Autophagy is a tightly regulated catabolic process that facilitates nutrient recycling from damaged organelles and other cellular components through lysosomal degradation. Deregulation of this process has been associated with the development of several pathophysiological processes, such as cancer and neurodegenerative diseases. In cancer, autophagy has opposing roles, being either cytoprotective or cytotoxic. Thus, deciphering the role of autophagy in each tumor context is crucial. Moreover, autophagy has been shown to contribute to chemoresistance in some patients. In this regard, autophagy modulation has recently emerged as a promising therapeutic strategy for the treatment and chemosensitization of tumors, and has already demonstrated positive clinical results in patients. In this review, the dual role of autophagy during carcinogenesis is discussed and current therapeutic strategies aimed at targeting autophagy for the treatment of cancer, both under preclinical and clinical development, are presented. The use of autophagy modulators in combination therapies, in order to overcome drug resistance during cancer treatment, is also discussed as well as the potential challenges and limitations for the use of these novel therapeutic strategies in the clinic.
Electromagnetic articulography (EMA) have been mostly employed to study articulatory movements of speech. This technology appears to be very promising for studying mandibular movements within the field of dentistry. However, there are no studies reporting the validity of EMA for such purpose. The aim of this study is to assess accuracy and reliability of Carstens three-dimensional EMA AG501 in order to validate its use for mandibular movement analysis in dentistry. A set of tests was conducted attaching 16 sensors to a rotating rigid structure placed inside the measurement area. Another set of tests were conducted using a mouth anatomical model with human-like articulatory behaviour. A function of the EMA system called “head correction” was applied to normalize the data of every recording. The system reliability was higher at the centre of the measurement area and decreased toward the edges. Dispersion was greater for raw data than for normalized data. Bland-Altman analysis of agreement between the AG501 and a millimetre ruler used to measure the distance between the sensors revealed limits of agreement between 0.5 mm and −0.9 mm. The results suggest that EMA AG501 is valid for three-dimensional analysis of mandibular biomechanics allowing natural movements.
Deglutition is a complex oral function, and the study of the whole process requires a precise analysis of the elements involved, especially of the tongue biomechanics. We described a three-dimensional analysis of tongue movements during both saliva and water deglutition in participants with normal occlusion. Fourteen participants (25.36 ± 4.85 years) were evaluated, and the movements of anterior, middle, and posterior portions of the tongue were recorded using AG501 3D-electromagnetic articulograph. An average volume (AVS) for water deglutition was determined for each participant. Saliva deglutition was classified according to Bourdiol et al. 35.71% was type I, 14.29% type II, and 50% type III. The greatest displacement on the inferior–superior axis was in the posterior portion, followed by the middle and anterior portions. In the posterior–anterior axis, smallest movement was in the anterior portion. During water deglutition, on the inferior–superior axis, there were statistical differences for 1-AVS between the anterior/middle and anterior/posterior portions of the tongue. There were statistical differences for both ½-AVS and ¼-AVS between the anterior/posterior portions of the tongue. On the posterior–anterior axis, there were no statistical differences among any volume–portion relations. On the medial–lateral axis, there was statistical difference for the ½-AVS between middle and posterior portions. The movement of the tongue portions was influenced by the volume and the element to be swallowed. The amplitude of the movement was directly proportional to the volume of water swallowed.
Objective: To assess the tooth survival rates, adverse events, and need for further treatment of teeth previously treated with regenerative endodontics undergoing orthodontic treatment. Material and Methods: A literature search was performed using MEDLINE, EMBASE, Cochrane, Scopus, and Lilacs databases, grey literature, and endodontic journals, and the date of the last search was 20 April 2022. The included studies involved patients undergoing orthodontic treatment and at least one tooth that was previously treated with regenerative endodontics. A narrative synthesis of the findings was made. The risk of bias and evidence quality were assessed using the Effective Public Health Practice Project tool and the GRADE approach. Results: Five case reports included seven patients and eight teeth with a follow-up of 4 to 11 years. The overall risk of bias was high, and the certainty of evidence was very low. The survival rate was 87.5%. Adverse effects included sinus tracts, root resorption, symptomatology, apical periodontitis, and intracanal tissue necrosis. Five out of eight teeth required further intervention after orthodontics. Conclusions: A high prevalence of adverse effects and further intervention is observed in teeth treated with regenerative endodontics undergoing orthodontic treatment. The low quality of evidence highlights the need for comparative studies and evidence-based guidelines for managing these teeth during orthodontic treatment.
Cancer is one of the leading causes of mortality worldwide due, in part, to limited success of some current therapeutic approaches. The clinical potential of many promising drugs is restricted by their systemic toxicity and lack of selectivity towards cancer cells, leading to insufficient drug concentration at the tumor site. To overcome these hurdles, we developed a novel drug delivery system based on polyurea/polyurethane nanocapsules (NCs) showing pH-synchronized amphoteric properties that facilitate their accumulation and selectivity into acidic tissues, such as tumor microenvironment. We have demonstrated that the anticancer drug used in this study, a hydrophobic anionophore named T21, increases its cytotoxic activity in acidic conditions when nanoencapsulated, which correlates with a more efficient cellular internalization. A biodistribution assay performed in mice has shown that the NCs are able to reach the tumor and the observed systemic toxicity of the free drug is significantly reduced in vivo when nanoencapsulated. Additionally, T21 antitumor activity is preserved, accompanied by tumor mass reduction compared to control mice. Altogether, this work shows these NCs as a potential drug delivery system able to reach the tumor microenvironment, reducing the undesired systemic toxic effects. Moreover, these nanosystems are prepared under scalable methodologies and straightforward process, and provide tumor selectivity through a smart mechanism independent of targeting ligands.