old Polish woman was diagnosed with GDCD and underwent penetrating corneal transplant. A blood sample was collected, and genetic analysis was performed.

Adaptive Modelling of Mutated FMO3 Enzyme Could Unveil Unexplored Scenarios Linking Variant Haplotypes to TMAU Phenotypes.

Background: Trimethylaminuria (TMAU) is a rare genetic disease characterized by the accumulation of trimethylamine (TMA) and its subsequent excretion trough main body fluids, determining the characteristic fish odour in affected patients. We realized an experimental study to investigate the role of several coding variants in the causative gene , that were only considered as polymorphic or benign, even if the available literature on them did not functionally explain their ineffectiveness on the encoded enzyme.

Methods: Mutational analysis of 26 TMAU patients was realized by Sanger sequencing.

Oxidative Stress and the Neurovascular Unit.

The neurovascular unit (NVU) is a relatively recent concept that clearly describes the relationship between brain cells and their blood vessels. The components of the NVU, comprising different types of cells, are so interrelated and associated with each other that they are considered as a single functioning unit. For this reason, even slight disturbances in the NVU could severely affect brain homeostasis and health.

New evaluation methods of read mapping by 17 aligners on simulated and empirical NGS data: an updated comparison of DNA- and RNA-Seq data from Illumina and Ion Torrent technologies.

Unlabelled: During the last (15) years, improved omics sequencing technologies have expanded the scale and resolution of various biological applications, generating high-throughput datasets that require carefully chosen software tools to be processed. Therefore, following the sequencing development, bioinformatics researchers have been challenged to implement alignment algorithms for next-generation sequencing reads. However, nowadays selection of aligners based on genome characteristics is poorly studied, so our benchmarking study extended the "state of art" comparing 17 different aligners.

N-retinylidene-N-retinylethanolamine adduct induces expression of chronic inflammation cytokines in retinal pigment epithelium cells.

Blindness due to photoreceptor degeneration is observed in both genetic and acquired eye disorders. Long blue light exposure can contribute to increase levels of oxidative compounds within the retinal pigment epithelium (RPE), enhancing risk of retinal damage. In retina, reactive oxygen species contribute to the activation of inflammatory cascade.

Impairments of Photoreceptor Outer Segments Renewal and Phototransduction Due to a Peripherin Rare Haplotype Variant: Insights from Molecular Modeling.

Background: Retinitis pigmentosa punctata albescens (RPA) is a particular form of retinitis pigmentosa characterized by childhood onset night blindness and areas of peripheral retinal atrophy. We investigated the genetic cause of RPA in a family consisting of two affected Egyptian brothers with healthy consanguineous parents.

Methods: Mutational analysis of four RPA causative genes was realized by Sanger sequencing on both probands, and detected variants were subsequently genotyped in their parents.

Gut-Brain Axis Cross-Talk and Limbic Disorders as Biological Basis of Secondary TMAU.

: Trimethylaminuria (TMAU) is a rare metabolic syndrome characterized by the accumulation and the excretion of trimethylamine (TMA), a volatile diet compound produced by gut microbiota. Gut microbiota alterations are mainly involved in the secondary TMAU, whose patients show also different psychiatric conditions. We hypothesized that the biological activity of several molecules acting as intermediate in TMA metabolic reaction might be at the basis of TMAU psychiatric comorbidities.

New Omics-Derived Perspectives on Retinal Dystrophies: Could Ion Channels-Encoding or Related Genes Act as Modifier of Pathological Phenotype?

Ion channels are membrane-spanning integral proteins expressed in multiple organs, including the eye. Here, ion channels play a role in several physiological processes, like signal transmission and visual processing. A wide range of mutations have been reported in the corresponding genes and their interacting subunit coding genes, which contribute significantly to a wide spectrum of ocular diseases collectively called channelopathies, a subgroup of inherited retinal dystrophies.

Antiretroviral treatment leading to secondary trimethylaminuria: Genetic associations and successful management with riboflavin.

What Is Known And Objective: Trimethylaminuria is a metabolic disorder characterized by excessive excretion of trimethylamine in body fluids following FMO3 gene mutations. Secondary forms of the disease may be due to consumption of trimethylamine precursor-rich foods or metabolism of some xenobiotics.

Case Summary: A HIV patient developed secondary trimethylaminuria following antiretroviral treatment.

Possible A2E Mutagenic Effects on RPE Mitochondrial DNA from Innovative RNA-Seq Bioinformatics Pipeline.

Mitochondria are subject to continuous oxidative stress stimuli that, over time, can impair their genome and lead to several pathologies, like retinal degenerations. Our main purpose was the identification of mtDNA variants that might be induced by intense oxidative stress determined by -retinylidene--retinylethanolamine (A2E), together with molecular pathways involving the genes carrying them, possibly linked to retinal degeneration. We performed a variant analysis comparison between transcriptome profiles of human retinal pigment epithelial (RPE) cells exposed to A2E and untreated ones, hypothesizing that it might act as a mutagenic compound towards mtDNA.

Expression of Pro-Angiogenic Markers Is Enhanced by Blue Light in Human RPE Cells.

Inherited retinal dystrophies are characterized by photoreceptor death. Oxidative stress usually occurs, increasing vision loss, and oxidative damage is often reported in retinitis pigmentosa (RP). More than 300 genes have been reported as RP causing.