Real-world data of 5-aminolevulinic acid-mediated photodynamic therapy for Bowen's disease: A 10-year retrospective study in the skin of color patients (2011-2021).

BACKGROUND: Photodynamic therapy (PDT) has been strongly recommended as an excellent alternative treatment for Bowen's disease (BD). However, reported data on 5-aminolevulinic acid-mediated PDT (ALA-PDT) with red light irradiation are limited and the long-term effectiveness remains to be determined, especially in dark-skinned populations. METHODS: Medical records of BD patients who received ALA-PDT with red light irradiation between February 2011 and June 2021 were reviewed and summarized. Univariate and multivariate analyses of clinically relevant variables that may affect treatment outcomes were performed to identify risk predictors. RESULTS: The overall clearance rate of 122 BD lesions was 89.3% with a median follow-up time of 36 months. The correlation between the effectiveness and fluorescence intensity of pre-PDT or PDT sessions was statistically significant after eliminating the interference of confounding factors. All recurrences occurred in the first two years following ALA-PDT. CONCLUSION: ALA-PDT is an effective treatment for BD in the skin of color patients. Well-executed operation and effective pre-treatment are the determinants of effectiveness. Fluorescence intensity of pre-PDT appeared to be a significant predictor of final effectiveness. In addition, two years of follow-up is necessary following ALA-PDT.

3D-printed coloured tooth model for inlay preparation in pre-clinical dental education.

INTRODUCTION: Accurate inlay preparation is extremely important in pre-clinical training. However, there is a lack of tools to guide students to efficiently practise inlay preparation. Therefore, a 3D-printed coloured tooth model for inlay preparation was designed to guide beginners to practise inlay preparation by themselves according to different colour prompts. This study aimed to evaluate the benefits of using a 3D-printed coloured tooth model in the pre-clinical training on inlay preparation. MATERIALS AND METHODS: Twenty-eight students in their fourth-year undergraduate dental program participated in this study. The participants were randomly assigned to two groups for the inlay preparation. Group 1 prepared a plain tooth model for the first and fourth attempts and a 3D-printed coloured tooth model for the second and third attempts (n = 14). Group 2 prepared four plain tooth models (n = 14). The first and fourth tooth models prepared by both groups were scored using an evaluation system (Fair Grade 2000, NISSIN). Next, questionnaires answered by students were used to evaluate the benefits of using a 3D-printed coloured tooth model and self-evaluate hands-on ability using a grading system (1 = strongly agree, 2 = agree, 3 = neutral, 4 = disagree, and 5 = strongly disagree). The scores were evaluated statistically using the Mann-Whitney U test, and the given grades are displayed as percentages and mean values. RESULTS: There was an overall increase in the clinical confidence of all students after repeated attempts to prepare an inlay; however, students from group 1, who had used the 3D-printed coloured tooth model, had more positive experiences and comments. The 3D-printed coloured tooth model for inlay preparation has been widely praised by participants. Comparing the average score of the first and fourth preparations, the average score of group 1 increased by 12% (Ø 54.46 ± 8.33, Ø 61.11 ± 7.13, p = .090), while that of group 2 increased by 0.72% (Ø 56.39 ± 9.59, Ø 56.80 ± 8.46, p = .925). CONCLUSION: Students favoured the use of the 3D-printed coloured tooth model, and this improved the average score for inlay preparation. The 3D-printed coloured tooth model for inlay preparation is expected to play an important role in dental education in the future.

5-Aminolevulinic acid photodynamic therapy versus minocycline for moderate-to-severe rosacea: A single-center, randomized, evaluator-blind controlled study.

BACKGROUND: 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) showed potential to treat rosacea according to recent studies; however, a lack of clinical evidence and unclear adverse effects limit its use. OBJECTIVE: To compare the effect of ALA-PDT vs minocycline on rosacea. METHODS: In this single-center, randomized, evaluator-blind, controlled study, patients with moderate-to-severe rosacea were allocated to receive 3 to 5 sessions of ALA-PDT or 8 weeks of 100 mg daily minocycline treatment, followed by a 24-week follow-up. RESULTS: Of all the 44 randomized patients, 41 received complete treatment (ALA-PDT: 20 and minocycline: 21 patients). At the end of treatment, ALA-PDT showed noninferior improvement of papulopustular lesions and Rosacea-specific Quality of Life compared with minocycline (median reduction of lesion count: 19 vs 22, median change of Rosacea-specific Quality of Life score: 0.48 vs 0.53). The Clinician's Erythema Assessment success of ALA-PDT was lower than that of minocycline's (35% vs 67%). Demodex density and relapse rate were comparable in both groups. Erythema, mild pain, and exudation were the most common adverse reactions of ALA-PDT. LIMITATIONS: Limited sample size restricted us from drawing further conclusions. CONCLUSION: As minocycline does, ALA-PDT can improve rosacea mainly in papulopustular lesions and patients' quality of life, indicating a new option for rosacea.

Modified red light 5-aminolevulinic acid photodynamic therapy versus low-dose isotretinoin therapy for moderate to severe acne vulgaris: A prospective, randomized, multicenter study.

BACKGROUND: Modified 5-aminolevulinic acid photodynamic therapy (M-PDT) and isotretinoin (ISO) are effective treatments for moderate to severe acne vulgaris. OBJECTIVE: To evaluate the efficacy and adverse effects of M-PDT and ISO for moderate to severe acne vulgaris. METHODS: A multicenter, randomized clinical trial was conducted with participants randomly assigned to the M-PDT group (up to 5 weekly sessions following manual comedone extraction) or the ISO group (oral ISO, 0.5 mg/kg/d for 6 months) and followed up to 6-months after therapy. RESULTS: A total of 152 patients were allocated. The overall effective rates in the M-PDT group were significantly higher than the ISO group at 1 month (67.74% vs 10.26%), whereas the opposite was the case 1 month after treatment (75.81% vs 97.44%). Time to achieve 50% lesion improvement in the M-PDT group was significantly less than the ISO group (1 vs 8 weeks). Overall, 70.67% of the ISO group patients experienced systemic side effects such as hepatotoxicity, whereas side effects were skin-limited in the M-PDT group. LIMITATIONS: Limitations of this study included relatively low numbers of participants and high withdrawal rate. CONCLUSION: M-PDT offers a more rapid onset of improvement, comparable overall efficacy, good tolerability, and comparable durability of response compared with ISO.

Modified painless photodynamic therapy for facial multiple actinic keratosis in China: A prospective split-face control study.

BACKGROUND: Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for multiple actinic keratosis (AK). However, PDT-induced pain often discontinues the therapy to reduce its efficacy, limiting its application. If modified painless PDT schedule with shorter photosensitizer dressing and higher dose illumination could achieve good efficacy in AK, it is still unknown. OBJECTIVES: To explore the efficacy and pain tolerance of the modified painless PDT (M-PDT) in facial multiple AK. METHODS: A split-face controlled clinical study including 14 patients with facial multiple AK was conducted. The patients received conventional PDT (C-PDT) on the left and M-PDT in the contralateral area. The left area (C-PDT) was illuminated by a red light-emitting diode light (144 J/cm2 ) after applying the 10% ALA cream for 3 h; the other had illumination for a total light dose of 288 J/cm2 after applying the 10% ALA cream for 0.5 h. The primary endpoint was the lesion clearance rate at 1-month postthree sessions of PDT. Secondary endpoints included pain scores, the incidence of adverse events during treatment, and cosmetic outcomes. RESULTS: At 1 month following three treatments, the total lesion clearance rate was comparable between M-PDT and C-PDT (91.6% vs. 89.0%). While the lesion clearance rate of M-PDT was higher than that of C-PDT in the Grade III lesions (86.5% vs. 72.0%, respectively) (p < 0.05). M-PDT achieved a 100% lesion clearance rate for Grade I lesions earlier than C-PDT, with M-PDT treated twice and C-PDT treated thrice. Moreover, the pain score during illumination was significantly lower for M-PDT than for C-PDT (p < 0.01). Regarding photoaging, the Global Subjective Skin Aging Assessment score showed that the total and atrophy scores of C-PDT and M-PDT were significantly improved, and M-PDT also reduced discoloration. There was no significant difference in adverse reactions between C-PDT and M-PDT. CONCLUSIONS: M-PDT is comparable to C-PDT's efficacy for treating facial multiple AK, resulting in much lower pain scores.

Green Tea-Derived Catechins Suppress the Acid Productions of Streptococcus mutans and Enhance the Efficiency of Fluoride.

Green tea-derived catechins, which can be divided into galloylated (epicatechin gallate: ECG, epigallocatechin gallate: EGCG) and non-galloylated (catechin: C, epicatechin: EC, epigallocatechin: EGC) catechins, are considered to be the main contributors to the caries control potential of green tea. In this study, we intended to compare the antimicrobial effects of these representative green tea-derived catechins and their combined effects with fluoride on the acid production and aggregation of Streptococcus mutans. The effects of different catechins on the growth, aggregation and acid production of S. mutans, and the combined effect of catechins and potassium fluoride (2 mm at pH 7.0, 0.3 mm at pH 5.5) on S. mutans acid production were measured by anaerobic culture, turbidity changes due to aggregation, and pH-stat methods. Molecular docking simulations were also performed to investigate the interactions between catechins and membrane-embedded enzyme II complex (EIIC), a component of the phosphoenolpyruvate-dependent phosphotransferase system (sugar uptake-related enzyme). ECG or EGCG at 1 mg/mL significantly inhibited the growth of S. mutans, induced bacterial aggregation, and decreased glucose-induced acid production (p < 0.05). All catechins were able to bind to EIIC in silico, in the following order of affinity: EGCG, ECG, EGC, EC, and C. Furthermore, they enhanced the inhibitory effects of fluoride at pH 5.5 and significantly inhibited S. mutans acid production by 47.5-86.6% (p < 0.05). These results suggest that both galloylated and non-galloylated catechins exhibit antimicrobial activity, although the former type demonstrates stronger activity, and that the caries control effects of green tea may be due to the combined effects of multiple components, such as catechins and fluoride. The detailed mechanisms underlying these phenomena and the in vivo effect need to be explored further.

Encapsulation of a novel peptide derived from histatin-1 in liposomes against initial enamel caries in vitro and in vivo.

OBJECTIVES: Biomimetic mineralization mediated by proteins and peptides is a promising strategy for enamel repair, and its specific application model needs more research. In this work, we exploited a liposomal delivery system for a novel peptide (DK5) derived from histatin-1 (DK5-Lips) as a new biomimetic mineralization strategy against initial enamel caries. MATERIALS AND METHODS: The DK5-Lips was prepared using calcium acetate gradient method and then the in vitro release, salivary stability, and cytotoxicity were studied. Initial enamel caries was created in bovine enamel blocks and subjected to pH-cycling model treated with DK5-Lips. Surface microhardness testing, polarized light microscopy (PLM), and transverse microradiography (TMR) were analyzed. Then the biocompatibility of DK5-Lips was evaluated in the caries model of Sprague-Dawley rats, and the anti-caries effect was assessed using Micro-CT analysis, Keyes scores, and PLM in vivo. RESULTS: DK5-Lips provided a mean particle size of (97.63 ± 4.94)nm and encapsulation efficiency of (61.46 ± 1.44)%, exhibiting a sustained release profile, excellent stability in saliva, and no significant toxicity on human gingival fibroblasts (HGFs). The DK5-Lips group had higher surface microhardness recovery, shallower caries depth, and less mineral loss in bovine enamel. Animal experiments showed higher volume and density values of residual molar enamel, lower Keyes score, and shallower lesion depth of the DK5-Lips group with good biocompatibility. CONCLUSION: As a safe and effective application model, DK5-Lips could significantly promote the remineralization of initial enamel caries both in vitro and in vivo. CLINICAL RELEVANCE: The potential of liposome utilization as vehicle for oral delivery of functional peptides may provide a new way for enamel restoration.

Union Rates With the Use of Structural Allograft in Lapidus Arthrodesis: A Comparison Between Two Fixation Constructs.

Although structural allograft has been previously described as acceptable practice for reconstructive foot and ankle surgery, results for an allograft bone wedge in Lapidus arthrodesis are unknown. Additionally, there is no consensus on the superiority of a single fixation construct in Lapidus cases. Our objective was (1) to report union rates for Lapidus arthrodesis with and without the use of an allograft bone wedge and (2) to determine if fixation construct impacts rates of union when using structural allograft. A review was performed for Lapidus cases with fixation constructs of 2 crossed compression screws (CS) and a medial locking plate with single transarticular screw (MPS), both with and without use of an allograft bone wedge. Inclusion required a CT scan to evaluate bony union. There was no significant difference in union rates (p = .41) between the use (90%) and the nonuse (97%) of an allograft bone wedge. Union rates were significantly different (p = .04) when comparing CS fixation (85%) and MPS fixation (98%). The comparative results between the fixation constructs highlight the importance of compression across the arthrodesis site as part of a robust fixation construct. Our findings demonstrate that the use of an allograft bone wedge in Lapidus arthrodesis may mitigate complications due to metatarsal shortening while providing satisfactory rates of union.

Construction and application of dental virtual reality simulation teaching system in China: Necessity and strategies.

INTRODUCTION: Following worldwide progress in digital technology, the utilization of advanced technology to update the concept and mode of education has become an important way to improve the quality and scale of talent training. Adoption of virtual reality technology has a positive effect on dental education. Virtual reality technology has been introduced into Chinese dental education nearly 10 years ago, and a holistic teaching system that employs virtual simulation technology to assist instructors in teaching and students in learning has gradually been formed. MATERIALS AND METHODS: Based on the work of the West China School of Stomatology, Sichuan University, we introduced the necessity and advantages of the application of virtual simulation technology in talent training in dentistry and the status of this teaching system. RESULTS: A virtual dental simulation teaching system was constructed and applied in China. Virtual reality technology was incorporated into the four elements of the teaching system. This reformed system carried out educational informatization in terms of the construction of a virtual simulation teaching platform, development of virtual simulation teaching resources, improvement of the student training model, and upgrading of teaching management. CONCLUSION: The holistic teaching system implemented at the West China School of Stomatology, Sichuan University, highlights the successful incorporation of virtual reality technology into various aspects of dental education. The construction of this system reflects the deep integration of modern information technology and dental education, with the aim of helping dental educators promote teaching methods and management model in the future.

[Research Progress in the Correlation Between Oral Microbiota and Chronic Kidney Disease].

Chronic kidney disease (CKD), one of the common clinical urological diseases, is increasingly more prevalent in recent years and has emerged as a major concern of public health around the globe. The continuous recurrence of CKD caused by renal function impairment leads eventually to irreversible renal failure and severe systemic complications, which causes severe negative impact on the quality of life of the patient. As an essential component of human microbiome, oral microbiota plays a major role in maintaining health, and there has been research suggesting close association between oral dysbiosis and CKD. It is therefore of great clinical significance to understand the correlation between CKD and oral microbiota. Herein, we reviewed the characteristics of oral microbiota of CKD patients, the possible mechanisms of oral microbiota's involvement in the pathogenesis and development of CKD, and the latest research findings on oral dysbiosis and CKD, with a view to finding new approaches to early prevention and control of CKD through oral microbial targets.

Development and evaluation of a chewing gum containing antimicrobial peptide GH12 for caries prevention.

The purpose of this study was to develop a chewing gum containing a novel antimicrobial peptide GH12 and evaluate its biocompatibility, antimicrobial activity, and caries-preventive effects in vivo and in vitro. GH12 chewing gum was developed using a conventional method and its extracts were prepared in artificial saliva. GH12 concentration in the extracts was determined by high-performance liquid chromatography; extracts were used for growth curve assay, time-kill assay, crystal violet staining assay, scanning electron microscopy, and Cell Counting Kit-8 assay. A rat caries model was established, and molars were treated topically with extracts for 5 weeks. Weight gain monitoring, hematoxylin-eosin staining, micro-computed tomography, and Keyes scoring were conducted. Significant inhibition of Streptococcus mutans growth and biofilm formation was observed. Extracts displayed low cytotoxicity against human gingival epithelial cells. No significant differences in weight gain or signs of harm to the mucosal tissues in any of the rats were observed. Keyes scores of caries lesions in the GH12 chewing gum group were lower than those of the negative control group. It was concluded that GH12 chewing gum showed good biocompatibility, antimicrobial activity, and caries-preventive effects, exhibiting great potential to prevent dental caries as an adjuvant to regular oral hygiene.

Comparison of red light and blue light therapies for mild-to-moderate acne vulgaris: A randomized controlled clinical study.

BACKGROUND: Red and blue light therapies are safe and effective treatments for mild-to-moderate acne vulgaris. However, very few previous studies have directly compared the characteristics of these two methods. OBJECTIVE: To compare the efficacy and side effects of red light (RL) and blue light (BL) for acne vulgaris and to assess these two therapies in different types of lesions. MATERIALS AND METHODS: A total of 28 subjects with mild-to-moderate acne vulgaris were randomized into the RL group or the BL group. Subjects in each group received different light treatments, and they were followed up regularly until 2 weeks after the last treatment. The improvement rates of different types of acne lesions were compared between the 2 groups, as well as the incidence of adverse reactions. RESULTS: At the 2-week follow-up, the average improvement rate of total acne lesions was 36.2% in the RL group and 30.7% in the BL group (p > .05). The average improvement rate of inflammatory and non-inflammatory lesions was 51.5% and 17.3% in the RL group, compared with 26.4% and 10.0% in the BL group (all p > .05). Treatment-related adverse reactions were observed distinctly in the BL group. CONCLUSIONS: Red light and BL therapies have similar efficacy in mild-to-moderate acne vulgaris, especially for inflammatory lesions. RL had advantages with fewer adverse reactions compared with BL.

Fluorescence kinetics study of twice laser irradiation based HpD-PDT for nonmelanoma skin cancer.

BACKGROUND: Hematoporphyrine injection (HpD)-based photodynamic therapy (HpD-PDT) has emerged as a promising cancer therapy. However, its tumor-targeting ability and metabolokinetics in nonmelanoma skin cancer (NMSC) have not been well explored. Importantly, photodynamic diagnosis is widely used for cancer lesion assessment and positioning to ensure effective therapy, while the photosensitizer metabolic kinetics study is utilized for biosafety assessment and light-protection instruction. These are particularly important for the optimization of therapeutic parameters. OBJECTIVES: In the present study, NMSC patients were subjected to twice laser irradiation-based HpD-PDT strategy. Broadly, the study aimed to assess long-term variations in fluorescence (FL) intensity in vivo in NMSC patients after intravenous (i.v.) administration of HpD, and thus obtain information regarding metabolism, biosafety, and light-protection instruction for HpD during the therapy. METHODS: In vitro experiments were used for the evaluation of absorption and fluorescent characterization of HpD in aqueous solution and cutaneous squamous cell carcinoma (SCC) cells. For in vivo assessment, 20 patients with NMSC, including SCC, basal cell carcinoma (BCC), Bowen disease (BD), extramammary Paget's disease (EMPD), and malignant proliferating tricholemmoma (APT), were recruited, and treated with HpD-PDT. To evaluate the selectivity and pharmacokinetics of HpD in vivo, relative changes in FL intensity for lesional, perilesional, and nonlesional skin of nonmelanoma skin cancer patients, before and after HpD injection, were semiquantitatively analyzed for 1 month, using the FL detection system and Wood's lamp. RESULTS: The absorption and FL spectra were detected and semiquantitatively analyzed in HpD diluted solution and SCC cells after coincubation with HpD. After i.v. administration of HpD in EMPD patients, FL was detected in the skin lesions at 24 hours, and it was characterized by clear edges. Importantly, FL intensity in the skin lesions increased significantly at 48 and 72 hours postinjection, which was suitable for HpD-PDT. After 72 h, it decreased gradually and reached close to the baseline value at 4 weeks postinjection. No severe side effects were observed during HpD injection and the therapy. Urinary tract infection was recorded in one patient (with a previous history of recurrent urinary tract infections) after HpD-PDT, and the patient was cured afterward. Transient light was observed in two patients after HpD-PDT and they soon recovered after therapy. CONCLUSIONS: The present study reported a significant increase in FL intensities at 48 and 72 hours after i.v. administration of HpD in patients with nonmelanoma skin cancers, which indicated accumulation of HpD at the cancer site. Importantly, HpD was found to be safe for NMSC patients. After therapy, FL intensities decreased, which indicated expending and metabolization of HpD. Thus, the results of the present study highlighted the suitability of a twice red-light laser irradiation strategy for the application of HpD-PDT in nonmelanoma skin cancer treatment.

Combined Treatment with Fluoride and Antimicrobial Peptide GH12 Efficiently Controls Caries in vitro and in vivo.

Combining fluoride and antimicrobial agents enhances regulation of acid and exopolysaccharide production by biofilms. The combination also weakens the acidogenic and aciduric bacteria that contribute to caries, achieving stronger caries-controlling effects with lower concentrations of fluoride. In previous studies, antimicrobial peptide GH12 has been shown to inhibit lactic acid and exopolysaccharide synthesis in various cariogenic biofilm models, and reduce the proportion of acidogenic bacteria and Keyes caries scores in a rat caries model. The current study aimed to elucidate the effect of a combination of low concentrations of sodium fluoride (NaF) and GH12 and to determine the mechanism by which GH12/NaF combination controls caries. The GH12/NaF combination contained 8 mg/L GH12 and 250 ppm NaF. A rat caries model was built, and rat dental plaque was sampled and cultivated on bovine enamel slabs in vitro and subjected to short-term treatment (5 min, 3 times/day). The caries-controlling effects were evaluated using Keyes scoring and transverse microradiography. The results showed that the GH12/NaF combination significantly decreased the onset and development of dental caries, as well as mineral content loss and lesion depth in vitro (p < 0.05). For the caries-controlling mechanisms, 16S rRNA sequencing of in vivo dental plaque revealed that populations of commensal bacteria Rothia spp. and Streptococcus parasanguinis increased in the GH12/NaF group. In contrast, Veillonella, Lactobacillus, and Streptococcus mutans decreased. Furthermore, the GH12/NaF combination significantly reduced biomass, lactic acid, and exopolysaccharides production of in vitro biofilm (p < 0.05). Overall, fluoride and GH12 efficiently arrested caries development and demineralization by regulating the microbiota and suppressing acid and exopolysaccharide production in biofilms.

Curriculum setting and students' feedback of pre-clinical training in different dental schools in China-A national-wide survey.

INTRODUCTION: Adequate time and effective training facilities are essential for undergraduate dental students participating in pre-clinical dental practice to ensure them providing safe treatment for patients in the future. The study aimed to explore the current status of pre-clinical dental training in China in relation to the curriculum setting and students' feedback of pre-clinical training in different dental schools and thus provide information for further standardise curricula. MATERIALS AND METHOD: An online questionnaire was distributed electronically to undergraduates in 44 Chinese dental schools of different levels according to China Discipline Ranking (CDR). The questionnaire collected information in relation to the training hour and student to facility ratio of four main dental courses (cariology and endodontics, periodontology, prosthodontics and oral surgery), as well as the application and effect of virtual reality (VR) simulator in pre-clinical dental practice in different schools. Students' feedback was also collected. RESULTS: A total of 565 valid questionnaires were recruited. Results of this cross-sectional survey show that training hour of periodontology course was the lowest, and oral surgery course showed most prominent shortage of facilities. The application of VR simulator amongst schools is uneven. Students from A and A+ level schools showed higher satisfaction with their pre-clinical courses and reported a more positive attitude towards the use of VR simulator than other students. (p < .05). CONCLUSION: Pre-clinical dental training in China remained imperfect in insufficient training time, training facility and students did not have access to standard pre-clinical training and quality assurance. VR technique has potential values in pre-clinical dental practice in China.

TVH-19, a synthetic peptide, induces mineralization of dental pulp cells in vitro and formation of tertiary dentin in vivo.

Functional peptides derived from the active domains of odontogenesis-related proteins have been reported to promote dental hard tissue regeneration. The purpose of this study was to evaluate the effects of an artificially synthesized peptide, TVH-19, on odontoblast differentiation and tertiary dentin formation in indirect pulp capping (IPC) using in vitro and in vivo experiments. TVH-19 did not exhibit any effect on the proliferation of human dental pulp cells (hDPCs) but significantly promoted cell migration, compared with the control (p < 0.05). TVH-19-treated hDPCs showed significantly higher alkaline phosphatase (ALP) activity and stronger alizarin red staining (ARS) reactivity than the control group (p < 0.05). TVH-19 also upregulated the mRNA and protein expression levels of odontogenic genes. After generating IPC in rats, the samples of teeth were studied using micro-computed tomography (Micro-CT), hematoxylin & eosin (HE) staining, and immunohistochemical staining to investigate the functions of TVH-19. The in vivo results showed that TVH-19 induced the formation of tertiary dentin, and reduced inflammation and apoptosis, as evident from the downregulated expression of interleukin 6 (IL-6) and cleaved-Caspase-3 (CL-CASP3). Overall, the results of our study suggest that TVH-19 induces differentiation of hDPCs, promotes tertiary dentin formation, relieves inflammation, and reduces apoptosis, indicating the potential applications of TVH-19 in IPC.

5-Aminolaevulinic acid photodynamic therapy amplifies intense inflammatory response in the treatment of acne vulgaris via CXCL8.

Acne vulgaris is a chronic inflammatory cutaneous disease. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is a novel and effective approach for severe acne vulgaris treatment. However, its specific treatment mechanism still remains unclear. In the present study, we investigated the potential mechanism of how ALA-PDT regulated intense inflammatory response in acne vulgaris. It appeared that ALA-PDT suppresses proliferation and lipid secretion of primary human sebocytes. Besides, ALA-PDT could up-regulate the expression of CXCL8 in vivo and in vitro, amplifying the inflammatory response by recruiting T cells, B cells, neutrophils and macrophages. We also found that ALA-PDT elevated the expression of CXCL8 via p38 pathway. SB203580, a p38 pathway inhibitor, decreased the expression of CXCL8 in sebocytes after ALA-PDT. These findings indicate that ALA-PDT amplifies the intense inflammatory response in the treatment of acne vulgaris via CXCL8. Our data decipher the mechanism of intense inflammatory response after ALA-PDT for acne vulgaris.

Green Tea-Derived Epigallocatechin Gallate Inhibits Acid Production and Promotes the Aggregation of Streptococcus mutans and Non-Mutans Streptococci.

It has been suggested that green tea-derived epigallocatechin gallate (EGCG), which has antimicrobial properties, might help prevent dental caries. However, the detailed properties of EGCG remain unclear. In this study, the antimicrobial properties of EGCG were evaluated by examining its bactericidal activity, its inhibitory effects against bacterial growth, acid production, acidic end-product formation, and sugar uptake (phosphoenolpyruvate-dependent phosphotransferase system, PEP-PTS activity), and its effects on bacterial aggregation, using monocultured planktonic cells of Streptococcus mutans and non-mutans streptococci. Coincubating S. mutans with EGCG (1 mg/mL) for 4 h had no bactericidal effects, while it decreased the growth and acid production of S. mutans by inhibiting the activity of the PEP-PTS. EGCG (2 mg/mL) caused rapid bacterial cell aggregation and had reduced the optical density of S. mutans cell suspension by 86.7% at pH 7.0 and 90.7% at pH 5.5 after 2 h. EGCG also reduced the acid production of non-mutans streptococci, including S. sanguinis, S. gordonii, and S. salivarius, and promoted the aggregation of these non-mutans streptococci. Furthermore, these antimicrobial effects of short-term EGCG treatment persisted in the presence of saliva. These results suggest that EGCG might have short-term antibacterial effects on caries-associated streptococci in the oral cavity.

The pH-Responsive Property of Antimicrobial Peptide GH12 Enhances Its Anticaries Effects at Acidic pH.

Dental caries is closely related to the acidification of the biofilms on the tooth surface, in which cariogenic bacteria bring about a dramatic pH decrease and disrupt remineralisation equilibrium upon the fermentation of dietary sugars. Thus, approaches targeting the acidified niches with enhanced anticaries activities at acidic pH are highly desirable. In our previous study, a cationic amphipathic α-helical antimicrobial peptide GH12 (Gly-Leu-Leu-Trp-His-Leu-Leu-His-His-Leu-Leu-His-NH2) was designed with good stability, low cytotoxicity, and excellent antibacterial effects. Considering its potent antibacterial activity against the acidogenic bacteria and its histidine-rich sequence, it was speculated that GH12 might show enhanced antimicrobial effects at an acidic pH. In this study, the pH-responsive property of GH12 was determined to evaluate its potential as a smart acid-activated anticaries agent. GH12 possessed much lower minimal inhibitory concentrations and minimal bactericidal concentrations against various kinds of bacteria at pH 5.5 than at pH 7.2. Employing Streptococcus mutans, the principal caries pathogen, as the model system, it was found that GH12 showed much stronger bactericidal effects on both planktonic S. mutans and S. mutans embedded in the biofilm at pH 5.5. In addition, short-term treatment with GH12 showed much more effective inhibitory effects on water-insoluble exopolysaccharides synthesis and lactic acid production of the preformed S. mutans biofilm at pH 5.5. As for the mechanism exploration, it was found that the net positive charge of GH12 increased and the tryptophan fluorescence intensity heightened with the peak shifting towards the short wavelength at pH 5.5, which demonstrated that GH12 could be more easily attracted to the anionic microbial cell membranes and that GH12 showed stronger interactions with the lipid membranes. In conclusion, acidic pH enhanced the antibacterial and antibiofilm activities of GH12, and GH12 is a potential smart anticaries agent targeting the cariogenic acidic microenvironment.

Antibacterial Effect of Caffeic Acid Phenethyl Ester on Cariogenic Bacteria and Streptococcus mutans Biofilms.

Dental caries is the most common disease in the human mouth. Streptococcus mutans is the primary cariogenic bacterium. Propolis is a nontoxic natural product with a strong inhibitory effect on oral cariogenic bacteria. The polyphenol-rich extract from propolis inhibits S. mutans growth and biofilm formation, as well as the genes involved in virulence and adherence, through the inhibition of glucosyltransferases (GTF). However, because the chemical composition of propolis is highly variable and complex, the mechanism of its antimicrobial action and the active compound are controversial and not completely understood. Caffeic acid phenethyl ester (CAPE) is abundant in the polyphenolic compounds from propolis, and it has many pharmacological effects. In this study, we investigated the antibacterial effects of CAPE on common oral cariogenic bacteria (Streptococcus mutans, Streptococcus sobrinus, Actinomyces viscosus, and Lactobacillus acidophilus) and its effects on the biofilm-forming and cariogenic abilities of S. mutans CAPE shows remarkable antimicrobial activity against cariogenic bacteria. Moreover, CAPE also inhibits the formation of S. mutans biofilms and their metabolic activity in mature biofilms. Furthermore, CAPE can inhibit the key virulence factors of S. mutans associated with cariogenicity, including acid production, acid tolerance, and the bacterium's ability to produce extracellular polysaccharides (EPS), without affecting bacterial viability at subinhibitory levels. In conclusion, CAPE appears to be a new agent with anticariogenic potential, not only via inhibition of the growth of cariogenic bacteria.