Dexamethasone turns tumor antigen-presenting cells into tolerogenic dendritic cells with T cell inhibitory functions

BackgroundDendritic cells (DCs) are usually immunogenic, but they are also capable of inducing tolerance under anti-inflammatory conditions. Immunotherapy based on autologous DCs loaded with an allogeneic melanoma cell lysate (TRIMEL/DCs) induces immunological responses and increases melanoma patient survival. Glucocorticoids can suppress DC maturation and function, leading to a DC-mediated inhibition of T cell responses.MethodsThe effect of dexamethasone, a glucocorticoid extensively used in cancer therapies, on TRIMEL/DCs phenotype and immunogenicity was examined.ResultsDexamethasone induced a semi-mature phenotype on TRIMEL/DC with low maturation surface marker expressions, decreased pro-inflammatory cytokine induction (IL-1β and IL-12) and increased release of regulatory cytokines (IL-10 and TGF-β). Dexamethasone-treated TRIMEL/DCs inhibited allogeneic CD4⁺ T cell proliferation and cytokine release (IFNγ, TNF-α and IL-17). Co-culturing melanoma-specific memory tumor-infiltrating lymphocytes with dexamethasone-treated TRIMEL/DC inhibited proliferation and effector T cell activities, including cytokine secretion and anti-melanoma cytotoxicity.ConclusionsThese findings suggest that dexamethasone repressed melanoma cell lysate-mediated DC maturation, generating a potent tolerogenic-like DC phenotype that inhibited melanoma-specific effector T cell activities. These results suggest that dexamethasone-induced immunosuppression may interfere with the clinical efficacy of DC-based melanoma vaccines, and must be taken into account for optimal design of cellular therapy against cancer.     

In vivo bracket bond strength using two adhesive systems applied under wet and dry conditions

The purpose of this study was to investigate, in vivo, the bond strength of two adhesive materials: a moisture insensitive primer (MIP)* and a one step self etching primer (SEP)*, both used with Transbond XT* on dry and wet enamel and an adhesion time of 10-15 minutes. First or second upper and/or lower bicuspids (n = 124), to be extracted for orthodontic reasons, were used. A comparison of the materials' behavior was conducted under four different situations: 1) MIP on enamel etched and dry; 2) MIP on a surface etched and wetted with patient's saliva; 3) SEP on a dry field, 4) SEP on a saliva-wet enamel. For statistical analysis, Dunn-Sidak's multiple comparison test was applied with a probability of less than 0.05 (before correction). Stainless steel brackets with mesh-backed pads were bonded to the teeth. Bond strength was tested with modified orthodontic pliers on which a strain-gage was fixed to measure handle deformation while debonding. Moisture insensitive primer tested on wet enamel showed the highest mean bond strength outcomes (8.98 MPa) compared to one step etching primer (5.81 MPa). Statistical difference between these groups was significant (p = 0.000). Standard deviation was lower for the one-step technique, under dry and wet conditions. Since the media bond strength of SEP proved sufficient for clinical purposes and its behavior tended to be more homogeneous, this was considered the best choice.     

Flapless sinus floor augmentation using endoscopy combined with CT scan-designed surgical templates: method and report of 6 consecutive cases

PURPOSE: Sinus floor augmentation has become a routine procedure with predictable results. Flapless implant placement is recommended for a series of indications with sufficient bone volume. Flapless surgery in the atrophic maxilla is presented as a refinement of the endoscopic subantroscopic laterobasal sinus floor augmentation (SALSA) technique. MATERIALS AND METHODS: Based on computerized tomography (CT) scans, the site of sinus trephination and implant positions are planned using a commercially available planning program, and surgical templates are fabricated according to the data of the treatment plan. Subantral space is augmented using the SALSA technique without raising a mucoperiosteal flap. Implants are placed transgingivally without raising a mucoperiosteal flap, with endoscopic control of the cover screw at the bone level. RESULTS: In a case series of 6 patients, 21 implants were placed and augmented simultaneously. The mean augmentation height was 10.7 mm (range, 5.7 to 16.6 mm); the mean residual bone height was 5.1 mm (range, 1.9 to 12.1 mm). Complications such as insufficient primary stability and sinus membrane perforation were treated without changing to an open surgical approach. DISCUSSION AND CONCLUSION: Flapless sinus augmentation (FSA) can reduce the surgical trauma significantly. The procedure has high acceptance by the patient and less postoperative discomfort. FSA enlarges the spectrum of minimally invasive surgery and may offer better vascularization and less alveolar resorption.     

Profile of herbal and dietary supplements induced liver injury in Latin America: A systematic review of published reports

Hepatotoxicity related to HDS is a growing global health issue. We have undertaken a systematic review of published case reports and case series from LA from 1976 to 2020 to describe the clinical features of HDS related hepatotoxicity in this region. We search in PubMed, Web of Science, Scopus and specific LA databases according to PRISMA guidelines. Only HILI cases published in LA that met criteria for DILI definition were included. Duplicate records or reports that lacked relevant data that precluded establishing causality were excluded. Finally, 17 records (23 cases) were included in this review. Centella asiatica, Carthamus tinctorius, and Herbalife® were the most reported HDS culprit products, the main reason for HDS consumption was weight loss. The clinical characteristics of HDS hepatotoxicity in our study were compared to those of other studies in the USA, Europe and China showing a similar signature with predominance of young females, hepatocellular damage, a high rate of ALF and mortality, more frequent inadvertent re‐challenge and chronic damage. This study underscores the challenge in causality assessment when multi‐ingredients HDS are taken and the need for consistent publication practice when reporting hepatotoxicity cases due to HDS, to foster HDS liver safety particularly in LA.     

Load cycling enhances bioactivity at the resin–dentin interface

Objectives

The purpose of this study was to evaluate if mechanical loading promotes bioactivity at the resin interface after bonding with three different adhesive approaches.

Methods

Dentin surfaces were subjected to three different treatments: demineralisation by (1) 37% phosphoric acid (PA) followed by application of an etch-and-rinse dentin adhesive Single Bond (SB) (PA + SB), (2) by 0.5 M ethylenediaminetetraacetic acid (EDTA) followed by SB (EDTA + SB), (3) application of a self-etch dentin adhesive: Clearfil SE Bond (SEB). Bonded interfaces were stored in simulated body fluid during 24 h or 3 w. One half of each tooth was submitted to mechanical loading. Remineralisation of the bonded interfaces was assessed by AFM imaging/nano-indentation, Raman spectroscopy/cluster analysis, dye assisted confocal microscopy evaluation (CLSM) and Masson's trichrome staining.

Results

Loading cycling for 3 w promoted an increase of mechanical properties at the resin–dentin interface. Cluster analysis demonstrated an augmentation of the mineral–matrix ratio in SB-loaded specimens. CLSM showed an absent micropermeability and nanoleakage after loading EDTA + SB and SEB specimens. Trichrome staining reflected a narrow demineralised dentin matrix after loading, almost not observable in EDTA + SB and SEB.

Significance

In vitro mechanical loading promoted mineralization in the resin–dentin interfaces, at 24 h and 3 w of storage.