Análisis de las Variaciones Anatómicas y Dimensionales del Canal Nasopalatino Mediante Tomografía Computarizada de Haz Cónico / Analysis of the Anatomical and Dimensional Variations of the Nasopalatine Canal by Cone Beam Computed Tomography

El conocimiento anatómico del canal nasopalatino (CNP) es fundamental para la realización de cirugías en el sector anterior del maxilar y así prever posibles complicaciones. El objetivo de este trabajo es evaluar y determinar las variaciones anatómicas y dimensionales del CNP según sexo, edad y estado dental. Este estudio transversal analizó un total de 251 imágenes de TCHC obtenidas de la base de datos del Servicio de Imagenología Oral y Maxilofacial de la Facultad de Odontología de la Universidad Andrés Bello, Viña del Mar, Chile. Para evaluar la asociación estadística entre variaciones del CNP con sexo, edad y estado dentario se realizó la prueba T de Student, chi-cuadrado y ANOVA (p0,05). Además, se detectó diferencia significativa entre el estado dentario y la dimensión de la tabla vestibular en relación con el CNP (p<0,01). Se deben considerar las variaciones de CNP para evitar posibles complicaciones durante los procedimientos quirúrgicos.

SUMMARY: Anatomical knowledge of the nasopalatine canal (PNC) is essential for performing surgeries in the anterior sector of the maxilla and thus anticipating possible complications. The objective of this work is to evaluate and determine the anatomical and dimensional variations of the CNP according to sex, age and dental status. This cross-sectional study analyzed a total of 251 CBCT images obtained from the database of the Oral and Maxillofacial Imaging Service of the Faculty of Dentistry of the Andrés Bello University, Viña del Mar, Chile. To evaluate the statistical association between CNP variations with sex, age and dental status, the Student's T test, chi-square and ANOVA (p0.05). In addition, a significant difference was detected between the dental state and the dimension of the vestibular table in relation to the CNP (p<0.01). CNP variations should be considered to avoid potential complications during surgical procedures.

A Protocol to Produce Genetically Edited Primary Oral Keratinocytes Using the CRISPR-Cas9 System.

The Nobel Prize awarded gene editing system, CRISPR-Cas9, is probably one of the greatest achievements of the last decades. CRISPR-Cas9 can introduce irreversible genomic changes in its target DNA by simple specifying a 20-nucleotide sequence within its RNA guide. Due to its simplicity, efficacy, and relative low cost in comparison with other genome editing systems, it has become the most common gene editing system used in research laboratories. Here we describe a step-by-step protocol to produce genetically edited primary oral keratinocytes using the CRISPR-Cas9 system.

Treatment alternatives for dry mouth: A scoping review.

Background: Saliva is a biological fluid essential for the maintenance of a proper oral health. Its absence predisposes to differences pathologies, including dental caries, fungal infections among many others, significantly affecting the oral health related quality of life (OHRQoL). There is a large variety of treatment alternatives available for dry mouth, which increases constantly. Objective: To identify new treatment alternatives for dry mouth. Material and Methods: We conducted a systematic search in PubMed/MEDLINE, Web of Science, Scopus and Ebsco. Articles published between January 2015 and January 2020 were retrieved and reviewed by two independent evaluators. Results: Nineteen studies met the inclusion criteria and were included for analysis. Local therapies were the most evaluated agents, followed by systemic and non-conventional treatments. Most local therapies showed certain utility for the management of dry mouth and the improvement of OHRQoL. These formulations were mainly based on natural agents, including malic acid, thyme honey, ginger, among others. Conclusions: Local agents are first line treatment alternatives for dry mouth sensation, with a reported efficiency that varies between studies, and with a low number of reported adverse side-effects. Nevertheless, care must be taken when interpreting these results, as is difficult to compare studies within each other due large heterogeneity in study design and outcomes being measured. Key words:Xerostomia, dry mouth, hyposalivation, saliva, mouth dryness.

Senescent Cells in Cancer: Wanted or Unwanted Citizens.

Over recent decades, the field of cellular senescence has attracted considerable attention due to its association with aging, the development of age-related diseases and cancer. Senescent cells are unable to proliferate, as the pathways responsible for initiating the cell cycle are irreversibly inhibited. Nevertheless, senescent cells accumulate in tissues and develop a pro-inflammatory secretome, known as the senescence-associated secretory phenotype (SASP), which can have serious deleterious effects if not properly regulated. There is increasing evidence suggesting senescent cells contribute to different stages of carcinogenesis in different anatomical sites, mainly due to the paracrine effects of the SASP. Thus, a new therapeutic field, known as senotherapeutics, has developed. In this review, we aim to discuss the molecular mechanisms underlying the senescence response and its relationship with cancer development, focusing on the link between senescence-related inflammation and cancer. We will also discuss different approaches to target senescent cells that might be of use for cancer treatment.

The role of icIL-1RA in keratinocyte senescence and development of the senescence-associated secretory phenotype.

There is compelling evidence that senescent cells, through the senescence-associated secretory phenotype (SASP), can promote malignant transformation and invasion. Interleukin-1 (IL-1) is a key mediator of this cytokine network, but the control of its activity in the senescence programme has not been elucidated. IL-1 signalling is regulated by IL-1RA, which has four variants. Here, we show that expression of intracellular IL-1RA type 1 (icIL-1RA1), which competitively inhibits binding of IL-1 to its receptor, is progressively lost during oral carcinogenesis ex vivo and that the pattern of expression is associated with keratinocyte replicative fate in vitro We demonstrate that icIL-1RA1 is an important regulator of the SASP in mortal cells, as CRISPR/Cas9-mediated icIL-1RA1 knockdown in normal and mortal dysplastic oral keratinocytes is followed by increased IL-6 and IL-8 secretion, and rapid senescence following release from RhoA-activated kinase inhibition. Thus, we suggest that downregulation of icIL-1RA1 in early stages of the carcinogenesis process can enable the development of a premature and deregulated SASP, creating a pro-inflammatory state in which cancer is more likely to arise.

Inflammatory Mediators in Oral Cancer: Pathogenic Mechanisms and Diagnostic Potential.

Approximately 15% of cancers are attributable to the inflammatory process, and growing evidence supports an association between oral squamous cell carcinoma (OSCC) and chronic inflammation. Different oral inflammatory conditions, such as oral lichen planus (OLP), submucous fibrosis, and oral discoid lupus, are all predisposing for the development of OSCC. The microenvironment of these conditions contains various transcription factors and inflammatory mediators with the ability to induce proliferation, epithelial-to-mesenchymal transition (EMT), and invasion of genetically predisposed lesions, thereby promoting tumor development. In this review, we will focus on the main inflammatory molecules and transcription factors activated in OSCC, with emphasis on their translational potential.

IL-1/IL-1R Signaling in Head and Neck Cancer.

Decades ago, the study of cancer biology was mainly focused on the tumor itself, paying little attention to the tumor microenvironment (TME). Currently, it is well recognized that the TME plays a vital role in cancer development and progression, with emerging treatment strategies focusing on different components of the TME, including tumoral cells, blood vessels, fibroblasts, senescent cells, inflammatory cells, inflammatory factors, among others. There is a well-accepted relationship between chronic inflammation and cancer development. Interleukin-1 (IL-1), a potent pro-inflammatory cytokine commonly found at tumor sites, is considered one of the most important inflammatory factors in cancer, and has been related with carcinogenesis, tumor growth and metastasis. Increasing evidence has linked development of head and neck squamous cell carcinoma (HNSCC) with chronic inflammation, and particularly, with IL-1 signaling. This review focuses on the most important members of the IL-1 family, with emphasis on how their aberrant expression can promote HNSCC development and metastasis, highlighting possible clinical applications.

Genetic Profile of Adenomatoid Odontogenic Tumor and Ameloblastoma. A Systematic Review.

Purpose: To perform a comprehensive and systematic critical appraisal of the genetic alterations reported to be present in adenomatoid odontogenic tumor (AOT) compared to ameloblastoma (AM), to aid in the understanding in their development and different behavior. Methods: An electronic search was conducted in PubMed, Scopus, and Web of Science during March 2021. Eligibility criteria included publications on humans which included genetic analysis of AOT or AM. Results: A total of 43 articles reporting 59 AOTs and 680 AMs were included. Different genomic techniques were used, including whole-exome sequencing, direct sequencing, targeted next-generation sequencing panels and TaqMan allele-specific qPCR. Somatic mutations affecting KRAS were identified in 75.9% of all AOTs, mainly G12V; whereas a 71% of the AMs harbored BRAF mutations, mainly V600E. Conclusions: The available genetic data reports that AOTs and AM harbor somatic mutations in well-known oncogenes, being KRAS G12V/R and BRAFV600E mutations the most common, respectively. The relatively high frequency of ameloblastoma compared to other odontogenic tumors, such as AOT, has facilitated the performance of different sequencing techniques, allowing the discovery of different mutational signatures. On the contrary, the low frequency of AOTs is an important limitation for this. The number of studies that have a assessed the genetic landscape of AOT is still very limited, not providing enough evidence to draw a conclusion regarding the relationship between the genomic alterations and its clinical behavior. Thus, the presence of other mutational signatures with clinical impact, co-occurring with background KRAS mutations or in wild-type KRAS cases, cannot be ruled out. Since BRAF and RAS are in the same MAPK pathway, it is interesting that ameloblastomas, frequently associated with BRAFV600E mutation have aggressive clinical behavior, but in contrast, AOTs, frequently associated with RAS mutations have indolent behavior. Functional studies might be required to solve this question.