Atorvastatin mucoadhesive tablets in the management of recurrent aphthous stomatitis: a randomized clinical study.

BACKGROUND: Aphthous stomatitis is one of the most common oral mucosal diseases. Due to the commonness of recurrent aphthous stomatitis and considering the anti-inflammatory, analgesic, and tissue regenerative properties of atorvastatin and the lack of a study on the effect of statins on minor recurrent aphthous stomatitis, this study investigates the effect of atorvastatin mucoadhesive tablets as a topical treatment on reduction of symptoms and duration of this disease. METHODS: This study is a randomized, double-blinded clinical trial. Patients were divided into two groups, atorvastatin and, placebo; each of the patients received three mucoadhesive tablets daily in the morning, noon, and night. Finally, the patients were examined on days 0 (baseline), 3, 5, and 7 to determine the diameter of the inflammatory halo. The VAS scale was used to evaluate pain intensity for up to 7 days after each meal. The data was entered into SPSS 24 software and analyzed. RESULTS: The halo diameter did not significantly differ between the two groups on baseline (P > 0.05). However, on the study's third, fifth, and seventh days, the difference between the two groups was remarkable, so in the atorvastatin group, the size of the lesions decreased in shorter healing time (P < 0.05). In addition, the patient's pain intensity (VAS) also showed a significant decrease in the atorvastatin group except on the first, second, and seventh days of the study (P < 0.05). CONCLUSION: Atorvastatin mucoadhesive tablets effectively reduce the pain of patients with minor recurrent aphthous stomatitis and reduce the size and healing time of the lesions, so their application should be considered in treating minor recurrent aphthous stomatitis. The present study was approved by the Medical Ethics Committee of Mazandaran University of Medical Sciences with the ethics code IR.MAZUMS.REC.1400.8346. Also, this study received code IRCT20170430033722N4.

Evaluation of cinnamaldehyde mucoadhesive patches on minor recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND & OBJECTIVE: The use of herbal medicines to treat common oral diseases increases rapidly. Recurrent aphthous stomatitis is one of the most common oral mucosal diseases, which has an unclear etiology and could lead to severe pain and dysfunction. Cinnamaldehyde is a major component of cinnamon bark oil. Biological properties of cinnamaldehyde, such as antioxidant, antitumor, antifungal, cytotoxic, and anti-mutational characteristics, have been identified. Considering the prevalence of recurrent aphthous stomatitis and the importance of using herbal resources for treatment, the present study aimed to evaluate the effect of mucosal adhesive patches containing Cinnamaldehyde on minor recurrent aphthous stomatitis lesions. MATERIAL & METHODS: In this randomized, double-blind clinical trial, patients were divided into two groups. The intervention group received three daily mucosal adhesive patches to be used in the morning, afternoon, and night. The control group also did the same with a placebo. To evaluate the healing and determine the diameter of the lesions, patients were clinically examined on days zero, 3, 5, and 7. The VAS scale evaluated pain at baseline and after each meal for seven days. The Fisher's exact test, t-test, Shapiro Wilk test, Friedman test, and the Mann-Whitney test were used to analyze the data using the SPSS 20 software. RESULTS: There was no statistically significant difference in the mean diameter of the inflammatory lesion and pain intensity in the two groups in the baseline (p > 0.05). However, the ulcer size was significantly reduced in the cinnamaldehyde group on the third, fifth, and seventh days of the study. Except for baseline, the mean pain intensity significantly decreased in the cinnamaldehyde group compared to the placebo group (p < 0.05). CONCLUSION: Cinnamaldehyde mucoadhesive patches effectively reduced and improved aphthous lesions and pain intensity in patients and can be considered a treatment for RAS. REGISTRATION NUMBER: IRCT20180312039060N2-First registration date: 20/07/2018. The present study was registered as a retrospective study.

Oral health-related quality of life (OHRQoL) in cardiovascular patients referring to Fatima Zahra Hospital in Sari, Iran.

BACKGROUND: Cardiovascular Disease (CVD) is one of the leading causes of mortality and morbidity and significantly impacts the health-related quality of life. Oral infections have been linked to cardiovascular diseases such as thrombosis, cardiac infarction, stroke, and peripheral vascular disease. This study aims to evaluate the effects of oral health on the quality of life in cardiovascular patients. METHODS: The oral health-related quality of life was measured using the OHIP-14 questionnaire. Demographic information, questions regarding smoke consumption, wearing removable prostheses, nine questions regarding xerostomia, and the existence of other systemic diseases were asked from 240 participants with cardiovascular diseases. The DMFT index was clinically examined in each patient. Also, the Plaque, Gingival, and Sulcular Bleeding Indices were measured on the Ramfjord teeth. Data analysis was conducted using SPSS version 16. The independent t test, Mann-Whitney test, the variance analysis, and the Kruskal-Wallis test were used to compare variables in the present study. Also, regression models were used to eliminate the effect of confounding variables. RESULTS: Gender variables, removable prosthesis, xerostomia, DMFT, and SBI were the main determinants of quality of life in CVD patients. The mean ADD-OHIP14 of participants in the study was calculated at 21.34 ± 17.40, and the SC-OHIP14 was 6.11 ± 5.07. The mean OHRQoL was higher in females than in males, and this difference was statistically significant. OHRQoL was significantly lower in patients wearing a removable prosthesis than in those without one. The relationship between age and xerostomia was significant in this study, and patients with xerostomia had a lower quality of life than those without xerostomia. Also, the mean DMFT index in subjects with xerostomia was 23.69 ± 7.76, which was statistically significant compared to those without xerostomia. CONCLUSION: Cardiovascular patients experienced a decreased OHRQoL. Prevention or treatment of these problems seems to justify improving the quality of life in these patients.

Genome-wide DNA methylation-analysis of blastic plasmacytoid dendritic cell neoplasm identifies distinct molecular features.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) constitutes a rare and aggressive malignancy originating from plasmacytoid dendritic cells (pDCs) with a primarily cutaneous tropism followed by dissemination to the bone marrow and other organs. We conducted a genome-wide analysis of the tumor methylome in an extended cohort of 45 BPDCN patients supplemented by WES and RNA-seq as well as ATAC-seq on selected cases. We determined the BPDCN DNA methylation profile and observed a dramatic loss of DNA methylation during malignant transformation from early and mature DCs towards BPDCN. DNA methylation profiles further differentiate between BPDCN, AML, CMML, and T-ALL exhibiting the most striking global demethylation, mitotic stress, and merely localized DNA hypermethylation in BPDCN resulting in pronounced inactivation of tumor suppressor genes by comparison. DNA methylation-based analysis of the tumor microenvironment by MethylCIBERSORT yielded two, prognostically relevant clusters (IC1 and IC2) with specific cellular composition and mutational spectra. Further, the transcriptional subgroups of BPDCN (C1 and C2) differ by DNA methylation signatures in interleukin/inflammatory signaling genes but also by higher transcription factor activity of JAK-STAT and NFkB signaling in C2 in contrast to an EZH2 dependence in C1-BPDCN. Our integrative characterization of BPDCN offers novel molecular insights and potential diagnostic applications.

Comparison of periodontal indices, DMFT, xerostomia, hyposalivation and oral health-related quality of life in Sjögren's syndrome patients versus healthy individuals: A case-control study.

BACKGROUND: Sjögren's syndrome (SS) is a common systemic autoimmune disease that affects oral health, and consequently oral health-related quality of life (OHRQoL) due to the involvement of exocrine glands. OBJECTIVES: The present study aimed to evaluate the oral health-related quality of life and oral health indicators in patients with SS in comparison with healthy individuals. MATERIAL AND METHODS: In the case and control groups (45 patients and 45 healthy individuals), questions about demographic data, other systemic disorders, medications, the years of infection, xerostomia, as well as inquiries about the quality of life (Oral Health Impact Profile-14 - OHIP-14) were asked. The patients were evaluated clinically, and oral health indicators, including the plaque index (PI), the gingival index (GI), the sulcus bleeding index (SBI), and the number of decayed, missing and filled teeth (DMFT) were assessed on the Ramfjord teeth. Unstimulated saliva samples from both groups were obtained and weighed. The data was analyzed using IBM SPSS Statistics for Windows, v. 24.0. Quantitative variables were compared between the case and control groups with the use of the independent t test or their nonparametric equivalent (the Mann-Whitney test). RESULTS: The comparison of the quantitative variables between the study groups showed a statistically significant difference in the OHRQoL scores (p = 0.037) and the unstimulated saliva flow rate (p = 0.002) between the case and control groups. Also, there was a statistically significant difference in the DMFT index between patients with primary and secondary SS in the case group (p = 0.048). CONCLUSIONS: The lower OHRQoL of patients with SS requires more attention and follow-up to solve periodontal and dental problems in this group of patients.

Identification of ATF3 as a novel protective signature of quiescent colorectal tumor cells.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death in the world. In most cases, drug resistance and tumor recurrence are ultimately inevitable. One obstacle is the presence of chemotherapy-insensitive quiescent cancer cells (QCCs). Identification of unique features of QCCs may facilitate the development of new targeted therapeutic strategies to eliminate tumor cells and thereby delay tumor recurrence. Here, using single-cell RNA sequencing, we classified proliferating and quiescent cancer cell populations in the human colorectal cancer spheroid model and identified ATF3 as a novel signature of QCCs that could support cells living in a metabolically restricted microenvironment. RNA velocity further showed a shift from the QCC group to the PCC group indicating the regenerative capacity of the QCCs. Our further results of epigenetic analysis, STING analysis, and evaluation of TCGA COAD datasets build a conclusion that ATF3 can interact with DDIT4 and TRIB3 at the transcriptional level. In addition, decreasing the expression level of ATF3 could enhance the efficacy of 5-FU on CRC MCTS models. In conclusion, ATF3 was identified as a novel marker of QCCs, and combining conventional drugs targeting PCCs with an option to target QCCs by reducing ATF3 expression levels may be a promising strategy for more efficient removal of tumor cells.

In vitro interactions of nystatin and micafungin combined with chlorhexidine against Candida albicans isolates.

Background and Purpose: Oral candidiasis has become a growing problem in hospitals worldwide, and the development of antifungal drug resistance in Candida species constitutes a serious concern. This study aimed to evaluate the in vitro efficacy of nystatin, and micafungin with chlorhexidine against fluconazole-resistant and fluconazole-sensitive Candida albicans (C. albicans) isolates. Materials and Methods: In this experimental-laboratory study, a total of 20 fluconazole-resistant (n=10) and fluconazole-susceptible (n=10) C. albicans strains were obtained from the reference culture collection of the Invasive Fungi Research Center in Mazandaran University of Medical Sciences, Sari, Iran. In vitro combination of nystatin and micafungin with chlorhexidine was performed using a microdilution checkerboard method based on the Clinical and Laboratory Standards Institute guideline. Results: Micafungin had the highest antifungal activity against C. albicans susceptible and resistant strains, with a Geometric mean of (GM) =0.008µg/ml and GM=0.008µg/ml, followed by nystatin with GM=0.06µg/ml and GM=0.042µg/ml and chlorhexidine with GM=0.25µg/ml and GM=0.165µg/ml against C. albicans resistant and sensitive strains, respectively. The interaction of micafungin and nystatin with chlorhexidine showed a synergistic interaction against most C. albicans strains. In addition, no antagonistic interaction was observed between micafungin, nystatin, and chlorhexidine against C. albicans strains. Conclusion: The synergistic interaction of micafungin with chlorhexidine against azole-resistant C. albicans suggests an alternative approach to overcome antifungal drug resistance. However, further studies are needed for in vivo evaluation.

Neuregulin1 types mRNA level changes in autism spectrum disorder, and is associated with deficit in executive functions.

BACKGROUND: Autism spectrum disorder (ASD) is a pediatric heterogeneous psychiatric and neurodevelopmental disorder with social and communication deficits, language impairment and ritualistic or repetitive behaviors. ASD has significant genetic bases but candidate genes and molecular mechanisms of disorder are not clarified. Neuregulin1 (NRG1) gene, located in 8p12 is involved in development of central nervous system and was indicated as candidate gene in schizophrenia. METHODS: mRNA level of types I, II and III of NRG1 gene were studied in peripheral blood of 1540 ASD patients (IQ > 70) and 1490 control children by quantitative Real Time PCR. Also three domains of executive functions (working memory, response inhibition and vigilance) were examined in all subjects. FINDINGS: All three types were significantly down regulated in ASD patients. Significant deficiencies in executive functions (EF) were found in ASD patients. EF deficiencies mostly were associated with down expression of mRNA level of types I and III. Also correlations were found between NRG1 expression with gender and severity of ASD symptoms. INTERPRETATIONS: Findings primarily have been suggested involvement of NRG1 in etiology of ASD. Also correlation of NRG1 mRNA level with EF deficiencies could shed lights on EF mechanisms and may suggest targeted treatments to improve particular executive functions. FUND: Young researchers and elites club funded the project due to the annual grant of special talents of Club that gave to Arvin Haghighatfard.

Salivary oxidant/ antioxidant status and hematological parameters in patients with recurrent aphthous stomatitis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is the most common inflammatory ulcerative condition of oral cavity. The aim of this study was to compare the levels of the salivary Malondialdehyde (MDA) and total antioxidant capacity (TAC) and blood parameter in RAS versus healthy controls. METHODS: This case-control study consisted of 28 patients with RAS and 28 age and sex -matched control without RAS. Cell blood count was assessed by sysmex system, serum iron and total iron binding capacity was measured by standard laboratory kit and for ferritin ELISA kit was utilized. Salivary TAC and MDA level determined using FRAP and TBARS method respectively. Statistical analysis was performed using SPSS Version 21, chi-square test was used to compare proportions, and student's t-test and Mann Whitney U-test were used for the comparison of quantitative variables. RESULTS: Salivary MDA level was significantly higher (p<0.001) and TAC level was significantly lower (p<0.042) in RAS as compared with the control group. Also, serum ferritin level was significantly higher in RAS patients (p<0.008). CONCLUSION: These findings indicate the alteration of oxidant/antioxidant status was observed in recurrent aphthous stomatitis, may be also associated with changing several hematinic parameters in this study. The finding maybe helpful to clarify the etiologies of RAS and possibely to improve the management or preventive options.