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Body messages : the quest for the proteins of cellular communication
This is a book about the research process that led scientists to the discovery of a group of molecules that act as carriers of information among the cells of our body, which the book refers to collectively as \"body messages.\" Among the thousands of body messages, the author selected those that are part of her own research, the cytokines, adipokines, and other proteins that regulate inflammation and metabolism. She also interviewed twenty researchers who contributed significantly to the field, asking details about their discoveries while also inquiring about their life and education. Along with scientists' personal recollections, the book reconstructs the discovery process based on published reports of the original experimental findings. Though the book's main theme is the process of discovery, it devotes considerable space to the biology of body messages and the consequence of their identification for medical practice.-- Provided by publisher
Book
Correction: Understanding the impact of moxifloxacin on immune function: Findings from cytokine analyses and immunological assays in mice
[This corrects the article DOI: 10.1371/journal.pone.0321961.].
Journal Article
Correction: Xi et al. Aerococcus viridans Phage Lysin AVPL Had Lytic Activity against Streptococcus suis in a Mouse Bacteremia Model. Int. J. Mol. Sci. 2023, 24, 16670
In the original publication [...]
Journal Article
Geobarrettin D, a Rare Herbipoline-Containing 6-Bromoindole Alkaloid from IGeodia barretti/I
Geobarrettin D (1), a new bromoindole alkaloid, was isolated from the marine sponge Geodia barretti collected from Icelandic waters. Its structure was elucidated by 1D, and 2D NMR (including [sup.1]H-[sup.15]N HSQC, [sup.1]H-[sup.15]N HMBC spectra), as well as HRESIMS data. Geobarrettin D (1) is a new 6-bromoindole featuring an unusual purinium herbipoline moiety. Geobarrettin D (1) decreased secretion of the pro-inflammatory cytokine IL-12p40 by human monocyte derived dendritic cells, without affecting secretion of the anti-inflammatory cytokine IL-10. Thus, compound 1 shows anti-inflammatory activity.
Journal Article
Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study
ObjectivesTo prospectively investigate in patients with severe COVID-19-associated cytokine storm syndrome (CSS) whether an intensive course of glucocorticoids with or without tocilizumab accelerates clinical improvement, reduces mortality and prevents invasive mechanical ventilation, in comparison with a historic control group of patients who received supportive care only.MethodsFrom 1 April 2020, patients with COVID-19-associated CSS, defined as rapid respiratory deterioration plus at least two out of three biomarkers with important elevations (C-reactive protein >100 mg/L; ferritin >900 µg/L; D-dimer >1500 µg/L), received high-dose intravenous methylprednisolone for 5 consecutive days (250 mg on day 1 followed by 80 mg on days 2–5). If the respiratory condition had not improved sufficiently (in 43%), the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, single infusion) was added on or after day 2. Control patients with COVID-19-associated CSS (same definition) were retrospectively sampled from the pool of patients (n=350) admitted between 7 March and 31 March, and matched one to one to treated patients on sex and age. The primary outcome was ≥2 stages of improvement on a 7-item WHO-endorsed scale for trials in patients with severe influenza pneumonia, or discharge from the hospital. Secondary outcomes were hospital mortality and mechanical ventilation.ResultsAt baseline all patients with COVID-19 in the treatment group (n=86) and control group (n=86) had symptoms of CSS and faced acute respiratory failure. Treated patients had 79% higher likelihood on reaching the primary outcome (HR: 1.8; 95% CI 1.2 to 2.7) (7 days earlier), 65% less mortality (HR: 0.35; 95% CI 0.19 to 0.65) and 71% less invasive mechanical ventilation (HR: 0.29; 95% CI 0.14 to 0.65). Treatment effects remained constant in confounding and sensitivity analyses.ConclusionsA strategy involving a course of high-dose methylprednisolone, followed by tocilizumab if needed, may accelerate respiratory recovery, lower hospital mortality and reduce the likelihood of invasive mechanical ventilation in COVID-19-associated CSS.
Journal Article
Genital Inflammation and the Risk of HIV Acquisition in Women
Background. Women in Africa, especially young women, have very high human immunodeficiency virus (HIV) incidence rates that cannot be fully explained by behavioral risks. We investigated whether genital inflammation influenced HIV acquisition in this group. Methods. Twelve selected cytokines, including 9 inflammatory cytokines and chemokines (interleukin [IL]-1α, IL-1β, IL-6, tumor necrosis factor-α, IL-8, interferon-γ inducible protein-10 [IP-10], monocyte chemoattractant protein-1, macrophage inflammatory protein [MIP]-1α, MIP-1β), hematopoietic IL-7, and granulocyte macrophage colony-stimulating factor, and regulatory IL-10 were measured prior to HIV infection in cervicovaginal lavages from 58 HIV seroconverters and 58 matched uninfected controls and in plasma from a subset of 107 of these women from the Centre for the AIDS Programme of Research in South Africa 004 tenofovir gel trial. Results. HIV seroconversion was associated with raised genital inflammatory cytokines (including chemokines MIP-1α, MIP-1β, and IP-10). The risk of HIV acquisition was significantly higher in women with evidence of genital inflammation, defined by at least 5 of 9 inflammatory cytokines being raised (odds ratio, 3.2; 95% confidence interval, 1.3–7.9; P = .014). Genital cytokine concentrations were persistently raised (for about 1 year before infection), with no readily identifiable cause despite extensive investigation of several potential factors, including sexually transmitted infections and systemic cytokines. Conclusions. Elevated genital concentrations of HIV target cell–recruiting chemokines and a genital inflammatory profile contributes to the high risk of HIV acquisition in these African women.
Journal Article
1186 ASKG193, a novel masked CD19 T-cell engager exhibited potency and expanded safety
BackgroundT-cell engager (TCE) is a potent antibody-based molecule that induced T cell-mediated killing by bridging CD3 and tumor-associated antigen(TAA). However, therapeutic potential has been significantly limited due to its poor pharmacokinetic, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS).MethodsTo improve the developability of TCEs, a proprietary TCE prodrug platform was established to achieve its overarching objective of modulating immune reactions at a disease site in a selective and controlled manner. Several prodrug-TCE molecules were designed and tested, including binding, cytotoxicity, and cytokine release assays in vitro, as well as safety and efficacy studies in vivo.ResultsHere, we reported ASKG193, a next generation CD19-CD3 TCE, with a masking strategy to attenuate off-target toxicity, extend half-life and improve systemic exposure. The non-activated ASKG193 showed no activity, while the activated form demonstrated >100 folds attenuation in vitro compared to a CD19 Bi-specific T-cell engager (BiTE). In ex vivo B-cell depletion assay, ASKG193 retained potent cytolytic activity comparable to the CD19 BiTE molecule. In addition, ASKG193 was well tolerated in vivo.ConclusionsIn summary, the masked CD19 TCE, ASKG193, exhibited superior anti-tumor efficacy, prolonged half-life, and a significantly improved safety profile. Our data demonstrated that the ASKG193 has the potential to substantially broaden the therapeutic window for CD19-targeted immunotherapies.
Journal Article