Overfeeding and overweight rapidly reprogram inflammatory signaling.

Epidemiologic studies have shown a continuous increase in mortality risk associated with overweight, thus highlighting the health risks beginning before the onset of obesity. However, early changes in inflammatory signaling induced by an obesogenic diet remain largely unknown since studies of obesity typically utilize models induced by months of continuous exposure to a high-fat diet. Here, we investigated how short-term overfeeding remodels inflammatory signaling.

Integrating circulating T follicular memory cells and autoantibody repertoires for characterization of autoimmune disorders.

Introduction: Autoimmune diseases are heterogeneous and often lack specific or sensitive diagnostic tests. Increased percentages of CD4CXCR5PD1 circulating T follicular helper (cTfh) cells and skewed distributions of cTfh subtypes have been associated with autoimmunity. However, cTfh cell percentages can normalize with immunomodulatory treatment despite persistent disease activity, indicating the need for identifying additional cellular and/or serologic features correlating with autoimmunity.

Rethinking Immunological Risk: A Retrospective Cohort Study of Severe SARS-Cov-2 Infections in Individuals With Congenital Immunodeficiencies.

Background: Debates on the allocation of medical resources during the coronavirus disease 2019 (COVID-19) pandemic revealed the need for a better understanding of immunological risk. Studies highlighted variable clinical outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in individuals with defects in both adaptive and innate immunity, suggesting additional contributions from other factors. Notably, none of these studies controlled for variables linked with social determinants of health.

Rethinking immunologic risk: a retrospective cohort study of severe SARS-CoV-2 infections in individuals with congenital immunodeficiencies.

Background: Debates on the allocation of medical resources during the COVID-19 pandemic revealed the need for a better understanding of immunologic risk. Studies highlighted variable clinical outcomes of SARS-CoV-2 infections in individuals with defects in both adaptive and innate immunity, suggesting additional contributions from other factors. Notably, none of these studies controlled for variables linked with social determinants of health.

The CIP2A-TOPBP1 axis safeguards chromosome stability and is a synthetic lethal target for BRCA-mutated cancer.

BRCA1/2-mutated cancer cells adapt to the genome instability caused by their deficiency in homologous recombination (HR). Identification of these adaptive mechanisms may provide therapeutic strategies to target tumors caused by the loss of these genes. In the present study, we report genome-scale CRISPR-Cas9 synthetic lethality screens in isogenic pairs of BRCA1- and BRCA2-deficient cells and identify CIP2A as an essential gene in BRCA1- and BRCA2-mutated cells.

Analysis of combinatorial CRISPR screens with the Orthrus scoring pipeline.

The continued improvement of combinatorial CRISPR screening platforms necessitates the development of new computational pipelines for scoring combinatorial screening data. Unlike for single-guide RNA (sgRNA) pooled screening platforms, combinatorial scoring for multiplexed systems is confounded by guide design parameters such as the number of gRNAs per construct, the position of gRNAs along constructs, and additional features that may impact gRNA expression, processing or capture. In this protocol we describe Orthrus, an R package for processing, scoring and analyzing combinatorial CRISPR screening data that addresses these challenges.

A Repeated State of Acidification Enhances the Anticariogenic Biofilm Activity of Glass Ionomer Cement Containing Fluoro-Zinc-Silicate Fillers.

This study aimed to evaluate the anticariogenic biofilm activity of a novel zinc-containing glass ionomer cement, Caredyne Restore (CR), using a flow-cell system that reproduces Stephan responses. biofilms were cultured on either CR or hydroxyapatite (HA) discs mounted on a modified Robbins device. The media were allowed to flow at a speed of 2 mL/min for 24 h while exposed to an acidic buffer twice for 30 min to mimic dietary uptake.

Current Prevalence of Oral among Japanese Adults Determined Using a Nested Polymerase Chain Reaction Assay.

In Japan, gastric infection prevalence has markedly decreased with socioeconomic development. We aimed to investigate the prevalence of oral in Japanese adults in 2020 by sex, age, sampling site, and medical history. Unstimulated saliva, supragingival biofilm, and tongue coating were obtained from 88 subjects-with no complaints of upper digestive symptoms-attending a dentist's office for dental check-up or disorders.

Effect of water aging on the anti-biofilm properties of glass ionomer cement containing fluoro-zinc-silicate fillers.

A previous study has reported that a novel fluoro-zinc-silicate glass ionomer cement (Caredyne Restore) showed superior anti-biofilm effects by interfering with bacterial adhesion. However, the active ions may degrade with time. This study aimed to assess the valid anti-biofilm effects of Caredyne Restore after being aged by water immersion for 3 weeks.

Sulfated vizantin causes detachment of biofilms composed mainly of the genus Streptococcus without affecting bacterial growth and viability.

Background: Sulfated vizantin, a recently developed immunostimulant, has also been found to exert antibiofilm properties. It acts not as a bactericide, but as a detachment-promoting agent by reducing the biofilm structural stability. This study aimed to investigate the mechanism underlying this activity and its species specificity using two distinct ex vivo oral biofilm models derived from human saliva.

Effect of aging on bone metabolism: the involvement of complement C1q.

Purpose Impairment of normal bone remodeling affects the successful osseointegration of dental implants. Recently, it has been reported that complement C1q level increases with age and delays wound healing by modulating Wnt signaling. As Wnt signaling is known to play an essential role in bone remodeling, we hypothesized that aging-dependent increases in C1q affect bone remodeling.

Adjunct use of mouth rinses with a sonic toothbrush accelerates the detachment of a Streptococcus mutans biofilm: an in vitro study.

Background: The aim of this in vitro study was to examine the possible enhancement of the biofilm peeling effect of a sonic toothbrush following the use of an antimicrobial mouth rinse.

Methods: The biofilm at a noncontact site in the interdental area was treated by sound wave convection with the test solution or by immersion in the solution. The biofilm peeling effect was evaluated by determining the bacterial counts and performing morphological observations.

Sulfated vizantin inhibits biofilm maturation by Streptococcus mutans.

Streptococcus mutans is the main pathogen of dental caries and adheres to the tooth surface via soluble and insoluble glucans produced by the bacterial glucosyltransferase enzyme. Thus, the S. mutans glucosyltransferase is an important virulence factor for this cariogenic bacterium.

Effects of a sub-minimum inhibitory concentration of chlorhexidine gluconate on the development of multi-species biofilms.

Following antimicrobial administrations in oral environments, bacteria become exposed to a sub-minimum inhibitory concentration (sub-MIC), which can induce single-species biofilms. This study explored the effects of chlorhexidine gluconate (CHG) at a sub-MIC on multi-species biofilms comprising , and . CHG at a sub-MIC was found to induce biofilm growth, although the bacterial growth was not significantly different from that in the control.

Modification of TRPV4 activity by acetaminophen.

-Acetyl-p-aminophenol (APAP/acetaminophen) is a widely used analgesic/antipyretic with weaker inhibitory effects on cyclooxygenase compared to those of non-steroidal anti-inflammatory drugs. The effect of APAP is mediated by its metabolites, -arachidonoyl-phenolamine and -acetyl--benzoquinone imine, which activate transient receptor potential (TRP) channels, including TRP vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) or cannabinoid receptor type 1. However, the exact molecular mechanism underlying the cellular actions of APAP remains unclear.

A Horizontal Sequential Cutting Method to Estimate the Effectiveness of Dentin Disinfection by Using Confocal Laser Scanning Microscopy.

Introduction: This study aimed to develop a technique to create sequential slices, allowing the fluorescent visualization of bacterial viability in all parts of an infected dentin.

Methods: Cylindrical dentin blocks were prepared from freshly extracted human teeth with a single-rooted canal. Each block was immersed in 5% sodium hypochlorite (NaOCl) and 17% EDTA for 5 minutes before being infected with Enterococcus faecalis.

Effect of a novel glass ionomer cement containing fluoro-zinc-silicate fillers on biofilm formation and dentin ion incorporation.

Objectives: This study is aimed at evaluating the effect of a new glass ionomer cement (GIC) containing fluoro-zinc-silicate fillers on biofilm formation and ion incorporation.

Materials And Methods: Streptococcus mutans biofilms were developed on two GIC materials: Caredyne Restore (CD) and Fuji VII (FJ); and hydroxyapatite (HA) for 24 h at 37 °C using a flow cell system. The morphological structure and bacterial viability were analyzed using a confocal laser scanning microscopy.

Evidence-based strategy for dental biofilms: Current evidence of mouthwashes on dental biofilm and gingivitis.

Therapeutic mouthwash (MW) is an adjunctive tool along with a regular oral hygiene routine of daily tooth brushing and daily flossing. Previous systematic reviews have demonstrated that it is effective against dental biofilm and gingival inflammation, for prevention of dental caries, and for managing one's bad breath condition according to the active ingredients. MWs prevent the microorganisms from bacterial adhesion that corresponds to the initial step in biofilm formation.

The effect of chlorhexidine on dental calculus formation: an in vitro study.

Background: Chlorhexidine gluconate (CHG) has been proven to be effective in preventing and controlling biofilm formation. At the same time, an increase in calculus formation is known as one of considerable side effects. The purpose of this study was to investigate whether mineral deposition preceding a calculus formation would occur at an early stage after the use of CHG using an in vitro saliva-related biofilm model.

Effect of acetaminophen on osteoblastic differentiation and migration of MC3T3-E1 cells.

Background: N-acetyl-p-aminophenol (APAP, acetaminophen, paracetamol) is a widely used analgesic/antipyretic with weak inhibitory effects on cyclooxygenase (COX) compared to non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism of action of APAP is mediated by its metabolite that activates transient receptor potential channels, including transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) or the cannabinoid receptor type 1 (CB1). However, the exact molecular mechanism and target underlying the cellular actions of APAP remain unclear.

Celecoxib inhibits osteoblast differentiation independent of cyclooxygenase activity.

Non-steroidal anti-inflammatory drugs (NSAIDs) exert their effects primarily by inhibiting the activity of cyclooxygenase (COX), thus suppressing prostaglandin synthesis. Some NSAIDs are known to perform functions other than pain control, such as suppressing tumour cell growth, independent of their COX-inhibiting activity. To identify NSAIDs with COX-independent activity, we examined various NSAIDs for their ability to inhibit osteoblastic differentiation using the mouse pre-osteoblast cell line MC3T3-E1.

Antimicrobial activity of ethylene-vinyl acetate containing bioactive filler against oral bacteria.

We developed an ethylene vinyl acetate (EVA) containing surface pre-reacted glass-ionomer (S-PRG) filler, as a new mouthguard material for preventing intraoral bacterial infection. We examined its physical properties, antimicrobial activity against a major cariogenic bacterium Streptococcus mutans and a periodontopathogen Porphyromonas gingivalis, and its cytotoxicity toward human gingival epithelial cells. S-PRG filler was added to EVA copolymer at 5, 10, 20, or 40 wt% and was processed into disc-shaped test specimens.

Human haploinsufficiency results in autosomal-dominant chronic mucocutaneous ulceration.

The treatment of chronic mucocutaneous ulceration is challenging, and only some patients respond selectively to inhibitors of tumor necrosis factor-α (TNF). TNF activates opposing pathways leading to caspase-8-mediated apoptosis as well as nuclear factor κB (NF-κB)-dependent cell survival. We investigated the etiology of autosomal-dominant, mucocutaneous ulceration in a family whose proband was dependent on anti-TNF therapy for sustained remission.

Expression of A-kinase anchor protein 13 and Rho-associated coiled-coil containing protein kinase in restituted and regenerated mucosal epithelial cells following mucosal injury and colorectal cancer cells in mouse models.

We demonstrate the expression patterns of A-kinase anchor protein 13 (AKAP13), a scaffold protein that acts upstream of Rho signaling, and Rho-associated coiled-coil containing protein kinase (ROCK) 1/2 in mouse colorectal cancer and during the healing stage of mouse colitis. BALB/c mice received an intraperitoneal injection of azoxymethane at 10mg/kg, followed by two 7-day cycles of 3% dextran sulfate sodium (DSS) administered through their drinking water to induce colon cancer, or a 7-day administration of 4% DSS to induce colitis. The colorectal tissue was then analyzed for gene expression, histopathology, and immunohistochemistry.