Possible role of ALDH1 and CD44 in lip carcinogenesis.

BACKGROUND: Lip squamous cell carcinoma (LSCC) accounts for 12% of all head and neck cancers. It is caused by chronic exposure to ultraviolet light solar radiation and related to previous actinic cheilitis (AC). This study aimed to investigate the immunostaining of the putative cancer stem cells (CSC) markers ALDH1 and CD44 in AC (n=30) and LSCC (n=20). ALDH1 positivity was found to be statistically higher in LSCC than in AC lesions (p=0.0045), whilst CD44 expression was statistically higher in AC than in LSCC lesions (p=0.0155). ALDH1+ cells in AC lesions were associated with specific clinical features: a younger age (<60 years old), the female gender, white skin, not smoking or consuming alcohol, and a fast evolution, and not associated with the chronic exposure to UV radiation (p<0.0001). CD44 positivity was associated with patients who were male, feoderm, smoked, consumed alcohol, underwent occupational exposure to UV-radiation, and demonstrated lesions with log-time evolution (p<0.0001). ALDH1 + cells were associated with mild dysplasia using a system from the World Health Organization (WHO), and with a low risk of malignant transformation, according to the binary system (p<0.0001). CD44+ cells were also associated with moderated dysplasia, according to the WHO system. In LSCC, ALDH1 + cells were positively associated with patients who were older (≥ 60 years old), smokers, and with those who consumed alcohol (p<0.0001). CD44 + cells in LSCC were associated with older (≥ 60 years old) patients as well, but also with female patients, white skin, non-smokers, and individuals who did not consume alcohol (p<0.0001), all of whom showed distinct patterns in pre- and malignant lesions of both markers. Additionally, in LSCC, both ALDH1 and CD44 staining were associated with smaller tumor sizes (T1/T2; p<0.0001). In summary, although both ALDH1 and CD44 were associated with the presence of dysplasia in AC lesions, the present findings suggest that ALDH1 and CD44 may be activated by different etiopathogenic pathways, predominantly in distinct steps of oral carcinogenesis. CD44 would thus be more significantly related to the potentially malignant lesion, while ALDH1 would be closely linked to malignancy.

Possible role of ALDH1 and CD44 in lip carcinogenesis

Abstract Lip squamous cell carcinoma (LSCC) accounts for 12% of all head and neck cancers. It is caused by chronic exposure to ultraviolet light solar radiation and related to previous actinic cheilitis (AC). This study aimed to investigate the immunostaining of the putative cancer stem cells (CSC) markers ALDH1 and CD44 in AC (n=30) and LSCC (n=20). ALDH1 positivity was found to be statistically higher in LSCC than in AC lesions (p=0.0045), whilst CD44 expression was statistically higher in AC than in LSCC lesions (p=0.0155). ALDH1+ cells in AC lesions were associated with specific clinical features: a younger age (<60 years old), the female gender, white skin, not smoking or consuming alcohol, and a fast evolution, and not associated with the chronic exposure to UV radiation (p<0.0001). CD44 positivity was associated with patients who were male, feoderm, smoked, consumed alcohol, underwent occupational exposure to UV-radiation, and demonstrated lesions with log-time evolution (p<0.0001). ALDH1 + cells were associated with mild dysplasia using a system from the World Health Organization (WHO), and with a low risk of malignant transformation, according to the binary system (p<0.0001). CD44+ cells were also associated with moderated dysplasia, according to the WHO system. In LSCC, ALDH1 + cells were positively associated with patients who were older (≥ 60 years old), smokers, and with those who consumed alcohol (p<0.0001). CD44 + cells in LSCC were associated with older (≥ 60 years old) patients as well, but also with female patients, white skin, non-smokers, and individuals who did not consume alcohol (p<0.0001), all of whom showed distinct patterns in pre- and malignant lesions of both markers. Additionally, in LSCC, both ALDH1 and CD44 staining were associated with smaller tumor sizes (T1/T2; p<0.0001). In summary, although both ALDH1 and CD44 were associated with the presence of dysplasia in AC lesions, the present findings suggest that ALDH1 and CD44 may be activated by different etiopathogenic pathways, predominantly in distinct steps of oral carcinogenesis. CD44 would thus be more significantly related to the potentially malignant lesion, while ALDH1 would be closely linked to malignancy.

Mesenchymal stem cells surpass the capacity of bone marrow aspirate concentrate for periodontal regeneration.

Regenerative approaches using mesenchymal stem cells (MSCs) have been evaluated to promote the complete formation of all missing periodontal tissues, e.g., new cementum, bone, and functional periodontal ligaments. MSCs derived from bone marrow have been applied to bone and periodontal defects in several forms, including bone marrow aspirate concentrate (BMAC) and cultured and isolated bone marrow mesenchymal stem cells (BM-MSCs). This study aimed to evaluate the periodontal regeneration capacity of BMAC and cultured BM-MSCs in the wound healing of fenestration defects in rats. METHODOLOGY: BM-MSCs were obtained after bone marrow aspiration of the isogenic iliac crests of rats, followed by cultivation and isolation. Autogenous BMAC was collected and centrifuged immediately before surgery. In 36 rats, fenestration defects were created and treated with suspended BM-MSCs, BMAC or left to spontaneously heal (control) (N=6). Their regenerative potential was assessed by microcomputed tomography (µCT) and histomorphometry, as well as their cell phenotype and functionality by the Luminex assay at 15 and 30 postoperative days. RESULTS: BMAC achieved higher bone volume in 30 days than spontaneous healing (p<0.0001) by enhancing osteoblastic lineage commitment maturation, with higher levels of osteopontin (p=0.0013). Defects filled with cultured BM-MSCs achieved higher mature bone formation in early stages than spontaneous healing and BMAC (p=0.0241 and p=0.0143, respectively). Moreover, significantly more cementum-like tissue formation (p<0.0001) was observed with new insertion of fibers in specimens treated with BM-MSCs within 30 days. CONCLUSION: Both forms of cell transport, BMAC and BM-MSCs, promoted bone formation. However, early bone formation and maturation were achieved when cultured BM-MSCs were used. Likewise, only cultured BM-MSCs were capable of achieving complete periodontal regeneration with inserted fibers in the new cementum-like tissue.

Poor oral health status and adverse COVID-19 outcomes: A preliminary study in hospitalized patients.

BACKGROUND: Most of the common risk factors for severe outcomes of coronavirus disease 2019 (COVID-19) are correlated with poor oral health, tooth loss, and periodontitis. This has pointed to a possible relationship between oral and systemic health in COVID-19 patients. Hence, this study aimed to assess the dental and periodontal status of hospitalized COVID-19 patients and their associations with the incidence of adverse COVID-19 outcomes. METHODS: We included 128 hospital patients aged between 20 and 97 years and with diagnoses of COVID-19 in this prospective observational study. Dental and periodontal status was assessed using in-hospital clinical examinations, including the Decayed, Missing, and Filled Teeth index, periodontal status, and tooth loss patterns (Eichner index). Associations between oral health measures, the severity of COVID-19 symptoms, and hospitalization endpoints were tested using chi-square test and incidence rate ratio (IRR) estimation using a generalized linear model with log-Poisson regression. The regression models used a block-wise selection of predictors for oral health-related variables, comorbidities, and patients' ages. RESULTS: Overall, poor oral health conditions were highly prevalent and associated with critical COVID-19 symptoms, higher risk for admission in the intensive care unit (ICU), and death. Periodontitis was significantly associated with ICU admission (IRR = 1.44; 95% confidence interval [95%CI] = 1.07-1.95; P = 0.017), critical symptoms (IRR = 2.56; 95%CI = 1.44-4.55; P = 0.001), and risk of death (IRR = 2.05; 95%CI = 1.12-3.76; P = 0.020) when adjusted for age and comorbidities. The Eichner index (classes B and C) was associated with ICU admission. CONCLUSION: There was a positive association between deleterious oral health-related conditions, especially periodontitis, and severe COVID-19 outcomes in hospitalized COVID-19 patients.

Validity and reliability of immunochromatographic IgM/IgG rapid tests for COVID-19 salivary diagnosis.

OBJECTIVES: To assess the accuracy of three immunochromatographic rapid tests for salivary detection of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens and the reliability of these tests comparing saliva with plasma samples. MATERIALS AND METHODS: Plasma and saliva samples from 62 patients diagnosed with coronavirus disease 2019 (COVID-19) and 20 healthy volunteers were assayed. IgM/IgG antibody against SARS-COV-2 was detected using three immunochromatographic rapid tests and compared with real-time reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: The tests' overall accuracy for detecting anti-SARS-CoV-2 antibodies ranged from 75.6 to 79.3 for saliva and 86.6-87.8 for plasma tests. The sensitivity of saliva and plasma tests increased with the severity of COVID-19 signs and symptoms. The chance of a positive plasma test in participants with a positive qRT-PCR test was 2.27 greater than a positive saliva test. CONCLUSIONS: Although rapid immunochromatographic tests are more accurate using plasma than saliva, which was expected considering its original use, our findings support the use of saliva as a straightforward supplementary method to assess seroconversion in patients with COVID-19, with important sensitivity and sensibility, especially in severe and critical cases.

Mesenchymal stem cells surpass the capacity of bone marrow aspirate concentrate for periodontal regeneration

Abstract Regenerative approaches using mesenchymal stem cells (MSCs) have been evaluated to promote the complete formation of all missing periodontal tissues, e.g., new cementum, bone, and functional periodontal ligaments. MSCs derived from bone marrow have been applied to bone and periodontal defects in several forms, including bone marrow aspirate concentrate (BMAC) and cultured and isolated bone marrow mesenchymal stem cells (BM-MSCs). This study aimed to evaluate the periodontal regeneration capacity of BMAC and cultured BM-MSCs in the wound healing of fenestration defects in rats. Methodology: BM-MSCs were obtained after bone marrow aspiration of the isogenic iliac crests of rats, followed by cultivation and isolation. Autogenous BMAC was collected and centrifuged immediately before surgery. In 36 rats, fenestration defects were created and treated with suspended BM-MSCs, BMAC or left to spontaneously heal (control) (N=6). Their regenerative potential was assessed by microcomputed tomography (µCT) and histomorphometry, as well as their cell phenotype and functionality by the Luminex assay at 15 and 30 postoperative days. Results: BMAC achieved higher bone volume in 30 days than spontaneous healing (p<0.0001) by enhancing osteoblastic lineage commitment maturation, with higher levels of osteopontin (p=0.0013). Defects filled with cultured BM-MSCs achieved higher mature bone formation in early stages than spontaneous healing and BMAC (p=0.0241 and p=0.0143, respectively). Moreover, significantly more cementum-like tissue formation (p<0.0001) was observed with new insertion of fibers in specimens treated with BM-MSCs within 30 days. Conclusion: Both forms of cell transport, BMAC and BM-MSCs, promoted bone formation. However, early bone formation and maturation were achieved when cultured BM-MSCs were used. Likewise, only cultured BM-MSCs were capable of achieving complete periodontal regeneration with inserted fibers in the new cementum-like tissue.

Preservação de alvéolo com uso de materiais xenógenos em área estética da maxila: relato de caso / Ridge preservation using xenografts in an aesthetic area of the maxilla: Case Report

INTRODUÇÃO: Para manter as dimensões ósseas e gengivais do alvéolo até a instalação de implantes tardios o cirurgião dentista pode lançar mão de diversas técnicas de regeneração óssea guiada, dentre estas existentes a associação de um substituto ósseo com um selador do alvéolo vem apresentando resultados clínicos satisfatórios. OBJETIVO: O objetivo do presente trabalho é relatar um caso clínico onde a preservação alveolar em área estética maxilar foi realizada com materiais xenógenos. RELATO DE CASO: Paciente gênero feminino com 50 anos, melanoderma, não fumante e sem alterações sistêmicas apresentou-se a pós-graduação em periodontia da Faculdade de Odontologia de Ribeirão Preto devido a incômodo estético nos elementos 11 e 21. No exame clínico verificou comprometimento periodontal extenso nos dentes 11 e 21 sendo indicada a exodontia com reabilitação oral via implantes dentários. O tratamento proposto foram as exodontias seguidas de preservação alveolar com materiais xenógenos para posterior instalação de implantes na área enxertada. Porém a pedido da paciente e por conta das condições periodontais e estéticas as exodontia foram realizadas em momentos diferentes demonstrando um planejamento diferenciado e individualizado. CONCLUSÃO: Podemos concluir que a associação entre o substituto ósseo com a membrana substituta de tecido mucoso conseguiu obter resultados satisfatórios na preservação e manutenção das dimensões ósseas e teciduais no caso apresentado (AU)

INTRODUCTION: To maintain the bone and gingival dimensions of the ridge until the installation of implants the dental surgeon can use several techniques of guided bone regeneration, among these the association of a bone substitute with a ridge's sealant has shown satisfactory clinical results. OBJECTIVE: The objective of this study is to report a clinical case where ridge preservation in maxillary aesthetic area was performed with xenogenic materials. CASE REPORT: A 50-year-old female patient, melanoderma, non-smoker and no systemic conditions presented at post-graduation in periodontics from the Faculty of Dentistry of Ribeirão Preto due to aesthetic discomfort in elements 11 and 21. At the clinical examination it was verified that there was extensive periodontal impairment on teeth 11 and 21, that why it was indicated an oral rehabilitation with dental implants. The proposed treatment was the exodontia followed by ridge preservation with xenogenic materials for posterior implant installation in the grafted area. However, at the request of the patient and due to the periodontal and aesthetic conditions, the exodontia were performed at different times, demonstrating a different and individualized treatment planning. CONCLUSION: We can conclude that the association between the bone substitute and the mucosal tissue replacement membrane was able to obtain satisfactory results in the preservation and maintenance of the bone and tissue dimensions in the presented case.tissue (AU)

Preservação de alvéolo com uso de enxerto ósseo particulado e matriz de colágeno suíno: revisão de literatura e relato de caso clínico / Ridge preservation using particulate bone graft and Matrix of porcine collagem: Literature Review and clinical case report

Para tentar preservar as dimensões teciduais (ósseas e de tecido mole) do alvéolo até o momento da instalação do implante pode-se lançar mão de técnicas de preservação de alvéolos dentários imediatamente após a exodontia. Dentre as diversas técnicas e biomateriais existentes, a associação de um substituto ósseo (Bio-Oss® Collagen) com um selador do alvéolo (Mucograft® Seal) vem apresentando resultados satisfatórios na literatura. O objetivo do presente trabalho é apresentar uma breve revisão de literatura e um relato de caso clínico usando essa abordagem. Os principais achados da revisão de literatura é que a utilização desses substitutos mucosos e ósseos são a redução do tempo cirúrgico e diminuição da morbidade e desconforto pós-operatório do paciente, já que não necessita da área doadora. No relato de caso, os resultados clínicos de 15 e 60 dias de pós-operatório mostraram que essa abordagem foi eficaz em manter as dimensões ósseas e de tecido queratinizado do alvéolo. (AU)

In an effort to preserve the alveolar tissue dimensions (bone and soft tissue) until the time of implant installation can make use of ridge preservation techniques after the dental extraction. Among the many techniques and biomaterials the association of a bone substitute (Bio-Oss® Collagen) with an alveolar sealer (Mucograft® Seal) has shown satisfactory results in the literature.The objective of this study is present a brief literature review and a clinical case report using this approach. The main findings of the literature review are that the use of these mucosal and bone substitutes are the reduction of surgical time and decrease of the postoperative morbidity and discomfort of the patient, since it does not need the donor area. In the case reportthe clinical results of 15 and 60 days postoperatively showed that this approach was effective in maintaining bone dimensions and keratinized alveolar tissue (AU)

Uso de matriz colágena tridimensional no tratamento de retrações gengivais / Use of three-dimensional collagem matrix in the treatment of gengival recession

A retração gengival (RG) é definida como a migração apical da margem gengival além da junção amelocementária, em consequência de danos causados aos tecidos moles, o que leva à exposição radicular juntamente com a perda óssea. Esse problema é muito prevalente na população brasileira, e tem sido comumente associado à sensibilidade dentinária e comprometimento estético. O tratamento consiste, usualmente, na associação de um enxerto de tecido conjuntivo subepitelial (ETCS) e um reposicionamento coronal do retalho, procedimento que exige dois sítios cirúrgicos. A utilização da matriz colágena acelular (MCA) e matriz colágena suína (MC) nas cirurgias plásticas periodontais e mucogengivais, como substitutas ao ETCS, é uma opção de tratamento com resultados semelhantes. Nesse contexto, o uso das matrizes colágenas tridimensionais (MCT) possui a vantagem de evitar possíveis intercorrências pré e pós-operatórias, além de suplantar as limitações apresentadas pelo enxerto autógeno. As diferentes técnicas cirúrgicas utilizadas para o recobrimento radicular buscam previsibilidade e sucesso. Para isso, além do tipo de incisão, os posicionamentos do retalho e do enxerto são de extrema importância, pois beneficiam a cicatrização e o resultado final. O objetivo deste estudo foi demonstrar, através de um caso clínico, o estado atual das MCT e suas aplicabilidades clínicas.

Recobrimento em dois estágios com uso de matriz colágena suína Mucograft / Root covering in two stages with the use of porcine collagen matrix Mucograft

As retrações gengivais são caracterizadas pelo deslocamento da margem gengival em direção apical, a partir da junção cemento-esmalte. O enxerto de tecido conjuntivo (ETC) associado ao retalho posicionado coronalmente (RPC) foi considerado como a técnica mais previsível e estável na obtenção do completo recobrimento radicular. Objetivando superar as limitações do ETC, diversos biomateriais de origem alogênica e xenogênica foram desenvolvidos e incansavelmente testados em estudos pré-clínicos e clínicos para substituir o ETC nos procedimentos cirúrgicos periodontais, formando, então, o chamado grupo dos substitutos mucosos. A matriz colágena suína (MG) é um produto recentemente lançado e seu uso é indicado como um substituto para enxertos gengivais, podendo ser utilizado para aumento de tecido mole ao redor de dentes e implantes, em regeneração óssea guiada, reconstrução de rebordo alveolar, fechamento de alvéolos, para cobrir tecido ósseo exposto e para recobrimento radicular. O produto possui nome comercial de Mucograft e está comercialmente disponível. O objetivo deste estudo foi, através de um caso clínico, relatar o estado atual da matriz colágena suína e mostrar suas aplicabilidades clínicas.

Protocolos terapêuticos complementares para candidatos aos implantes nos casos de pacientes com diabetes, osteoporose e hábito de fumar / Supplementary therapeutic protocols for implant candidates in cases of diabetes, osteoporosis, and smoking – a literature review

O objetivo do estudo foi apresentar uma revisão da literatura relacionada à influência de fatores sistêmicos (diabetes, osteoporose e hábito de fumar) e possíveis protocolos de tratamento na terapia com implantes dentários nesses pacientes. A interrupção do tabagismo e o uso de antibióticos sistêmicos pré e pós-operatórios parecem otimizar o tratamento com implantes em fumantes ativos. Na presença de diabetes mellitus, apenas pacientes bem controlados podem ser candidatos a receber tratamento com implantes, não havendo evidências concretas de que pacientes diabéticos controlados apresentem risco aumentado na falha de implantes. O uso de antibióticos sistêmicos e bochechos com clorexidina 0,12% no pré e pós-operatório tem demonstrado aumento na sobrevivência de implantes em pacientes diabéticos. A osteoporose e o uso de bifosfonatos orais também não representam uma contraindicação absoluta para instalação de implantes dentários, sendo que o principal determinante para falhas no tratamento com implantes é a qualidade óssea local. A contraindicação absoluta está relacionada ao uso de bifosfonatos intravenosos. Sendo assim, concluiu-se que nenhum dos fatores sistêmicos analisados constitui uma contraindicação ao tratamento com implantes dentários, que o tratamento para pacientes com comprometimento sistêmico deve ser realizado mediante estabilização do quadro e avaliação óssea local, através de exames pré-operatórios, e que tratamentos complementares e técnicas menos traumáticas otimizam a terapia.

The aim of this study is to present a literature review on the influence of systemic factors (diabetes, osteoporosis, and smoking) and possible treatment protocols for dental implant therapy. Stop smoking and use of pre and postoperative systemic antibiotics seems to optimize implant treatment in active smokers. In the presence of diabetes mellitus, only well-controlled patients can be considered suitable for treatment with implants and there is no concrete evidence that controlled diabetic patients have an increased risk of implant failure. The use of systemic antibiotics and chlorhexidine mouthwashes before and after surgery has shown an increase in implant survival for diabetic patients. Osteoporosis and the use of oral bisphosphonates do not represent a contraindication for implant placement, being local bone quality the main determinant for implant failure. Absolute contraindications are related to the use of intravenous bisphosphonates. In conclusion, none of the analyzed systemic factors constitute a contraindication to implant placement; treatment for systemic patients should be achieved by stabilization of the systemic condition through preoperative tests, local bone assessment, and supplementary treatments with less traumatic techniques to optimize implant therapy.