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OBJECTIVES Decontamination of biofilm-colonized rough implant surfaces remains challenging. We investigated the effect of airflow with glycine powder (AFG) on decontamination of mature oral multispecies biofilm from a sandblasted and acid etched (SLA) titanium surface. MATERIALS AND METHODS Subgingival dental plaque was cultured on SLA disks anaerobically for 21 days. AFG with various settings and distances was applied directly on the disks with or without previous rinse of 0.9% NaCl. The specimens were then analyzed through scanning electron microscope and remaining bacteria on the implant surface were quantified and statistically compared. RESULTS Mature oral biofilm with cocci and rods as major morphotypes, as well as spiral- and filamentous-shaped organisms, was formed on the untreated disks. Saline rinsing removed the thick biofilm layer but left numerous of coccoid bacteria in rough surface pits. AFG effectively removed most of the bacteria from the pits. Both 25% and 50% power settings were equally effective at 3-mm distance. With 50% power, AFG successfully removed bacteria at both 3- and 6-mm distance. When AFG was applied on native biofilm without prior rinsing with saline, it effectively removed the biofilm including bacteria in the pits. CONCLUSION Application of AFG appears effective in removing bacteria from rough implant surfaces.

Autophagy plays a complicated role in the occurrence and development of cancer. Beclin 1 is a significant autophagy-related protein that plays an essential role in tumorigenesis, but its expression is controversial in melanoma. In this meta-analysis, we searched seven studies involving 638 melanoma patients. PubMed, Web of Science, Google Scholar, Elsevier, and Chinese National Knowledge Infrastructure were used for literature retrieval. The I2 index was used to assess heterogeneity. The expression of Beclin 1 in the primary melanoma group was significantly lower than the non-tumor group tissues (P0.01), while higher than the metastatic melanoma group (P0.01). Beclin 1 expression status could not distinguish between patients with melanoma by sex (male vs. female), lymph node metastasis (metastasis vs. non-metastasis), melanin deposition (present vs. absent), ulcer formation (present vs. absent), tumor necrosis status (present vs. absent), and Breslow thickness (1.5 mm vs. ≥1.5 mm) for the subgroups (all P values0.05). Different expression intensities of Beclin 1 did not affect the overall survival and disease-free survival of melanoma patients. This study showed a trend of low expression of Beclin 1 in melanoma; patients with low expression of Beclin 1 were prone to the possibility of distant metastasis. The inconsistent profile of Beclin 1 expression in the prognosis of melanoma patients warrants further clinical investigation.

Background Leucocyte- and platelet-rich fibrin (L-PRF) is a blood-derived biomaterial rich in leucocytes and platelets embedded in a high-density fibrin network that can be compressed into a membrane and used in surgical applications to stimulate tissue regeneration and wound healing, especially in oral cavity. This study aimed to determine the combined effects of the growth factors and cells present in L-PRF on fibroblasts that directly face the L-PRF membranes placed during surgical procedures. Methods The effect of L-PRF from six donors on the expression of 84 key wound healing genes in normal human gingival fibroblasts was tested by RT-qPCR. Results L-PRF significantly regulated the expression of 33 fibroblast genes (39%), including interleukins, myofibroblast-, extracellular matrix- and angiogenesis-associated genes, and matrix metalloproteinase-1 and -3. L-PRF regulated fibroblast gene expression both time- and dose-dependently, and the effects were mediated by mitogen-activated protein kinases ERK1/2, JNK and p38. L-PRF also stimulated fibroblast wound closure and promoted the ability of fibroblasts to induce endothelial tube formation. L-PRF-induced gene expression changes in fibroblast were similar to those observed in early human and pig wounds. Conclusions This study provides new insights into the biological mechanism by which L-PRF regulates key gingival fibroblast functions important in wound healing.

Nitidine chloride (NC) is a natural alkaloid and has strong antitumor activity. However, its clinical application is limited due to the observed non-specific toxicity and low bioavailability. In this study, we synthesized nanoscale metal–organic frameworks MIL-100(Fe), which was used as a nanocarrier to deliver NC. MIL-100(Fe) was characterized by X-ray diffraction (XRD), Fourier transform infrared spectrometer (FT-IR), Brunauer–Emmett–Teller (BET), dynamic light scattering (DLS), and scanning electron microscopy (SEM). NC was encapsulated in MIL-100(Fe) with a high loading capacity of 33.43 wt%. It shown that NC has progressive releasing behavior with 68% in 4 days under phosphate-buffered saline. The in vitro cytotoxicity of free NC and NC@MIL-100(Fe) were investigated by the MTT assay using the healthy liver cell line (LO2) and a liver cancer cell line (HepG2). Interestingly, NC@MIL-100(Fe) exhibited low toxicity on LO2 cells and high cytotoxicity in HepG2 cells compared to free NC.

Soft tissue calcification occurs in many parts of the body, including the gingival tissue. Epithelial cell-derived MVs can control many functions in fibroblasts but their role in regulating mineralization has not been explored. We hypothesized that microvesicles (MVs) derived from gingival epithelial cells could regulate calcification of gingival fibroblast cultures in osteogenic environment. Human gingival fibroblasts (HGFs) were cultured in osteogenic differentiation medium with or without human gingival epithelial cell-derived MV stimulation. Mineralization of the cultures, localization of the MVs and mineral deposits in the HGF cultures were assessed. Gene expression changes associated with MV exposure were analyzed using gene expression profiling and real-time qPCR. Within a week of exposure, epithelial MVs stimulated robust mineralization of HGF cultures that was further enhanced by four weeks. The MVs taken up by the HGF's did not calcify themselves but induced intracellular accumulation of minerals. HGF gene expression profiling after short exposure to MVs demonstrated relative dominance of inflammation-related genes that showed increases in gene expression. In later cultures, OSX, BSP and MMPs were significantly upregulated by the MVs. These results suggest for the first time that epithelial cells maybe associated with the ectopic mineralization process often observed in the soft tissues.

Transformer is widely used in Natural Language Processing (NLP), in which numerous papers have been proposed. Recently, the transformer has been borrowed for many computer vision tasks. However, there are few papers to give a comprehensive survey on the vision-based transformer. To this end, we give an in-depth review of the vision-based transformer. We conclude 15 articles covering transformers on image object detection, multiple object tracking, action classification, and visual segmentation. Furthermore, we summarize 6 related datasets for corresponding tasks as well as their metrics. We also provide a comprehensive experimental comparison to validate the strength of transformer-based methods. We provide a brief introduction to the transformer and its applications on computer vision tasks, which can help beginners to recognize it.

A zirconium-based nano metal–organic framework (NMOF) UiO-67-NH2 was prepared solvothermally using shape modifier triethylamine. Its loading capacity for topoisomerase inhibitor compound camptothecin (CPT) was investigated. The structure and CPT loading properties of UiO-67-NH2 were assessed with the help of X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC). The XRD and SEM results indicated the successful synthesis of the nano-sized UiO-67-NH2. Further, FTIR spectroscopy indicated that UiO-67-NH2 could be loaded with CPT. Also, the HPLC experiments revealed that nano-sized UiO-67-NH2 shows high CPT loading capacity of up to 36.53 wt%.

Background Decontamination of biofilm-infected rough implant surfaces is challenging. Platelet rich blood products have been shown to have anti-microbial properties against periodontal pathogens. Our aim was to investigate the effect of a potential biological implant surface disinfectant, leukocyte- and platelet-rich fibrin (L-PRF), on a mature oral multispecies biofilm on a rough titanium surface. Methods Sandblasted, large grit, acid-etched (SLA) titanium disks were inoculated with subgingival dental plaque and cultured anaerobically for 21 days. The L-PRF membranes were collected from 12 donors in three trials (four donors in each trial). The disks were rinsed with 0.9% NaCl and exposed to the cell-rich portion of the L-PRF membranes for 48 hours followed by scanning electron microscope (SEM) analysis immediately or after rinsing with 0.9% NaCl prior to fixation. The presence of platelet factor-4 in the rinse samples was analyzed by Western blotting. Remaining bacteria were quantified from SEM images of the implant surfaces and their numbers statistically compared. Results The L-PRF-treated samples without rinsing displayed numerous cells with multiple pseudopodia in immediate contact with bacteria that appeared perforated and increased in size. The cells were identified as platelets based on morphological criteria and by positive reaction for platelet factor-4 by Western blotting. After post-treatment rinsing, the L-PRF-treated disks displayed a significant reduction in bacterial counts (in average 92% reduction). Conclusion Application of L-PRF significantly reduced bacterial counts on contaminated SLA titanium surface, most likely through anti-microbial action by platelets.

Aim No studies have tested disinfectants on mature multispecies oral biofilms on titanium substrata. The aim of this study was to investigate the efficacy of commonly used antimicrobial agents in decontamination of multispecies mature oral biofilm on sandblasted, large-grit, acid-etched (SLA) titanium implants. Methods SLA titanium disks were inoculated with dental plaque and cultured anaerobically for 21 days. The disks were rinsed with 0.9% NaCl, exposed for 2 min. to tetracycline paste, 1% Chlorhexidine gel (CHX), 35% phosphoric acid gel (Etch) or a novel chemical formula (0.3% cetrimide, 0.1% CHX and 0.5% EDTA) and then rinsed again with 0.9% NaCl. Bacteria were quantified from scanning electron micrographs of the implant surfaces. Living bacteria were quantified with confocal laser scanning microscopy (CLSM). Results and Conclusions Rinsing the surfaces with 0.9% NaCl removed the majority of the biofilm. However, bacteria persisted in all specimens and none of the disinfectants was superior to the double saline rinse group. CLSM analysis showed that CHX and Etch groups had a statistically significant reduction of viable bacteria, although small. Overall the results show that many disinfection agents used in the clinic are ineffective in biofilm removal and leave live bacteria on the surface.

In periodontal disease (PD), bacterial biofilms cause gingival inflammation, leading to bone loss. In healthy individuals, αvβ6 integrin in junctional epithelium maintains anti-inflammatory transforming growth factor-β1 (TGF-β1) signaling, whereas its expression is lost in individuals with PD. Bacterial biofilms suppress β6 integrin expression in cultured gingival epithelial cells (GECs) by attenuating TGF-β1 signaling, leading to an enhanced pro-inflammatory response. In the present study, we show that GEC exposure to biofilms induced activation of mitogen-activated protein kinases and epidermal growth factor receptor (EGFR). Inhibition of EGFR and ERK stunted both the biofilm-induced ITGB6 suppression and IL1B stimulation. Furthermore, biofilm induced the expression of endogenous EGFR ligands that suppressed ITGB6 and stimulated IL1B expression, indicating that the effects of the biofilm were mediated by autocrine EGFR signaling. Biofilm and EGFR ligands induced inhibitory phosphorylation of the TGF-β1 signaling mediator Smad3 at S208. Overexpression of a phosphorylation-defective mutant of Smad3 (S208A) reduced the β6 integrin suppression. Furthermore, inhibition of EGFR signaling significantly reduced bone loss and inflammation in an experimental PD model. Thus, EGFR inhibition may provide a target for clinical therapies to prevent inflammation and bone loss in PD. This article has an associated First Person interview with the first author of the paper.

Skin wound healing is a complex physiological process that maintains the integrity of the skin tissues, involving a variety of distinct cell types and signaling molecules. The specific signaling pathways or extracellular cues that govern the healing processes remain elusive. Microvesicles (MVs) have recently emerged as critical mediators of cell communication by delivery of genetic materials to target cells. In this study, we found the direct delivery of HEKa-MVs expressing miR-21 mimics significantly promoted the healing of skin wound in diabetic rats. In-depth studies showed that MV miR-21 promoted fibroblast migration, differentiation, and contraction, induced a pro-angiogenic process of endothelial cells and mediated a pro-inflammatory response. Mechanically, MV miR-21 might target specific essential effector mRNA in fibroblasts such as MMP-1, MMP-3, TIMP3, and TIMP4 to increase MMPs expression and enzymatic activities. Moreover, MV miR-21 regulated ɑ-SMA and N-cadherin to induce fibroblast-myofibroblast differentiation. MV miR-21 up-regulated the IL-6 and IL-8 expressions and their secretion to amplify the immune response. Furthermore, MV miR-21 down-regulated PTEN and RECK in protein level, and activate MAPK/ERK signaling cascade, thereby promoting fibroblast functions. Thus, our study has provided for the first time the basis for the potential application of HEKa-MVs, and MV miR-21 in particular for wound healing.

Microvesicles (MVs) are extracellular vesicles secreted by various cell types that are involved in intercellular communication. We hypothesized that in human periodontal disease, the pocket epithelium releases MVs, which then modulate gene expression in the underlying fibroblasts to control periodontal inflammation. MVs were isolated from culture medium of gingival epithelial cells (GECs) treated with oral bacterial biofilm extract or left untreated. Biofilm treatment significantly increased MV release from the GECs. Mass spectrometry of GEC-MVs identified a total of 2,173 proteins, of which about 80% were detected in MVs from both control and biofilm-treated GECs. Among 80 signature genes of human gingival fibroblasts, 20 were significantly regulated ( P < 0.05) by MVs from control and biofilm-treated GECs in a similar manner. Matrix metalloproteinase 1 and 3 and interleukin 6 and 8 showed the strongest regulation at the mRNA and protein levels. Several cellular signaling pathways were activated by GEC-MVs in human gingival fibroblasts, including Smad and mitogen-activated protein kinase–associated pathways ERK1/2, JNK, and p38. However, ERK1/2 signaling dominated in the MV-induced gene expression changes. The results demonstrate that GEC-MVs have a strong regulatory effect on the expression of fibroblast genes associated with inflammation and matrix degradation and that bacterial biofilm stimulates the generation of GEC-MVs. This suggests that bacterial biofilms can contribute to the initiation and progression of periodontal disease by promoting a tissue-destructive phenotype in gingival fibroblasts via the enhanced secretion of epithelial MVs.

Extracellular vesicles released from cells regulate many normal and pathological conditions. Little is known about the role of epidermal keratinocyte microvesicles (KC-MVs) in epithelial–stromal interaction that is essential for wound healing. We investigated, therefore, whether MV-like structures are present in human wounds and whether they affect wound healing–associated gene expression in dermal fibroblasts. In human wounds, MV-like vesicles were observed during active epithelial migration and early granulation tissue formation. When KC-MVs derived from keratinocyte-like cells (HaCaT) were added to fibroblast cultures, expression of 21 genes was significantly regulated (P

Pyogenic granuloma (PG) is typically a localised and vascular granulation tissue growth that occurs on both the oral cavity and the skin. PG is the most common gingival tumour, although it can also...

Integrins are cell surface receptors that traditionally mediate cell-to-extracellular matrix and cell-to-cell adhesion. They can, however, also bind a large repertoire of other molecules. Integrin αvβ6 is exclusively expressed in epithelial cells where it can, for example, serve as a fibronectin receptor. However, its hallmark function is to activate transforming growth factor-β1 (TGF-β1) to modulate innate immune surveillance in lungs and skin and along the gastrointestinal tract, and to maintain epithelial stem cell quiescence. The loss of αvβ6 integrin function in mice and humans leads to an altered immune response in lungs and skin, amelogenesis imperfecta, periodontal disease and, in some cases, alopecia. Elevated αvβ6 integrin expression and aberrant TGF-β1 activation and function are associated with organ fibrosis and cancer. Therefore, αvβ6 integrin serves as an attractive target for cancer imaging and for fibrosis and cancer therapy.

Traditionally, periodontal hand instruments are honed or sharpened during patient care as they dull easily during contact with enamel, calculus and cementum. This approach is taught in dental and hygiene schools around the world and remains the standard of care. Recently, some professional organizations have questioned whether this practice should be abandoned because of safety issues. Questions have been raised whether sharpening stones can be properly sterilized and whether the sharpening of contaminated instruments poses a health hazard for the provider. Using bacteria culture techniques and scanning electron microscopy, we tested whether contaminated ceramic sharpening stones can be sterilized. Our results demonstrate that the stones were sterile after being subjected to the manufacturer's sterilization protocol. In addition, over the last year, no incidents related to periodontal instrument sharpening have been reported among nearly 400 students at the faculty of dentistry, University of British Columbia, where chair-side sharpening is taught. Therefore, we conclude that ceramic sharpening stones can be sterilized using normal office protocols and that chair-side sharpening adds little risk beyond routine handling of operatory or periodontal instruments during patient care when proper protocols are followed.

Periodontal diseases manifest by the formation of deep pockets between the gingiva and teeth where multispecies bacterial biofilms flourish, causing inflammation and bone loss. Epithelial cell receptor αvβ6 integrin that regulates inflammation by activating the anti-inflammatory cytokine transforming growth factor-β1, is highly expressed in healthy junctional epithelium that connects the gingiva to the tooth enamel. However, its expression is attenuated in human periodontal disease. Moreover, Itgb6−/− mice display increased periodontal inflammation compared to wild-type mice. We hypothesized that bacterial biofilms present in the periodontal pockets suppress αvβ6 integrin levels in periodontal disease and that this change aggravates inflammation. To this end, we generated three-week-old multi-species oral biofilms in vitro and treated cultured gingival epithelial cells (GECs) with their extracts. The biofilm extracts caused suppression of β6 integrin expression and upregulation of pro-inflammatory cytokines, including interleukin-1β and -6. Furthermore, GECs with β6 integrin siRNA knockdown showed increased interleukin-1β expression, indicating that αvβ6 integrin-deficiency is associated with pro-inflammatory cytokine responsiveness. FSL-1, a synthetic bacterial lipopeptide, also suppressed β6 integrin expression in GECs. Therefore, biofilm components, including lipopeptides, may downregulate αvβ6 integrin expression in the pocket epithelium and thus promote epithelial cell-driven pro-inflammatory response in periodontal disease.

A novel in vivo fluorescence spectroscopic diagnostic method has been developed in an animal model to make a quantified precancer diagnosis. In the study, 40 golden hamsters were randomly divided into four groups (groups A, B, C, and D), with group A being the control group and the other three groups being inducted at different precancer stages. A 1% Rose Bengal (RB) solution was used for the fluorescence spectroscopic diagnosis. A parameter K defined as K = I(RB)/I(auto) was introduced to reflect the amount of RB in the tissue, where I(RB) and I(auto) represent the fluorescence peak intensity of the RB in the tissue and the autofluorescence intensity of tissue at 580 nm, respectively. The average K values of the four groups were calculated and statistically analyzed by analysis of variance (ANOVA), which revealed statistically significant differences within each group as well as between groups (p0.001). After analysis by Clementine 11.1 CR Tree modeling (CART), the following diagnostic criteria were set: normal, K ≤ 8.91; simple hyperplasia, 8.91K ≤ 41.92; mild dysplasia, 41.92K ≤ 70.79; moderate and severe dysplasia, K70.79. The sensitivity and specificity to detect precancerous lesions compared with scalpel biopsy were calculated. The results of this study showed that the spectrofluorometric method mediated by RB could accurately discriminate different precancer stages.

Roadway work zone forms as a result of traffic accidents or road maintenance. In this paper, to analyze roadway work zone effects on vehicular flow in a freeway ring, a macroscopic multi-lane traffic model is proposed, the model describes the mandatory net lane-changing rate just upstream the roadway work zone with a random number model based on golden section analysis, and the net-changing rate in normal road segment with a lane-changing time model. Assuming that the free flow speeds on lanes I–III are 120, 100 and 90[Formula: see text]km/h, respectively, with a numerical method of third-order accuracy, the model equations are solved numerically to simulate vehicular flows in a three-lane freeway ring with a roadway work zone with a total length of 160[Formula: see text]m and lane III completely banned. Numerical results show that the roadway work zone generates traffic shock when initial density normalized by jam density is around 0.18. While the ramp flows have little effect on mean travel time through the freeway ring road with a total length of 100[Formula: see text]km, but can cause observable deviation of the root mean square value of travel time.