Efficacy and safety of a 0.05 % nanoencapsulated imiquimod hydrogel for the treatment of actinic cheilitis: Drug release analysis and clinical study.

Actinic cheilitis (AC) is a lip disorder, with no standard treatment. Imiquimod (IMIQ) is an immunomodulator that treat precancerous lesions; however, its commercial form causes severe adverse effects. This study aimed to assess IMQ release from a chitosan hydrogel containing 0.05 % nanoencapsulated (NANO) imiquimod (IMIQ-0.05 %-NANO) and its efficacy in AC treatment. The hydrogels were prepared by incorporating chitosan into polymeric nanocapsules (NCimiq) loaded with IMQ, produced using the interfacial deposition of preformed polymer method. IMQ release was evaluated using automated Franz Cells. A triple-blind randomized controlled trial (49 subjects) compared the efficacy of: IMIQ-0.05 %-NANO, 5 % free imiquimod (IMIQ-5 %), 0.05 % free imiquimod (IMIQ-0.05 %), and placebo hydrogel. The IMIQ-NANO-0.05 % and IMIQ-5 % groups exhibited significantly higher rates of clinical improvement (p < 0.05); however, the IMIQ-5 % group experienced more adverse effects (92.3 % of subjects) compared to other groups (p < 0.05). In conclusion, in the studied sample, IMIQ-NANO-0.05 % was a safe and effective option to treat AC.

Efficacy of ozone therapy for oral mucosa wound healing: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to assess the effectiveness of ozone therapy in oral ulcers healing when compared to placebo or active treatments. MATERIALS AND METHODS: The search was carried out using PubMed, EMBASE, Scopus, and Lilacs databases. Clinical trials involving human participants were included. The Risk Ratio (RR) and the standardized mean difference (SMD) with 95%CI (confidence interval) were calculated. The ROBINS-I (risk of bias in non-randomized studies of interventions) and RoB2 (risk of bias tool for randomized trials) assessment tool was used to detect bias. RESULTS: After the selection process, 12 studies were included. The meta-analysis showed that ozone therapy helps to reduce the size of the traumatic and autoimmune ulcers (RR=-0.44; 95% CI -0.71,-0.17; I2=0%) in comparison to placebo. Regarding pain reduction, ozone was superior to placebo (RR = 1.29, 95% CI -1.6 to -0.95); I2=0%), and equivalent to topical corticosteroid and laser photobiomodulation (RR = 0.26, 95% CI -0.27,0.78, p = 0.34). CONCLUSION: Ozone therapy is an alternative for accelerating healing and reducing pain for both traumatic and autoimmune ulcers. However, the quality of evidence is limited. CLINICAL RELEVANCE: Oral ulcerations are usually painful and impact quality of life requiring different approaches to boost wound healing and reduce symptoms. For this purpose, ozone therapy is a promising strategy.

Melatonin improves nitric oxide bioavailability in isoproterenol induced myocardial injury.

Isoproterenol administration is associated with cardiac inflammation and decreased NO availability. Melatonin has been reported to have cardioprotective effect. The aim of this study was to investigate the effect of melatonin on NO bioavailability and inflammation in myocardial injury induced by isoproterenol. Isoproterenol was administrated in male Wistar rats for 7 days to induce cardiac injury. The animals were divided into 3 groups: Control, Isoproterenol, Isoproterenol + Melatonin. Animals received melatonin for 7 days. Echocardiographic analysis was performed and the hearts were collected for molecular analysis. Animals that received isoproterenol demonstrated a reduction in left ventricle systolic and diastolic diameter, indicating the presence of concentric hypertrophy. Melatonin was able to attenuate this alteration. Melatonin also improved NO bioavailability and decreased NF-κß, TNFα and IL-1ß expression. In conclusion, melatonin exhibited a cardioprotective effect which was associated with improving NO bioavailability and decreasing the pro-inflammatory proteins.

Is vitamin D receptor (VDR) polymorphism associated with head and neck cancer risk? A systematic review and meta-analysis.

BACKGROUND: Head and neck cancer encompasses neoplasms affecting the oral cavity, pharynx, larynx, and thyroid. Identifying factors that modulate the carcinogenesis process can aid in identifying subgroups at higher risk of developing the disease, enabling implementation of prevention programs. Vitamin D receptor polymorphisms can affect the carcinogenesis of various tumors by altering vitamin D metabolism and cellular response. METHODS: To elucidate the role of vitamin D receptor polymorphisms in head and neck cancer, a systematic review was performed, searching the Embase, PubMed, Scopus, and Lilacs databases. A total of 19 articles met the inclusion criteria. The frequency of vitamin D receptors polymorphism alleles (FokI, ApaI, BsmI, TaqI, Cdx2, rs2107301, rs2238135) was recorded and pooled to calculate the odds ratio in a meta-analysis using the Review Manager software. RESULTS: Subgroup analysis demonstrated significant associations in the anatomical site of cancer (oral cancer in ApaI and BsmI, and unspecified subsites of head and neck cancer in TaqI), genotyping method (FokI and BsmI), and continent of the study (ApaI, FokI, and BsmI). CONCLUSION: Our findings were heterogeneous, as with other evidence available in the literature. Therefore, more clinical studies with larger sample sizes are needed to obtain more accurate results on the relationship between vitamin D receptor polymorphism and head and neck cancer.

Oral lesions of systemic lupus erythematosus: A collaborative Latin American study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that may affect the oral mucosa. The variable spectrum of oral lesions observed in SLE can pose challenges in diagnosis, particularly when the lesions occur in isolation. The aim of this study was to describe the oral lesions occurring in patients with SLE from Latin America. METHODS: This collaborative record-based study involving 11 oral and maxillofacial pathology and medicine services across Venezuela, Argentina, Chile, Brazil, and Mexico describes the clinicopathological profile of SLE-related oral lesions. RESULTS: Seventy patients with SLE and oral lesions were included in the study. The majority were females (75.7%; female/male ratio: 3.1:1) and white (62.1%), with a mean age of 38.4 years (range: 11-77 years). The most common site of oral lesions was the hard/soft palate (32.0%). Clinically, oral lesions predominantly presented as ulcers (26.6%), erosions (26.6%), and white lesions (23.4%). Isolated oral lesions occurred in 65.2% of individuals, while cutaneous manifestations occurred in 80.3%. The main clinical diagnostic hypothesis in 71.4% of cases was an immune-mediated disease. Oral biopsies followed by histopathological analysis were performed in 50 cases. CONCLUSION: Oral lesions of SLE exhibit a variety of clinical and histopathological features. A key point in diagnosis is that unusual oral changes without an obvious local cause may indicate a possible systemic condition presenting with oral lesions. A multidisciplinary approach, which includes regular oral examination, is warranted to identify oral lesions and provide treatment.

Impact of dental imaging on pregnant women and recommendations for fetal radiation safety: A systematic review.

Purpose: This study was conducted to investigate the safety of dental imaging in pregnant women with respect to fetal health. Materials and Methods: Searches were conducted of the PubMed, Scopus, and Web of Science databases in May 2023. The inclusion criteria encompassed cross-sectional and longitudinal studies that focused on the analysis of diagnostic dental imaging in pregnant women, as well as studies utilizing phantoms to simulate imaging examinations. The exclusion criteria consisted of reviews, letters to the editor, book chapters, and abstracts from scientific conferences and seminars. Results: A total of 3,913 articles were identified. Based on a review of the titles and abstracts, 3,892 articles were excluded, leaving 21 articles remaining for full-text review. Of these, 18 were excluded, and 4 additional articles were included as cross-references. Ultimately, 7 articles underwent quantitative-qualitative analysis. Three retrospective studies were focused on pregnant women who underwent dental imaging procedures. The remaining 4 studies utilized female phantoms to simulate imaging examinations and represent the radiation doses absorbed by the uterus or thyroid. Conclusion: Few dental radiology studies have been conducted to determine the safe radiation threshold for pregnant women. Additionally, the reviewed articles did not provide numbers of dental examinations, by type, corresponding to this dose. Dental imaging examinations of pregnant women should not be restricted if clinically indicated. Ultimately, practitioners must be able to justify the examination and should adhere to the "as low as diagnostically acceptable, being indication-oriented and patient-specific" (ALADAIP) principle of radioprotection.

Amitriptyline effectiveness in burning mouth syndrome: An in-depth case series analysis.

OBJECTIVES: To assess the effectiveness of amitriptyline (AMT), and to identify the determinants of the treatment's effectiveness in patients diagnosed with burning mouth syndrome (BMS). BACKGROUND: Treatment of BMS is challenging and no established treatment protocol is available. AMT may be an important treatment option, cout not all patients benefit from this drug. Studies assessing factors related to treatment response are valuable in improving decision-making. MATERIALS AND METHODS: This case series study examined the medical records of all patients diagnosed with BMS at an oral medicine unit in a university hospital from 2008 to 2022. The patients were divided into responders to AMT and non-responders to AMT. Data on demographic information, comorbidities, medications, types of symptoms and oral subsites affected were collected. Descriptive and bivariate analyses were conducted to assess the association between the independent variables and the outcome, using the Chi-squared test (P < .05). RESULTS: Three hundred and fourty-nine patients reported a burning mouth sensation, 50 of them (14.3%) being diagnosed with primary BMS. Of these, 35 were treated with AMT, and 26 (74.2%) responded significantly to AMT. All males responded to AMT, whereas only 67.9% of females responded. The mean dose of AMT among responders was 29.8 ± 12.3 mg, with most patients achieving a response with 25 mg (61.5% of patients), followed by 50 mg (23%). The concomitant use of an anticonvulsant resulted in non-response. CONCLUSIONS: AMT may be effective in BMS management for most patients.

The Role of SOX2 and SOX9 in Radioresistance and Tumor Recurrence.

Head and neck squamous cell carcinoma (HNSCC) exhibits considerable variability in patient outcome. It has been reported that SOX2 plays a role in proliferation, tumor growth, drug resistance, and metastasis in a variety of cancer types. Additionally, SOX9 has been implicated in immune tolerance and treatment failures. SOX2 and SOX9 induce treatment failure by a molecular mechanism that has not yet been elucidated. This study explores the inverse association of SOX2/SOX9 and their distinct expression in tumors, influencing the tumor microenvironment and radiotherapy responses. Through public RNA sequencing data, human biopsy samples, and knockdown cellular models, we explored the effects of inverted SOX2 and SOX9 expression. We found that patients expressing SOX2LowSOX9High showed decreased survival compared to SOX2HighSOX9Low. A survival analysis of patients stratified by radiotherapy and human papillomavirus brings additional clinical relevance. We identified a gene set signature comprising newly discovered candidate genes resulting from inverted SOX2/SOX9 expression. Moreover, the TGF-ß pathway emerges as a significant predicted contributor to the overexpression of these candidate genes. In vitro findings reveal that silencing SOX2 enhances tumor radioresistance, while SOX9 silencing enhances radiosensitivity. These discoveries lay the groundwork for further studies on the therapeutic potential of transcription factors in optimizing HNSCC treatment.

Autophagy and nuclear morphometry are associated with histopathologic features in esophageal squamous cell carcinoma.

Less than 15% of patients with esophageal squamous cell carcinoma (ESCC) survive 5 years after diagnosis. A better understanding of the biology of these tumors and the development of clinical biomarkers is needed. Autophagy is a physiological mechanism involved in the turnover of cellular components that plays a key role in cancer. This study evaluated the differential levels of three key regulators of autophagy (SQSTM1, MAP1LC3B, and BECN1) in patients with ESCC, associating autophagy with histopathologic features, including the grade of differentiation, mitotic rate, inflammation score, and the intensity of tumor-infiltrating lymphocytes. Nuclear morphometry of the tumor parenchyma was also assessed, associating it with autophagy and histopathology. All three markers significantly increased in patients with ESCC compared to the control group. Based on the mean expression of each protein in the control group, 57% of patients with ESCC had high levels of all three markers compared to control patients (14%). The most frequent profiles found in ESCC were BECNhigh/MAP1LC3high and BECNhigh/SQSTM1high. According to the TCGA database, we found that the main autophagy genes were upregulated in ESCC. Moreover, high levels of autophagy markers were associated with a poor prognosis. Considering nuclear morphometry, ESCC samples showed a significant reduction in nuclear area, which was strongly negatively correlated with autophagy. Finally, the percentage of normal nuclei was associated with tumor differentiation, while poorly differentiated tumors showed lower SQSTM1 levels. ESCC progression may involve increased autophagy and changes in nuclear structure, associated with clinically relevant histopathological features. KEY MESSAGES: Autophagy markers are co-increased in primary ESCC. Autophagy negatively correlates with nuclear morphometry in ESCC parenchyma. Autophagy and nuclear morphometry are associated with histopathological features. Autophagy is increased in ESCC-TCGA database and associated with poor prognosis.

Is imiquimod a promising drug to treat oral mucosa diseases? A scoping review and new perspectives.

Imiquimod (IMQ) is a chemotherapeutic and immunostimulant drug that is applied topically, demonstrating antitumor and antiviral activities. The objective of this review was to compile data on the off-label use of IMQ in oral mucosal diseases. IMQ has exhibited effectiveness in the treatment of various oral mucosal conditions, including oral carcinogenic lesions, neoplasms, HPV-related lesions and autoimmune disorders. Although IMQ holds promise as a potential strategy for addressing oral mucosal lesions, it is important to note that significant side effects have been frequently reported. Nonetheless, it is crucial to develop and test new technological systems, such as the combination of nanotechnology with innovative drug delivery platforms. These advancements aim to minimize side effects and prolong the drug's contact time with the mucosa, preventing its removal by salivary flow.

Comparison of different DNA preservation solutions for oral cytological samples.

OBJECTIVE: The objective of this study was to compare the DNA preservation capacity of buccal mucosa exfoliated cells when stored in different solutions under varying time and temperature conditions. DESIGN: DNA preservation solutions, including Dimethyl sulphoxide disodium-EDTA-saturated NaCl (DESS), Tris-EDTA-NaCl-Tween20 buffer (TENT), Nucleic Acid Preservation Buffer (NAP), and phosphate-buffered saline (PBS), were prepared. Buccal mucosa cells from a single patient were collected, dispensed into these solutions, and stored at room temperature (RT) and 4 °C for 24 h, 72 h, 30 days, 90 days, and 180 days. DNA was extracted using the salting-out method and the QIAamp DNA Mini Kit. DNA concentration and purity were determined using the QuBit device and NanoDrop, while DNA integrity was assessed using the Agilent 4200 TapeStation system. The ability to amplify the IFNA primer was also evaluated by PCR. RESULTS: The salting-out method yielded better concentration and purity results, with PBS, TENT, and DESS buffers demonstrating superior concentration values when stored at 4 °C, resulting in mean values exceeding 10 ng/µL for up to 30 days. DESS consistently exhibited the best integrity values over time for both temperature conditions. Amplification capacity was enhanced when samples were stored at 4 °C. When stored at RT, PBS achieved 100% amplification within 24 h. NAP yielded the poorest results. CONCLUSION: In the context of long-term preservation, the DESS buffer emerges as the most effective solution, maintaining requisite DNA quality and quantity standards for up to 30 days at RT and up to 3 months at 4 °C.

Clinical outcomes and prognostic factors of head and neck squamous cell carcinoma: a ten-year follow-up study.

Traditional guidelines for determining the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) are used to make therapeutic decisions. However, only 50% of the patients had lived for more than five years. The present study aimed to analyze the correlation of traditional prognostic factors such as tumor size, histological grading, regional metastases, and treatment with the survival of patients with HNSCC. A total of 78 patients diagnosed with HNSCC were followed up for 10 years after diagnosis and treatment. The health status of the patients was tracked at four time points, and according to the evolution of the patients and their final clinical status, we performed a prognostic analysis based on the clinical outcomes observed during the follow-up period. The final study cohort comprised 50 patients. Most patients had tumors < 4 cm in size (64%) and no regional metastases (64%); no patients had distant metastases at the time of diagnosis. Most individuals had tumors with good (48%) and moderate (46%) degrees of malignancy. At the end of the follow-up period, only 14% of the patients were discharged, 42% died of the tumor, and 44% remained under observation owing to the presence of a potentially malignant disorder, relapse, or metastases. This analysis showed that traditional prognostic factors were not accurate in detecting subclinical changes or predicting the clinical evolution of patients.

Does liraglutide alleviate inflammation in brain-dead donors? A randomized clinical trial.

Brain death triggers an inflammatory cascade that damages organs before procurement, adversely affecting the quality of grafts. This randomized clinical trial aimed to compare the efficacy of liraglutide compared to placebo in attenuating brain death-induced inflammation, endoplasmic reticulum stress, and oxidative stress. We conducted a double-blinded, placebo-controlled, randomized clinical trial with brain-dead donors. Fifty brain-dead donors were randomized to receive subcutaneous liraglutide or placebo. The primary outcome was the reduction in IL-6 plasma levels. Secondary outcomes were changes in other plasma pro-inflammatory (IL-1ß, interferon-γ, TNF) and anti-inflammatory cytokines (IL-10), expression of antiapoptotic ( BCL2 ), endoplasmic reticulum stress markers ( DDIT3/CHOP , HSPA5/BIP ), and antioxidant ( superoxide dismutase 2 , uncoupling protein 2 ) genes, and expression TNF, DDIT3, and superoxide dismutase 2 proteins in liver biopsies. The liraglutide group showed lower cytokine levels compared to the placebo group during follow-up: Δ IL-6 (-28 [-182, 135] vs. 32 [-10.6, 70.7] pg/mL; p = 0.041) and Δ IL-10 (-0.01 [-2.2, 1.5] vs. 1.9 [-0.2, 6.1] pg/mL; p = 0.042), respectively. The administration of liraglutide did not significantly alter the expression of inflammatory, antiapoptotic, endoplasmic reticulum stress, or antioxidant genes in the liver tissue. Similar to gene expression, expressions of proteins in the liver were not affected by the administration of liraglutide. Treatment with liraglutide did not increase the organ recovery rate [OR = 1.2 (95% CI: 0.2-8.6), p = 0.82]. Liraglutide administration reduced IL-6 and prevented the increase of IL-10 plasma levels in brain-dead donors without affecting the expression of genes and proteins related to inflammation, apoptosis, endoplasmic reticulum stress, or oxidative stress.

Systemic non-steroidal immunomodulators for oral lichen planus treatment-a scoping review.

OBJECTIVE: The aim of this scoping review was to evaluate the efficacy and safety of the use of systemic nonsteroidal immunomodulators (SNSI) for oral lichen planus (OLP) treatment. MATERIALS AND METHODS: This review was conducted according to PRISMA-ScR guidelines and registered at PROSPERO (CRD42021243524). Consulted databases were Pubmed, Embase, Scopus, and Web of Science. The inclusion criteria was as follows: clinical trials, case series, prospective, and retrospective studies conducted with participants presenting OLP of any sex and age. RESULTS: Thirty-two studies were selected, assessing 9 different SNSI: methotrexate, dapsone, levamisole, hydroxychloroquine, thalidomide, metronidazole, azathioprine, mycophenolate mofetil, and colchicine. Methotrexate and dapsone were the drugs with the best evidence among the options included, regarding number and quality of studies. Methotrexate resulted in significant improvement in the clinical condition and remission of symptoms, ranging between 63 and 93% of cases. Dapsone presented a similar effect to the use of topical corticosteroids and tacrolimus CONCLUSION: Among SNSI therapeutic options, methotrexate, and dapsone showed promising efficacy and safety. However, large-scale randomized clinical trials are still needed. CLINICAL RELEVANCE: SNSI have been used in the treatment of recalcitrant OLP; however, so far, it is not clear which are the best options. This scoping review highlights the potential use of methotrexate and dapsone.

Synthesis of films based on chitosan and protic ionic liquids to be used as wound dressing on the oral mucosa.

Oral mucosal ulcerations expose connective tissue to different pathogens and this can progress to systemic infection. This study aimed to synthesize environmentally-friendly films with chitosan and protic ionic liquids, possessing mucoadhesive properties, activity against opportunistic microorganisms, enhanced malleability and mechanical resistance to be used as a wound dressing on the oral mucosa. Therefore, films with chitosan and 10, 35, and 50 % (wt/wt) of 2-hydroxy diethylammonium lactate, salicylate, and maleate protic ionic liquids were synthesized. Thickness measurements and mechanical properties analysis were performed. In addition, oral mucoadhesion, antimicrobial activity, and cytotoxicity properties were investigated. Results showed that the addition of 35wt% and 50wt% of all kinds of protic ionic liquids tested presented significant improvements in film thickness and mechanical properties. Films based on chitosan and the protic ionic liquid 2-hydroxy diethylammonium salicylate at percentages of 35 and 50wt% exhibited superior mucoadhesive properties, antimicrobial activity on opportunistic microorganisms and an improvement in their flexibility after immersion in synthetic saliva. Cytotoxicity results suggest that all kinds of chitosan/protic ionic liquids films tested are safe for intra-oral use. Therefore, the results of this study indicate that these materials could be good candidates for efficient and environmentally-friendly wound dressing films on the oral mucosa.

Characterization of heart disease in mucopolysaccharidosis type II mice.

Mucopolysaccharidosis type II (MPSII) is a progressive lysosomal storage disease caused by mutations in the IDS gene, that leads to iduronate 2-sulfatase (IDS) enzyme deficiency. The enzyme catalyzes the first step of degradation of two glycosaminoglycans (GAGs), heparan sulfate (HS) and dermatan sulfate (DS). The consequences of MPSII are progressively harmful and can lead to death by cardiac failure. The aim of this study was to characterize the cardiovascular disease in MPSII mice. Thus, we evaluated the cardiovascular function of MPSII male mice at 6, 8, and 10 months of age, through functional, histological, and biochemical analyzes. Echocardiographic analyses showed a progressive loss in cardiac function, observed through parameters such as reduction in ejection fraction (46% in control versus 28% in MPS II at 10 months, P < .01) and fractional area change (31% versus 23%, P < .05). Similar results were found in parameters of vascular competence, obtained by echo Doppler. Both aortic dilatation and an increase in pulmonary resistance were observed at all time points in MPSII mice. The histological analyses showed an increase in the thickness of the heart valves (2-fold thicker than control values at 10 months). Biochemical analyzes confirmed GAG storage in these tissues, with a massive elevation of DS in the myocardium. Furthermore, an important increase in the activity of proteases such as cathepsin S and B (up to 5-fold control values) was found and could be related to the progressive loss of cardiac function observed in MPSII mice. In this work, we demonstrated that loss of cardiac function in MPSII mice started at 6 months of age, although its global cardiac capacity was still preserved at this time. Disease progressed at later time points leading to heart failure. The MPSII mice at later times reproduce many of the cardiovascular events found in patients with Hunter's disease.

Puricelli biconvex arthroplasty: an experimental study in sheep.

BACKGROUND: The aim of this study was to establish a sheep model of the Puricelli biconvex arthroplasty (ABiP) technique in sheep for evaluating its functional, biological and histological parameters. METHODS: Ten Corriedale black sheep were submitted to TMJ total reconstruction with poly(methyl methacrylate) (PMMA) using ABiP and euthanized after 45 (n = 5) or 90 (n = 5) days. Control animals (n = 2) underwent sham operations and were euthanized after 45 days. Variables were assessed before the surgery (T0), immediately after (T1) and at 45 or 90 postoperative days (T2). RESULTS: Histological analyses showed regression of inflammatory cells over the follow-up period. PMMA showed reduced porosity and roughness in the articular contact area. PMMA temporal components showed linear and volumetric wear in comparison to control, but no foreign body reaction was observed. The reconstructions were stable in all animals. The amplitude of mouth opening and left lateral movements were maintained, except for a reduction in the range of right lateral movements at day 90 in the experimental group. Clinical, macroscopic and radiographic observations showed that the reconstructions were stable. CONCLUSIONS: The analysis of functional, biological and histological parameters in sheep submitted to ABiP showed stable results of the procedure, with maintenance of body weight and all mandibular movements, save contralateral mandibular movement, suggesting that joint function was completely maintained following the procedure. This experimental study provides support for clinical results previously reported of the ABiP technique in TMJ reconstruction procedures.