The Intracerebroventricular Injection of Murine Mesenchymal Stromal Cells Engineered to Secrete Epidermal Growth Factor Does Not Prevent Loss of Neurogenesis in Irradiated Mice.

Decreased neurogenesis after brain exposure to ionizing radiation is linked to neurocognitive impairments. Using transgenic mouse models, we previously showed that abrogation of radiation-induced senescence, or apoptosis, can partially rescue neurogenesis in the subventricular and hippocampus regions. Here, we evaluate whether the injection of recombinant epidermal growth factor (rEGF) or mesenchymal stromal cells (MSC) engineered to secrete EGF (MSC-EGF) can preserve neurogenesis. Using doublecortin (Dcx) expression and BrdU incorporation assays, we found that the injection of rEGF into the subventricular zone (SVZ) promotes neurogenesis, despite increasing apoptosis, in the brain of irradiated mice. The effect of rEGF was mostly localized, as Dcx expression was not induced in the hippocampus region and limited in the contralateral SVZ. Surprisingly, the injection of bone marrow-derived MSC alone, or secreting EGF, did not result in increased neurogenesis despite the fact that part of the MSC survived a few weeks after injection. Our results suggest that only a supraphysiological concentration of rEGF can promote neurogenesis, likely through a direct mitogenic effect.

Correction to: Protocol for a double-blind, randomized controlled trial on the dose-related efficacy of omalizumab in multi-food oral immunotherapy.

[This corrects the article DOI: 10.1186/s13223-020-00419-z.].

Protocol for a double-blind, randomized controlled trial on the dose-related efficacy of omalizumab in multi-food oral immunotherapy.

BACKGROUND: Previous proof-of-concept studies have shown that a short course of omalizumab can safely accelerate the oral immunotherapy schedule for multiple allergens simultaneously. Considering the high cost of medication, the dose-related efficacy of omalizumab at decreasing the duration of oral immunotherapy up-dosing phase must be objectively quantified before cost-benefit analyses can be performed. The primary objective of this trial will be to compare the efficacy of 2 omalizumab dosages to placebo at decreasing time-to-maintenance dose during a symptom-driven multi-food OIT protocol. METHODS: A total of 90 participants aged 6 to 25 with multiple food allergies (3 or more) will be enrolled at four sites in Canada. Participants will be randomized to: (A) Omalizumab 8 mg/kg per month (n = 36); (B) Omalizumab 16 mg/kg per month (n = 36); or (C) Placebo (n = 18). Study drug will be administered at full dosage for 12 weeks, then progressively tapered at 50% dosage (8 mg/kg vs 4 mg/kg vs placebo) for 4 weeks and at 25% dosage (4 mg/kg vs 2 mg/kg vs placebo) for another 4 weeks. After a pre-treatment period of 8 weeks, participants will undergo an initial food escalation (IFE) to an OIT mix containing 3 allergens and start daily home dosing with biweekly increases until a target daily maintenance of 1500 mg protein is achieved. The amount escalated at each visit will vary based on treatment tolerance according to a standardized up-dosing algorithm. Participants will be followed for at least 12 months following the initial food escalation. The primary endpoint will be time from IFE to the target maintenance dose of 1500 mg protein. Time-to-event analytic methods, including the log-rank test, will be used to compare the 3 arms. DISCUSSION: This trial uses a novel pragmatic approach to compare OIT with omalizumab to OIT without omalizumab in a blinded manner, which allows to single out the effect of this anti-IgE medication on treatment effectiveness speed without the recourse to predetermined schedules. The innovative patient-centered up-dosing algorithm allows to maximise treatment effectiveness speed without compromising patient safety, regardless of whether the patient is on omalizumab or not. This study will also provide novel prospective data to inform on the optimal and most cost-effective dosage for this indication.Trial registration ClinicalTrials.gov, NCT04045301, Registered 5 August 2019, https://clinicaltrials.gov/ct2/show/NCT04045301.

Cigarette smoke condensate increases C. albicans adhesion, growth, biofilm formation, and EAP1, HWP1 and SAP2 gene expression.

BACKGROUND: Smokers are more prone to oral infections than are non-smokers. Cigarette smoke reaches the host cells but also microorganisms present in the oral cavity. The contact between cigarette smoke and oral bacteria promotes such oral diseases as periodontitis. Cigarette smoke can also modulate C. albicans activities that promote oral candidiasis. The goal of this study was to investigate the effect of cigarette smoke condensate on C. albicans adhesion, growth, and biofilm formation as well as the activation of EAP1, HWP1 and secreted aspartic protease 2. RESULTS: Cigarette smoke condensate (CSC) increased C. albicans adhesion and growth, as well as biofilm formation. These features may be supported by the activation of certain important genes. Using quantitative RT-PCR, we demonstrated that CSC-exposed C. albicans expressed high levels of EAP1, HWP1 and SAP2 mRNA and that this gene expression increased with increasing concentrations of CSC. CONCLUSION: CSC induction of C. albicans adhesion, growth, and biofilm formation may explain the increased persistence of this pathogen in smokers. These findings may also be relevant to other biofilm-induced oral diseases.