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Objective: It has recently been highlighted how a short healthy life-style program (LSP) can improve the functional outcomes of older people admitted to a Long-Term Care (LTC) facility. Although it is known that life-style medicine-based interventions can exert anti-aging effects through the modulation of oxidative stress and mitochondrial function, the mechanisms underlying the aforementioned effects have not been clarified, yet. For this reason, in this study, the outcomes were focused on the investigation of the possible mechanisms underlying the benefits of a short LSP in older people. This was achieved by examining circulating markers of oxidative stress and immunosenescence, such as Tymosin β (Tβ4), before and after LSP and the effects of plasma of older people undergone or not LSP on endothelial cells. Methods: Fifty-four older people were divided into two groups (n = 27 each): subjects undergoing LSP and subjects not undergoing LSP (control). The LSP consisted of a combination of caloric restriction, physical activity, and psychological intervention and lasted 3 months. Plasma samples were taken before (T0) and after LSP (T1) and were used to measure thiobarbituric acid reactive substances (TBARS), 8-hydroxy-2-deoxyguanosine (8OHdG), 8-Isoprostanes (IsoP), glutathione (GSH), superoxide dismutase (SOD) activity and Tβ4. In addition, plasma was used to stimulate human vascular endothelial cells (HUVEC), which were examined for cell viability, mitochondrial membrane potential, reactive oxygen species (ROS) and mitochondrial ROS (MitoROS) release. Results: At T1, in LSP group we did not detect the increase of plasma TBARS and IsoP, which was observed in control. Also, plasma levels of 8OHdG were lower in LSP group vs control. In addition, LSP group only showed an increase of plasma GSH and SOD activity. Moreover, plasma levels of Tβ4 were more preserved in LSP group. Finally, at T1, in HUVEC treated with plasma from LSP group only we found an increase of the mitochondrial membrane potential and a reduction of ROS and MitoROS release in comparison with T0. Conclusions: The results of this study showed that a short LSP in older persons exerts antiaging effects by modulating oxidative stress also at cellular levels. Implications of those findings could be related to both prognostic and therapeutic strategies, which could be pursued as antiaging methods.

Aims: This pilot study investigates the potential pathogenic role of G-quadruplex (G4) structures in RPGR-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. Our specific focus was the RPGR gene, which hosts a high concentration of predicted G4-forming motifs and is implicated in most X-linked retinal degeneration cases. To understand the potential interference of G4 structures, we applied computational and 3D molecular modeling to visualize interferences in DNA replication and transcription regulation. Key findings: Our data confirmed the obstruction of DNA polymerase enzymes by G4 structures, particularly when stabilized by the compound pyridostatin. This obstruction was evident in the reduced amplification of RPGR gene regions and a shift in the start/end sites of putative G4 motifs. Moreover, the modeling indicated a potential disruption of critical promoter elements and RNA polymerase binding, which could drastically alter gene expression. Significance: Our findings suggest that G4 formation in the RPGR gene could lead to genetic instability and affect the expression of RPGR, contributing to retinal dystrophy. Moreover, this study underscores the broader implications of G4 structures in other genetic disorders. Improved understanding of G4 structures could reveal novel therapeutic targets to combat genetic disorders, promoting the advancement of personalized medicine and precision health.

ABSTRACT In this prospective study, we used droplet digital (dd)PCR to determine the SARS-CoV-2 viral load determination in saliva samples collected from two cohorts of Italian health care workers (HCWs) who had tested positive for SARS-CoV-2 breakthrough infections in nasopharyngeal swabs (NPS). The study encompasses two distinct periods: one from February to May 2021 (n = 16), characterized by Alpha variant predominance, and another from January to March 2022 (n = 23), marked by the prevalence of the Omicron variant. To assess the temporal pattern of virus shedding, we performed dd-PCR analysis of self-collected longitudinal saliva harvested the day after NPS testing and every 3 days until SARS-CoV-2 negativization, determined by real-time PCR (RT-PCR). Using saliva harvested within 24 h from the initial SARS-CoV-2-positive NPS tested by real-time quantitative PCR (RT-qPCR), we found that 11/16 [68.7%, confidence interval (CI) 95% 44.0%–93.4%] HCWs in the “Alpha wave” and 6/23 (26.1%, CI 95% 7.1%–45.1%) in the “Omicron wave” were negative for the presence of SARS-CoV-2 by ddPCR. The viral loads obtained with these samples were negatively correlated with the cycle threshold (Ct) values measured in the NPS specimens (P < 0.0001). The median Ct values of the double-positive (RT-qPCR and ddPCR) subjects were significantly higher when compared to the single-positive (RT-qPCR only) ones. In addition, we found that using ddPCR in self-collected saliva, 80% of the HCWs in the “Alpha wave” and 53% in the “Omicron wave” would have been freed from isolation within four working days from the initial positive NPS, sparing 176 working days among the HCWs enrolled in the study. Overall, this study highlights the effectiveness of using ddPCR in self-collected saliva as part of a surveillance program. It ultimately aims to identify individuals who still test positive by RT-PCR in NPS but retains a residual, non-active infection. This diagnostic approach is likely to not only prevent unnecessary isolation but also spare working days. IMPORTANCE Real-time quantitative PCR (RT-qPCR) on nasopharyngeal swabs (NPS) has been used as the standard method for detecting and monitoring SARS-CoV-2 infection during the pandemic. However, NPS collection often causes discomfort and poses a higher risk of transmission to health care workers (HCW). Furthermore, RT-qPCR only provides relative quantification and does not allow distinguishing those samples with residual, no longer active infection, whereas droplet digital PCR (ddPCR) allows for precise quantification of viral load, offering greater sensitivity and reproducibility. This study highlights the effectiveness of using self-collected saliva as a convenient and reliable sampling method. By utilizing ddPCR to measure the SARS-CoV-2 viral load in saliva samples, individuals with low or undetectable viral loads can be quickly identified. This approach is particularly advantageous for surveillance programs targeting HCW, as it enables the early identification and release of uninfected personnel, minimizing lost workdays. Additionally, analyzing viral load in saliva samples by ddPCR is valuable in determining virus shedding duration across different SARS-CoV-2 variants, informing transmission and disease control. Finally, testing saliva could overcome the detection of historic cases due to prolonged RNA swabbing past-infection and the unnecessary exclusion of those individuals from the workplace.

BackgroundDefensive medicine (DM) is a deviation from medical practice that is induced primarily by a threat of liability. While the DM behavior is well studied in the developed countries, little is known in developing countries and never been evaluated in Jordan.ObjectiveTo evaluate the prevalence of DM practice in Jordan among physicians and to investigate reasons behind its practice and potential strategies to alleviate this practice.MethodsIn this Cross-sectional study, self-administered questionnaire was distributed to a sample of physicians in both public and private sectors in Jordan. The collection period was from Jan 2021 to June 2021. The prevalence of DM practice was estimated among the study sample. Frequency scores of different DM behaviors, reasons of DM behaviors, and effectiveness of strategies in changing DM behaviors were summarized as average frequency scores with standard deviations. Multivariable linear regression models were conducted to evaluate potential predictors of total assurance and avoidance behavior scores.ResultsA total of 175 Jordanian physicians completed the survey. The prevalence of adopting (or witnessing) DM behaviors among the study sample was 68% (n = 119). Diagnostic laboratory exams followed by prescribed medications were the most practiced behaviors in excessive rate during a typical working week. Unfavorable legislation for the physician was reported as the headmost reason for practicing DM, followed by pressure from the public and mass media opinion. Continuous update of knowledge, abilities, and performance and following specific protocols and/or appropriate clinical evidence and appropriate multidisciplinary and multi-professional communication were the most effective strategies that can mitigate DM behaviors.ConclusionsDefensive medicine practice is common among Jordanian physicians with concerns about increasing pattern in the future.

Alzheimer disease is a progressive neurodegenerative disorder, mainly affecting older people, which severely impairs patients' quality of life. In the recent years, the number of affected individuals has seen a rapid increase. It is estimated that up to 107 million subjects will be affected by 2050 worldwide. Research in this area has revealed a lot about the biological and environmental underpinnings of Alzheimer, especially its correlation with β-Amyloid and Tau related mechanics; however, the precise molecular events and biological pathways behind the disease are yet to be discovered. In this review, we focus our attention on the biological mechanics that may lie behind Alzheimer development. In particular, we briefly describe the genetic elements and discuss about specific biological processes potentially associated with the disease.

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. Affected family members underwent ophthalmological examinations and a proband, blind from 50 years, underwent whole genome and exome sequencing. Variant analysis was enriched by pathway analysis and relevant variants were, then, investigated in other family members and in 100 healthy controls from Messina. CORD diagnosis with an intricate pattern of symptoms was confirmed by ophthalmological examinations. A total of about 50,000 variants were identified in both proband’s genome and exome. All affected family members presented specific genotypes mainly determined by mutated GUCY2D gene, and different phenotypical traits, mainly related to focus and color perception. Thus, we looked for possible modifier genes. According to relationship with GUCY2D, predicted functional effects, eye localization, and ocular disease affinity, only 9 variants, carried by 6 genes (CACNG8, PAX2, RXRG, CCDC175, PDE4DIP and LTF), survived the filtering. These genes encode key proteins involved in cone development and survival, and retina neurotransmission. Among analyzed variants, CACNG8c.*6819A>T and the new CCDC175 c.76C>T showed extremely low frequency in the control group, suggesting a key role on disease phenotypes. Such discovery could enforce the role of modifier genes into CORD onset/progression, contributing to improve diagnostic test towards a better personalized medicine.

Mitochondrial pathologies are clinically composite and show highly variable phenotypes amongst all inherited disorders, mainly due to their heteroplasmic nature. Mutations in mitochondrial DNA (mtDNA) and the nuclear genome (gDNA), or both, have been reported in mitochondrial diseases, suggesting common pathophysiological pathways. Nuclear gene mutations identified in mitochondrial diseases are mostly involved in mtDNA replication, transcription and translation, oxidative phosphorylation (OXPHOS), the biosynthesis of mtDNA, nucleoside transport, salvage or synthesis, and the homeostasis of mitochondrial deoxyribonucleoside triphosphates (dNTP) pool. The m.3243 A>G mtDNA mutation in the MT-TL1 gene coding for the tRNALeu (UUR) is one of the most common mitochondrial disease-causing mutations, with a carrier rate as high as 1:400. Recent studies suggest that patients with the m.3243 A>G mutation present a huge clinical heterogeneity supporting the necessity to investigate the nuclear genome to improve the knowledge on composite mitochondrial disorders, such as mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD) and myopathy. MIDD is a multi-system disorder characterized by diabetes, hearing impairment, and maculopathy but can present several other clinical manifestations. The present study aimed to analyze the whole mitochondrial genome and the whole exome of a clinically characterized MIDD family, negative to the m.3243 A>G variant, and identify mutations in both gDNA and mtDNA, as well as their biological role in their heterogeneous phenotype. The obtained results permitted us to hypothesize that the mitochondrial defects might be due to the epigenetic deregulation of the mitochondrial and nuclear-encoded genes coding for mitochondrial structure and functions. Thus, epigenetic modifications in the context of mitochondrial dysfunctions represent an emerging area of research, possibly useful for innovative mtDNA-related disease differential analyses.

Background/Aims: It is widely known that the imbalance between reactive oxygen species (ROS)/antioxidants and mitochondrial function could play a pivotal role in aging and in the physiopathology of viral infections. Here, we correlated the plasma oxidants/antioxidants levels of the elderly admitted to a long-term care (LTC) unit with clinical data in relation to flu-like disease/COVID-19. Moreover, in vitro we examined the effects of plasma on cell viability, ROS release and mitochondrial function.Materials and Methods: In 60 patients admitted to LTC unit for at least 1 year at moderate or high care load, demographic and clinical variables were taken. Blood samples were collected for the evaluations of oxidants/antioxidants, as thiobarbituric acid reactive substances, 8-hydroxy-2-deoxyguanosine, 8-isoprostanes, superoxide dismutase activity, glutathione, and vitamin D. In vitro, human umbilical vascular endothelial cells (HUVEC) were used to examine the effects of plasma on viability, ROS release and mitochondrial membrane potential.Results: The results obtained showed that the redox state of the elderly was quite balanced; mitochondrial membrane potential of HUVEC was reduced by about 20%, only. Also, the correlation analysis evidenced the association between mitochondrial function and the patients’ outcomes. Interestingly, lower levels of mitochondrial membrane potential were found in the elderly who had symptoms suggestive of COVID-19 or with a confirmed diagnosis of COVID-19.Conclusion: The results of this study highlight the importance of mitochondrial function in the tendency to get a flu-like syndrome like COVID-19 in the elderly admitted to LTC unit. This information could have clinical implications for the management of old population.

PTEN is a gate-keeper tumor-suppressor gene involved in various cell cycle pathways. Germline mutations of one allele of PTEN were found associated with Cowden syndrome, which is an inherited disease characterized by multiple hamartomas. PTEN is frequently inactivated also by somatic mutations in various array of human tumors. In this study,a cohort of 50 Sicilian breast cancer patients, negative to screening for pathogenic mutations in BRCA1/2 genes, was analyzed. Variant c.492+46 G>A (rs775537003) in intron 5 of PTEN gene was identified. The possible role of this variant in splicing mechanisms was evaluated by in silico analysis. Alteration of an ESE and ESS site was found. This is a preliminary study with the aim to investigate about the involvement of PTEN genein the breast cancer and the possible role of splicing alteration events into the risk of the disease.

Introduction: Compared to old people who live at home, depressive symptoms are more prevalent in those who live in long-term care facilities (LTCFs). Different kinds of non-pharmacological treatment approaches in LTCFs have been studied, including behavioral and cognitive-behavioral therapy, cognitive bibliotherapy, problem-solving therapy, brief psychodynamic therapy and life review/reminiscence. The aim of the current review was to systematically review non-pharmacological treatments used to treat depressed older adults with no or mild cognitive impairment (as described by a Mini Mental State Examination score > 20) living in LTCFs.Methods: A research was performed on PubMed and Scopus databases. Following the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) flowchart, studies selection was made. The quality of each Randomized Controlled Trial was scored using the Jadad scale, Quasi-Experimental Design studies and Non-Experimental studies were scored based on the Newcastle-Ottawa Scale (NOS)Results: The review included 56 full text articles; according to the type of intervention, studies were grouped in the following areas: horticulture/gardening (n = 3), pet therapy (n = 4), physical exercise (n = 9), psychoeducation/rehabilitation (n = 15), psychotherapy (n = 3), reminiscence and story sharing (n = 14), miscellaneous (n = 8).Discussion and Conclusion: Despite mixed or negative findings in some cases, most studies included in this systematic review reported that the non-pharmacological interventions assessed were effective in the management of depressed elderly in the LTCFs context. Regrettably, the limitations and heterogeneity of the studies described above hinder the possibility to generalize and replicate results.

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. Approximately 19% of these RNA editing sites were found within 3′ UTR, including sites common to all time points that were predicted to change the binding capacity of 359 miRNAs towards 9654 target genes. A2E exposure also determined significant gene expression differences in deaminase family ADAR, APOBEC and ADAT members, involved in canonical and tRNA editing events. On GO and KEGG enrichment analyses, genes that showed different RNA editing levels are mainly involved in pathways strongly linked to a possible neovascularization of retinal tissue, with induced apoptosis mediated by the ECM and surface protein altered signaling. Collectively, this work demonstrated dynamic RNA editome profiles in RPE cells for the first time and shed more light on new mechanisms at the basis of retinal degeneration.

Abstract The discovery of thousands of non-coding RNAs has revolutionized molecular biology, being implicated in several biological processes and diseases. To clarify oxidative stress role on Retinitis pigmentosa, a very heterogeneous and inherited ocular disorder group characterized by progressive retinal degeneration, we realized a comparative transcriptome analysis of human retinal pigment epithelium cells, comparing two groups, one treated with oxLDL and one untreated, in four time points (1 h, 2 h, 4 h, 6 h). Data analysis foresaw a complex pipeline, starting from CLC Genomics Workbench, STAR and TopHat2/TopHat-Fusion alignment comparisons, followed by transcriptomes assembly and expression quantification. We then filtered out non-coding RNAs and continued the computational analysis roadmap with specific tools and databases for long non-coding RNAs (FEELnc), circular RNAs (CIRCexplorer, UROBORUS, CIRI, KNIFE, CircInteractome) and piwi-interacting RNAs (piRNABank, piRNA Cluster, piRBase, PILFER). Finally, all detected non-coding RNAs underwent pathway analysis by Cytoscape software. Eight-hundred and fifty-four non-coding RNAs, between long non-coding RNAs and PIWI-interacting, were differentially expressed throughout all considered time points, in treated and untreated samples. These non-coding RNAs target host genes involved in several biochemical pathways are related to compromised response to oxidative stress, visual functions, synaptic impairment of retinal neurotransmission, impairment of the interphotoreceptor matrix and blood – retina barrier, all leading to retinal cell death. These data suggest that non-coding RNAs could play a relevant role in Retinitis pigmentosa etiopathogenesis.

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 FMO3, 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. Detected variants were, subsequently, deeply statistically and in silico characterized to determine their possible effects on the enzyme activity. To achieve this goal, a docking prediction for TMA/FMO3 and an unbinding pathway study were performed. Finally, a TMAO/TMA urine quantification by 1H-NMR spectroscopy was performed to support modelling results. Results: The FMO3 screening of all patients highlighted the presence of 17 variants distributed in 26 different haplotypes. Both non-sense and missense considered variants might impair the enzymatic kinetics of FMO3, probably reducing the interaction time between the protein catalytic site and TMA, or losing the wild-type binding site. Conclusions: Even if further functional assays will confirm our predictive results, considering the possible role of FMO3 variants with still uncertain effects, might be a relevant step towards the detection of novel scenarios in TMAU etiopathogenesis.

Abstract Background Autosomal recessive forms of retinitis punctata albescens (RPA) have been described. RPA is characterized by progressive retinal degeneration due to alteration in visual cycle and consequent deposit of photopigments in retinal pigment epithelium. Five loci have been linked to RPA onset. Among these, the retinaldehyde-binding protein 1 gene, RLBP1, is the most frequently involved and several founder mutations were reported. We report results of a genetic molecular investigation performed on a large Sicilian family in which appears a young woman with RPA. Results The proband is in homozygous condition for a novel RLBP1 single-pair deletion, and her healthy parents, both heterozygous, are not consanguineous. Thenovelc.398delC (p.P133Qfs*258) involves the exon 6 and leads to a premature stop codon, resulting in a truncated protein entirely missing of CRAL-TRIO lipid-binding domain. Pedigree analysis showed other non-consanguineous relatives heterozygous for the same mutation in the family. Extension of mutation research in the native town of the proband revealed its presence also in healthy subjects, in a heterozygous condition. Conclusions A novel RLBP1 truncating mutation was detected in a young girl affected by RPA. Although her parents are not consanguineous, the mutation was observed in a homozygous condition. Being them native of the same small Sicilian town of Fiumedinisi, the hypothesis of a geographical area-related mutation was assessed and confirmed.

Molecular signaling that leads to brain arteriovenous malformation (bAVM) is to date elusive and this is firstly due to the low frequency of familial cases. Conversely, sporadic bAVM is the most diffuse condition and represents the main source to characterize the genetic basis of the disease. Several studies were conducted in order to detect both germ-line and somatic mutations linked to bAVM development and, in this context, next generation sequencing technologies offer a pivotal resource for the amount of outputted information. We performed whole exome sequencing on a young boy affected by sporadic bAVM. Paired-end sequencing was conducted on an Illumina platform and filtered variants were validated by Sanger sequencing. We detected 20 likely gene-disrupting variants affecting as many loci. Of these variants, 11 are inherited novel variants and one is a de novo nonsense variant, affecting STK4 gene. Moreover, we also considered rare known variants affecting loci involved in vascular differentiation. In order to explain their possible involvement in bAVM pathogenesis, we analyzed molecular networks at Cytoscape platform. In this study we focus on some genetic point variations detected in a child affected by bAVM. Therefore, we suggest these novel affected loci as prioritized for further investigation on pathogenesis of bAVM lesions.

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. In this review, we aim to describe the current state of knowledge concerning the role of oxidative stress on the neurovascular unit and the role of a single cell type in the NVU crosstalk.

Endogenous antioxidants protect cells from reactive oxygen species (ROS)-related deleterious effects, and an imbalance in the oxidant/antioxidant systems generates oxidative stress. Glyoxalase 1 (GLO1) is a ubiquitous cellular enzyme involved in detoxification of methylglyoxal (MG), a cytotoxic byproduct of glycolysis whose excess can produce oxidative stress. In retinitis pigmentosa, one of the most diffuse cause of blindness, oxidative damage leads to photoreceptor death. To clarify the role of GLO1 in retinitis pigmentosa onset and progression, we treated human retinal pigment epithelium cells by the oxidant agent A2E. Transcriptome profiles between treated and untreated cells were performed by RNA-Seq, considering two time points (3 and 6 h), after the basal one. The exposure to A2E highlighted significant expression differences and splicing events in 370 GLO1 first-neighbor genes, and 23 of them emerged from pathway clustered analysis as main candidates to be associated with retinitis pigmentosa. Such a hypothesis was corroborated by the involvement of previously analyzed genes in specific cellular activities related to oxidative stress, such as glyoxylate and dicarboxylate metabolism, glycolysis, axo-dendritic transport, lipoprotein activity and metabolism, SUMOylation and retrograde transport at the trans-Golgi network. Our findings could be the starting point to explore unclear molecular mechanisms involved in retinitis pigmentosa etiopathogenesis.

Oxidative stress represents one of the principal inductors of lifestyle-related and genetic diseases. Among them, inherited retinal dystrophies, such as age-related macular degeneration and retinitis pigmentosa, are well known to be susceptible to oxidative stress. To better understand how high reactive oxygen species levels may be involved in retinal dystrophies onset and progression, we performed a whole RNA-Seq experiment. It consisted of a comparison of transcriptomes’ profiles among human retinal pigment epithelium cells exposed to the oxidant agent N-retinylidene-N-retinylethanolamine (A2E), considering two time points (3h and 6h) after the basal one. The treatment with A2E determined relevant differences in gene expression and splicing events, involving several new pathways probably related to retinal degeneration. We found 10 different clusters of pathways involving differentially expressed and differentially alternative spliced genes and highlighted the sub- pathways which could depict a more detailed scenario determined by the oxidative-stress-induced condition. In particular, regulation and/or alterations of angiogenesis, extracellular matrix integrity, isoprenoid-mediated reactions, physiological or pathological autophagy, cell-death induction and retinal cell rescue represented the most dysregulated pathways. Our results could represent an important step towards discovery of unclear molecular mechanisms linking oxidative stress and etiopathogenesis of retinal dystrophies.

Long non-coding RNAs (lncRNAs) are untranslated transcripts which regulate many biological processes. Changes in lncRNA expression pattern are well-known related to various human disorders, such as ocular diseases. Among them, retinitis pigmentosa, one of the most heterogeneous inherited disorder, is strictly related to oxidative stress. However, little is known about regulative aspects able to link oxidative stress to etiopathogenesis of retinitis. Thus, we realized a total RNA-Seq experiment, analyzing human retinal pigment epithelium cells treated by the oxidant agent N-retinylidene-N-retinylethanolamine (A2E), considering three independent experimental groups (untreated control cells, cells treated for 3 h and cells treated for 6 h). Differentially expressed lncRNAs were filtered out, explored with specific tools and databases, and finally subjected to pathway analysis. We detected 3,3’-overlapping ncRNAs, 107 antisense, 24 sense-intronic, four sense-overlapping and 227 lincRNAs very differentially expressed throughout all considered time points. Analyzed lncRNAs could be involved in several biochemical pathways related to compromised response to oxidative stress, carbohydrate and lipid metabolism impairment, melanin biosynthetic process alteration, deficiency in cellular response to amino acid starvation, unbalanced regulation of cofactor metabolic process, all leading to retinal cell death. The explored lncRNAs could play a relevant role in retinitis pigmentosa etiopathogenesis, and seem to be the ideal candidate for novel molecular markers and therapeutic strategies.

Background: Cyclin D1 gene (CCND1) plays pivotal roles in the development of several human cancers, including breast cancer, functioning as an oncogene. The aim of this study was to better understand the molecular dynamics of ductal carcinomas with regard to proliferation and the ageing process.