Cellular adaptations impact the biological activity of naphthalene diimide G-quadruplex ligands in ALT-positive osteosarcoma cells.

Telomeric G-quadruplexes (G4s) represent intriguing targets for tumours characterized by the Alternative Lengthening of Telomere (ALT) mechanism. Here we have investigated the effects of two naphthalene diimide (NDI)-based G4 interacting agents (NMe2 and QN-302) in a pair of ALT-positive human osteosarcoma (U-2 OS and Saos-2) cell lines. Both NDIs displayed marked cell growth inhibitory activity associated with the induction of telomere dysfunctions.

Integrating datasets to dissect RNA- and transcription-dependent functions: comparative transcriptome profiling of knockdown strategies.

The recent discovery of antisense RNAs (asRNAs) as key regulators of biological processes has highlighted the need to challenge their mechanism(s) of action using complementary approaches. Indeed, asRNAs can act on their sense gene or on distally located targets, by exploiting either transcription- or RNA-dependent mechanisms. Here we present a comparative transcriptome profiling of cancer cells knocked-down for the asRNA with two different approaches: i) Gapmer Antisense Oligonucleotides to assess RNA-dependent mechanisms, and ii) CRISPR/Cas9 deletion of the transcription start site to study transcription-dependent mechanisms.

Functional analysis and transcriptome profile of meninges and skin fibroblasts from human-aged donors.

The central nervous system (CNS) is surrounded by three membranes called meninges. Specialised fibroblasts, originating from the mesoderm and neural crest, primarily populate the meninges and serve as a binding agent. Our goal was to compare fibroblasts from meninges and skin obtained from the same human-aged donors, exploring their molecular and cellular characteristics related to CNS functions.

Study of lncRNAs in Pediatric Neurological Diseases: Methods, Analysis of the State-of-Art and Possible Therapeutic Implications.

Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various cellular processes, and their roles in pediatric neurological diseases are increasingly being explored. This review provides an overview of lncRNA implications in the central nervous system, both in its physiological state and when a pathological condition is present. We describe the role of lncRNAs in neural development, highlighting their significance in processes such as neural stem cell proliferation, differentiation, and synaptogenesis.

Identification of a novel pathway in sporadic Amyotrophic Lateral Sclerosis mediated by the long non-coding RNA ZEB1-AS1.

Background: Deregulation of transcription in the pathogenesis of sporadic Amyotrophic Lateral Sclerosis (sALS) is taking central stage with RNA-sequencing analyses from sALS patients tissues highlighting numerous deregulated long non-coding RNAs (lncRNAs). The oncogenic lncRNA ZEB1-AS1 is strongly downregulated in peripheral blood mononuclear cells of sALS patients. In addition, in cancer-derived cell lines, ZEB1-AS1 belongs to a negative feedback loop regulation with hsa-miR-200c, acting as a molecular sponge for this miRNA.

Navigating the Multiverse of Antisense RNAs: The Transcription- and RNA-Dependent Dimension.

Evidence accumulated over the past decades shows that the number of identified antisense transcripts is continuously increasing, promoting them from transcriptional noise to real genes with specific functions. Indeed, recent studies have begun to unravel the complexity of the antisense RNA (asRNA) world, starting from the multidimensional mechanisms that they can exert in physiological and pathological conditions. In this review, we discuss the multiverse of the molecular functions of asRNAs, describing their action through transcription-dependent and RNA-dependent mechanisms.

Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer's Disease Patients.

Background: Bisdemethoxycurcumin (BDC) might be an inflammation inhibitor in Alzheimer's Disease (AD). However, BDC is almost insoluble in water, poorly absorbed by the organism, and degrades rapidly. We thus developed a new nanoformulation of BDC based on H-Ferritin nanocages (BDC-HFn).

RNA-seq dataset of subcutaneous adipose tissue: Transcriptional differences between obesity and healthy women.

In this data article, we present the dataset from the RNA-Seq analysis of subcutaneous adipose tissue collected from 5 healthy normal weight women (NW, age 37 ± 6.7 years, BMI 24.3 ± 0.

α-Synuclein antisense transcript SNCA-AS1 regulates synapses- and aging-related genes suggesting its implication in Parkinson's disease.

SNCA protein product, α-synuclein, is widely renowned for its role in synaptogenesis and implication in both aging and Parkinson's disease (PD), but research efforts are still needed to elucidate its physiological functions and mechanisms of regulation. In this work, we aim to characterize SNCA-AS1, antisense transcript to the SNCA gene, and its implications in cellular processes. The overexpression of SNCA-AS1 upregulates both SNCA and α-synuclein and, through RNA-sequencing analysis, we investigated the transcriptomic changes of which both genes are responsible.

MINCR: A long non-coding RNA shared between cancer and neurodegeneration.

The multitasking nature of lncRNAs allows them to play a central role in both physiological and pathological conditions. Often the same lncRNA can participate in different diseases. Specifically, the MYC-induced Long non-Coding RNA MINCR is upregulated in various cancer types, while downregulated in Amyotrophic Lateral Sclerosis patients.

COVID-19 patients and Dementia: Frontal cortex transcriptomic data.

Since the association of SARS-Cov-2 infection with Nervous System (NS) manifestations, we performed RNA-sequencing analysis in Frontal Cortex of COVID-19 positive or negative individuals and affected or not by Dementia individuals. We examined gene expression differences in individuals with COVID-19 and Dementia compared to Dementia only patients by collecting transcript counts in each sample and performing Differential Expression analysis. We found eleven genes satisfying our significance criteria, all of them being protein coding genes.

Neural Precursor Cells Expanded Inside the 3D Micro-Scaffold Nichoid Present Different Non-Coding RNAs Profiles and Transcript Isoforms Expression: Possible Epigenetic Modulation by 3D Growth.

Non-coding RNAs show relevant implications in various biological and pathological processes. Thus, understanding the biological implications of these molecules in stem cell biology still represents a major challenge. The aim of this work is to study the transcriptional dysregulation of 357 non-coding genes, found through RNA-Seq approach, in murine neural precursor cells expanded inside the 3D micro-scaffold Nichoid versus standard culture conditions.

Transcriptional characterization of subcutaneous adipose tissue in obesity affected women highlights metabolic dysfunction and implications for lncRNAs.

Obesity is a complex disease with multifactorial causes, and its prevalence is becoming a serious health crisis. For this reason, there is a crucial need to identify novel targets and players. With this aim in mind, we analyzed via RNA-sequencing the subcutaneous adipose tissue of normal weight and obesity-affected women, highlighting the differential expression in the two tissues.

Advances with Long Non-Coding RNAs in Alzheimer's Disease as Peripheral Biomarker.

One of the most compelling needs in the study of Alzheimer's disease (AD) is the characterization of cognitive decline peripheral biomarkers. In this context, the theme of altered RNA processing has emerged as a contributing factor to AD. In particular, the significant role of long non-coding RNAs (lncRNAs) associated to AD is opening new perspectives in AD research.

Detection of SARS-CoV-2 genome and whole transcriptome sequencing in frontal cortex of COVID-19 patients.

SARS-Cov-2 infection is frequently associated with Nervous System manifestations. However, it is not clear how SARS-CoV-2 can cause neurological dysfunctions and which molecular processes are affected in the brain. In this work, we examined the frontal cortex tissue of patients who died of COVID-19 for the presence of SARS-CoV-2, comparing qRT-PCR with ddPCR.

RNA-seq Characterization of Sex-Differences in Adipose Tissue of Obesity Affected Patients: Computational Analysis of Differentially Expressed Coding and Non-Coding RNAs.

Obesity is a multifactorial disease presenting sex-related differences including adipocyte functions, sex hormone effects, genetics, and metabolic inflammation. These can influence individuals' risk for metabolic dysfunctions, with an urgent need to perform sex-based analysis to improve prevention, treatment, and rehabilitation programs. This research work is aimed at characterizing the transcriptional differences present in subcutaneous adipose tissue (SAT) of five obesity affected men versus five obesity affected women, with an additional focus on the role of long non-coding RNAs.

Transcriptome Analysis of Subcutaneous Adipose Tissue from Severely Obese Patients Highlights Deregulation Profiles in Coding and Non-Coding Oncogenes.

Obesity is a major risk factor for a large number of secondary diseases, including cancer. Specific insights into the role of gender differences and secondary comorbidities, such as type 2 diabetes (T2D) and cancer risk, are yet to be fully identified. The aim of this study is thus to find a correlation between the transcriptional deregulation present in the subcutaneous adipose tissue of obese patients and the oncogenic signature present in multiple cancers, in the presence of T2D, and considering gender differences.

Alzheimer's, Parkinson's Disease and Amyotrophic Lateral Sclerosis Gene Expression Patterns Divergence Reveals Different Grade of RNA Metabolism Involvement.

Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by a progressive degeneration of the central or peripheral nervous systems. A central role of the RNA metabolism has emerged in these diseases, concerning mRNAs processing and non-coding RNAs biogenesis. We aimed to identify possible common grounds or differences in the dysregulated pathways of AD, PD, and ALS.

Curcumin Formulations and Trials: What's New in Neurological Diseases.

Curcumin's pharmacological properties and its possible benefits for neurological diseases and dementia have been much debated. In vitro experiments show that curcumin modulates several key physiological pathways of importance for neurology. However, in vivo studies have not always matched expectations.

Dissecting the Effect of a 3D Microscaffold on the Transcriptome of Neural Stem Cells with Computational Approaches: A Focus on Mechanotransduction.

3D cell cultures are becoming more and more important in the field of regenerative medicine due to their ability to mimic the cellular physiological microenvironment. Among the different types of 3D scaffolds, we focus on the Nichoid, a miniaturized scaffold with a structure inspired by the natural staminal niche. The Nichoid can activate cellular responses simply by subjecting the cells to mechanical stimuli.

RNA-Seq profiling in peripheral blood mononuclear cells of amyotrophic lateral sclerosis patients and controls.

Coding and long non-coding RNA (lncRNA) metabolism is now revealing its crucial role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. In this work, we present a dataset obtained via Illumina RNA-seq analysis on Peripheral Blood Mononuclear Cells (PBMCs) from sporadic and mutated ALS patients (mutations in FUS, TARDBP, SOD1 and VCP genes) and healthy controls. This dataset allows the whole-transcriptome characterization of PBMCs content, both in terms of coding and non-coding RNAs, in order to compare the disease state to the healthy controls, both for sporadic patients and for mutated patients.

Curcumin and Novel Synthetic Analogs in Cell-Based Studies of Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is associated with the most common type of dementia and is characterized by the presence of deposits of the protein fragment amyloid beta (Aβ) in the brain. The natural product mixture of curcuminoids that improves certain defects in innate immune cells of AD patients may selectively enhance Aβ phagocytosis by alteration of gene transcription. In this work, we evaluated the protective effects of curcuminoids in cells from AD patients by investigating the effect on NF-κB and BACE1 signaling pathways.