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Significance: Skin inevitably heals with the formation of a fibrotic scar. Patients affected by skin scarring suffer from long-term psychological and physical burdens. Recent Advances: Since the di...

The major requirement for a dosage form to be successful is its ability to penetrate the site of application and the bioavailability of the drug released from the dosage form. The buccal drug delivery is an influential route to deliver the drug into the body. Here, in this context, various novel approaches that include lipoidal carriers like ethosomes, transferosomes, niosomes etc and electrospun nanofibers are discussed, with respect to buccal drug delivery. These carriers can be easily incorporated into buccal dosage forms like patches and gels that are responsible for increased permeation across the buccal epithelium. The in vivo methods of evaluation on animal models are conscribed here. The novel biocarriers of lipoidal and non-lipoidal nature can be utilized by loading the drug into them, which are helpful in preventing drug degradation and other drawbacks as compared to conventional formulations. The globally patented buccal formulations give us a wide context in literature about the patents filed and granted in the recent years. When it comes to patient compliance, age is an issue, which is also solved by the buccal route. The pediatric buccal formulations are researched for the customization to be delivered to children. Diseases like mouth ulcers, oral cancer, Parkinson’s disease, aphthous stomatitis etc. have been successfully treated through the buccal route, which infers that the buccal drug delivery system is an effective and emerging area for formulation and development in the field of pharmaceutics.

Double lip or macrocheilitis is a rare facial anomaly, mostly congenital in origin. It commonly involves the upper lip than the lower lip. It may occur in isolation or as part of the Ascher’s syndrome. It results due to deposition of excessive areolar tissue and non-inflammatory hyperplasia of labial mucosa gland of pars villosa. It may be acquired as a result of injury to the lips or lip-biting habit. The double lip becomes conspicuous when the lips are retracted during smiling resulting in the characteristic ‘cupid’s bow’ appearance. This disfigurement can pose aesthetic and functional problems and may result in psychological distress. A surgical intervention is must for restoration of functions and to address the aesthetic concerns. The present article reports a case of non-syndromic double upper lip with triple labial frena and its surgical management with laser on one side and with scalpel on the other side.

This study evaluated and compared the expression of secreted protein acidic and rich in cysteine (SPARC) in epithelial cells and fibroblasts of oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) using normal oral mucosa as a control.The expression of SPARC was determined in samples of normal oral mucosa (n = 12), OL without dysplasia (n = 31), OL with dysplasia (n = 54), and OSCC (n = 69) using immunohistochemistry. The percentage of positive cells in epithelial cells and fibroblasts was independently evaluated.Epithelial SPARC was found in 33.3%, 35.5%, 25.9%, and 66.7% of normal oral mucosa, OL without dysplasia, OL with dysplasia, and OSCC, respectively. Fibroblast SPARC was found in 50.0%, 29.0%, 46.3%, and 84.1% of normal oral mucosa, OL without dysplasia, OL with dysplasia, and OSCC, respectively. OSCC had higher epithelial and fibroblast SPARC expression than normal oral mucosa, OL without dysplasia, and OL with dysplasia (P.05). No significant differences were observed in epithelial and fibroblast SPARC among normal oral mucosa or OL with and without dysplasia.Overexpression of epithelial and fibroblast SPARC was observed in OSCC but not in OL, suggesting that SPARC is involved in the late stage of oral carcinogenesis.

There is a lack of effective clinical management of oral epithelial dysplasias to reduce their risk of malignant transformation and considerable gaps in knowledge regarding the most effective means of treating such lesions. A retrospective cohort of biopsy-confirmed oral epithelial dysplasias consecutively diagnosed in the period 1995–2014 and followed-up until 2017 was identified from pathology department files. Demographic, clinical and follow-up information was collected. Multivariate Cox proportional-hazards models were performed to evaluate sociodemographic, clinical and pathological factors associated with progression to oral squamous cell carcinoma. The study included 144 oral epithelial dysplasias, of which 42% progressed to oral cancer at the end of follow-up (21 years). Clinical aspect of the lesion was described for 77 (53.5%) of the patients. Treatment, age, grade of the lesion and diagnostic period were independent prognostic factors for progression. When considering only patients with described clinical aspect, only treatment and grade of the lesion were independently associated with cancer. The results from this non-selected retrospective cohort of oral epithelial dysplasias underscore the existing limitations of the current standard-of-care of the patients and provide novel insights on the management of these lesions with and without described clinical aspect. Well-designed, robust prospective studies, a homogenized staging system and multidisciplinary treatment guidelines are warranted.

Summary Oral papillary lesions represent a variety of developmental and neoplastic conditions. Early diagnoses of different papillary lesions are challenging for oral medicine specialists. Malignant acanthosis nigricans (MAN) is a rare cutaneous disorder and a potential marker of underlying hidden tumours. It is characterized by papillary lesions that always involve the oral mucosa. In oral medicine specialities, MAN is not well understood. When the early signs of MAN are extensive oral lesions and slight cutaneous pigmentation without obvious florid cutaneous papillomatosis, the diagnosis can be incorrect or delayed. Oral medicine specialists should ask affected patients to provide details of their medical history and conduct a timely systemic examination.

Background/purpose Actually, many individuals have opted for the vegetarian diet. The objective of this study was to evaluate the impact of the vegetarian diet on the oral epithelium through cytopathology. Methods Oral smears of the tongue and buccal mucosa of 60 adult subjects (30 vegetarians and 30 controls) were collected. Smears were analyzed morphologically and for three morphometric variables: nucleus area (NA), cytoplasm area (CA) and nucleus/cytoplasm ratio. Results Vegetarians were classified as ovolactovegetarian (53.3%), vegans (30%) and strict vegetarians (16.7%). The NA and CA of the epithelial cells of vegetarian individuals were smaller when compared to controls both in the region of the buccal mucosa and tongue. However, there was no statistically significant difference according to the Student's t-test. For the NA/CA ratio, cells in the oral mucosa region were larger for vegetarians compared to controls. For the tongue, both groups had the same value and the Mann–Whitney U test confirmed that there is no difference between the groups for this cytomorphometric variable. Results: Vegan individuals had a smaller (but not larger) area of CA when compared to controls for the tongue (vegan = 2604.2 ± 179.2 versus control = 3256.7 ± 463.8 p = 0.013). Most smears showed normal epithelial cells and some individuals had changes of an inflammatory nature, mainly in the tongue. Conclusion Despite the small sample size, the results of this study raise the hypothesis that the vegetarian diet (especially the vegan diet) can compromise the thickness of the oral epithelium of the tongue.

Background/purpose Emerging evidence suggests the significance of microRNA-155 (miR-155) in fibrogenesis and oxidative stress accumulation, but its function in oral submucous fibrosis (OSF) has not been investigated. In this study, we assessed the expression of miR-155 and its effects on the maintenance of myofibroblast activation. Methods qRT-PCR was conducted to assess the expression of miR-155 in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF samples. Collagen gel contraction, migration, and invasion capabilities were examined in fBMFs. DCFDA ROS assay was used to examine ROS generation. A luciferase reporter assay was carried out to verify the relationship between miR-155 and its potential target RPTOR. Results We showed that the expression of miR-155 was aberrantly upregulated in OSF specimens and fBMFs. Inhibition of miR-155 ameliorated various myofibroblast activities, including collagen gel contraction, migration, and invasion abilities as well as ROS production. Results from the luciferase reporter assay demonstrated that miR-155 directly interacted with its target RPTOR. Conclusion Taken together, these findings indicate that miR-155 is implicated in the pathogenesis of oxidative stress-associated OSF, possibly through the regulation of RPTOR.

Objective To describe the technique, feasibility and short-term outcomes of buccal mucosa grafts in robotic lower urinary tract reconstruction. Methods We reviewed 9 patients who underwent single-port robotic posterior urethroplasty with buccal mucosa graft from May–December 2019. Variables included patient demographics, diagnosis/etiology, and intraoperative parameters. Intraabdominal or extraperitoneal transvesical approaches are used for the stricture via supraumbilical access, and if necessary, perineal dissection is performed. Cystoscopy identifies the extent of stenosis. Anastomosis is completed with buccal mucosal graft and rectus abdominis, omental or gracilis flaps as needed. Results The mean age was 65.4 years. Robotic urethroplasty with buccal mucosa graft was performed for vesicourethral anastomotic strictures (n=7), urethral strictures (n=4), pubic fistula after robotic posterior urethroplasty (n=1), and anastomotic distraction (n=1). Strictures occurred after prostate cancer treatments (n=8) and trauma (n=1). All patients had prior failed endoscopic interventions: balloon dilatation, resection/incision of bladder neck, internal urethrotomy under direct vision, urethral stents, and posterior urethroplasty. Mean defect length was 3.9 cm. Five of 9 patients had ancillary procedures including rectus abdominis (n=3), omental or gracilis (both n=1) flap harvests. No intraoperative complications occurred. Median operative time was 377 minutes, blood loss was 200 mL, and length of stay was 2 days. Postoperative 30-day complications included urinary tract infection, epididymitis, anemia, recurrent stricture, and small bowel obstruction requiring surgery (all n=1). Median follow-up was 11.7 months. Conclusions Buccal mucosa grafts with ancillary maneuvers such as flap interposition or adjacent tissue transfer in robotic lower tract reconstruction is durable, safe, and comparable to open approaches.

Purpose To assess the effects of buccal mucosal graft site non-closure versus closure on postoperative oral morbidity for male undergoing augmentation urethroplasty for urethral stricture. Materials and methods We included randomized controlled trials. Inclusion criteria were male over the age of 18 with urethral stricture disease requiring reconstruction with buccal mucosal graft harvest. Primary outcomes of the review were postoperative oral pain, need for secondary oral procedures and cosmetic defects. Results We included 5 studies with 346 randomized patients with urethral strictures, of whom 260 completed the trials. In terms of primary outcomes, non-closure graft site may reduce oral pain on postoperative day #1 (standard mean difference [SMD] 0.24 lower; 95% confidence interval [CI] 0.61 lower to 0.12 higher; low certainty evidence [CoE]) but we are uncertain how this impacts pain on postoperative days 3 to 6 (SMD 0.35; 95% CI 0.12 to 0.81 higher; very low CoE). We are also very uncertain as to how it affects the need for secondary oral procedures (risk ratio [RR] 0.22; 95% CI 0.01 to 4.28; very low CoE). Non-closure may increase the risk of cosmetic defects (RR 2.40; 95% CI 0.93 to 6.22; low CoE). Conclusions This review describes the trade-off for buccal mucosal graft site non-closure versus closure for various patient-important outcomes; decision-making will likely hinge on the relative value individual patients and surgeons place on them. The supporting evidence was rated as low and very low, thereby signaling substantial underlying uncertainty and the need for better trials.

Background Congenital esophageal atresia postoperative anastomotic stricture occurs in 30–50% of cases. Patients with severe dysphagia are treated with endoscopic balloon dilatation (EBD) and/or local injection of steroids, but many patients continue to experience frequent stricture. In this study, we investigated the transplantation of autologous oral mucosa-derived cell sheets (epithelial cell sheets) as a prophylactic treatment for congenital esophageal atresia postoperative anastomotic stricture. Methods Epithelial cell sheets were fabricated from a patient’s oral epithelial tissue, and their safety was confirmed by quality control tests. The epithelial cell sheets were transported under controlled conditions from the fabrication facility to the transplantation facility and successfully transplanted onto the lacerations caused by EBD using a newly developed transplantation device for pediatric patients. The safety of the transplantation was confirmed by follow-up examinations over 48 weeks. Results The dates that EBD was performed were recorded for one year before and after epithelial cell sheet transplantation, and the intervals (in days) were evaluated. For about 6 months after transplantation, the intervals between EBDs were longer than in the year before transplantation. The patients were also aware of a reduction in dysphagia after transplantation. Conclusions These results suggest that cell sheet transplantation may be effective in preventing anastomotic stricture after surgery for congenital esophageal atresia, but the effect was temporary and limited in this case. Although we chose a very severe case for the first human clinical study, it may be possible to obtain a more definitive effect if the transplantation is performed before the disease becomes so severe. Future studies are needed to identify cases in which cell sheet transplantation is most effective and to determine the appropriate timeframes for transplantation. Trial registration: UMIN, UMIN000034566, registered 19 October 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393.

Background Oral mucositis (OM) associated with cancer treatment not only impairs patients’ quality of life but also causes treatment delays or changes. This prospective exploratory study was conducted to evaluate the efficacy of Episil® oral liquid, which is an approved protective formulation for the oral mucosa in patients with OM. The extent of the pain-relieving effect, feeling during use, and adverse events or problems were evaluated. Methods In total, 10 Japanese cancer patients with OM receiving chemotherapy, pretreatment therapy for hematopoietic stem cell transplantation, or radiation therapy for head and neck cancer were enrolled. Results A numerical rating scale (NRS) was used to assess oral pain intensity due to OM. Compared to baseline, the mean NRS began to decrease at 5 min after using Episil® (7.1 ± 1.4 to 4.6 ± 2.87; p = 0.264). A significant decrease was observed in the pain score after using Episil® compared with that before using Episil®, and this effect lasted up to 120 min. The protective effects of Episil® were observed 3–5 min after application. Some patients felt slight soreness or discomfort when applying Episil®. However, this discomfort due to Episil®’s stimulation was within the allowable range and transient. No adverse events were observed in any of the cases. Conclusions The results of this prospective study showed that Episil® could be an effective treatment to relieve oral pain in Japanese patients with moderate to severe OM, and this newly approved product might adequately support patients’ oral intake. Trial registration University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) (UMIN000031921).

Objective To describe and assess the outcomes of dorsal onlay oral mucosa graft urethroplasty for female urethral stricture. Methods We retrospectively reviewed the charts of all female patients who underwent dorsal onlay oral (buccal or lingual) mucosa urethroplasty for urethral stricture between 2011 and 2020 at two academic institutions. The primary endpoint was clinical success defined as any subjective improvement in LUTS self-assessed by the patients 1-3 months after catheter removal. Four surgeons performed the urethroplasties using a standardized technique: suprameatal incision, dissection and longitudinal opening of the dorsal aspect of the urethra, harvest of the oral mucosa graft, graft onlay sutured into the urethral opening. Results Nineteen patients were included. The clinical success rate was 94.7% at 1-3 months and 90.9% at 1 year. After a median follow-up of 12 months (range 1-49) there was one recurrence (5.3%), clinical success was achieved in 17 patients (89.5%) and both the maximum urinary flow rate and post void residual were significantly improved (15.2 vs 7.4 ml/s preoperatively; P = .008 and 71.5 vs 161.1 ml preoperatively; P = .001 respectively). The de novo stress urinary incontinence rate was 15.7% at 1-3 months and 9.1% at 1 year. Conclusion Dorsal onlay oral mucosa graft urethroplasty for female urethral stricture appears feasible across multiple surgeons and is associated with a low perioperative morbidity, satisfactory functional outcomes and a low recurrence rate. Other series with larger sample size and longer follow-up are needed to confirm these findings.

Summary Background Ventral skin deficiency in complicated hypospadias is a difficult problem to treat. The aim of our study is to report our technique and outcomes of vascularized islanded scrotal raphe flap for ventral skin deficiency in complicated hypospadias. Methods A retrospective review was conducted at Northwest General Hospital & Research Centre, Peshawar, from January 2012 to January 2019. Complicated hypospadias patients who underwent two-stage surgery employing islanded scrotal flap were identified. Patients underwent surgery in two stages: scar tissue removal, chordee correction and buccal mucosal graft in the first stage; neourethral tubularization, water proofing, and skin coverage with vascularized islanded scrotal raphe flap in the second stage. The primary outcome was 6-month flap survival rate. Secondary outcomes were 6-month complication rate (fistula, persistent chordee, distal stenosis) and end-of-follow-up patient self-reported satisfaction rate. Results A total of 1845 patients underwent hypospadias surgery, of which 380 patients had complications. Scrotal raphe flap was used in 45 patients. Mean age was 14.09 (±8.02) years. Mean follow-up was 29.78 (±12.18) months. Mean number of previous surgeries was 4.31 (±2.59). The flap survived in all cases. Nine patients (20%) developed complications. One patient (2.2%) developed distal stenosis. Eight patients (17.8%) developed fistulas, one of whom additionally had persistent chordee. Five fistulas closed spontaneously within 3 months, while the rest were repaired surgically after 6 months. All patients self-reported satisfaction with results at end-of-follow-up. Conclusions Islanded Scrotal Raphe flap is a promising option for treating complicated hypospadias when there is significant ventral deficiency of skin, as it not only provides vascularized pliable skin but also fascia as a waterproofing layer.

Eosinophilic ulcer of the oral mucosa is a benign, reactive, self-limited lesion. Its pathogenesis is unclear, and it clinically manifests as a punched-out ulcer with surrounding indurated border, raising suspicion for a possible malignancy. On histology, an acute and chronic dense inflammatory infiltrate can be appreciated, which can extend to the deep underlying tissue (including skeletal muscle). Eosinophils are especially conspicuous on hematoxylin and eosin staining and might play an important role in the development of the ulcer. Removal of possible triggers followed by monitoring and possible biopsy are among the initial recommendations. Most lesions heal spontaneously without the need for intervention. This review aims at assisting dermatologists to easily recognize this entity, avoiding unnecessary interventions and apprehension.

Introduction: Oral cytopathology is able to detect incipient cellular alterations, but it is not routinely applied to this purpose. We aimed to establish a model to screen individuals with no oral lesion exposed to smoking/alcohol, by means of the nuclear area, cell proliferation rate, and analysis of genetic damage. Methods: In this cross-sectional pilot study, 90 patients were allocated into 3 groups: oral cancer group (patients with oral squamous cell carcinoma), tobacco/alcohol group (patients without oral lesions and exposed to these risk factors), and control group (individuals with no lesion and not exposed to tobacco and alcohol). The cytological smears performed in these individuals were stained with Papanicolaou, a silver-staining and a Feulgen reaction. The nuclei of cells were measured, and AgNORs/nucleus and micronuclei (MN) were quantified. The cutoff values were stipulated evaluating the healthy mucosa (control group) and the cancerization field mucosa (oral cancer group). Results: Cutoff values for the screening of individuals exposed to carcinogens were ≥8% of nuclei larger than 100 μm2, ≥3.38 AgNOR/nucleus, and ≥3 MN per 1,000 cells. Conclusions: Nuclear area measurement and AgNORs/nucleus and MN quantification identified the incipient phase of oral carcinogenesis. A screening model for individuals without oral lesion exposed to smoking/alcohol was proposed.

International journal of legal medicine 136(2), 405-413 (2022). doi:10.1007/s00414-021-02736-3, Published by Springer, Berlin ; Heidelberg

Background Monoclonal gammopathy is a biological reality encountered in approximately 1% of the general population. In the absence of clinical and biological signs, it is considered of undetermined significance; however, it can be a biological signature of a monoclonal lymphocytic or plasma-cell proliferation. Their localisation to the oral mucosa remains rare and difficult to diagnose, particularly in indolent forms that escape imaging techniques. Case presentation Here, we report the case of a 73-year-old woman with a history of IgM kappa gammopathy followed for 13 years. The patient did not have a chronic infection or an autoimmune disease, and all the biological investigations and radiological explorations were unremarkable during this period. The discovery of a submucosal nodule in the cheek led to the diagnosis of MALT lymphoma and regression of half of the IgM kappa level after resection. The review of the literature shows the dominance of clinical signs (i.e., a mass or swelling) in the diagnosis of primary MALT lymphomas of the oral cavity after surgical resection. Conclusions Our case illustrates the role of examination of the oral cavity in the context of a monoclonal gammopathy. The absence of clinical and radiological evidence in favor of lymphoplasmacytic proliferation, does not exclude a primary indolent MALT lymphoma of the oral mucosa.

Spindle cell lipoma (SCL) is an uncommon histological variant of lipoma that accounts for 1.5% of all adipose tumors. It rarely occurs in the oral cavity. The most common sites of involvement are the buccal mucosa, tongue, lip, alveolar mucosa, gingiva, and palate. Submandibular space is a very rare site of occurrence for SCL. When occurs in this site, SCL mainly involves the 4th–7th decade with a female predominance. Due to wide communications of submandibular space, the actual extent and appearance of the lesions present here gets masked up especially those involving the deeper tissues leading to an inaccurate diagnosis. Wide overlap of clinical and histopathological features of SCL to other clinical pathologies leads to a challenging task for the clinicians to reach an accurate diagnosis. To our knowledge, only four cases of intraoral SCL involving the submandibular region directly or indirectly have been reported in the literature. Here we represent another rare case of SCL in an 18-year-old male patient along with a concise review of the literature. This case appears to be quite rare due to its location (submandibular space), age, and sex of the patient (18/M).

Background/purpose The habit of areca nut chewing has been regarded as an etiological factor of precancerous oral submucous fibrosis (OSF). In the present study, we aimed to evaluate the anti-fibrosis effect of honokiol, a polyphenolic component derived from Magnolia officinalis. Methods The cytotoxicity of honokiol was tested using normal and fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF tissues. Collagen gel contraction, Transwell migration, invasion, and wound healing capacities were examined. Besides, the expression of TGF-β/Smad2 signaling as well as α–SMA and type I collagen were measured as well. Results Honokiol exerted higher cytotoxicity of fBMFs compared to normal cells. The arecoline-induced myofibroblast activities, including collagen gel contractility, cell motility and wound healing capacities were all suppressed by honokiol treatment. In addition, the expression of the TGF-β/Smad2 pathway was downregulated along with a lower expression of α–SMA and type I collagen in honokiol-receiving cells. Conclusion Our data suggest that honokiol may be a promising compound to alleviate the progression of oral fibrogenesis and prevent the transformation of OSF oral epithelium into cancer.

Objective To present the pathologic analysis of female urethral strictures obtained during reconstructive urethroplasty. Methods Nine separate female urethral tissue specimens were obtained during dorsal vaginal graft urethroplasty by a single surgeon (S.P.P.). Samples were serially sectioned and fixed in 10% formalin 6 to 12 hours before routine processing in paraffin blocks. Serial 5-µm sections were subjected to H&E, Masson trichrome, and elastin staining. End point analysis included evaluation for epithelial hyperplasia and cell type, mucosal edema, degree of fibroblast/inflammatory cell infiltrate, and elastin fiber density and distribution. Results Nine specimens were examined. Six specimens had epithelial linings of stratified squamous epithelium overlying fibrosis (67%), 1 had mixed squamous and urothelial epithelium, and 2 had only urothelial epithelium. Two specimens (29%) showed acute injury with prominent squamous papillary hyperplasia, focal erosion, and patchy mucosal hemorrhage. Areas of urethral stricture were variably thickened, with increased, densely packed collagen fibers and associated mucosal lymphocytic inflammation ranging from mild and patchy to focally dense with lymphoid aggregates. The highest elastin fiber density appeared to be associated with vessels and overlying muscle bundles in the submucosa. Conclusions Further elucidation of histopathologic characteristics may illuminate more appropriate therapeutic pathways for female urethral stricture disease management.

Background/Purpose Oral submucous fibrosis (OSF) a well-recognized oral premalignant disorder. Several studies have demonstrated that periostin, a matricellular protein, is involved in the development and pathogenesis of fibrosis diseases. Nevertheless, the contribution of periostin in OSF remains to be uncovered. The purpose of the study was to illustrate the functional role of periostin involved in OSF pathogenesis. Methods RNA-sequencing was employed to screen for differentially expressed genes in normal and OSF tissues. Validation of the upregulation of periostin in OSF specimens and fibrotic buccal mucosal fibroblasts (fBMFs) was conducted by qRT-PCR. The correlation of the gene expression of periostin and various fibrosis markers was analyzed. In addition, the functional role of periostin in myofibroblast features was tested using collagen gel contraction and transwell migration assays. Results We observed overexpression of periostin in OSF specimens using RNA-sequencing and confirmed its upregulation in OSF tissues and patient-derived fBMFs. Besides, there was a positive relationship between the expression of periostin and several fibrosis-associated markers, including ACTA2 (α-smooth muscle actin; α-SMA), COL1A1 (type 1 collagen α1 chain), TGFB1 (TGF-β1), and FN1 (fibronectin). Furthermore, we examined the effect of silencing periostin on the maintenance of myofibroblast characteristics and showed that knockdown of periostin suppressed the expression of α-SMA. Also, inhibition of periostin markedly downregulated the myofibroblast activities (collagen gel contraction and migration capacities). Conclusion Our results indicate the aberrant expression of periostin in OSF tissues and myofibroblasts. Moreover, the expression of periostin is positively associated with fibrosis markers, and repression of periostin may be a promising direction to alleviate the progression of OSF.

Changes in the oral mucosa can appear in the course of inflammatory bowel disease in both children and adults. They often precede the appearance of gastrointestinal symptoms. The aim of the study was to determine the nature of changes in the oral cavity at the time of diagnosis of inflammatory bowel disease in children compared to children without systemic diseases. 49 children diagnosed with inflammatory bowel disease and 60 children without systemic diseases were examined. The prevalence of the aphthae stomatitis and angular cheilitis was 24.5% in the examined group and 10% in the control group (p = 0.0772). Changes in the oral mucosa occurred more frequently in children with Crohn's disease 35.3% than with ulcerative colitis 18.7%. In children with Crohn's disease, the most frequently observed lesion was aphthous stomatitis 23.5%, and in ulcerative colitis, angular cheilitis 12.5%. Changes in the oral mucosa are a therapeutic problem requiring in general diseases patients both local and systemic treatment and interdisciplinary cooperation between dentists, paediatricians and gastroenterologists. The finding of repeated changes in the oral mucosa during a dental examination should be the reason for referring the patient to a paediatrician for the foreclosure or make a diagnosis of inflammatory bowel diseases.

The aim of this review was to evaluate if micronucleus assay in oral exfoliated cells is a suitable tool for biomonitoring children exposed to environmental pollutants. Through the electronic databases PubMed/Medline, Scopus, and Web of Science, all published studies until April 2021 that examined the relationship between exposure to environmental pollutants and micronucleus frequency in oral cells were searched. All relevant articles using a combination of the following keywords-"children," "micronucleus," "oral cells," and "environmental pollution"-were considered. A total of 20 papers met the criteria for inclusion in the systematic review. The results regarding the cytogenetic damage induced by environmental pollutants are conflicting. Some authors have demonstrated that environmental pollution induces mutagenesis in oral cells while others did not. Following the parameters of the Project for Effective Public Health Practices (EPHPP) and after extensive reading of all the articles included, a total of 12 articles had moderate and strong scores and 8 had a classification considered weak. Taken together, this review was able to demonstrate the association between micronucleus frequency and exposure to environmental pollutants in oral exfoliated cells of children.

Performing 1-stage urethroplasty in patients with urethral strictures caused by lichen sclerosus (LS) is hotly debated among reconstructive urologists due to conflicting reports of success. Therefore, the objective of this study was to determine the pooled incidence of stricture recurrence following 1-stage buccal mucosal graft (BMG) urethroplasty in patients with LS, to determine the impact of surgical technique on recurrence and to compare recurrence risk between patients with and without LS after 1-stage repairs.A systematic review was conducted in accordance with PRISMA criteria. The primary outcome was pooled incidence of recurrence, which was calculated using a Der-Simonian-Laird binary random effects model with a Freeman-Tukey arcsine transformation. A total of 21 studies were included, of which 15 provided data for comparative analyses.Pooled data from 625 LS patients revealed a stricture recurrence rate of 10% (95% CI 6-14). Among studies with longer followup (≥24 months), this increased to 18%. Among patients with penile urethral involvement, studies utilizing a penile skin incision had significantly higher pooled recurrence rates than those utilizing penile invagination (p=0.004). Across all studies, there was no evidence to suggest a difference in pooled recurrence rate between patients with and without LS (p=0.36). However, across only long-term studies, recurrence risk was significantly higher for patients with LS (OR 1.83, p=0.05).One-stage BMG urethroplasty is likely a viable surgical option for patients with LS-related strictures; however, high-quality data are limited. Future multi-institutional, long-term prospective studies are needed to assess durability of 1-stage repair.

Purpose To evaluate the contralateral lymph node recurrence rate (clLNRR) of stage IVA to IVB well-lateralized oral cavity cancer. To evaluate the risk factors of clLNRR. Materials and methods Pathologic stage IVA-B squamous cell carcinoma of oral cavity, originating from buccal mucosa, gingiva, or retromolar trigone were retrospectively recruited. Those who did not receive definitive surgery, with previous cancer history, or with contralateral nodal metastasis at diagnosis were excluded. Results From 2010 to 2017, 120 cases were enrolled, including 103 pT4 and 38 pN2. Thirty-one patients underwent contralateral neck dissection, and 18 had contralateral elective nodal irradiation. After median follow up of 35.1 months, the 3-year clLNRR was 15.7% (95% CI: 8.8 - 22.6%) as first event and was 17.1% (95% CI: 9.8 - 24.4%) for overall recurrences. The 3-year disease-free survival and overall survival were 52.8% and 63.1%, respectively. In multivariate analysis, positive nodal metastasis, gingival origin, and perineural invasion were associated with significantly higher clLNRR. Nodal metastasis was the strongest prognostic factor for clLNRR (pN1, HR: 17.1, p = 0.010; pN2, HR: 16.7, p = 0.004, comparing to pN0). The 3-year clLNRR were 2.9% for pN0 (n = 71, 95% CI: 0 - 6.8%), 37.7% for pN1 (n = 11, 95% CI: 8.3 - 67.1%), and 38.4% for pN2 (n = 38, 95% CI: 19.2 - 57.6%). Advanced T classification, elective contralateral neck dissection, and contralateral nodal irradiation did not have significant impact on clLNRR. Conclusions Positive homolateral nodal metastasis, gingival origin, and perineural invasion were risk factors correlated with significantly higher clLNRR. For patient without nodal metastasis, the clLNRR was low and elective contralateral neck management might be safely omitted. For patients with homolateral nodal disease, the contralateral nodal recurrence was not unusual. The optimal treatment for these high risk patients warrant further research.

Purpose We aim to reveal postoperative morphological correlations between the nasolabial components in patients with unilateral cleft lip (UCL). The hypothetical correlations are first, a correlation between the vertical height of the cleft-side alar base and the length of the cleft-side red lip, and second, a correlation between the length of the cleft-side red lip and the vertical position of the cleft-side oral commissure. We explain how these morphological balances are controlled by surgery. Methods Three-dimensional bilateral measurements of the length of the red lip, vertical height of the nasal alar base, and vertical height of the oral commissure were conducted retrospectively on 31 patients with UCL and palate (complete UCL: 26; incomplete UCL: 5) who underwent primary lip plasty at Osaka Women's and Children's Hospital from 2017 to 2019. Results We found a statistically significant correlation between the vertical height of the cleft-side alar base and cleft-side red lip length (P = .012, r = 0.45); thus, the longer the red lip, the lower was the nasal alar base. The correlation between the cleft-side red lip length and the vertical height of the cleft-side oral commissure also showed a statistical significance (P = .00074, r = 0.57); thus, the shorter the red lip, the higher was the oral commissure. Conclusions The present results provided objective evidence showing basic morphological relationships between the postoperative nasolabial features of patients with UCL. The results lead to a reasonable approach to define the proposed peak of the Cupid's bow, an unsettled major controversy in cleft lip surgery.

Objective To describe the outcomes of single-stage and staged repairs in properly selected patients with phalloplasty anastomotic strictures. Methods A bi-institutional retrospective review was performed of all patients who underwent anastomotic stricture repairs between 7/2014-8/2020. Those who had prior augmented urethroplasties or poorly vascularized tissue underwent two-stage repairs (Group-2), all others underwent single-stage repair with a double-face (dorsal inlay and ventral onlay) buccal mucosal graft urethroplasty (Group-1). Postoperatively, urethral patency and patient reported outcome measures (PROMs) were assessed. Results Twenty-three patients with anastomotic strictures were identified. Fourteen patients met inclusion criteria and had 1-year follow-up (9 in Group-1; 5 in Group-2). Nine patients (64%) had prior failed interventions (56% Group-1; 80% Group-2). At a mean follow-up of 33.9 (Group-1) and 35.2 months (Group-2) there were two stricture recurrences in Group-1 (22%) and none in Group-2. PROMs were completed by 12 patients. All patients reported the ability to void standing. Post-void dribbling was present in the majority of patients (7/7 Group-1; 2/4 in Group-2). Mean IPSS was 3.9 (0-14) for Group-1 and 1 (0-3) for Group-2. All reported at least a moderate improvement in their condition on GRA (Group-1 +3 71%, +2 29%; Group-2 +3 100%). Conclusion Single-stage repairs are feasible for patients with anastomotic strictures who have well vascularized tissue and no prior single-stage buccal mucosa augmented urethroplasty failures. Staged repairs are feasible for patients with poor tissue quality. Proper patient selection is important for successful reconstruction.

Following injury, the oral mucosa undergoes a complex sequences of biological healing processes to restore homeostasis. While general similarities exist, there are marked differences in the genomics and kinetics of wound healing between the oral cavity and cutaneous epithelium. The lack of successful therapy for oral mucosal wounds has influenced clinicians to explore alternative treatments and potential autotherapies to enhance intraoral healing. The present in-depth review discusses current gold standards for oral mucosal wound healing and compares endogenous factors that dictate the quality of tissue remodeling. We conducted a review of the literature on in vivo oral wound healing models and emerging regenerative therapies published during the past twenty years. Studies were evaluated by injury models, therapy interventions, and outcome measures. The success of therapeutic approaches was assessed, and research outcomes were compared based on current hallmarks of oral wound healing. By leveraging therapeutic advancements, particularly within in cell-based biomaterials and immunoregulation, there is great potential for translational therapy in oral tissue regeneration.

Numerous beneficial microbes thrive in the oral cavity where they form biofilms on dental and mucosal surfaces to get access to nutrients, and to avoid being carried away with the saliva. However, biofilm formation is also a virulence factor as it also protects pathogenic bacteria, providing them with an environment for proliferation causing oral infections. Oral hygiene relies on mechanical removal of biofilms. Some oral care products also contain antimicrobials, but effective eradication of biofilms with antimicrobials requires both a high concentration and long exposure time. In the present communication, we investigate the potential of using miniaturized drug delivery devices, known as microcontainers (MCs), to deliver the antimicrobial peptide, nisin to an oral multi-species biofilm. MCs are loaded with nisin and X-ray micro-computed tomography reveals a full release of nisin through a chitosan lid within 15 min. Chitosan-coated MCs display substantial bioadhesion to the buccal mucosa compared to non-coated MCs (68.6 ± 14.3% vs 33.8 ± 5.2%). Confocal monitoring of multi-species biofilms reveals antibacterial effects of nisin-loaded chitosan-coated MCs with a faster onset (after 3 h) compared to solution-based delivery (after 9 h). Our study shows the potential of using MCs for treatment of multi-species oral biofilms and is encouraging for further design of drug delivery devices to treat oral diseases.

OBJECTIVES: To assess the outcomes of soft tissue augmentation, in terms of change in level and thickness of mid-buccal mucosa, at implants sites in the zone of the aesthetic priority. MATERIAL AND METHODS: MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases were searched (last search on 1 June 2020). Inclusion criteria were studies reporting outcomes of different materials and timing of grafting in patients undergoing soft tissue augmentation at implant sites in the aesthetic zone with a follow-up of ≥1 year after implant placement. Outcome measures assessed included changes in level and thickness of mid-buccal mucosa, implant survival, peri-implant health and patients' satisfaction. RESULTS: Eighteen out of 2,185 articles fulfilled the inclusion criteria. Meta-analysis revealed a significant difference in vertical mid-buccal soft tissue change (0.34 mm, 95% CI: 0.13-0.56, p = .002) and mid-buccal mucosa thickness (0.66 mm, 95% CI: 0.35-0.97, p < .001) following immediate implant placement in favour of the use of a graft versus no graft. Mean difference in mid-buccal mucosa level following delayed implant placement (0.17 mm, 95% CI: 0.01-0.34, p = .042) was also in favour of the use of a graft versus no graft. With regard to mucosa thickness, the use of a graft was not in favour compared with no graft following delayed implant placement (0.22 mm, 95% CI: -0.04-0.47, p = .095). Observed changes remained stable in the medium term. CONCLUSION: Soft tissue augmentation in the zone of the aesthetic priority results in less recession and a thicker mid-buccal mucosa following immediate implant placement and less recession in mid-buccal mucosa following delayed implant placement compared with no graft.

Aim and objective To define the genotoxic potential of tobacco and alcohol in the oral mucosa through a micronuclei (MN) test. Materials and methods Samples of exfoliative cells from oral mucosa were collected using superficial scraping of the right- and left-cheek mucosa of 83 patients divided into four groups, namely: (G1) 24 individuals abstaining from tobacco and alcoholic beverages; (G2) 23 individuals who smoke and abstain from alcoholic beverages; (G3) 24 smokers and alcoholics; and (G4) 12 individuals who consume alcohol and abstain from tobacco. The samples were stained with Giemsa-Wright, and the frequencies of MN, binucleated cells, and metanuclear changes were recorded in the samples of each group (1,000 cells per patient). Results Analysis of variance (ANOVA) showed a difference between groups for changes concerning karyorrhexis (p = 0), pycnosis (p = 0.002), karyolysis (p = 0.003), and binucleated cells (p = 0.046). As for the total number of changes, G3, G2, and G4, respectively, were significantly higher than G1. Conclusion It is suggested that the influence of smoking and drinking on exfoliating cells of oral mucosa may cause metanuclear changes due to genetic changes that these products cause, and the MN test is effective in detecting and monitoring such changes. Clinical significance MN test may work for constantly monitoring the oral mucosa of smokers and/or alcoholic patients, so that early cell changes may be diagnosed, preventing the genesis of oral cancer.

Severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to more than 3.25 million recorded deaths worldwide as of May 2021. COVID-19 is known to be clinically heterogeneous, and whether the reported oral signs and symptoms in COVID-19 are related to the direct infection of oral tissues has remained unknown. Here, we review and summarize the evidence for the primary infection of the glands, oral mucosae, and saliva by SARS-CoV-2. Not only were the entry factors for SARS-CoV-2 found in all oral tissues, but these were also sites of SARS-CoV-2 infection and replication. Furthermore, saliva from asymptomatic individuals contained free virus and SARS-CoV-2-infected oral epithelial cells, both of which were found to transmit the virus. Collectively, these studies support an active role of the oral cavity in the spread and transmission of SARS-CoV-2 infection. In addition to maintaining the appropriate use of personal protective equipment and regimens to limit microbial spread via aerosol or droplet generation, the dental community will also be involved in co-managing COVID-19 "long haulers"-now termed Post-Acute COVID-19 Syndrome. Consequently, we propose that, as SARS-CoV-2 continues to spread and as new clinical challenges related to COVID-19 are documented, oral symptoms should be included in diagnostic and prognostic classifications as well as plans for multidisciplinary care.

Recurrent aphthous stomatitis (RAS) is a disease marked by painful oral lesions on the buccal and labial mucosa or tongue. Drug delivery systems (DDS) for RAS include topical forms that manage wound healing, cover the ulcer, and relieve the associated pain. DDS targeting the oral mucosa face a major challenge, especially the short residence times in the mouth due to the effect of “saliva wash-out”, which continually removes the drug. The objective of this review is to study the development of preparation forms and delivery systems of various types and preparations that have been used for RAS management from 1965 until February 2020. There are 20 types of DDS for RAS which were discussed in 62 articles. The preparations were classified into 4 preparation forms: liquid, semi-solid, solid, and miscellaneous. In addition, the ultimate DDS for RAS preparations is the semi-solid forms (41.94%), which include 5 types of DDS are gel, paste, patch, cream, and ointment. This preparation was developed into new preparation form (11.29%), such as adhesive alginates, dentifrice, OraDisc, membranes, bioresorbable plates, pellicles, and gelosomes. Generally, the mucosal drug delivery system is the method of choice in RAS treatment because the ulcer is commonly located in the oral mucosa. In conclusion, these preparations are designed to improve drug delivery and drug activity for the treatment of RAS ulcers. Moreover, almost all of these DDS are topical preparations that use various types of mucoadhesive polymers to increase both residence time in the oral mucosa and pain relief in RAS treatment., Graphical Abstract

Aim The aim of this review was to evaluate the scientific literature regarding the cytogenetic damage in oral exfoliated cells of adult patients submitted to panoramic X-ray. Materials and methods An extensive search of the literature was conducted on PubMed, Scopus and Web of Science databases for all studies published until April 2021 using combinations of the following keywords: "panoramic X-ray," "DNA damage," "genetic damage", "genotoxicity", "mutagenicity", cytotoxicity", "buccal cells", "oral mucosa", "tongue", "gingiva", "micronucleus assay", according to the PRISMA guidelines. All clinical studies in English language were included in the study. A total of 10 studies were identified. Results As expected, the results regarding the cytogenetic damage induced by panoramic X-ray are conflicting. Some authors have demonstrated that panoramic X-ray induces mutagenesis in oral cells, whereas others did not. After reviewing the 10 studies, two were classified as strong, four were considered moderate, and four were considered weak, according to the quality assessment components of the Effective Public Health Practice Project (EPHPP). Meta-analysis data revealed a negative response related to mutagenicity in oral cells by panoramic X-ray. Conclusion Taken together, this review failed to demonstrate the association between micronucleus frequency and panoramic X-ray.

Objectives Irritation fibroma in the oral cavity causes atrophy or squamous epithelium thickening with respect to external injury-associated factors. However, ulcers do not occur in most cases. This study aimed to elucidate the mechanism by which ulcers do not form, focusing on the vascular network in the mucosal epithelium of irritation fibroma. Methods Immunostaining was performed using an enzyme antibody method with primary antibodies against CD31 and Ki-67 in 17 cases of irritation fibroma in the buccal mucosa. One section was taken at three points from the margin and three points from just above the lesion for measurement. The number of blood vessels in the superficial and deep lamina propria at the measurement site were determined, and the area per blood vessel was measured. Results The number and area of blood vessels in the superficial lamina propria just below the lesion epithelium were smaller than those in the margin. No difference was observed in the number and area of blood vessels in the deep lamina propria between the margins and lesions. Conclusions Our results suggest that the vascular network in the deep lamina propria is maintained and compensates for the nutrient supply to the covering epithelium.

Corrosion of metal orthodontic appliances caused by professional fluoride products has been recently concerned. Therefore, the objective of this study was to evaluate the cytotoxic and genotoxic effect of these products on buccal mucosal cells from patients wearing fixed orthodontic appliances.A total of 44 patients, aged 12 to 35 years, who began orthodontic treatment with fixed appliances were included in this single-center, prospective, randomized clinical trial. Patients were randomly allocated into 4 parallel groups according to the type of professional fluoride treatment applied after placing the appliances: acidulated phosphate fluoride gel (APF); neutral fluoride gel (NGel); fluoride varnish (FVa); and without fluoride treatment (control). Buccal cells were collected before treatment (T1) and 3 months after appliance placement (T2). The cells were assayed for cell viability and underwent Papanicolaou staining. Cells with micronuclei and degenerative nuclear alterations were scored using a light microscope. Cell metal content was quantified by inductively coupled plasma-mass spectrometry. The data were analyzed with the Kruskal-Wallis test.The intracellular nickel content in the APF group significantly increased (P0.05), whereas that of the control, NGel, and FVa groups did not. The changes in chromium concentration in all groups were not significantly different compared with control. Use of APF resulted in a significantly higher decrease in cell viability and increase in morphologic signs of cell death compared with control (P0.05). The change in frequency of micronucleated cells was not significantly different from that in the control group.Applying APF gel on fixed orthodontic appliances increased the cell metal content and decreased cell viability; however, genotoxic effects were absent. FVa and NGel are suggested as the products of choice to use during orthodontic treatment.

The benefits and harms of the available types of surgical management for lichen sclerosus-related (LS) strictures remain unclear and, thus, clear and robust clinical practice recommendations cannot be given. To assess the role of single-stage OMGU in the management of LS strictures and explore how its benefits and harms compare with the alternative management options. Medline, Embase and Cochrane controlled trial databases (CENTRAL, CDSR) were systematically searched. Randomized (RCTs) and nonrandomized studies (NRCSs) comparing single-stage OMGU with other surgical management options for LS strictures and single-arm studies on single-stage OMGU were included. Risk of bias (RoB) was assessed. Of the 1912 abstracts identified, 15 studies (1 NRCS and 14 single-arm studies) were included, recruiting in total 649 patients. All studies were at high RoB. In the only NRCS available, stricture-free rate (SFR) for single-stage and staged OMGU was 88% vs 60%, respectively (p = 0.05), at a mean follow-up of 66.5 months. SFR range for single-stage OMGU in single-arm studies was 65–100% (mean/median follow-up, 12–59 months). Single-stage OMGU had low complication rates and beneficial impact on LUTS and QoL. The present SR highlights the methodological limitations of the available literature. In the absence of adverse local tissue conditions, and taking into consideration benefit–harm balance and surgeon’s skills and expertise, single-stage OMGU can be justified in patients with LS strictures.

A systematic review of case reports and series of oral syphilis found that the most affected anatomical site was the tongue (37.5%), followed by the lips (29.5%), palates (19.3%), and buccal mucosa (6.8%). Supplemental digital content is available in the text., Rapid emergence of syphilis and oral sexual behaviors has focused attention on oral syphilis, and published reports of cases with oral syphilis have increased in the recent decades. We performed a systematic literature review by searching articles from PubMed, EMBSE, and Google Scholar, looking for case reports or series that would potentially have the clinical characteristics and outcomes for each individual case with oral syphilis. A total of 145 cases with the infection, from 95 studies, were identified to include in our review. Two main clinical phenotypes (ulcerative lesions and mucous patches) appeared to be of particular relevance to oral manifestations. A solitary ulcer was mostly manifested as the lesion of primary syphilis (91.7%) preferentially located on the upper lip, tongue, palate, and buccal mucosa. The most affected anatomical site in the patients with single location involved was the tongue (37.5%), followed by the lips (29.5%), palates (19.3%), and buccal mucosa (6.8%). It is concluded that oral syphilis has its predominant clinical phenotypes although it can manifest in diverse manners.

Arecoline, a major alkaloid within areca nut extract, is recognized as the primary active carcinogen promoting oral squamous cell carcinoma (OSCC) pathological development. Dysregulation of N6‐methyladenosine (m6A) methyltransferase components (e.g., Fat mass and obesity‐associated protein [FTO] and methyltransferase‐like 3 [METTL3]) are closely associated with multiple cancer progression, including oral cancer. However, the biological function role of FTO in arecoline‐induced oral cancer is largely unknown. We identified that FTO was significantly upregulated in OSCC tissues from patients with areca nut chewing habits and chronic arecoline‐treated OSCC cell lines. Depletion of FTO attenuated the arecoline‐promoted stemness, chemoresistance, and oncogenicity of OSCC cells. Finally, we revealed that FTO was negatively regulated by a transcription factor forkhead box protein A2 (FOXA2) in OSCC cells. This study, for the first time, demonstrated that FTO plays an oncogenic role in arecoline‐induced OSCC progression. Thus, developing new therapeutic agents targeting FTO may serve as a promising method to treatment OSCC patients, especially those with areca nut chewing habits., We identified that FTO was significantly upregulated in OSCC tissues from patients with areca nut chewing habits and chronic arecoline‐treated OSCC cell lines. Depletion of FTO attenuated the arecoline‐promoted stemness, chemoresistance, and oncogenicity of OSCC cells. Therapeutic agents targeting FTO may serve as a promising method to treat OSCC patients, especially those with areca nut chewing habits.

We aimed to collect and analyze available cases of intraoral acantholytic squamous cell carcinoma (aSCC), that consisted of the authors’ cases and cases derived from the existing literature, with an emphasis on the pathological staging and patient outcome. Our research question was whether aSCC is more aggressive than conventional SCC. The literature was searched for documented cases of aSCC involving the intra-oral mucosa, excluding those from the lips and tonsils, and seven new cases were added from our files. The authors compared the obtained aSCC data to existing data for conventional SCC. Fisher Exact or Pearson’s χ(2) tests were used for categorical variables. Fifty-five cases of intraoral aSCC were reviewed, of which 48 were retrieved from the literature. Analysis of the published cases was reinforced by contacting the authors of all the papers with incomplete data for further clarifications. The most common sites of aSCC were the tongue (24/55) and the maxilla/maxillary gingiva and/or palate (11/55). The overall survival rate was 36/53 (67.9%) with a mean follow-up period of 22 months against 62.5% for conventional SCC (p = 0.6). No statistically significant difference between the two variants of the tumor with respect to the oral cavity was detected. The differences in age, sex, survival rate, staging, and locations were not statistically significant. Based on the available data from 55 cases, there is no evidence to suggest that aSCC is more aggressive than conventional SCC in intraoral cases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12105-021-01368-8.

Background The objective of this study was to compare patient-reported outcome measures (PROMs) and clinical outcomes after augmentation with xenogeneic collagen matrix (XCM) or free gingival graft (FGG) during different postoperative phases. Methods Forty-two patients (21 per group) with keratinized mucosa width (KMW) of < 2 mm at buccal implant sites in the posterior mandible were enrolled. All underwent vestibuloplasty and were allocated to either FGG (control) or XCM (test) group. Intraoperative morbidity of pain, stress, nausea, tolerance to time, and acceptance of surgery were evaluated immediately after surgery. The severity and duration of subjective pain, swelling, and bleeding were compared within a 2-week postoperative period. The willingness to retreat and satisfaction were assessed at 6 months. All PROMs were obtained using questionnaires and visual analog scales. The buccal KMW and other peri-implant parameters were also evaluated. Results No significant between-group differences were observed in PROMs immediately after surgery, except acceptance of surgery (0, 0–30.0 vs. 30, 0–50.0, p = 0.025). At 2 weeks, pain severity (46.7 ± 25.9 vs 61.9 ± 20.2, p = 0.040) and duration (5.52 ± 3.57 vs 8.48 ± 2.80, p = 0.005) were significantly lower in the test group, and pain perception during speaking and chewing was significantly higher for FGG, with no significant between-group differences in swelling and bleeding. At 6 months, the test group showed a higher willingness to retreat (76% vs 43%, p = 0.021); however, satisfaction with treatment outcomes was similar in both groups. At 6 months, the gain of KMW was significantly higher in FGG than in XCM (XCM: 1.57 ± 1.69 mm, FGG: 2.68 ± 1.80 mm, p = 0.003). Other peri-implant parameters did not show significant differences. Conclusions Within the limitation of the present nonrandomized study, XCM demonstrated more positive PROMs than FGG during different postoperative phases, mainly for less pain perception during the early healing stage, but was inferior to FGG in terms of gain of KMW. For KMW augmentation in the posterior mandible, XCM may be indicated when patients can bear little pain. Clinical trial registration ChiCTR1900022575, date of registration: 17/4/2019, retrospectively registered

Cytokines can induce a chronic inflammatory response in the periodontium, leading to periodontitis. Quercetin, a naturally occuring flavonoid, has been shown to inhibit periodontitis, but how it works is poorly understood. In this study, we assessed the impact of quercetin on lipopolysaccharide (LPS)-induced inflammatory damage in oral mucosal keratinocytes (hOMK107) and explored its underlying mechanism.The viability and apoptosis of hOMK107 cells were measured after exposure to LPS, followed or not by quercetin. The production of IL-1β, IL-6, IL-8, TNF-ɑ, iNOS, and COX-2 was quantified by enzyme-linked immunosorbent assay (ELISA), while levels of Akt, AMPK, and mTOR and their phosphorylation were detected semi-quantitatively by western blotting.Quercetin significantly improved cell viability and apoptosis by reversing LPS-induced upregulation of Bax and downregulation of Bcl-2 in hOMK107 cells. Quercetin decreased the production of IL-1β, IL-6, IL-8, TNF-ɑ, iNOS, and COX-2, as well as signal transductionThese results indicate that quercetin may have a potential protective effect against the chronic inflammation-related periodontitis

Background: Common surgical techniques aim to turn the entire vomerine mucosa with vomer flaps either to the oral side or to the nasal side. The latter approach is widely performed due to the similarity in color to the nasal mucosa. However, we lack a histologic description of the curved vomerine mucosa in cleft lip and palate malformations. Methods: We histologically examined an excess of curved vomerine mucosa in 8 patients using hematoxylin–eosin, periodic acid–Schiff, Elastin van Gieson, and Alcian blue stains. Tissue samples were obtained during surgery at 8 months of age. Results: Our histological analysis of the mucoperiosteum overlying the curved vomer revealed characteristics consistent with those of an oral mucosa or a squamous metaplasia of the nasal mucosa, as exhibited by a stratified squamous epithelium containing numerous seromucous glands. Some areas showed a palisaded arrangement of the basal cells compatible with metaplasia of respiratory epithelium, but no goblet cells or respiratory cilia were identified. Abundant fibrosis and rich vascularity were present. Conclusion: The vomer mucosa showed no specific signs of nasal mucosa. These findings should be considered in presurgical cleft orthopedics and palatal surgery for further refinement. Shifting the vomer mucosa according to a fixed physiologic belief should not overrule other important aspects of cleft repair such as primary healing and establishing optimal form and function of palatal roof and nasal floor.

The role of human papillomavirus (HPV) in the development of oral lesions is controversial. There has been no comprehensive study about HPV prevalence in Iran. This systematic review and meta-analysis were aimed at finding HPV prevalence of oral lesions and normal oral mucosa in Iran. International (PubMed, Web of Science, and Scopus) and national (Iranmedex, Irandoc, and SID) databases were searched systematically until October 2020. Studies that examined the prevalence of HPV in oral lesions by polymerase chain reaction method were included. The heterogeneity of articles was assessed with the Cochran test and I-Square statistics. The prevalence rate of HPV was calculated using a random-effect model. Of 3729 initially searched articles, 29 articles were eligible for inclusion. The overall prevalence of HPV in oral lesions was 21%. The prevalence was the highest in Rasht (50%) city. Lip lesions had the highest HPV prevalence (40%). According to the classification of lesions, the highest prevalence was of precancerous lesions (29%) and the lowest in normal mucosa (8%). Well-differentiated tumors showed a higher prevalence than poorly-differentiated ones. The highest prevalence of HPV was hairy leukoplakia (70%) and the lowest was of pyogenic granuloma (6%). Also, the prevalence was 31% in oral squamous cell carcinoma. There are differences between HPV prevalence according to the geographical area, intraoral location, type of lesion, and grading. As HPV prevalence was fairly high, further attention to vaccination and treatment for HPV in Iran, as a potential risk factor for oral precancerous and cancerous lesions is recommended.

Demographic and clinical findings of patients with mucocutaneous morphea have not been well characterized, to our knowledge.To determine the demographic and clinical characteristics of morphea patients with mucocutaneous lesions who were enrolled in the Morphea in Adults and Children cohort.Cross-sectional study of 735 patients in the Morphea in Adults and Children cohort from 2007 to 2018.A total of 4.6% of linear morphea patients had oral involvement versus 2.4% among the entire cohort, whereas 10.3% of generalized morphea patients had genital involvement versus 3.7% among the entire cohort. Patients with genital lesions were older at disease onset than those with oral morphea (57 versus 11.5 years; P .001) and had more frequent extragenital lichen sclerosus et atrophicus (59.2% versus 5.6%; P = .004).Selection bias and limited number of affected subjects.Oral morphea lesions predominate in younger patients with facial linear morphea, whereas genital lesions predominate in postmenopausal women with overlying extragenital lichen sclerosus et atrophicus.

Objective Transplantation of minor salivary glands (MSGs) to the conjunctiva is a treatment option for patients suffering from dry eye disease. As there is not enough information about labial and buccal MSGs in dogs, the aim of this study was to provide evidence of the presence of these glands and to investigate their spatial arrangement and excretory ducts. Methods The oral mucosa of the lower lip of 4 dogs and the whole lower jaw of 1 dog were used for histological and microCT analysis. Presence, number, volumes and the tissue depth of MSGs were assessed. Results Histological analysis showed that compact tubulo‐acinar glands were located in the submucosal connective tissue. MicroCT images revealed that 9 to 21 MSGs were arranged in a single row at the level of the dental alveolae. The volume of the MSGs increased from rostral to caudal and the total volume of glandular tissue per animal ranged from 35.01 mm3 to 549.43 mm3. The mean tissue depth of MSGs ranged from 0.57 mm to 1.37 mm (upper surface of glands) and between 1.43 mm and 3.09 mm (lower surface of the glands). Excretory ducts left the dorsal part of the glands and ran in dorso‐rostral direction. Conclusions The location, number and volume of the labial and buccal MSGs in the dog could be detected and described using microCT scans and histology. The present results can provide valuable information for future transplantation of labial MSGs as therapeutic measure against keratoconjunctivitis sicca.