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Targeting Signaling Pathway Downstream of RIG-I/MAVS in the CNS Stimulates Production of Endogenous Type I IFN and Suppresses EAE.

Type I interferons (IFN), including IFNβ, play a protective role in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Type I IFNs are induced by the stimulation of innate signaling, including via cytoplasmic RIG-I-like receptors. In the present study, we investigated the potential effect of a chimeric protein containing the key domain of RIG-I signaling in the production of CNS endogenous IFNβ and asked whether this would exert a therapeutic effect against EAE. We intrathecally administered an adeno-associated virus vector (AAV) encoding a fusion pr

Zika virus vertical transmission in interferon receptor1-antagonized Rag1-/- mice results in postnatal brain abnormalities and clinical disease.

The mechanisms by which vertically transmitted Zika virus (ZIKV) causes postnatal brain development abnormalities and congenital disease remain poorly understood. Here, we optimized the established anti-IFNAR1 treated, Rag1-/- (AIR) mouse model of ZIKV infection to examine the consequence of vertical transmission on neonate survival and postnatal brain development. We found that modulating the infectious dose and the frequency of anti-IFNAR1 treatment of pregnant mice (termed AIRlow mice) prolonged neonatal survival allowing for pathogenesis studies of brain tissues at critical postnatal time

IFN-α: A key therapeutic target for multiple autoimmune rheumatic diseases.

Interferon (IFN)-α has emerged as a major therapeutic target for several autoimmune rheumatic diseases. In this review, we focus on clinical and preclinical advances in anti-IFN-α treatments in systemic lupus erythematosus (SLE), primary Sjögren syndrome (pSS), systemic sclerosis (SSc), and dermatomyositis (DM), for which a high medical need persists. Promising achievements were obtained following direct IFN-α neutralization, targeting its production through the cytosolic nucleic acid sensor pathways or by blocking its downstream effects through the type I IFN receptor. We further focus on mol

Pharmacological interventions for acute hepatitis C infection.

BACKGROUND: Hepatitis C virus (HCV) is a single-stranded RNA (ribonucleic acid) virus that has the potential to cause inflammation of the li … icipants) compared interferon-alpha versus no intervention. Three trials (90 participants) compared interferon-beta versus no intervention. One trial (21 participants) compared pegylated interferon-alpha versus no intervention, but it did not provide any data for analysis. One trial (41 participants) compared MTH-68/B vaccine versus no intervention. Two trials (2 …

Modulation of natural killer activity by aspirin: I. In vitro effect of aspirin.

It has been previously shown that the Natural Killer (NK) cell activity of peripheral blood mononuclear cells (NMC) from healthy donors can be augmented by in vitro coculture of MNC with melanoma cells. This augmentation was not seen when the blood donors had taken acetylsalicylic acid (ASA) 12 h before venipuncture. To examine the direct action of ASA on the NK cell activity we treated MNC in vitro by ASA and tested the cytotoxic activity on NK-sensitive target cells. Neither the spontaneous NK cell activity nor the in vitro stimulation of NK cell activity by beta-interferon (IFN) was influen

Cytokine Indicators Associated with Disease Severity in Severe Fever with Thrombocytopenia Syndrome: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study is to study cytokine indicators for the identification of severe fever with thrombocytopenia syndrome (SFTS) severity. METHODS: We searched the literature in PubMed, Embase, and Web of Science published before 7 April 2026. The main results are presented as forest plots. Subgroup analyses, sensitivity analyses, and publication bias were also performed. RESULTS: A total of 22 articles were eventually included in our study. Our findings demonstrate that circulating concentrations of Interleukin-6 (IL-6) (SMD = 2.02, 95% CI: 1.53-2.51, I2 = 95.2%), Interleuk

Изучение общественного интереса к множественному склерозу и его лечению в Соединенных Штатах: Google Trends Analysis.

Множественный склероз (MS) затрагивает более 2,8 миллиона человек во всем мире и является одной из основных причин неврологических расстройств у молодых людей. В этом исследовании анализируется интерес общественности к НР и его вариантам лечения в Соединенных Штатах за последнее десятилетие с использованием данных Google Trends. Цель заключается в анализе того, как тенденции поиска отражают взаимодействие общественности с РС, особенно в том, что касается регулирования рецидивов, замедления развития заболеваний, смягчения симптомов и повышения качества жизни. В период с января 2014 года по дека

Совпадение в аннотации оригинала
Introduction Multiple sclerosis (MS) afflicts over 2.8 million individuals worldwide and is a leading cause of neurological impairment in yo … terms for MS and various treatment modalities were analyzed, including traditional therapies (e.g., interferon-beta, glatiramer acetate) and newer treatments (e.g., ocrelizumab, siponimod). Statistical analysis was performed using the Mann-Whitney U test to compare relative search volumes (RSV) between the two periods. Results  Significant fluctuations in RSV wer …

Treatment patterns in pediatric patients with multiple sclerosis in Germany-a nationwide claim-based analysis.

BackgroundThe manifestation of multiple sclerosis (MS) in childhood and adolescence occurs in 3%-5% of all MS cases. However, the immunomodulatory and symptomatic treatment options in this population group are still limited.ObjectiveWe aimed to elucidate the prescription frequency of medications used in pediatric patients with multiple sclerosis (PwMS) compared with the general population, considering the entire spectrum of medications prescribed.MethodsBased on nationwide outpatient drug prescription data and statutory health insurance (SHI) physicians' claims data from 2018, we conducted a p

Liver injury is independently associated with adverse clinical outcomes in patients with COVID-19.

OBJECTIVE: Data on serial liver biochemistries of patients infected by different human coronaviruses (HCoVs) are lacking. The impact of liver injury on adverse clinical outcomes in coronavirus disease 2019 (COVID-19) patients remains unclear. DESIGN: This was a retrospective cohort study using data from a territory-wide database in Hong Kong. COVID-19, severe acute respiratory syndrome (SARS) and other HCoV patients were identified by diagnosis codes and/or virological results. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation was defined as ALT/AST ≥2 × upper limit of

Th2 and regulatory immune reactions are increased in immunoglobin G4-related sclerosing pancreatitis and cholangitis.

UNLABELLED: Immunoglobin G (IgG) 4-related sclerosing pancreatitis and cholangitis (autoimmune pancreato-cholangitis [AIPC]) are recently recognized disease entities characterized by high serum IgG4 concentrations and sclerosing inflammation with numerous IgG4-positive plasma cells, although the underlining immune mechanism remains only speculative. In this study, the immunopathogenesis of AIPC was examined with respect to the production of cytokines in situ and the possible involvement of regulatory T cells (Tregs) using fresh (5 cases) and formalin-fixed (28 cases) specimens of AIPC and rela

SARS-CoV-2 omicron sub-lineages differentially modulate interferon response in human lung epithelial cells.

Although most of the attention was focused on the characterization of changes in the Spike protein among variants of SARS-CoV-2 virus, mutations outside the Spike region are likely to contribute to virus pathogenesis, virus adaptation and escape to the immune system. Phylogenetic analysis of SARS-CoV-2 Omicron strains reveals that several virus sub-lineages could be distinguished, from BA.1 up to BA.5. Regarding BA.1, BA.2 and BA.5, several mutations concern viral proteins with antagonistic activity to the innate immune system, such as NSP1 (S135R), which is involved in mRNAs translation, exhi

Disease-modifying therapies and cost-of-illness progression among people newly diagnosed with multiple sclerosis: a national register-based cohort study covering treatment initiation with interferons, glatiramer acetate or natalizumab.

OBJECTIVES: Disease-modifying therapies (DMTs) can slow disease progression in multiple sclerosis (MS). The objective of this study was to explore the cost-of-illness (COI) progression among newly diagnosed people with MS in relation to the first DMT received. DESIGN AND SETTING: A cohort study using data from nationwide registers in Sweden. PARTICIPANTS: People with MS (PwMS) in Sweden first diagnosed in 2006-2015, when aged 20-55, receiving first-line therapy with interferons (IFN), glatiramer acetate (GA) or natalizumab (NAT). They were followed up through 2016. OUTCOME MEASURES: Outcome

TRIM25 Suppresses Rabies Virus Fixed HEP-Flury Strain Production by Activating RIG-1-Mediated Type I Interferons.

Rabies remains a great threat to public health worldwide. So far, the mechanism of rabies virus (RABV) infection is not fully understood, and there is no effective treatment for rabies. Identifying more host restriction factors of RABV will spur the development of novel therapeutic interventions against rabies. Accumulating studies suggest that tripartite motif-containing (TRIM) proteins have great effects on virus replication. TRIMs control the antiviral responses through either direct interaction with viral proteins or indirect regulation of innate immune signaling molecules in the host. The

Specific activation of embryonic IFNAR1 and endometrial IFNAR2 induced by embryonic IFNτ directs normal uterine fate for bovine early implantation.

Interferon-tau (IFNτ), as an antiluteolytic factor secreted by trophoderm during the pregnancy of ruminants, actually functions by activating the IFNτ receptor 1 (IFNAR1) and IFNτ receptor 2 (IFNAR2). However, it has not been clearly understood how IFNτ-IFNAR cascade regulation processes between the embryo and uterine epithelial cells in ruminants. In this study, we found the expression and location of IFNτ in the bovine blastocysts from different production sources. IFNτ, IFNAR1 and IFNAR2 were all located in the trophoblast cells of the blastocyst. However, the fluorescence intensity of IFNA

Severe Acute Respiratory Syndrome Coronavirus 2 ORF8 Protein Inhibits Type I Interferon Production by Targeting HSP90B1 Signaling.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has currently infected over 430 million individuals worldwide. With the variant strains of SARS-CoV-2 emerging, a region of high mutation rates in ORF8 was identified during the early pandemic, which resulted in a mutation from leucine (L) to serine (S) at amino acid 84. A typical feature of ORF8 is the immune evasion by suppressing interferon response; however, the mechanisms by which the two variants of ORF8 antagonize the type I interferon (IFN-I) pathway ha

Comparative analysis of cytokine gene expression in cerebrospinal fluid of horses without neurologic signs or with selected neurologic disorders.

OBJECTIVE: To determine gene transcription for cytokines in nucleated cells in CSF of horses without neurologic signs or with cervical stenotic myelopathy (CSM), West Nile virus (WNV) encephalitis, equine protozoal myeloencephalitis (EPM), or spinal cord trauma. ANIMALS: 41 horses (no neurologic signs [n = 12], CSM [8], WNV encephalitis [9], EPM [6], and spinal cord trauma [6]). PROCEDURES: Total RNA was extracted from nucleated cells and converted into cDNA. Gene expression was measured by use of real-time PCR assay and final quantitation via the comparative threshold cycle method. RESULTS

Gene expression profiles of some cytokines, growth factors, receptors, and enzymes (GM-CSF, IFNγ, MMP-2, IGF-II, EGF, TGF-β, IGF-IIR) during pregnancy in the cat uterus.

Early pregnancy is one of the most critical periods of pregnancy, and many factors such as cytokines, enzymes, and members of the immune system have to cooperate in a balanced way. In the present study, the gene expression profiles of factors associated with pregnancy such as EGF, transforming growth factor beta, granulocyte-macrophage colony-stimulating factor, interferon gamma, insulin-like growth factor 2, insulin-like growth factor 2 receptor, and matrix metalloproteinase 2 were analyzed in uterine tissues of female cats. The cats were assigned to five groups: G1 (embryo positive, n = 7; 7

Multiple sclerosis: management issues during pregnancy.

Care of pregnant women with multiple sclerosis (MS) is challenging because of the multiple physiological changes associated with pregnancy a … icity in humans. Until information is available regarding safety, glatiramer acetate, mitoxantrone, interferon-beta-1a and interferon-beta-1b should be discontinued before an anticipated pregnancy. Women with MS are no more likely to experience delivery complications than are women without MS and the mode of delivery should be decided strictly on obstetrical crit …

Cytokine and T-cell subset abnormalities in immunodeficient wasted mice.

Wasted mice bear an autosomal recessive mutation (wst/wst) that manifests itself in neurologic abnormalities, immunologic deficiency, and faulty DNA repair evident by 21 days of age. The immunodeficiency is characterized by a reduction in the thymus-to-body weight ratio, low levels of IgA plasma cells at secretory sites, and increased sensitivity of T-cells to the killing effects of ionizing radiation. Experiments were designed to examine measures of T-cell activity in wasted mice. The initial experiments established that wst/wst mice have percentages of thymic and splenic Thy1+ cells equivale

Normal mouse lung tissue produces a growth-inhibitory factor(s) preferential for mouse monocytic leukemia cells.

A growth-inhibitory (GI) factor, that specifically inhibits the growth of mouse monocytic leukemia cells, was found in conditioned medium of mouse lung tissue, but not in that of mouse brain, heart, liver, or kidney tissue. Conditioned medium of spleen or bone marrow cells had low GI activity. Pulmonary macrophages were as active as peritoneal and bone-marrow-derived macrophages in production of the GI activity. The GI factor inhibited the growth of murine monocytic leukemia cell lines Mm-A and J774.1, but scarcely inhibited the growth of other mouse cell lines, such as a myeloblastic leukemia