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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. We specifically focused on long non-coding RNAs, as 6 of these emerged as dysregulated in the diseased-tissue (COL4A2-AS2, RPS21-AS, PELATON, ITGB2-AS1, ACER2-AS and CTEPHA1). For each of them, we performed both a thorough in silico dissection and in vitro validation, to predict their function during adipogenesis. We report the lncRNAs expression during adipose derived stem cells differentiation to adipocytes as model of adipogenesis and their potential modulation by adipogenesis-related transcription factors (C/EBPs and PPARγ). Moreover, inhibiting CTEPHA1 expression we investigated its impact on adipogenesis-related transcription factors, showing its significative dysregulation of C/EBPα expression. Lastly, we dissected the subcellular localization, pathway involvement and disease-correlation for coding differentially expressed genes. Together, these findings highlight a transcriptional deregulation at the basis of obesity, impacted by both coding and long non-coding RNAs.

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). Methods: We tested the BDC-HFn solubility, stability, and ability to cross a blood–brain barrier (BBB) model. We tested the effect of BDC-HFn on AD and control (CTR) PBMCs to evaluate the transcriptomic profile by RNA-seq. Results: We developed a nanoformulation with a diameter of 12 nm to improve the solubility and stability. The comparison of the transcriptomics analyses between AD patients before and after BDC-HFn treatment showed a major number of DEG (2517). The pathway analysis showed that chemokines and macrophages activation differed between AD patients and controls after BDC-HFn treatment. BDC-HFn binds endothelial cells from the cerebral cortex and crosses through a BBB in vitro model. Conclusions: Our data showed how BDC-Hfn could improve the stability of BDC. Significant differences in genes associated with inflammation between the same patients before and after BDC-Hfn treatment have been found. Inflammatory genes that are upregulated between AD and CTR after BDC-HFn treatment are converted and downregulated, suggesting a possible therapeutic approach.

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 ± 0.9 kg/m2) and 5 obese women (OBF, age 41 ± 12.5 years, BMI 38.2 ± 4.6 kg/m2). Raw data obtained from Illumina NextSeq 500 sequencer were processed through BlueBee® Genomics Platform while differential expression analysis was performed with the DESeq2 R package and deposited in the GEO public repository with GSE166047 as accession number. Specifically, 20 samples divided between NW (control), OBF (obese women), OBM (obese male) and OBT2D (obese women with diabetes) are deposited in the GSE166047. We hereby describe only 10 samples (5 healthy normal weight women reported as NW and 5 obese women reported as OBF) because we refer to the data published in the article “Transcriptional characterization of Subcutaneous Adipose Tissue in obesity affected women highlights metabolic dysfunction and implications for lncRNAs” (DOI: 10.1016/j.ygeno.2021.09.014 ). Pathways analyses were performed on g:Profiler, Enrichr, ClueGO and GSEA to gain biological insights on gene expression. Raw data reported in GEO database along with detailed methods description reported in this data article could be reused for comparisons with other datasets on the topic to obtain transcriptional differences in a wider co-hort. Moreover, detailed pathways analysis along with cross-referenced data with other datasets will allow to identify novel dysregulated pathways and genes responsible for this regulation. The biological interpretation of this dataset, along with related in vitro experiments, is reported by Rey et al., in Genomics (DOI: 10.1016/j.ygeno.2021.09.014 ).

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. We highlight how they impact neurites' extension and synapses' biology, through specific molecular signatures. We report a reduced expression of markers associated with synaptic plasticity, and we specifically focus on GABAergic and dopaminergic synapses, for their relevance in aging processes and PD, respectively. A reduction in SNCA‐AS1 expression leads to the opposite effect. As part of this signature is co‐regulated by the two genes, we discriminate between functions elicited by genes specifically altered by SNCA‐AS1 or SNCA's overexpression, observing a relevant role for SNCA‐AS1 in synaptogenesis through a shared molecular signature with SNCA. We also highlight how numerous deregulated pathways are implicated in aging‐related processes, suggesting that SNCA‐AS1 could be a key player in cellular senescence, with implications for aging‐related diseases. Indeed, the upregulation of SNCA‐AS1 leads to alterations in numerous PD‐specific genes, with an impact highly comparable to that of SNCA's upregulation. Our results show that SNCA‐AS1 elicits its cellular functions through the regulation of SNCA, with a specific modulation of synaptogenesis and senescence, presenting implications in PD., In this work, we aim to characterize SNCA‐AS1, antisense transcript to the SNCA gene, and its implications in cellular processes. Through RNA‐sequencing, we investigated the transcriptomic changes of which both genes are responsible, highlighting a role for them in Parkinson's disease, synapses biology, and aging processes.

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. These data are suitable for integration with supplemental samples and for analysis according to different individuals' classification. Also, differential expression evaluation may be implemented with other scientific purposes, such as research of unannotated genes, mRNA splicing and genes isoforms. The analysis of Differential Expressed genes in COVID-19 positive patients compared to non-COVID-19 patients is published in: S. Gagliardi, E.T. Poloni, C. Pandini, M. Garofalo, F. Dragoni, V. Medici, A. Davin, S.D. Visona, M. Moretti, D. Sproviero, O. Pansarasa, A. Guaita, M. Ceroni, L. Tronconi, C. Cereda, Detection of SARS-CoV-2 genome and whole transcriptome sequencing in frontal cortex of COVID-19 patients., Brain. Behav. Immun. (2021). https://doi.org/10.1016/j.bbi.2021.05.012.

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. Through weighted co-expression network analysis and functional enrichment, we highlight the role of non-coding RNAs in altering the expression of coding genes involved in mechanotransduction, stemness, and neural differentiation. Moreover, as non-coding RNAs are poorly conserved between species, we focus on those with human homologue sequences, performing further computational characterization. Lastly, we looked for isoform switching as possible mechanism in altering coding and non-coding gene expression. Our results provide a comprehensive dissection of the 3D scaffold Nichoid’s influence on the biological and genetic response of neural precursor cells. These findings shed light on the possible role of non-coding RNAs in 3D cell growth, indicating that also non-coding RNAs are implicated in cellular response to mechanical stimuli.

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. This class of RNAs may offer numerous starting points for new investigations about pathogenic mechanisms and, in particular, about peripheral biomarkers. Indeed, altered lncRNA signatures are emerging as potential diagnostic biomarkers. In this review, we have collected and fully explored all the presented data about lncRNAs and AD in the peripheral system to offer an overview about this class of non-coding RNAs and their possible role in AD.

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. We also investigated the transcriptomic profile of frontal cortex from COVID-19 patients and matched controls by RNA-seq analysis to characterize the transcriptional signature. Our data showed that SARS-CoV-2 could be detected by ddPCR in 8 (88%) of 9 examined samples while by qRT-PCR in one case only (11%). Transcriptomic analysis revealed that 11 genes (10 mRNAs and 1 lncRNA) were differential expressed when frontal cortex of COVID-19 patients were compared to controls. These genes fall into categories including hypoxia, hemoglobin-stabilizing protein, hydrogen peroxide processes. This work demonstrated that the quantity of viral RNA in frontal cortex is minimal and it can be detected only with a very sensitive method (ddPCR). Thus, it is likely that SARS-CoV-2 does not actively infect and replicate in the brain; its topography within encephalic structures remains uncertain. Moreover, COVID-19 may have a role on brain gene expression, since we observed an important downregulation of genes associated to hypoxia inducting factor system (HIF) that may inhibit the capacity of defense system during infection and oxigen deprivation, showing that hypoxia, well known multi organ condition associated to COVID-19, also marked the brain.

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. The subcutaneous adipose tissue (SAT) of five healthy, normal-weight women, five obese women, five obese women with T2D and five obese men were subjected to RNA-sequencing, leading to the identification of deregulated coding and non-coding RNAs, classified for their oncogenic score. A panel of DE RNAs was validated via Real-Time PCR and oncogene expression levels correlated the oncogenes with anthropometrical parameters, highlighting significant trends. For each analyzed condition, we identified the deregulated pathways associated with cancer, the prediction of possible prognosis for different cancer types and the lncRNAs involved in oncogenic networks and tissues. Our results provided a comprehensive characterization of oncogenesis correlation in SAT, providing specific insights into the possible molecular targets implicated in this process. Indeed, the identification of deregulated oncogenes also in SAT highlights hypothetical targets implicated in the increased oncogenic risk in highly obese subjects. These results could shed light on new molecular targets to be specifically modulated in obesity and highlight which cancers should receive the most attention in terms of better prevention in obesity-affected patients.

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. Therefore, this work aims to investigate MINCR potential mechanisms of action and its implications in cancer and neurodegeneration in relation to its expression levels in SH-SY5Y cells through RNA-sequencing approach. Our results show that MINCR overexpression causes massive alterations in cancer-related genes, leading to disruption in many fundamental processes, such as cell cycle and growth factor signaling. On the contrary, MINCR downregulation influences a small number of genes involved in different neurodegenerative disorders, mostly concerning RNA metabolism and inflammation. Thus, understanding the cause and functional consequences of MINCR deregulation gives important insights on potential pathogenetic mechanisms both in cancer and in neurodegeneration.

Alzheimer&rsquo, s disease (AD), Parkinson&rsquo, 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. To do so, we performed RNA-seq analysis to investigate the deregulation of both coding and long non-coding RNAs (lncRNAs) in ALS, AD, and PD patients and controls (CTRL) in peripheral blood mononuclear cells (PBMCs). A total of 293 differentially expressed (DE) lncRNAs and 87 mRNAs were found in ALS patients. In AD patients a total of 23 DE genes emerged, 19 protein coding genes and four lncRNAs. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses, we found common affected pathways and biological processes in ALS and AD. In PD patients only five genes were found to be DE. Our data brought to light the importance of lncRNAs and mRNAs regulation in three principal neurodegenerative disorders, offering starting points for new investigations on deregulated pathogenic mechanisms.

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. Thus, improved formulations of curcumin are emerging as powerful tools in overcoming the bioavailability and stability limitations of curcumin. New studies in animal models and recent double-blinded, placebo-controlled clinical trials using some of these new formulations are finally beginning to show that curcumin could be used for the treatment of cognitive decline. Ultimately, this work could ease the burden caused by a group of diseases that are becoming a global emergency because of the unprecedented growth in the number of people aged 65 and over worldwide. In this review, we discuss curcumin’s main mechanisms of action and also data from in vivo experiments on the effects of curcumin on cognitive decline.

Alterations in RNA metabolism play an important role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. The literature has described, so far, a small number of long non coding RNAs (lncRNAs) associated to ALS demonstrating that how there is still much to do to identify and understand their role in ALS. This class of RNAs may offer numerous starting points for new investigations about pathogenic mechanism involved in ALS disease. In this review, we have collected all the presented data about lncRNAs and ALS to offer an overview about this class of non-coding RNAs and their possible role in ALS disease. Keywords: ALS, lncRNAs

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. This kind of influence results in different cellular morphology and organization, but the molecular bases of these changes remain largely unknown. Through RNA-Seq approach on murine neural precursors stem cells expanded inside the Nichoid, we investigated the deregulated genes and pathways showing that the Nichoid causes alteration in genes strongly connected to mechanobiological functions. Moreover, we fully dissected this mechanism highlighting how the changes start at a membrane level, with subsequent alterations in the cytoskeleton, signaling pathways, and metabolism, all leading to a final alteration in gene expression. The results shown here demonstrate that the Nichoid influences the biological and genetic response of stem cells thorough specific alterations of cellular signaling. The characterization of these pathways elucidates the role of mechanical manipulation on stem cells, with possible implications in regenerative medicine applications.

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. Our dataset is a starting point for the omni-comprehensive analysis of coding and lncRNAs, from an easy to withdraw, manage and store tissue that shows to be a suitable model for RNA profiling in ALS. Machine-accessible metadata file describing the reported data (ISA-Tab format)

Alteration in RNA metabolism, concerning both coding and long non-coding RNAs (lncRNAs), may play an important role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. In this work, we performed a whole transcriptome RNA-seq analysis to investigate the regulation of non-coding and coding RNAs in Sporadic ALS patients (SALS), mutated ALS patients (FUS, TARDBP and SOD1) and matched controls in Peripheral Blood Mononuclear Cells (PBMC). Selected transcripts were validated in spinal cord tissues. A total of 293 differentially expressed (DE) lncRNAs was found in SALS patients, whereas a limited amount of lncRNAs was deregulated in mutated patients. A total of 87 mRNAs was differentially expressed in SALS patients; affected genes showed an association with transcription regulation, immunity and apoptosis pathways. Taken together our data highlighted the importance of extending the knowledge on transcriptomic molecular alterations and on the significance of regulatory lncRNAs classes in the understanding of ALS disease. Our data brought the light on the importance of lncRNAs and mRNAs regulation in central and peripheral systems, offering starting points for new investigations about pathogenic mechanism involved in ALS disease.