Overgrowth of white adipose tissue (WAT) in obesity occurs as a result of adipocyte hypertrophy and hyperplasia. Expansion and renewal of adipocytes relies on proliferation and differentiation of white adipocyte progenitors (WAP); however, the requirement of WAP for obesity development has not been proven. Here, we investigate whether depletion of WAP can be used to prevent WAT expansion. We test this approach by using a hunter-killer peptide designed to induce apoptosis selectively in WAP. We show that targeted WAP cytoablation results in a long-term WAT growth suppression despite increased caloric intake in a mouse diet-induced obesity model. Our data indicate that WAP depletion results in a compensatory population of adipose tissue with beige adipocytes. Consistent with reported thermogenic capacity of beige adipose tissue, WAP-depleted mice display increased energy expenditure. We conclude that targeting of white adipocyte progenitors could be developed as a strategy to sustained modulation of WAT metabolic activity.

Progression of many cancers is associated with tumor infiltration by mesenchymal stromal cells (MSC). Adipose stromal cells (ASC) are MSC that serve as adipocyte progenitors and endothelium-supporting cells in white adipose tissue (WAT). Clinical and animal model studies indicate that ASC mobilized from WAT are recruited by tumors. Direct evidence for ASC function in tumor microenvironment has been lacking due to unavailability of approaches to specifically inactivate these cells. Here, we investigate the effects of a proteolysis-resistant targeted hunter-killer peptide D-WAT composed of a cyclic domain CSWKYWFGEC homing to ASC and of a proapoptotic domain KLAKLAK2. Using mouse bone marrow transplantation models, we show that D-WAT treatment specifically depletes tumor stromal and perivascular cells without directly killing malignant cells or tumor-infiltrating leukocytes. In several mouse carcinoma models, targeted ASC cytoablation reduced tumor vascularity and cell proliferation resulting in hemorrhaging, necrosis, and suppressed tumor growth. We also validated a D-WAT derivative with a proapoptotic domain KFAKFAK2 that was found to have an improved cytoablative activity. Our results for the first time demonstrate that ASC, recruited as a component of tumor microenvironment, support cancer progression. We propose that drugs targeting ASC can be developed as a combination therapy complementing conventional cancer treatments.

These results indicate that when associated with the surfactant SDS, the aPDT can be used as an adjutant and a convenient agent to promote the oral decontamination in clinical practice.

Objectives The release of unpolymerized monomers and by-products of resin composites influences biofilm growth and confounds the measurement of metabolic activity. Current assays to measure biofilm viability have critical limitations and are typically not performed on relevant substrates. The objective of the present study was to determine the utility of firefly luciferase assay for quantification of the viability of intact biofilms on a resin composite substrate, and correlate the results with a standard method (viable colony counts). Methods Disk-shaped specimens of a dental resin composite were fabricated, wet-polished, UV-sterilized, and stored in water. Biofilms of S. mutans (strain UA159 modified by insertion of constitutively expressed firefly luc gene) were grown (1:500 dilution; anaerobic conditions, 24h, 37°C) in two media concentrations (0.35x and 0.65x THY medium supplemented with 0.1% sucrose; n=15/group). An additional group of specimens with biofilms grown in 0.65x + sucrose media was treated with chlorhexidine gluconate solution to serve as the control group. Bioluminescence measurements of non-disrupted biofilms were obtained after addition of D-luciferin substrate. The adherent biofilms were removed by sonication, and bioluminescence of sonicated bacteria was then measured. Viable colony counts were performed after plating sonicated bacteria on THY agar plates supplemented with spectinomycin. Bioluminescence values and cell counts were correlated using Spearman Correlation tests (α=0.05). Results Strong positive correlations between viable colony counts and bioluminescence values, both before- and after-sonication, validated the utility of this assay. Significance A novel non-disruptive, real-time bioluminescence assay is presented for quantification of intact S. mutans biofilms grown on a resin composite, and potentially on antibacterial materials and other types of dental biomaterials.

Gingivitis is still considered a major risk factor for the occurrence and progression of periodontal disease. The aim of the present study was to compare the long-term (1, 12, and 18 weeks) antiplaque and antigingivitis efficacies of two commercially available toothpastes, Colgate Total® (CT) and BlueM® (BM), against attached supragingival dental plaque and gingival inflammation in an experimental gingivitis model. A parallel double-blinded randomized clinical trial including 39 dental students who refrained from all plaque control methods (manual or chemical) for 7 days was conducted. After the establishment of clinical gingivitis, participants were randomized into two experimental groups (CT and BM). Plaque index (PI) and gingival index (GI) were then calculated according to Turesky’s modified Quigley and Hein index. Participants were assessed in four time periods (preclinical trial phase (W −1), gingivitis phase (W0), one week (W1), twelve weeks (W12), and eighteen weeks (W18)). Participants’ stimulated saliva was collected and cultured (either aerobically or anaerobically, 37°C, 48 hours) in each time period (W −1, W0, W1, W12, and W18) for the count of viable colonies. Obtained data were analyzed using 2-way ANOVA and Tukey’s test (α = 0.05). No significant differences were found (p>0.05) between experimental groups at W −1. Significant differences between groups were observed at W0 (p<0.05) for the parameter time period, but not for the interaction between parameters (time period ∗ toothpastes). Lower bacterial counts were observed in both groups after one week of toothbrushing; however, no significant differences were found between investigated dentifrices. Intra- and intergroup comparisons revealed that significant differences were not found (p>0.05) between dentifrices at W1, W12, and W18 for both GI and PI. The present study demonstrated that toothpastes containing active oxygen and lactoferrin (BM) have comparable antiplaque and antigingivitis efficacies with triclosan-containing toothpastes (CT).