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Type I interferon drives tumor necrosis factor-induced lethal shock.

Tumor necrosis factor (TNF) is reputed to have very powerful antitumor effects, but it is also a strong proinflammatory cytokine. Injection of TNF in humans and mice leads to a systemic inflammatory response syndrome with major effects on liver and bowels. TNF is also a central mediator in several inflammatory diseases. We report that type I interferons (IFNs) are essential mediators of the lethal response to TNF. Mice deficient in the IFN-alpha receptor 1 (IFNAR-1) or in IFN-beta are remarkably resistant to TNF-induced hypothermia and death. After TNF injection, IFNAR-1(-/-) mice produced les

Transcriptomic subtyping of COVID-19 reveals three distinct immune response profile.

The current clinical classification of coronavirus disease 2019 (COVID-19) does not adequately capture the biological heterogeneity observed among patients. To address this gap, the present study aimed to identify distinct subtypes of severe COVID-19 through unsupervised clustering analysis. We analyzed nine publicly available RNA sequencing datasets of peripheral blood samples from the GEO database. After identifying differentially expressed genes (DEGs), we applied a consensus clustering algorithm to classify the samples into distinct subtypes. To further characterize these subtypes, we perf

Нано-исцеление: изучение терапевтических возможностей наномедицины для выявления нарушений, связанных с ОВН.

ВВЕДЕНИЕ: Наномедицина обладает огромным потенциалом в области лечения расстройств Центральной нервной системы (ЦСН), включая такие заболевания, как болезнь Альцгеймера, болезнь Паркинсона, множественный склероз, эпилепсия и инсульт. МЕТОД: Благодаря использованию систем доставки наркотиков нанотехнологий можно повысить эффективность лекарственных средств, свести к минимуму их токсичность и увеличить их биодоступность, что позволит им эффективно добраться до предполагаемого места в ЦНС. Цель этого обзора заключается в изучении терапевтических возможностей, которые предоставляет наномедицина в

Совпадение в аннотации оригинала
INTRODUCTION: Nanomedicine offers immense potential in the field of Central Nervous System (CNS) disorder treatment, encompassing conditions … er's disease, liposomes for delivering L-DOPA in Parkinson's disease, and dendrimers for delivering interferon-beta in multiple sclerosis. RESULTS: Additionally, the potential of nanotechnology-based approaches in the treatment of epilepsy and stroke is discussed. The review concludes by addressing the challenges faced and emphasizes the significant potential of …

Latent tuberculosis prevalence, diagnosis and treatment in Multiple Sclerosis as a strategy for reducing infection reactivation during immunosuppressant therapy.

BACKGROUND: Tuberculosis is an infectious disease with a risk of reactivation in Multiple Sclerosis patients on immunosuppressant therapy. Diagnosis and treatment of Latent Tuberculosis Infection (LTBI) prevents the infection. OBJECTIVE: To diagnose and treat LTBI in Multiple Sclerosis (MS). METHODS: Cross-sectional study of the prevalence and treatment of LTBI in MS, between February 2021 and June 2023. LTBI was defined as an absence of symptoms, positive PPD or IGRA and normal chest X-ray. RESULTS: Of the 58 patients with MS, 17 (29.3 %) were diagnosed with LTBI, 15 with PPD > 5 mm and 2

The potential mechanism of the progression from latent to active tuberculosis based on the intestinal microbiota alterations.

INTRODUCTION: Tuberculosis (TB) poses a serious challenge to global health systems. The altered intestinal microbiota is associated with the pathogenesis of TB, but the exact links remain unclear. METHODS: 16 S rDNA sequencing was performed to comprehensively detect the changes in the intestinal microbiota of feces from active TB (ATB), latent TB infection (LTBI) and healthy controls (HC). RESULTS: The rarefaction curves demonstrated the sequencing results' validity. The alpha diversity was lowest in ATB, while highest in HC. Boxplot of beta diversity showed significant differences in every

Neuroprotective Effects of Novel Treatments on Acute Optic Neuritis-A Meta-Analysis.

Optic neuritis, inflammation of the optic nerve, can cause visual impairment through retinal nerve fiber layer (RNFL) degeneration. Optical … 2) LogMAR visual acuity (VA). Seven studies involving five novel agents (memantine, erythropoietin, interferon-beta, phenytoin, and clemastine) were analyzed. When compared with the baseline RNFL thickness of the affected eye, the neuroprotective effects of novel add-on treatments could not be demonstrated. The difference in visual outcomes was also not significa …

Reprogrammed Pteropus Bat Stem Cells as A Model to Study Host-Pathogen Interaction during Henipavirus Infection.

Bats are natural hosts for numerous zoonotic viruses, including henipaviruses, which are highly pathogenic for humans, livestock, and other mammals but do not induce clinical disease in bats. Pteropus bats are identified as a reservoir of henipaviruses and the source of transmission of the infection to humans over the past 20 years. A better understanding of the molecular and cellular mechanisms allowing bats to control viral infections requires the development of relevant, stable, and permissive cellular experimental models. By applying a somatic reprogramming protocol to Pteropus bat primary

Suppression of Zika Virus Infection in the Brain by the Antiretroviral Drug Rilpivirine.

Zika virus (ZIKV) infection is associated with microcephaly in neonates and Guillain-Barré syndrome in adults. ZIKV produces a class of nonstructural (NS) regulatory proteins that play a critical role in viral transcription and replication, including NS5, which possesses RNA-dependent RNA polymerase (RdRp) activity. Here we demonstrate that rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of HIV-1 infection, inhibits the enzymatic activity of NS5 and suppresses ZIKV infection and replication in primary human astrocytes. Similarly, other members

Altered humoral immunity to mycobacterial antigens in Japanese patients affected by inflammatory demyelinating diseases of the central nervous system.

Mycobacterium avium subsp. paratuberculosis (MAP) and Mycobacterium bovis (BCG) have been associated to several human autoimmune diseases su … (AUC = 0.67, p = 0.01), and the anti-MAP antibodies were more prevalent in MS patients treated with interferon-beta (OR = 11.9; p = 0.004). Anti-BCG IgG antibodies were detected in 8% of MS, 32% of NMOSD and 18% of HCs, the difference between MS and NMOSD groups was statistically significant (AUC = 0.66, p = 0.005). Competition experiments showed that nonspecific …

Experimental evidence and molecular modeling of the interaction between hRSV-NS1 and quercetin.

Human Respiratory Syncytial Virus is one of the major causes of acute respiratory infections in children, causing bronchiolitis and pneumonia. Non-Structural Protein 1 (NS1) is involved in immune system evasion, a process that contributes to the success of hRSV replication. This protein can act by inhibiting or neutralizing several steps of interferon pathway, as well as by silencing the hRSV ribonucleoproteic complex. There is evidence that quercetin can reduce the infection and/or replication of several viruses, including RSV. The aims of this study include the expression and purification of

Clinical evaluation of natalizumab for formulary consideration.

IMPORTANCE OF THE FIELD: Natalizumab is a monotherapy for relapsing forms of multiple sclerosis (MS) and maintaining remission in Crohn's disease (CD). Evaluation of natalizumab's clinical relevance must be performed before considering its place in treatment of these diseases. AREAS COVERED IN THIS REVIEW: MEDLINE and PubMed searches were performed using the keywords multiple sclerosis, Crohn's disease, natalizumab and clinical trials. The manufacturer's product information was consulted to extract additional data. Pivotal clinical trials included: Natalizumab Safety and Efficacy in Relapsing

Induction of IFN-alphabeta enables Listeria monocytogenes to suppress macrophage activation by IFN-gamma.

Production of type I interferon (IFN; IFN-alphabeta) increases host susceptibility to Listeria monocytogenes, whereas type II IFN (IFN-gamma) activates macrophages to resist infection. We show that these opposing immunological effects of IFN-alphabeta and IFN-gamma occur because of cross talk between the respective signaling pathways. We found that cultured macrophages infected with L. monocytogenes were refractory to IFN-gamma treatment as a result of down-regulation of the IFN-gamma receptor (IFNGR). The soluble factor responsible for these effects was identified as host IFN-alphabeta. Accor

Immune response of vaccinated and non-vaccinated mice to Coccidioides posadasii infection.

An immunogenic, recombinant protein of the fungal respiratory pathogen, Coccidioides posadasii, was previously identified as a beta-1,3-glucanosyltransferase homolog (Gel1) and shown to confer protection to C57BL/6 mice against coccidioidomycosis. However, little is known about the nature of the humoral and cellular immune responses of these vaccinated mice to intranasal infection with a lethal inoculum of C. posadasii spores compared to non-immune control animals. Our studies showed that protective immunity in mice vaccinated with two 1 microg doses of the recombinant Gel1 (rGel1) plus adjuva

Indoleamine 2,3-dioxygenase mediates cell type-specific anti-measles virus activity of gamma interferon.

Gamma interferon (IFN-gamma) has been shown to be increased in sera from patients with acute measles and after vaccination, to exhibit protective functions in brains of patients with subacute sclerosing panencephalitis, and to mediate a noncytolytic clearance of measles virus (MV) from rodent brains. In order to reveal a possible intracellular antiviral activity in the absence of antigen presentation and cytotoxic T cells, we investigated IFN-gamma-induced effects on MV replication in various tissue culture cells. While attenuated MV strains are more sensitive to IFN-alpha/beta than are wild-t

Current insights into the pathogenesis, diagnosis and therapy of inflammatory cardiomyopathy.

Persistence of cardiotropic viruses (enterovirus, adenovirus) and anticardiac autoimmunity constitute the predominant etiopathogenic pathway … cardiotropic viral infections in DCM. In InfCM patients with enterovirus or adenoviral persistence, interferon-beta administration leads to viral elimination and cessation of the intramyocardial inflammation, paralleled by a significant improvement of left ventricular systolic function and heart failure symptoms. The biopsy-guided etiopathogenic differentiation o …

Self-reported visual dysfunction in multiple sclerosis: results from the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25).

Visual impairment is one of the most common clinical manifestations of Multiple Sclerosis (MS), and is strongly related to overall health-related quality of life (HRQOL) in MS and other disorders. However, the assessment of vision-specific HRQOL in patients with MS has been limited. The purpose of this study was to examine self-reported visual dysfunction in a clinically heterogeneous MS cohort using the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25). The VFQ-25 was administered by telephone interview to a subset of participants in a follow-up study to a phase III trial

GLI3 zinc-finger gene interrupted by translocations in Greig syndrome families.

The Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder affecting limb and craniofacial development in humans. GCP … ne in 7p12-13 (ref. 8). Of the genes that map to this region, those encoding T cell receptor-gamma, interferon-beta 2, epidermal growth factor receptor, and Hox1.4, a potential candidate gene for GCPS, have been excluded from the region in which the deletions overlap. Here we show that two of the three translocations interup the GLI3 gene, a zinc-finger gene of t …

Molecular and cytogenetic analysis in two patients with microdeletions of 7p and Greig syndrome: hemizygosity for PGAM2 and TCRG genes.

Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder that has been mapped to 7p13. We have investigated two patient … loss of the phosphoglycerate mutase muscular form (PGAM2) gene locus in both patients. Hox 1.4 and interferon-beta 2 (IFNB2) showed a normal gene dosage. Our investigations revealed the following ordering and assignments of the studied genes: PGAM2 and GCPS in 7p12.3-13; TCRG in the distal part of 7p13-7p14.2; Hox 1.4 and IFNB2 distal to 7p14.2. Our results sugg …

Mutations in the macrodomain 1 of nsp3 attenuate PEDV virulence in vivo without impairing in vitro replication.

The conserved macrodomain 1 (Mac1) within coronavirus nsp3 reverses ADP-ribosylation of proteins and contributes to viral virulence. While Mac1 has been characterized in several coronaviruses, its role in porcine epidemic diarrhea virus (PEDV) remains unknown. Since D445 and N462 are functionally important residues in several betacoronaviruses, we mutated the two residues in both the PEDV Mac1 recombinant protein and the infectious virus and analyzed them in vitro and in vivo. Sequence alignment revealed that N462 is highly conserved, whereas D445 is less conserved among porcine coronaviruses.

Generation of polarized antigen-specific CD8 effector populations: reciprocal action of interleukin (IL)-4 and IL-12 in promoting type 2 versus type 1 cytokine profiles.

We have generated primary effector populations from naive CD8 T cells in response to antigen and determined their patterns of cytokine secretion upon restimulation. The effect of exogenous factors on the effector generation was examined and compared with responses of antigen-specific CD4 effectors generated under comparable conditions. CD8 cells from bm1 mice were stimulated with C57BL/6 (B6) antigen presenting cells (APCs) bearing allogeneic class I and CD8 cells from female severe combined immunodeficiency (SCID) B6 mice, transgenic for a T cell receptor alpha/beta (TCR-alpha/beta) that reco