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JC virus PCR assay reporting for PML: promises, perils, and pitfalls.

One of the most devastating central nervous system infections, progressive multifocal leukoencephalopathy (PML), is caused by the JC virus ( … s. In neurological settings, those treated with natalizumab, rituximab, ocrelizumab, fingolimod, or dimethyl fumarate can be at risk of developing PML. The gold standard for diagnosing PML is the detection of JCV DNA in cerebrospinal fluid (CSF) by PCR in the context of compatible clinical and MRI findings. In cases where JCV PCR assay results are negative or incon …

FTY720 Exacerbates Blood-Brain Barrier Dysfunction Induced by IgG Derived from Patients with NMO and MOG Disease.

Neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein (MOG) antibody-related disease (MOG disease) are inflammatory demyelinati … on BBB integrity. We also examined the effects of disease-modifying drugs (fingolimod [FTY720] and dimethyl fumarate [DMF]) on IgG-treated brain capillary endothelial cells. We used in vitro BBB models constructed with rat brain capillary endothelial cells (RBECs) to examine the effects on BBB function. The integrity of the RBECs was assessed by measuring transend …

A highly purified enrichment culture couples the reductive dechlorination of tetrachloroethene to growth.

A microscopically pure enrichment culture of a gram-negative anaerobic bacterium, in the present article referred to as PER-K23, was isolated from an anaerobic packed-bed column in which tetrachloroethene (PCE) was reductively transformed to ethane via trichloroethene (TCE), cis-1,2-dichloroethene (cis-1,2-DCE), chloroethene, and ethene. PER-K23 catalyzes the dechlorination of PCE via TCE to cis-1,2-DCE and couples this reductive dechlorination to growth. H2 and formate were the only electron donors that supported growth with PCE or TCE as an electron acceptor. The culture did not grow in the

Dimethylfumarate Impairs Neutrophil Functions.

Host defense against pathogens relies on neutrophil activation. Inadequate neutrophil activation is often associated with chronic inflammatory diseases. Neutrophils also constitute a significant portion of infiltrating cells in chronic inflammatory diseases, for example, psoriasis and multiple sclerosis. Fumarates improve the latter diseases, which so far has been attributed to the effects on lymphocytes and dendritic cells. Here, we focused on the effects of dimethylfumarate (DMF) on neutrophils. In vitro, DMF inhibited neutrophil activation, including changes in surface marker expression, re

De-escalation of Disease-Modifying Therapy for People with Multiple Sclerosis Due to Safety Considerations: Characterizing 1-Year Outcomes in 25 People Who Switched from Ocrelizumab to Diroximel Fumarate.

INTRODUCTION: Switching disease-modifying therapy (DMT) may be considered for relapsing-remitting multiple sclerosis (RRMS) if a patient's current therapy is no longer optimal. This was particularly important during the recent COVID-19 pandemic because of considerations around immune deficiency and impaired vaccine response associated with B cell-depleting DMTs. This real-world, single-center study aimed to evaluate change or decline in functional ability and overall disease stability in people with RRMS who were switched from B cell-depleting ocrelizumab (OCRE) to diroximel fumarate (DRF) bec

Changing therapeutic strategies and persistence to disease-modifying treatments in a population of multiple sclerosis patients from Veneto region, Italy.

BACKGROUND: The availability of new disease-modifying treatments (DMTs) in the last years has changed the therapeutic strategies used in Multiple Sclerosis (MS). We aimed to describe trend in DMTs utilization and persistence to treatment in a large sample of patients attending 10 MS centres from four provinces of Veneto, Italy. METHODS: Demographic, clinical and DMTs information of patients regularly followed from January 2011 to August 2018 were recorded and analysed. Persistence at 12, 24 months and at last follow-up was assessed by Kaplan Meier survival analysis. Multivariable Cox- proport

Facioscapulohumeral muscular dystrophy (FSHD) and multiple sclerosis: a case report.

Facioscapulohumeral muscular dystrophy 1 (FSHD1) is an autosomal dominant neuromuscular disorder, associated with reduction of tandemly arrayed repetitive DNA elements D4Z4 (DRA), at 4q35. Few cases, especially carriers of 1-3 DRA show a syndromic form. Anecdotally the association of FSHD with multiple sclerosis (MS) is reported. Herein we report a 33 years old Caucasian with a molecular diagnosis of FSHD1 with classical phenotype (clinical category A2) and concomitant white matter lesions suggestive of MS. White matter lesions in patients with FSHD have often been described but rarely investi

Experimental Therapies in Multiple Sclerosis: Epstein-Barr Virus and Potential EBV-Related Therapeutic Strategies-A Systematic Review.

Background/Objectives: Multiple sclerosis (MS) constitutes a chronic autoimmune, inflammatory, and neurodegenerative disease, with dissemina … tinct but complementary mechanisms. Other interventions, including interferons, glatiramer acetate, dimethyl fumarate, autologous hematopoietic stem cell transplantation, and vitamin D supplementation, may also modulate EBV-specific cellular or humoral responses, although the magnitude and durability of these effects vary. Emerging EBV-directed approaches, includin …

Epithelial Regnase-1 inhibits colorectal tumor growth by regulating IL-17 signaling via degradation of NFKBIZ mRNA.

Regnase-1 is a ribonuclease that regulates inflammation in immune cells by degrading cytokine mRNA. Regnase-1 was identified as one of the f … tumor-suppressive effect of Regnase-1 depended on Nfkbiz expression. Remarkably, oral treatment of dimethyl fumarate, a potential inhibitor of Regnase-1 protein inactivation, suppressed tumor growth, downregulated Nfkbiz, and suppressed ERK activation. Furthermore, TCGA data analysis revealed that low Regnase-1 expression in colorectal cancer tissue was related to …

Nuclear factor erythroid 2-related factor improves depression and cognitive dysfunction in rats with ischemic stroke by mediating wolfram syndrome 1.

OBJECTIVE: This research aims to investigate the molecular mechanism of nuclear factor erythroid 2-related factor (Nrf2) in improving post-stroke depression and cognitive impairment (PSDCI) by mediating wolfram syndrome 1 (Wfs1). METHODS: PSDCI rat model was established through middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress (CUMS). Dimethyl fumarate (DMF) was utilized as an Nrf2 activator, while Wfs1 knockdown lentiviral plasmid was injected into rats for functional investigations. Cognitive function- and depression-relevant parameters were assessed using Morris…

Trained Immunity in sepsis: Exploring the molecular link to long-term cardiometabolic disorders.

Sepsis, a life-threatening systemic infection, has long been recognized for its immediate risks, but its long-term consequences on health ar … ming; metformin, which restores metabolic balance by activating AMPK and reducing oxidative stress; dimethyl fumarate (DMF), a potent Nrf2 activator that counteracts inflammation; and probiotics, which help restore gut microbiota balance and limit endotoxin-driven inflammation. These therapies offer promising strategies to mitigate long-term metabolic dysfunction a …

Association of non-phthalate plasticizer exposure during early pregnancy with gestational diabetes mellitus: The potential mediation effect of plasma lipidome.

Given the well-documented endocrine-disrupting effects of phthalate plasticizers (PAEs) on human health, their use has been subjected to stringent regulatory restrictions, prompting a global shift toward non-phthalate plasticizers (non-PAEs) as alternatives. While epidemiological evidence has established significant associations between PAE exposure and gestational diabetes mellitus (GDM), the potential role of non-PAEs in GDM pathogenesis represents a critical knowledge gap in environmental epidemiology. To address this, we conducted a case-control study nested within a well-established prosp

De-Escalation Treatment Strategies From Natalizumab in Patients With Relapsing Multiple Sclerosis in Austria.

OBJECTIVES: This study aims to assess the efficacy of de-escalating from natalizumab (NTZ) to cladribine (CLAD), dimethyl fumarate (DMF), fingolimod (FTY), ponesimod (PONE), siponimod (SIPO) and teriflunomide (TERI). MATERIAL AND METHODS: We analyzed data from 388 patients in the Austrian MS Treatment Registry who initiated NTZ treatment and remained on therapy for at least 3 months before switching to one of the moderately effective therapies within 1 year. Patients were required to remain on the de-escalation therapy for at least 3 months. RESULTS: Over a mean treatment duration of 42 mont…

Индекс свободной световой цепи Каппа коррелирует с прогнозирующими биомаркерами в многоразовом склерозе и уменьшает медленное лечение.

ЦЕЛЬ: Изучение взаимосвязи между внутритехническим производством антител, нашедшим отражение в показателях свободной цепи освещения (КФЛК), и множественными маркерами, связанными с склерозом (МС), и изучение их модуляции после лечения MS. МЕТОДЫ: Это исследование включало в себя образцы совпадающей плазмы и цереброспиновой жидкости (CSF) из в общей сложности 130 человек с MS (pwMS), 99 из которых не подвергались обработке в базовом порядке. Для анализа воздействия лечения на показатели КФЛК использовались пробы из 73 ПТМС (18 на диметилфумарате (ДМП), 10 на финголимоде, 6 на натализумабе, 25 н

Совпадение в аннотации оригинала
OBJECTIVE: To investigate the relation between intrathecal antibody production, as reflected by kappa free light chain (KFLC) metrics, and m … 0 persons with MS (pwMS), 99 of whom were untreated at baseline. Paired samples from 73 pwMS (18 on dimethyl fumarate (DMF), 10 on fingolimod, 6 on natalizumab, 25 on rituximab (RTX) and 14 after autologous hematopoietic stem cell transplantation (HSCT)) were used to analyze treatment effects on KFLC metrics. KFLC was measured by nephelometry while clinical and par …

Serum neurofilament light chain levels suggest neuroprotection following bexarotene-induced remyelination in people with relapsing remitting multiple sclerosis.

BACKGROUND: Remyelination offers a potential neuroprotective strategy in multiple sclerosis (MS). In the Cambridge Centre of Myelin Repair O … CCMR-One trial. Participants were aged 18-50 years, had baseline EDSS 0-6.0 and had been stable on dimethyl fumarate for at least 6 months. Consenting participants contributed serum samples at baseline and month 6, which were analysed for neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total Tau protein (Tau), and C-terminal hydrolase L1 ( …

Преодолеть предположение: эффективность терапии, корректирующей болезни, и степень рецидива при повторном выбросе множественных склерозов.

В случае пациентов, проходящих лечение с помощью ДДТ, степень рецидивов ниже, чем в случае пациентов, не прошедших лечение. Несмотря на то, что методы коррекции заболеваний (ДМР) существенно различаются в плане их эффективности с точки зрения предупреждения рецидивов, конкретное воздействие различных ДРТ на степень серьезности рецидивов еще не было тщательно изучено. ЦЕЛЬ: Изучение взаимосвязи между использованием ДМТ, интенсивностью рецидива и результатами восстановления при повторном выпуске многократного склероза (РРМС).МЕТОДЫ: В ходе реанимирующего когортного исследования было проанализиро

Совпадение в аннотации оригинала
BACKGROUND: The severity of relapses is lower in patients treated with DMTs compared to untreated patients. Although Disease-modifying treat … atients treated with either moderate-efficacy DMTs (interferons, glatiramer acetate, teriflunomide, dimethyl fumarate; n = 48) or high-efficacy DMTs (fingolimod, natalizumab, ocrelizumab, alemtuzumab, cladribine; n = 37). Regular EDSS assessments were used to evaluate relapse severity and subsequent recovery. RESULTS: Although patients on high-efficacy DMTs tended …

Infection Risk Associated with High-Efficacy Disease-Modifying Agents in Multiple Sclerosis: A Retrospective Cohort Study.

In patients with multiple sclerosis (MS), infections represent a significant concern, particularly given the immunomodulatory effects of dis … mab, and ocrelizumab) or meDMAs (interferon beta-1a, interferon beta-1b, fingolimod, teriflunomide, dimethyl fumarate, and glatiramer acetate) were included. The outcomes of interest were comparative risk of overall infection, serious infection, and frequently reported types of infection. Adjusted hazard ratios (aHR) were estimated in inverse probability treatment …

Monkeypox virus infection of human astrocytes causes gasdermin B cleavage and pyroptosis.

Monkeypox virus (MPXV) infections in humans cause neurological disorders while studies of MPXV-infected animals indicate that the virus pene … e dehydrogenase and increased cellular nucleic acid staining, indicative of PMR. Pre-treatment with dimethyl fumarate reduced cleavage of GSDMB and associated PMR in MPXV-infected astrocytes. Human astrocytes support productive MPXV infection, resulting in inflammatory gene induction with accompanying GSDMB-mediated pyroptosis. These findings clarify the recently r …

1,3-Dichloro-2-propanol-Induced Renal Tubular Cell Necroptosis through the ROS/RIPK3/MLKL Pathway.

1,3-Dichloro-2-propanol (1,3-DCP), as a food pollutant, exists in a variety of foods. Studies have shown that it has nephrotoxicity. In the … inhibited the expressions of nuclear and cytoplasmic Nrf2. But pretreatment with an Nrf2 activator dimethyl fumarate (DMF) up-regulated the expressions of nuclear and cytoplasmic Nrf2 and down-regulated ROS levels and RIPK3 and MLKL expressions. We also examined the effects of mitophagy on 1,3-DCP-induced ROS. The data manifested that 1,3-DCP suppressed mitophagy …

Insulin-Like Growth Factor Binding Protein (IGFBP-6) as a Novel Regulator of Inflammatory Response in Cystic Fibrosis Airway Cells.

Cystic Fibrosis (CF) patients are prone to contracting bacterial lung infections with opportunistic pathogens, especially Pseudomonas aerugi … ments increased the IGFBP-6 mRNA level, that was reduced after treatment with an anti-inflammatory (Dimethyl Fumarate) in CFBE cell line and in patient-derived nasal epithelial cultures. Lastly, we demonstrated that IGFBP-6 reduced the level of pro-inflammatory cytokines in both CFBE and primary nasal epithelial cells, without affecting rescued CFTR expression and …