The association of menopausal hormone levels with progression-related biomarkers in multiple sclerosis.

Background: Multiple sclerosis (MS) progression coincides temporally with menopause. However, it remains unclear whether the changes in disease course are related to the changes in reproductive hormone concentrations. We assessed the association of menopausal hormonal levels with progression-related biomarkers of MS and evaluated the changes in serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels during menopausal hormone therapy (MHT) in a prospective baseline-controlled design.

Temporal variability of serum miR-191, miR-223, miR-128, and miR-24 in multiple sclerosis: A 4-year follow-up study.

Background: Circulating microRNAs (miRNA) are suggested to be a promising biomarker for multiple sclerosis (MS). Previously, miR-128-3p, miR-24-3p, miR-191-5p and miR-223-3p have been reported to associate with MS pathology. However, their longitudinal changes and association with the disease activity have not been studied.

Establishment of a human induced pluripotent stem cell line (TAUi008-A) derived from a multiple sclerosis patient.

Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system where the main pathogenetic events include demyelination and axonal degeneration. Here, we generated a human induced pluripotent stem cell (hiPSC) line from peripheral blood mononuclear cells of an MS patient utilizing Sendai virus reprogramming. The produced hiPSC line expressed pluripotency markers, differentiated into three germ layers, showed a normal karyotype and was free of virus vectors, transgenes and mycoplasma.

A kainic acid-induced seizure model in human pluripotent stem cell-derived cortical neurons for studying the role of IL-6 in the functional activity.

Human pluripotent stem cell (hPSC)-derived neural cultures have attracted interest for modeling epilepsy and seizure-like activity in vitro. Clinical and experimental evidence have shown that the multifunctional inflammatory cytokine interleukin (IL)-6 plays a significant role in epilepsy. However, the role of IL-6 in neuronal networks remains unclear.

Oxygen-Glucose Deprivation-Induced Stroke Models with Human Neuroblastoma Cell- and Induced Pluripotent Stem Cell-Derived Neurons.

Stroke is a devastating neurological disorder and one of the leading causes of mortality and disability. To understand the cellular and molecular mechanisms of stroke and to develop novel therapeutic approaches, two different human cell-based stroke models were established using oxygen-glucose deprivation (OGD) conditions. In addition, the effect of adipose stem cells (ASCs) on OGD-induced injury was studied.

Co-stimulation with IL-1β and TNF-α induces an inflammatory reactive astrocyte phenotype with neurosupportive characteristics in a human pluripotent stem cell model system.

Astrocyte reactivation has been discovered to be an important contributor to several neurological diseases. In vitro models involving human astrocytes have the potential to reveal disease-specific mechanisms of these cells and to advance research on neuropathological conditions. Here, we induced a reactive phenotype in human induced pluripotent stem cell (hiPSC)-derived astrocytes and studied the inflammatory natures and effects of these cells on human neurons.

Gene expression profiles of TNF-like cytokine 1A (TL1A) and its receptors death receptor 3 (DR3) and decoy receptor 3 (DcR3) in multiple sclerosis.

TL1A/DR3/DcR3 pathway is an important mediator of inflammatory responses and contributes to the pathogenesis of several chronic inflammatory diseases. Therefore, we analysed PBMC gene expression of these molecules in 30 relapsing-remitting multiple sclerosis (RRMS) patients, 8 secondary progressive MS (SPMS), 9 primary progressive MS (PPMS), 11 clinically isolated syndrome (CIS) patients, and 16 healthy controls (HCs), to evaluate their biomarker potential in MS. The results showed significant decrease in TL1A expression in RRMS compared to other study groups.

Diffusion tensor imaging and disability progression in multiple sclerosis: A 4-year follow-up study.

Objectives: Diffusion tensor imaging (DTI) is sensitive technique to detect widespread changes in water diffusivity in the normal-appearing white matter (NAWM) that appears unaffected in conventional magnetic resonance imaging. We aimed to investigate the prognostic value and stability of DTI indices in the NAWM of the brain in an assessment of disability progression in patients with a relapsing-onset multiple sclerosis (MS).

Methods: Forty-six MS patients were studied for DTI indices (fractional anisotropy (FA), mean diffusivity (MD), radial (RD), and axial (AD) diffusivity) in the NAWM of the corpus callosum (CC) and the internal capsule at baseline and at 1 year after.

Effects of inflammatory cytokines IFN-γ, TNF-α and IL-6 on the viability and functionality of human pluripotent stem cell-derived neural cells.

Multiple Sclerosis (MS) is an inflammatory neurodegenerative disease, where neural progenitor cell (NPC) transplantation has been suggested as a potential neuroprotective therapeutic strategy. Since the effect of inflammation on NPCs is poorly known, their effect on the survival and functionality of human NPCs were studied. Treatment with interleukin (IL)-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ did not induced cytotoxicity, but IFN-γ treatment showed decreased proliferation and neuronal migration.

JCPyV microRNA in plasma inversely correlates with JCPyV seropositivity among long-term natalizumab-treated relapsing-remitting multiple sclerosis patients.

Sensitive biomarkers are needed to better manage multiple sclerosis (MS) patients for natalizumab (NTZ)-associated risk of progressive multifocal leukoencephalopathy (PML). A currently used risk stratification algorithm, mainly based on JC polyomavirus (JCPyV) serology, has not led to a reduction of PML incidence. Therefore, this study was designed to evaluate the presence and prevalence of JCPyV miRNAs in plasma of NTZ-treated MS patients, and to explore their biomarker potential for NTZ-associated PML risk assessment.

Circulating microRNAs as biomarkers in progressive multiple sclerosis.

Background: In multiple sclerosis (MS), microRNA (miRNA) dysregulation is mostly reported in different immune cells, but less information is available on circulating miRNAs that exert strong biomarker potential due to their exceptional stability in body fluids.

Objective: The aim of this study was to profile expression of circulating miRNAs in primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS) and assess their association with neurological worsening.

Methods: The expressions of 84 different miRNAs were profiled in serum of 83 subjects (62 MS and 21 controls) using miScript miRNA techniques.

Adipsin Is Associated with Multiple Sclerosis: A Follow-Up Study of Adipokines.

Background and Objective. The role of adipokines in regulation of immune responses has been recognized, but very little is known about their impact on multiple sclerosis (MS). In this study, we analysed whether the major adipokines are differentially expressed in plasma of patients with different MS subtypes and clinically isolated syndrome (CIS) and explored their association with major disease characteristics.

Association between soluble L-selectin and anti-JCV antibodies in natalizumab-treated relapsing-remitting MS patients.

Objective: In relapsing-remitting MS (RRMS) patients treated with natalizumab, the low level of L-selectin-expressing CD4+ T cells has been associated with the risk of progressive multifocal leukoencephalopathy (PML). In this study, our aim was to correlate the levels of soluble L-selectin and the anti-JCV antibody index in the sera of RRMS patients treated with natalizumab.

Methods: This study included 99 subjects, including 44 RRMS patients treated with natalizumab, 30 with interferon beta (IFN-β) and 25 healthy controls.

Analysis of apoptosis-related genes in patients with clinically isolated syndrome and their association with conversion to multiple sclerosis.

To analyse whether the expression of apoptotic transcripts is associated with the conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS). Eleven candidate transcripts belonging to the death receptor pathway, BCL-2, the inflammasome complex and NF-ΚB family were studied in the nonconverting and converting CIS patients during the four-year follow-up period. Conversion to MS was associated with marked variability in the expression of proapoptotic genes that were linked to TGF-B1 gene levels.

Longitudinal assessment of clinically isolated syndrome with diffusion tensor imaging and volumetric MRI.

The potential of diffusion tensor imaging (DTI) indices and volumes of focal lesions on conventional magnetic resonance imaging to predict conversion to multiple sclerosis (MS) was analyzed in subjects with clinically isolated syndrome (CIS) over 4 years. Twenty patients with CIS and 10 healthy controls were included in the study. The data showed an association between the volumes of T1 and fluid-attenuated inversion recovery (FLAIR) lesions and conversion to MS (T1: P=.

Hemispheric asymmetry measured by texture analysis and diffusion tensor imaging in two multiple sclerosis subtypes.

Background: This paper addresses two subtypes of multiple sclerosis (MS), primary progressive multiple sclerosis (PPMS) and relapsing-remitting multiple sclerosis (RRMS). The separation of PPMS and RRMS is challenging in certain cases.

Purpose: To quantitatively determine MS subtypes using texture analysis (TA) and diffusion tensor imaging (DTI).

Diffusion Tensor Imaging in NAWM and NADGM in MS and CIS: Association with Candidate Biomarkers in Sera.

The aim of this study was to evaluate diffusion tensor imaging (DTI) indices in the corpus callosum and pyramidal tract in normal-appearing white matter (NAWM) and the caudate nucleus and thalamus in deep grey matter (NADGM) in all MS subtypes and clinically isolated syndrome (CIS). Furthermore, it was determined whether these metrics are associated with clinical measures and the serum levels of candidate immune biomarkers. Apparent diffusion coefficients (ADC) values were significantly higher than in controls in all six studied NAWM regions in SPMS, 4/6 regions in RRMS and PPMS and 2/6 regions in CIS.

Healthy human CSF promotes glial differentiation of hESC-derived neural cells while retaining spontaneous activity in existing neuronal networks.

The possibilities of human pluripotent stem cell-derived neural cells from the basic research tool to a treatment option in regenerative medicine have been well recognized. These cells also offer an interesting tool for in vitro models of neuronal networks to be used for drug screening and neurotoxicological studies and for patient/disease specific in vitro models. Here, as aiming to develop a reductionistic in vitro human neuronal network model, we tested whether human embryonic stem cell (hESC)-derived neural cells could be cultured in human cerebrospinal fluid (CSF) in order to better mimic the in vivo conditions.

Melatonin pathway genes are associated with progressive subtypes and disability status in multiple sclerosis among Finnish patients.

In this study we investigated the relationship between melatonin pathway and multiple sclerosis (MS) in a high-risk Finnish population by studying the single nucleotide polymorphisms (SNPs) in the genes coding for critical enzymes and receptors involved in the melatonin pathway. A total of 590 subjects (193 MS patients and 397 healthy controls) were genotyped for seven SNPs in four genes including tryptophan hydroxylases (TPH)1 and 2, arylalkylamine N-acetyltransferase (AANAT) and melatonin receptor 1B (MTNR1B). An overrepresentation of T allele carriers of a functional polymorphism (G-703T, rs4570625) in the promoter region of TPH2 gene was observed in the progressive MS subtypes.

Disease-associated inflammatory biomarker profiles in blood in different subtypes of multiple sclerosis: prospective clinical and MRI follow-up study.

To identify biomarkers of disease activity and progression in multiple sclerosis (MS), we analyzed the serum profiles of cytokines, chemokines and apoptotic molecules in different subtypes of MS including clinically isolated syndrome (CIS) and correlated their levels with clinical and volumetric MRI findings obtained over a one-year follow up. Upregulated levels of apoptotic sFas molecule were found in MS patients with a worsening EDSS score and an accumulation of hypointense lesions in MRI. In such patients, the levels of MIF appeared to be higher than in non-progressing patients.