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Ganoderma lucidum mediates microglial polarization and ameliorates experimental autoimmune encephalomyelitis by reducing oxidative stress and inhibiting NF-κB/STAT3 pathway.

Multiple Sclerosis (MS) is a neuroinflammatory disease affecting the central nervous system (CNS), for which effective therapeutic strategies remain limited. Ganoderma Lucidum (GL) is a nature healthy food supplement whose effects on MS remain unknown. Using an experimental autoimmune encephalomyelitis (EAE) mouse model, we tested the hypothesis that GL could mitigate MS by inhibiting microglial activation and promoting a shift toward an anti-inflammatory M2-like phenotype. We demonstrate that early preventive administration of GL significantly reduced disease severity, inflammatory infiltrati…

Toxocara canis-originated recombinant C-type lectin improves the disability scores of experimental autoimmune encephalomyelitis in murine in vivo models.

BACKGROUND: The recombinant C-type lectin protein (r-CTL) derived from Toxocara canis larvae is thought to play a role in promoting regulatory T cell-dominant immune responses in toxocariasis. This study aimed to highlight the therapeutic potential of the r-CTL protein in improving the disability scores of EAE by enhancing the Foxp3+-CD25+ T cells population. METHODS: The r-CTL was expressed in prokaryotic systems and purified using Ni-NTA spin columns. Balb/C57 mice were divided into six groups, with EAE induced in four of them, excluding the healthy control group and the group receiving onl

Seizure Circuit Activity in the Theiler's Murine Encephalomyelitis Virus Model of Infection-induced Epilepsy Using Transient Recombination in Active Populations.

Epilepsy affects one in twenty-six individuals. A major cause of epilepsy worldwide is viral encephalitis. Central nervous system infections can provoke seizures in the short term and increase the risk of spontaneous, recurrent seizures post-infection. However, the neural mechanisms underlying seizures during acute infection are unknown. These neuronal changes can be studied in C57BL6/J mice infected with Theiler's murine encephalomyelitis virus (TMEV). TMEV-infected mice experience seizures 3-8 days post-injection (DPI), clear the virus by DPI 14, and may develop chronic, acquired temporal lo…

Profiling blood-based neural biomarkers and cytokines in experimental autoimmune encephalomyelitis model of multiple sclerosis using single-molecule array technology.

Experimental autoimmune encephalomyelitis (EAE) is a preclinical animal model widely used to study multiple sclerosis (MS). Blood-based cytokines and neural biomarkers are predictors of neurodegeneration, disease activity, and disability in patients with MS. However, understudied confounding factors cause variation in reports on EAE across animal strains/studies, limiting the utility of these biomarkers for predicting disease activity. In this study, we investigated blood-based analyte profiles, including neural markers (NFL and GFAP) and cytokines (IL-6, IL-17, IL-12p70, IL-10, and TNF-α), in…

Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Gulf War Syndrome (GWS), and Fibromyalgia (FM) are complex, chronic illnesses with overlapping clinical features. Symptoms that are reported across these conditions include post-exertional malaise (PEM), fatigue, and pain, yet the etiology of these illnesses remains largely unknown. Diagnosis is challenging in patients with these conditions as definitive biomarkers are lacking; patients are required to meet clinical criteria and often undergo lengthy testing to exclude other conditions, a process that is often prolonged, costly, and …

A comparison of genome-wide association analyses of persistent symptoms after Lyme disease, fibromyalgia, and myalgic encephalomyelitis - chronic fatigue syndrome.

BACKGROUND: Up to 20% of Lyme disease cases experience post-treatment Lyme disease syndrome (PTLDS). The biological basis for PTLDS is poorl … wo separate conditions that have hypothesized overlapping pathophysiology, fibromyalgia and myalgic encephalomyelitis - chronic fatigue syndrome (ME/CFS). GWAS analyses were performed using logistic regression in SUGEN, assuming an additive genetic model, and adjusting for age, sex, array, and the first 10 principal components calculated from whole genome genotypin …

Myelin-реактивные CD8+T клетки оказывают влияние на обычные дендритные поднаборы клеток в направлении зрелого и регулируемого фенотипа в экспериментальном аутоиммунном энцефаломиэлите.

Множественный склероз (MS) — аутоиммунное демиелинизирующее заболевание центральной нервной системы, моделируемое в мышах как экспериментальный аутоиммунный энцефаломиелит (EAE). В то время как CD4+T клетки, в первую очередь TH1 и TH17, движут патогенезом болезней, точная функция CD8+T клеток остается неясной. Ранее мы продемонстрировали, что переносимые миелином-реактивные CD8+T клетки (PLP-CD8) предотвращают индукцию EAE и подавляют текущие заболевания путем вовлечения MHC класса I в мышей-реципиента. Здесь мы показываем, что PLP-CD8 вызывает регулятивные изменения в обоих подмножествах обыч

Совпадение в аннотации оригинала
Multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system, is modeled in mice as experimental autoimmune encephalomyelitis (EAE). While CD4+ T cells, primarily Th1 and Th17 subsets, drive disease pathogenesis, the exact function of CD8+ T cells remains unclear. We previously demonstrated that adoptively transferred myelin-rea…

Винт-активированные иммунорегулирующие Myeloid Cells предотвращают релапс в экспериментальном аутоиммунном энцефаломелите и предлагают потенциальную терапевтическую стратегию для множественного склероза.

Множественный склероз (MS) — хроническое аутоиммунное заболевание центральной нервной системы (CNS), характеризующееся периодическими рецидивами и нейродегенерацией. Миэлоидные клетки играют важнейшую роль в формировании подстрекательской среды и влиянии на прогрессию заболеваний. Здесь мы показываем, что активация Wnt сигнального пути перепрограммирует миэлоидные клетки в иммунорегулирующий фенотип, что ведет к снижению нейроинфламмации и серьезности заболеваний. Используя как экспериментальный аутоиммунный энцефаломиелит (EAE), так и миелиоидные клетки человека, мы показываем, что Wnt агонис

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by recurrent inflammatory relapses … type, leading to reduced neuroinflammation and disease severity. Using both experimental autoimmune encephalomyelitis (EAE) and human-derived myeloid cells, we show that Wnt agonist treatment promotes the expression of inhibitory molecules such as PD-L1 and PD-L2, suppressing pro-inflammatory responses. In the chronic and relapsing-remitting EAE models, Wnt activat …

Association analysis between symptomology and herpesvirus IgG antibody concentrations in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS) are two complex and multifactorial diseases whose patients experience persistent fatigue, cognitive impairment, among other shared symptoms. The onset of these diseases has also been linked to acute herpesvirus infections or their reactivations. In this work, we re-analyzed a previously-described dataset related to IgG antibody responses to 6 herpesviruses (CMV - cytomegalovirus; EBV - Epstein-Barr virus; HHV6 - human herpesvirus-6; HSV1 and HSV2 - herpes simplex virus-1 and -2, respectively; VZV - varicell…

EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating, multisystem illness of unknown etiology for which no cure and no diagnostic tests are available. Despite increasing evidence implicating EBV and human herpesvirus 6A (HHV-6A) as potential causative infectious agents in a subset of patients with ME/CFS, few mechanistic studies address a causal relationship. In this study we examined a large ME/CFS cohort and controls and demonstrated a significant increase in activin A and IL-21 serum levels, which correlated with seropositivity for antibodies against the EB…

The Emerging Role of Gut Microbiota in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Current Evidence and Potential Therapeutic Applications.

The well-known symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are chronic pain, cognitive dysfunction, post-exertional malaise and severe fatigue. Another class of symptoms commonly reported in the context of ME/CFS are gastrointestinal (GI) problems. These may occur due to comorbidities such as Crohn's disease or irritable bowel syndrome (IBS), or as a symptom of ME/CFS itself due to an interruption of the complex interplay between the gut microbiota (GM) and the host GI tract. An altered composition and overall decrease in diversity of GM has been observed in ME/CFS …

Exercise modifies glutamate and other metabolic biomarkers in cerebrospinal fluid from Gulf War Illness and Myalgic encephalomyelitis / Chronic Fatigue Syndrome.

Myalgic encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) share many symptoms of fatigue, pain, and cognitive dysfunction that are not relieved by rest. Patterns of serum metabolites in ME/CFS and GWI are different from control groups and suggest potential dysfunction of energy and lipid metabolism. The metabolomics of cerebrospinal fluid was contrasted between ME/CFS, GWI and sedentary controls in 2 sets of subjects who had lumbar punctures after either (a) rest or (b) submaximal exercise stress tests. Postexercise GWI and control subjects were subdivided accord…

Altered expression patterns of complement factor H and miR-146a genes in acute-chronic phases in experimental autoimmune encephalomyelitis mouse.

Considerable advances have been made in identification of the involvement of immune modulators in diseases. There is growing evidence on the role of complement pathway in pathogenesis and course of multiple sclerosis (MS). Moreover, it has been recognized that microRNAs (miRNAs) play an essential role in modulation and development of immune response in the central nervous system. We aimed to investigate the expression profile of complement factor H (CFH) and miR-146a genes in experimental autoimmune encephalomyelitis (EAE) mouse model of MS to detect the possible roles of CFH and miR-146a as b…

Capparis ovata treatment suppresses inflammatory cytokine expression and ameliorates experimental allergic encephalomyelitis model of multiple sclerosis in C57BL/6 mice.

Since ancient times, Capparis species have been widely used in traditional medicine to treat various diseases. Our recent investigations have suggested Capparis ovata's potential anti-neuroinflammatory application for the treatment of multiple sclerosis (MS). The present study was designed to precisely determine the underlying mechanism of its anti-neuroinflammatory effect in a mouse model of MS. C. ovata water extract (COWE) was prepared using the plant's fruit, buds, and flower parts (Turkish Patent Institute, PT 2012/04,093). We immunized female C57BL/6J mice with MOG35-55/CFA. COWE was adm

Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway.

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a complex condition. Causal factors are not established, although underlying psychological or immunological susceptibility has been proposed. We studied primary care diagnoses for children with CFS/ME, with children with another hospital diagnosis (type 1 diabetes mellitus [T1DM]) and the general child population as comparison groups. METHODS: All Norwegian children born 1992-2012 constituted the study sample. Children with CFS/ME (n = 1670) or T1DM (n = 4937) were identified in the Norwegian Patient Register (NPR) (20…

Glutathione PEGylated liposomal methylprednisolone (2B3-201) attenuates CNS inflammation and degeneration in murine myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis.

Methylprednisolone (MP) pulses are the mainstay for relapse therapy in multiple sclerosis (MS). To improve the efficacy of treatment and reduce the side effects of MP, a long circulating brain-targeted formulation was developed; glutathione polyethylene glycol (PEG)ylated liposomal MP (2B3-201). Here we investigate the efficacy of 2B3-201 in murine myelin oligodendrocyte induced experimental autoimmune encephalomyelitis (MOG-EAE), an animal model mimicking inflammatory features and neurodegenerative aspects of MS. After disease onset, mice were randomized to receive either saline, three inject…

A mushroom extract Piwep from Phellinus igniarius ameliorates experimental autoimmune encephalomyelitis by inhibiting immune cell infiltration in the spinal cord.

The present study aimed to evaluate the therapeutic potential of a mushroom extract from Phellinus igniarius in an animal model of multiple sclerosis. The medicinal mushroom, Phellinus igniarius, contains biologically active compounds that modulate the human immune system. Experimental autoimmune encephalomyelitis (EAE) was induced by immunization with myelin oligodendrocyte glycoprotein (MOG 35-55) in C57BL/6 female mice. A water-ethanol extract of Phellinus igniarius (Piwep) was delivered intraperitoneally every other day for the entire experimental course. Three weeks after the initial immu…

Shifting hierarchies of interleukin-10-producing T cell populations in the central nervous system during acute and persistent viral encephalomyelitis.

Interleukin-10 (IL-10) mRNA is rapidly upregulated in the central nervous system (CNS) following infection with neurotropic coronavirus and remains elevated during persistent infection. Infection of transgenic IL-10/green fluorescent protein (GFP) reporter mice revealed that CNS-infiltrating T cells were the major source of IL-10, with minimal IL-10 production by macrophages and resident microglia. The proportions of IL-10-producing cells were initially similar in CD8(+) and CD4(+) T cells but diminished rapidly in CD8(+) T cells as the virus was controlled. Overall, the majority of IL-10-prod

Quercetin, a flavonoid phytoestrogen, ameliorates experimental allergic encephalomyelitis by blocking IL-12 signaling through JAK-STAT pathway in T lymphocyte.

Experimental allergic encephalomyelitis (EAE) is a Th1 cell-mediated inflammatory demyelinating autoimmune disease model of multiple sclerosis (MS). Quercetin (3,3'4',5,7-pentahydroxy flavone) is a flavonoid phytoestrogen that has profound anticancer and anti-inflammatory activities. In this study, we show that in vivo treatment of SJL/J mice with quercetin (i.p. 50 or 100 microg every other day) ameliorates EAE in association with the inhibition of IL-12 production and neural antigen-specific Th1 differentiation. In vitro treatment of activated T cells with quercetin blocks IL-12-induced tyro…