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NLRC5-Mediated Epigenetic and Proteomic Regulation of Microglial Panoptosis Drives Neuroinflammation in Multiple Sclerosis.

Microglial dysfunction contributes to multiple sclerosis (MS) pathogenesis, yet the link between epigenetic regulation and inflammatory cell death (PANoptosis) remains unclear. This study explores NOD-like receptor family CARD domain containing 5 (NLRC5) as a regulator of microglial PANoptosis in MS. Transcriptomic data from experimental autoimmune encephalomyelitis (EAE) microglia (GSE253318) and GEO datasets (GSE78809, GSE154228) were integrated to identify PANoptosis-related genes. Mendelian randomization (MR) linked NLRC5 expression to proteomic targets using UK Biobank and deCODE Iceland …

Стандартизированная экстрактная выписка из Zingber officinale Roscoe регулирует клинические и биологические результаты в двух различных моделях мыши EAE.

Фон/цели: Множественный склероз (MS) является хроническим воспалительным заболеванием центральной нервной системы, характеризующимся обезвоживанием и нервными повреждениями. Текущие методы лечения MS являются неудовлетворительными, и поощряется новая терапия. Предположительно, существует корреляция между потреблением питательных веществ и НР. Дополнение санкционированной иммунодуляторной терапии лекарственными препаратами, обладающими антиоксидантами и средствами борьбы с воспламенением, может принести пользу пациентам, страдающим НР. Джинджер является одним из самых распространенных пищевых д

Совпадение в аннотации оригинала
Background/Objectives: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelinatio … er officinale Roscoe extract (ZOE) was orally administered for 14 days. Two experimental autoimmune encephalomyelitis (EAE) models in mice were used. The PLP139-151-EAE relapsing-remitting model and MOG35-55-EAE chronic model. Clinical score, von Frey, hot plate, and rotarod tests were used for behavioral tests. ELISA and Western blotting were used to measure cytok …

Ребалансировка гомеостаза: ключевой регулятор пути CGAS-STING в аутоиммунных болезнях.

Аутоиммунные заболевания (АД) возникают в результате нарушения иммунной терпимости к самоантигенам, что приводит к патологическому поврежден … c lupus erythematosus", "Тип 1 диабет", "Rheumatoid artritis", "Multiple sclerosis", "Experimentale encephalomyelitis", "Psoriasis" и т.д. Заголовки и резюме были рассмотрены для включения в настоящий обзор. После исключения дубликатов и не относящихся к делу исследований 174 статьи отвечали критериям включения (оригинальные исследования, английский язык).

Aldehyde dehydrogenase-2 deficiency aggravates neuroinflammation, nociception, and motor impairment in a mouse model of multiple sclerosis.

Aldehyde dehydrogenase-2 deficiency (ALDH2∗2) found in 36 % of Han Chinese, affects approximately 8 % of the world population. ALDH2 is a mi … LDH2 activity heightens motor disabilities, and hypernociception induced by experimental autoimmune encephalomyelitis (EAE). The deleterious clinical signs are followed by glial cell activation in the spinal cord and increased 4-HNE levels in the spinal cord and serum. Importantly, the pharmacological ALDH2 activation by Alda-1 ameliorates EAE-induced hypernocicept …

Discovery of a brain penetrant small molecule antagonist targeting LPA1 receptors to reduce neuroinflammation and promote remyelination in multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurological disease characterized by inflammatory demyelination that disrupts neuronal transmission re … sing of PIPE-791 in vivo increased oligodendrocyte number, and in the mouse experimental autoimmune encephalomyelitis (EAE) model of MS, we observed that PIPE-791 promoted myelination, reduced neuroinflammation, and restored visual evoked potential latencies (VEP). These findings support targeting LPA1 for remyelination and encourage development of PIPE-791 for tre …

Postacute Sequelae of SARS-CoV-2 in Children.

The coronavirus disease 2019 (COVID-19) pandemic has caused significant medical, social, and economic impacts globally, both in the short an … ildren may develop conditions de novo, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune conditions and multisystem inflammatory syndrome in children. This state-of-the-art narrative review provides a summary of our current knowledge about PASC in children, including prevalence, epidemiology, risk fa …

Selected Acute Safety Events Following the Use of Nirmatrelvir/Ritonavir or Molnupiravir for COVID-19: A Nationwide Cohort Study in South Korea.

There had been concerns about the acute complications during or shortly after coronavirus disease 2019 (COVID-19) treatment with nirmatrelvi … i.e., atrial fibrillation, other arrhythmia, bradycardia), neurological (i.e., seizure, neuropathy, encephalomyelitis), and miscellaneous (i.e., acute pancreatitis, acute liver injury, dysgeusia) events. A total of 739,935 NMVr users were matched with 2,951,690 comparators and 150,431 MOL users with 759,521 comparators. NMVr users were at lower risk for developing …

Naturally acquired adaptive immunity to Streptococcus pneumoniae is impaired in rheumatoid arthritis patients.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have an increased susceptibility to infections, including those caused by Streptococcus pneumoniae. Why RA is associated with increased susceptibility to S. pneumoniae is poorly understood. This study aims to assess the effects of RA and B-cell depletion therapy on naturally acquired antibody responses to 289 S. pneumoniae protein antigens using a novel protein array. METHODS: IgG responses to S. pneumoniae were characterised in serum from RA patients and disease controls (myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)) using wh…

Bilateral optic neuritis and encephalopathy as the atypical presentations of multiple sclerosis following severe acute respiratory syndrome coronavirus 2 infection.

Numerous evidence suggests coronavirus disease 2019 (COVID-19) potentially triggers demyelinating diseases, inclusive of multiple sclerosis (MS), and acute disseminated encephalomyelitis (ADEM), and various mechanisms have been proposed. We report a 42-year-old male presented with bilateral optic neuritis and encephalopathy, 2 weeks following COVID-19 infection. He denied any history or family history of neurological and ocular diseases. Severe bilateral visual impairment (only light perception) and pain with eye movement were reported. Fundoscopy revealed bilateral optic disc swelling. Magnet…

Neuroinflammatory Disorders of the Central Nervous System Associated with Monkeypox Virus Infection: A Systematic Review and Call to Action.

BACKGROUND: The Monkeypox virus, a zoonotic pathogen of the Orthopoxvirus genus, has shown a marked global spread, resulting in cases of neu … es with central nervous system involvement, the most common manifestations were encephalitis (40%), encephalomyelitis (30%), and meningoencephalitis (10%). Additional rarer presentations included Guillain-Barré syndrome (5%) and transverse myelitis (5%). The mean age of affected individuals was 27.9±13.69 years, and 75% were male. Fever, fatigue, and myalgia were t …

Dengue-Associated Acute Necrotizing Encephalopathy Is an Acute Necrotizing Encephalopathy Variant Rather than a Mimic: Evidence From a Systematic Review.

BACKGROUND: Bilateral hemorrhagic thalamic lesions in dengue encephalitis resemble lesions seen in acute necrotizing encephalopathy (ANE). We investigate whether dengue-associated ANE (DANE) should be considered an ANE variant or a mimic. METHODS: Systematic review of dengue encephalitis literature from PubMed and SCOPUS (inception to December 31, 2022). Diagnostic criteria for ANE, acute encephalitis (AE), acute disseminated encephalomyelitis (ADEM), and infection-triggered encephalopathy syndromes were applied. RESULTS: Data on 162 patients (median age 20 [0.4 to 79] years; 69 [42.3%] fema…

Selection Pressure Profile Suggests Species Criteria among Tick-Borne Orthoflaviviruses.

Orthoflaviviruses are arthropod-borne viruses that are transmitted by mosquitoes or ticks and cause a range of significant human diseases. A … ars necessary. This species criterion suggests that all subtypes of TBEV, all related ovine/caprine encephalomyelitis viruses, and Omsk hemorrhagic fever virus (OHFV) together correspond to a single species. Within this species, viruses make up 11 subtypes that are reliably segregated by a 10% nucleotide distance cut-off suggested earlier for TBEV. The same 10% sub …

Encephalitis is an Important Phenotype of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Diseases: A Single-Center Cohort Study.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is considered a demyelinating disease of the central ner … k included acquired demyelinating syndromes (105 [55%]), encephalitis other than acute disseminated encephalomyelitis (82 [43%]), and isolated meningitis (3 [2%]). After a median follow-up of 30.4 months (interquartile range: 14.8-43.7), 64 (34%) patients had relapses. Fifty-one of the 64 (80%) patients who had relapse received maintenance therapy, including MMF (4 …

Exercise-induced changes in gene expression do not mediate post exertional malaise in Gulf War illness.

BACKGROUND: Post-exertional malaise (PEM) is considered a characteristic feature of chronic multi-symptom illnesses (CMI) like Gulf War illness (GWI); however, its pathophysiology remains understudied. Previous investigations in other CMI populations (i.e., Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) have reported associations between PEM and expression of genes coding for adrenergic, metabolic, and immune function. OBJECTIVES: To investigate whether PEM is meditated by gene expression in Veterans with GWI. METHODS: Veterans with GWI (n = 37) and healthy control Gulf War Veterans (n …

Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review.

Long COVID disproportionately affects premenopausal women, but relatively few studies have examined Long COVID's impact on female reproductive health. We conduct a review of the literature documenting the female reproductive health impacts of Long COVID which may include disruptions to the menstrual cycle, gonadal function, ovarian sufficiency, menopause, and fertility, as well as symptom exacerbation around menstruation. Given limited research, we also review the reproductive health impacts of overlapping and associated illnesses including myalgic encephalomyelitis/chronic fatigue syndrome (M…

Neurological manifestations of an emerging zoonosis-Human monkeypox virus: A systematic review.

BACKGROUND: The last few decades have witnessed an appalling rise in several emerging and re-emerging viral and zoonotic outbreaks. Amongst … also present with visual deficit (0.57%), seizure (0.34%), encephalitis (0.8%), dizziness (0.34%), encephalomyelitis (0.23%), coma (0.11%), and transverse myelitis (0.11%). DISCUSSIONS: Monkeypox virus usually presents with self-limiting painful rash, lymphadenitis, and fever, complications like secondary skin infection, eye problems and pneumonia can be life thr …

Critical role of TLR activation in viral replication, persistence, and pathogenicity of Theiler's virus.

Theiler's murine encephalomyelitis virus (TMEV) establishes persistent viral infections in the central nervous system and induces chronic inflammatory demyelinating disease in susceptible mice. TMEV infects dendritic cells, macrophages, B cells, and glial cells. The state of TLR activation in the host plays a critical role in initial viral replication and persistence. The further activation of TLRs enhances viral replication and persistence, leading to the pathogenicity of TMEV-induced demyelinating disease. Various cytokines are produced via TLRs, and MDA-5 signals linked with NF-κB activatio…

Autoimmune glial fibrillary acidic protein astrocytosis mimicking tuberculous meningitis: a retrospective study.

BACKGROUND: This study aimed to summarize the clinical features of Autoimmune Glial Fibrillary Acidic Protein Astrocytosis mimicking tubercu … veloped limb weakness and numbness with clinical manifestations of meningitis, meningoencephalitis, encephalomyelitis, or meningomyelitis. Cerebrospinal fluid analysis revealed an increased cell count in five cases, with a lymphocyte majority. All five cases had a CSF protein level > 1.0 g/L, CSF/blood glucose ratio < 0.5, and two patients had CSF glucose < 2.2 mmo …

Alterations of the axon initial segment in multiple sclerosis grey matter.

Grey matter damage has been established as a key contributor to disability progression in multiple sclerosis. Aside from neuronal loss and a … initial segment alterations in different pathological models, among which experimental auto-immune encephalomyelitis, whether the axon initial segment is affected in multiple sclerosis is still unknown. Using immunohistochemistry, we analysed axon initial segments from control and multiple sclerosis tissue, focusing on layer 5/6 pyramidal neurons in the neocortex …

CCR1 antagonist J-113863 corrects the imbalance of pro- and anti-inflammatory cytokines in a SJL/J mouse model of relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS), an immune-mediated and neurodegenerative disorder of the central nervous system (CNS), is characterized by infiltrating myelin-reactive T lymphocytes and demyelinating lesions. Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model used to study MS. To explore the impact of chemokine receptor CCR1 blockade in EAE and the underlying mechanisms, we used CCR1 antagonist J-113863 in PLP139-151-induced EAE in SJL/J mice. Following EAE induction, mice were treated with J-113863 (10 mg/kg) daily from day 14 until day 25. We investigated the effect …