The effect of metiamide in in vitro and in vivo canine models of type I hypersensitivity reactions

Biologic drugs are widely used in pediatric medicine. Monoclonal antibodies (mAbs) in particular are a therapeutic option for rheumatic, autoinflammatory and oncologic diseases. Adverse drug reactions and hypersensitivity reactions (HSR) to mAbs may occur in children. Clinical presentation of HSRs to mAbs can be classified according to phenotypes in infusion-related reactions, cytokine release syndrome, both alpha type reactions and type I (IgE/non-IgE), type III, and type IV reactions, all beta-type reactions. The aim of this review is to focus on HSRs associated with the most frequent mAbs in childhood, with particular attention to beta-type reactions. When a reaction to mAbs is suspected a diagnostic work-up including in-vivo and in-vitro testing should be performed. A drug provocation test is recommended only when no alternative drugs are available. In selected patients with immediate IgE-mediated drug allergy a desensitization protocol is indicated. Despite the heavy use of mAbs in childhood, studies evaluating the reliability of diagnostic test are lacking. Although desensitization may be effective in reducing the risk of reactions in children, standardized pediatric protocols are still not available.

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Peculiarities of the course of type I allergic reactions in patients with blood diseases

Terapevt (General Physician) ◽

10.33920/med-12-2004-06 ◽

2020 ◽

pp. 40-50

Author(s):

A. Nikitina

Keyword(s):

Search Engines ◽

Anaphylactic Shock ◽

Type I ◽

Allergic Reactions ◽

Common Cause ◽

Blood Diseases ◽

Treatment Regimens ◽

Modern Methods

Analysis of literature data presented in search engines — Elibrary, PubMed, Cochrane — concerning the risk of developing type I allergic reactions in patients with blood diseases is presented. It is shown that the most common cause of type I allergic reactions is drugs included in the treatment regimens of this category of patients. The article presents statistics on the increase in the number of drug allergies leading to cases of anaphylactic shock in patients with blood diseases. Modern methods for the diagnosis of type I allergic reactions in vivo and in vitro are considered.

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Protein domains involved in both in vivo and in vitro interactions between human T-cell leukemia virus type I tax and CREB.

Journal of Virology ◽

10.1128/jvi.69.6.3420-3432.1995 ◽

1995 ◽

Vol 69 (6) ◽

pp. 3420-3432 ◽

Cited By ~ 51

Author(s):

M J Yin ◽

E J Paulssen ◽

J S Seeler ◽

R B Gaynor

Keyword(s):

T Cell ◽

Leukemia Virus ◽

Type I ◽

Cell Leukemia ◽

Cell Leukemia Virus Type ◽

Human T Cell ◽

T Cell Leukemia Virus ◽

In Vitro Interactions

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Collagen-Based Electrospun Materials for Tissue Engineering: A Systematic Review

Bioengineering ◽

10.3390/bioengineering8030039 ◽

2021 ◽

Vol 8 (3) ◽

pp. 39

Author(s):

Britani N. Blackstone ◽

Summer C. Gallentine ◽

Heather M. Powell

Keyword(s):

Systematic Review ◽

Tissue Engineering ◽

Collagen Type I ◽

The Body ◽

Pool Data ◽

Type I ◽

High Concentrations ◽

Increased Strength

Collagen is a key component of the extracellular matrix (ECM) in organs and tissues throughout the body and is used for many tissue engineering applications. Electrospinning of collagen can produce scaffolds in a wide variety of shapes, fiber diameters and porosities to match that of the native ECM. This systematic review aims to pool data from available manuscripts on electrospun collagen and tissue engineering to provide insight into the connection between source material, solvent, crosslinking method and functional outcomes. D-banding was most often observed in electrospun collagen formed using collagen type I isolated from calfskin, often isolated within the laboratory, with short solution solubilization times. All physical and chemical methods of crosslinking utilized imparted resistance to degradation and increased strength. Cytotoxicity was observed at high concentrations of crosslinking agents and when abbreviated rinsing protocols were utilized. Collagen and collagen-based scaffolds were capable of forming engineered tissues in vitro and in vivo with high similarity to the native structures.

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E3 ligase Nedd4l promotes antiviral innate immunity by catalyzing K29-linked cysteine ubiquitination of TRAF3

Nature Communications ◽

10.1038/s41467-021-21456-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Peng Gao ◽

Xianwei Ma ◽

Ming Yuan ◽

Yulan Yi ◽

Guoke Liu ◽

...

Keyword(s):

Posttranslational Modifications ◽

Type I Interferon ◽

Zinc Fingers ◽

E3 Ligase ◽

Type I ◽

E3 Ligases ◽

Protein Posttranslational Modifications ◽

Antiviral Innate Immunity

AbstractUbiquitination is one of the most prevalent protein posttranslational modifications. Here, we show that E3 ligase Nedd4l positively regulates antiviral immunity by catalyzing K29-linked cysteine ubiquitination of TRAF3. Deficiency of Nedd4l significantly impairs type I interferon and proinflammatory cytokine production induced by virus infection both in vitro and in vivo. Nedd4l deficiency inhibits virus-induced ubiquitination of TRAF3, the binding between TRAF3 and TBK1, and subsequent phosphorylation of TBK1 and IRF3. Nedd4l directly interacts with TRAF3 and catalyzes K29-linked ubiquitination of Cys56 and Cys124, two cysteines that constitute zinc fingers, resulting in enhanced association between TRAF3 and E3 ligases, cIAP1/2 and HECTD3, and also increased K48/K63-linked ubiquitination of TRAF3. Mutation of Cys56 and Cys124 diminishes Nedd4l-catalyzed K29-linked ubiquitination, but enhances association between TRAF3 and the E3 ligases, supporting Nedd4l promotes type I interferon production in response to virus by catalyzing ubiquitination of the cysteines in TRAF3.

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Effects of chitosan-collagen dressing on wound healing in vitro and in vivo assays

Journal of Applied Biomaterials & Functional Materials ◽

10.1177/2280800021989698 ◽

2021 ◽

Vol 19 ◽

pp. 228080002198969

Author(s):

Min-Xia Zhang ◽

Wan-Yi Zhao ◽

Qing-Qing Fang ◽

Xiao-Feng Wang ◽

Chun-Ye Chen ◽

...

Keyword(s):

Wound Healing ◽

Wound Dressing ◽

Type I Collagen ◽

Inhibition Zone ◽

Negative Control ◽

Type I ◽

Nih3t3 Cells ◽

Post Operation

The present study was designed to fabricate a new chitosan-collagen sponge (CCS) for potential wound dressing applications. CCS was fabricated by a 3.0% chitosan mixture with a 1.0% type I collagen (7:3(w/w)) through freeze-drying. Then the dressing was prepared to evaluate its properties through a series of tests. The new-made dressing demonstrated its safety toward NIH3T3 cells. Furthermore, the CCS showed the significant surround inhibition zone than empty controls inoculated by E. coli and S. aureus. Moreover, the moisture rates of CCS were increased more rapidly than the collagen and blank sponge groups. The results revealed that the CCS had the characteristics of nontoxicity, biocompatibility, good antibacterial activity, and water retention. We used a full-thickness excisional wound healing model to evaluate the in vivo efficacy of the new dressing. The results showed remarkable healing at 14th day post-operation compared with injuries treated with collagen only as a negative control in addition to chitosan only. Our results suggest that the chitosan-collagen wound dressing were identified as a new promising candidate for further wound application.

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mTOR inhibitors potentially reduce TGF-β2-induced fibrogenic changes in trabecular meshwork cells

Scientific Reports ◽

10.1038/s41598-021-93580-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nozomi Igarashi ◽

Megumi Honjo ◽

Makoto Aihara

Keyword(s):

Trabecular Meshwork ◽

Transforming Growth Factor ◽

Smooth Muscle Actin ◽

Mtor Inhibitors ◽

In Vivo Model ◽

Type I ◽

Fibrotic Response ◽

Alpha Smooth Muscle Actin

AbstractWe examined the effects of mTOR inhibitors on the fibrotic response induced by transforming growth factor-beta2 (TGF-β2) in cultured human trabecular meshwork (hTM) cells. TGF-β2-induced expression of fibronectin, collagen type I, alpha 1 chain (COL1A1), and alpha-smooth muscle actin (αSMA) in hTM cells was examined in the presence or absence of mTOR inhibitors using quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry. The migration rates of hTM cells were examined in the presence of TGF-β2 with or without mTOR inhibitors. An in vitro study showed that the expression of fibronectin, COL1A1, and αSMA was upregulated by TGF-β2 treatment of hTM cells; such upregulation was significantly suppressed by mTOR inhibitors. The inhibitors significantly reduced the migration rate of TGF-β2-stimulated hTM cells. mTOR inhibitors may usefully reduce the fibrotic response of hTM cells and we may have to explore if it is also effective in in vivo model.

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In Vitro Effects of Sulforaphane on Interferon-Driven Inflammation and Exploratory Evaluation in Two Healthy Volunteers

Molecules ◽

10.3390/molecules26123602 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3602

Author(s):

Elena Genova ◽

Maura Apollonio ◽

Giuliana Decorti ◽

Alessandra Tesser ◽

Alberto Tommasini ◽

...

Keyword(s):

Healthy Volunteers ◽

Supportive Therapy ◽

P Value ◽

Type I ◽

Interferon Signature ◽

Interferon Stimulated Genes ◽

Immune System Activation ◽

In Vitro Effects

Interferonopathies are rare genetic conditions defined by systemic inflammatory episodes caused by innate immune system activation in the absence of pathogens. Currently, no targeted drugs are authorized for clinical use in these diseases. In this work, we studied the contribution of sulforaphane (SFN), a cruciferous-derived bioactive molecule, in the modulation of interferon-driven inflammation in an immortalized human hepatocytes (IHH) line and in two healthy volunteers, focusing on STING, a key-component player in interferon pathway, interferon signature modulation, and GSTM1 expression and genotype, which contributes to SFN metabolism and excretion. In vitro, SFN exposure reduced STING expression as well as interferon signature in the presence of the pro-inflammatory stimulus cGAMP (cGAMP 3 h vs. SFN+cGAMP 3 h p value < 0.0001; cGAMP 6 h vs. SFN+cGAMP 6 h p < 0.001, one way ANOVA), restoring STING expression to the level of unstimulated cells. In preliminary experiments on healthy volunteers, no appreciable variations in interferon signature were identified after SFN assumption, while only in one of them, presenting the GSTM1 wild type genotype related to reduced SFN excretion, could a downregulation of STING be recorded. This study confirmed that SFN inhibits STING-mediated inflammation and interferon-stimulated genes expression in vitro. However, only a trend towards the downregulation of STING could be reproduced in vivo. Results obtained have to be confirmed in a larger group of healthy individuals and in patients with type I interferonopathies to define if the assumption of SFN could be useful as supportive therapy.

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Slow viral propagation during initial phase of infection leads to viral persistence in mice

Communications Biology ◽

10.1038/s42003-021-02028-x ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Haifeng C. Xu ◽

Ruifeng Wang ◽

Prashant V. Shinde ◽

Lara Walotka ◽

Anfei Huang ◽

...

Keyword(s):

T Cell ◽

Immune Evasion ◽

Protein Transport ◽

Adaptive Immune System ◽

Viral Persistence ◽

Lymphocytic Choriomeningitis ◽

Type I ◽

Viral Propagation

AbstractImmune evasion of pathogens can modify the course of infection and impact viral persistence and pathology. Here, using different strains of the lymphocytic choriomeningitis virus (LCMV) model system, we show that slower propagation results in limited type I interferon (IFN-I) production and viral persistence. Specifically, cells infected with LCMV-Docile exhibited reduced viral replication when compared to LCMV-WE and as a consequence, infection with LCMV-Docile resulted in reduced activation of bone marrow derived dendritic cells (BMDCs) and IFN-I production in vitro in comparison with LCMV-WE. In vivo, we observed a reduction of IFN-I, T cell exhaustion and viral persistence following infection of LCMV-Docile but not LCMV-WE. Mechanistically, block of intracellular protein transport uncovered reduced propagation of LCMV-Docile when compared to LCMV-WE. This reduced propagation was critical in blunting the activation of the innate and adaptive immune system. When mice were simultaneously infected with LCMV-Docile and LCMV-WE, immune function was restored and IFN-I production, T cell effector functions as well as viral loads were similar to that of mice infected with LCMV-WE alone. Taken together, this study suggests that reduced viral propagation can result in immune evasion and viral persistence.

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