Semiquantitative Cardiac-Specific Gene Expression Validation of the DNA Methylation Microarray in Human Mesenchymal Stem Cells.

Epigenetic events such as DNA methylation and histone modifications affect a wide range of genomic functions without impacting the nucleotide sequence. Aberrant DNA methylation has been related to a variety of disorders, including cancer, obesity, and addiction. DNA methylation is defined by the presence of a methyl group at the fifth position of the cytosine pyrimidine ring, which occurs in roughly 80% of CpG dinucleotides in the human genome.

Transcriptome-wide profiling identifies colon cancer-associated m6A transcripts and potential RNA methyl modifiers.

Background: N6-methyladenosine (m6A) is a prevalent and crucial RNA methylation modification that plays a significant role in various biological and pathological processes. The dysregulation of m6A has been linked to the initiation, progression, and metastasis of several cancer types, including colon cancer. The transcriptome of colon cancer indeed provides insight into dysregulated coding and non-coding RNAs, but it does not reveal the mechanisms, such as m6A modifications, that determine post-transcriptional and pre-translational regulations.

Functional alteration due to structural damage is network dependent: insight from multiple sclerosis.

Little is known about how the brain's functional organization changes over time with respect to structural damage. Using multiple sclerosis as a model of structural damage, we assessed how much functional connectivity (FC) changed within and between preselected resting-state networks (RSNs) in 122 subjects (72 with multiple sclerosis and 50 healthy controls). We acquired the structural, diffusion, and functional MRI to compute functional connectomes and structural disconnectivity profiles.

Locus-Specific Enrichment Analysis of 5-Hydroxymethylcytosine Reveals Novel Genes Associated with Breast Carcinogenesis.

An imbalance in DNA methylation is a hallmark epigenetic alteration in cancer. The conversion of 5-methylcytosine (5-mC) to 5-hydroxymethyl cytosine (5-hmC), which causes the imbalance, results in aberrant gene expression. The precise functional role of 5-hydroxymethylcytosine in breast cancer remains elusive.

Experimental and Computational Approaches for Non-CpG Methylation Analysis.

Cytosine methylation adjacent to adenine, thymine, and cytosine residues but not guanine of the DNA is distinctively known as non-CpG methylation. This CA/CT/CC methylation accounts for 15% of the total cytosine methylation and varies among different cell and tissue types. The abundance of CpG methylation has largely concealed the role of non-CpG methylation.

Lower cerebral arterial blood flow is associated with greater serum neurofilament light chain levels in multiple sclerosis patients.

Background And Purpose: Hypoperfusion, vascular pathology, and cardiovascular risk factors are associated with disease severity in multiple sclerosis (MS). We aimed to assess relationships between cerebral arterial blood flow (CABF) and serum neurofilament light chain (sNfL) as neuronal damage biomarkers.

Methods And Materials: Total CABF was measured in 137 patients (86 with clinically isolated syndrome/relapsing-remitting (RR) MS and 51 with progressive MS [PMS]) and 48 healthy controls using Doppler ultrasonography.

Time course of lesion-induced atrophy in multiple sclerosis.

Background And Purpose: White matter (WM) tract disruption impacts volume loss in connected deep gray matter (DGM) over 5 years in people with multiple sclerosis (PwMS). However, the timeline of this phenomenon remains poorly characterized.

Materials And Methods: Annual serial MRI for 181 PwMS was retrospectively analyzed from a 10-year clinical trial database.

Patient-Reported Outcome Severity and Emotional Salience Network Disruption in Multiple Sclerosis.

Background: Overall burden of white matter damage is associated with increased self-report fatigue severity in people with multiple sclerosis. However, a paradoxically opposite association was reported for white matter damage to tracts in specific subnetworks including the amygdala, temporal pole, and insula. Based on neuroanatomical principles and other data from the literature, we hypothesized that these results might be indicative of a broader relationship between damage to these subnetworks and impaired recognition of negative emotional salience central to patient-reported outcomes.

Genome-wide methylome pattern predictive network analysis reveal mesenchymal stem cell's propensity to undergo cardiovascular lineage.

Unlabelled: Mesenchymal stem cells (MSCs) differentiation toward cardiovascular lineage prediction using the global methylome profile will highlight its prospective utility in regenerative medicine. We examined the propensity prediction to cardiovascular lineage using 5-Aza, a well-known cardiac lineage inducer. The customized 180 K microarray was performed and further analysis of global differentially methylated regions by Ingenuity pathway analysis (IPA) in both MSCs and 5-AC-treated MSCs.

Brain atrophy and lesion burden are associated with disability progression in a multiple sclerosis real-world dataset using only T2-FLAIR: The NeuroSTREAM MSBase study.

Background: Methodological challenges limit the use of brain atrophy and lesion burden measures in the follow-up of multiple sclerosis (MS) patients on clinical routine datasets.

Objective: To determine the feasibility of T2-FLAIR-only measures of lateral ventricular volume (LVV) and salient central lesion volume (SCLV), as markers of disability progression (DP) in MS.

Methods: A total of 3,228 MS patients from 9 MSBase centers in 5 countries were enrolled.

Non-CpG methylation-a key epigenetic modification in cancer.

The methylation of cytosine residues that precede adenine/thymine or other cytosine nucleotides instead of guanine in DNA is known as non-CpG methylation. It is a pronounced epigenetic modification with a central role in gene regulation similar to CpG methylation. Due to technological limitations, the locus-specific role of non-CpG methylation was scarcely understood.

Quantifying disease pathology and predicting disease progression in multiple sclerosis with only clinical routine T2-FLAIR MRI.

Background: Although quantitative measures from research-quality MRI provide a means to study multiple sclerosis (MS) pathology in vivo, these metrics are often unavailable in legacy clinical datasets.

Objective: To determine how well an automatically-generated quantitative snapshot of brain pathology, measured only on clinical routine T2-FLAIR MRI, can substitute for more conventional measures on research MRI in terms of capturing multi-factorial disease pathology and providing similar clinical relevance.

Methods: MRI with both research-quality sequences and conventional clinical T2-FLAIR was acquired for 172 MS patients at baseline, and neurologic disability was assessed at baseline and five-years later.

Identification of novel dysregulated circular RNAs in early-stage breast cancer.

Breast cancer is a major cause of cancer-related death in women worldwide. Non-coding RNAs are a potential resource to be used as an early diagnostic biomarker for breast cancer. Circular RNAs are a recently identified group of non-coding RNA with a significant role in disease development with potential utility in diagnosis/prognosis in cancer.

Clinical feasibility of longitudinal lateral ventricular volume measurements on T2-FLAIR across MRI scanner changes.

Background: Greater brain atrophy is associated with disability progression (DP) in patients with multiple sclerosis (PwMS). However, methodological challenges limit its routine clinical use.

Objective: To determine the feasibility of atrophy measures as markers of DP in PwMS scanned across different MRI field strengths.

Leptomeningeal, dura mater and meningeal vessel wall enhancements in multiple sclerosis.

Background: Leptomeningeal contrast enhancement (LMCE) has previously shown potential to be an indirect marker for leptomeningeal inflammation in multiple sclerosis (MS). Dura mater (DME), inclusive falx cerebri (FCE) enhancement and meningeal vessel wall enhancement (VWE) represent two other meningeal enhancement patterns in MS that have not been extensively studied.

Objectives: To investigate the frequency of LMCE, DME/FCE and VWE in patients with MS and their associations with demographic, clinical and MRI characteristics in a longitudinal retrospective study.

Late onset multiple sclerosis is associated with more severe ventricle expansion.

Background: Late-onset multiple sclerosis (LOMS) is associated with faster disability progression than persons with adult-onset MS (PwAOMS). The differences in brain atrophy are currently unknown.

Objectives: To determine MRI-derived atrophy rates in persons with late-onset MS (PwLOMS) and compare them to an age-matched and disease duration-matched sample of PwAOMS.

Longitudinal Magnetic Resonance Imaging of Cerebral Microbleeds in Multiple Sclerosis Patients.

We hypothesized that cerebral microbleeds (CMBs) in multiple sclerosis (MS) patients will be detected with higher prevalence compared to healthy controls (HC) and that quantitative susceptibility mapping (QSM) will help remove false positives seen in susceptibility weighted imaging (SWI). A cohort of 100 relapsing remitting MS subjects scanned at 3T were used to validate a set of CMB detection guidelines specifically using QSM. A second longitudinal cohort of 112 MS and 25 HCs, also acquired at 3T, was reviewed across two time points.

Relationships Among Circulating Levels of Hemostasis Inhibitors, Chemokines, Adhesion Molecules, and MRI Characteristics in Multiple Sclerosis.

Several studies suggested cross talk among components of hemostasis, inflammation, and immunity pathways in the pathogenesis, neurodegeneration, and occurrence of cerebral microbleeds (CMBs) in multiple sclerosis (MS). This study aimed to evaluate the combined contribution of the hemostasis inhibitor protein C (PC) and chemokine C-C motif ligand 18 (CCL18) levels to brain atrophy in MS and to identify disease-relevant correlations among circulating levels of hemostasis inhibitors, chemokines, and adhesion molecules, particularly in CMB occurrence in MS. Plasma levels of hemostasis inhibitors (ADAMTS13, PC, and PAI1), CCL18, and soluble adhesion molecules (sNCAM, sICAM1, sVCAM1, and sVAP1) were evaluated by multiplex in 138 MS patients [85 relapsing-remitting (RR-MS) and 53 progressive (P-MS)] and 42 healthy individuals (HI) who underwent 3-T MRI exams.

Subcutaneous anti-CD20 antibody treatment delays gray matter atrophy in human myelin oligodendrocyte glycoprotein-induced EAE mice.

Background: The human myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (huMOG-EAE) model, generates B-cell driven demyelination in mice, making it a suitable multiple sclerosis model to study B cell depletion.

Objectives: We investigated the effect of subcutaneous anti-CD20 antibody treatment on huMOG-EAE gray matter (GM) pathology.

Methods: C57Bl/6, 8-week old mice were immunized with 200 huMOG and treated with 50 μg/mouse of anti-CD20 antibody (n = 16) or isotype control (n = 16).

High density lipoprotein cholesterol and apolipoprotein A-I are associated with greater cerebral perfusion in multiple sclerosis.

Background: The pathophysiological mechanisms underlying the associations of multiple sclerosis (MS) neurodegeneration serum cholesterol profiles is currently unknown.

Objective: To determine associations between lipid profile measures and cerebral perfusion-based indices in MS patients.

Methods: Seventy-seven MS patients underwent 3 T MRI.

Serum Neurofilament Light Chain Levels are Associated with Lower Thalamic Perfusion in Multiple Sclerosis.

Both perfusion-weighted imaging (PWI) measures and serum neurofilament light (sNfL) chain levels have been independently associated with disability in multiple sclerosis (MS) patients. This study aimed to determine whether these measures are correlated to each other or independently describe different MS processes. For this purpose, 3T MRI dynamic susceptibility contrast (DSC)-PWI and single-molecule assay (Simoa)-based sNfL methods were utilized when investigating 86 MS patients.

Cortical and Deep Gray Matter Perfusion Associations With Physical and Cognitive Performance in Multiple Sclerosis Patients.

Reports suggest presence of cerebral hypoperfusion in multiple sclerosis (MS). Currently there are no studies that examine if the cerebral MS perfusion is affected by presence of cardiovascular comorbidities. To investigate associations between cerebral perfusion and disease outcomes in MS patients with and without comorbid cardiovascular diseases (CVD).

Neuroprotective associations of apolipoproteins A-I and A-II with neurofilament levels in early multiple sclerosis.

Background: The role of cholesterol homeostasis in neuroaxonal injury in multiple sclerosis is not known.

Objective: The objective of the study is to investigate the associations of cerebrospinal fluid (CSF) and serum neurofilament light chain levels (CSF-NfL and sNfL, respectively), which are biomarkers of neuroaxonal injury, with cholesterol biomarkers at the clinical onset of multiple sclerosis.

Methods: sNfL, serum cholesterol profile (total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), serum apolipoprotein (Apo) levels (ApoA-I, ApoA-II, ApoB, and ApoE), and albumin quotient were obtained for 133 patients (63% female, age: 29.

Diagnosis of depression in multiple sclerosis is predicted by frontal-parietal white matter tract disruption.

Background: Persons with multiple sclerosis (PwMS) are at an elevated risk of depression. Decreased Conscientiousness may affect patient outcomes in PwMS. Low Conscientiousness has a strong correlation with depression.

Sex-Specific Differences in Life Span Brain Volumes in Multiple Sclerosis.

Background And Purpose: Numerous sex-specific differences in multiple sclerosis (MS) susceptibility, disease manifestation, disability progression, inflammation, and neurodegeneration have been previously reported. Previous magnetic resonance imaging (MRI) studies have shown structural differences between female and male MS brain volumes. To determine sex-specific global and tissue-specific brain volume throughout the MS life span in a real-world large MRI database.