Cholangiocarcinoma Malignant Traits Are Promoted by Schwann Cells through TGFß Signaling in a Model of Perineural Invasion.

The term cholangiocarcinoma (CCA) defines a class of epithelial malignancies originating from bile ducts. Although it has been demonstrated that CCA patients with perineural invasion (PNI) have a worse prognosis, the biological features of this phenomenon are yet unclear. Our data show that in human intrahepatic CCA specimens with documented PNI, nerve-infiltrating CCA cells display positivity of the epithelial marker cytokeratin 7, lower with respect to the rest of the tumor mass. In an in vitro 3D model, CCA cells move towards a peripheral nerve explant allowing contact with Schwann cells (SCs) emerging from the nerve. Here, we show that SCs produce soluble factors that favor the migration, invasion, survival and proliferation of CCA cells in vitro. This effect is accompanied by a cadherin switch, suggestive of an epithelial-mesenchymal transition. The influence of SCs in promoting the ability of CCA cells to migrate and invade the extracellular matrix is hampered by a specific TGFß receptor 1 (TGFBR1) antagonist. Differential proteomic data indicate that the exposure of CCA cells to SC secreted factors induces the upregulation of key oncogenes and the concomitant downregulation of some tumor suppressors. Taken together, these data concur in identifying SCs as possible promoters of a more aggressive CCA phenotype, ascribing a central role to TGFß signaling in regulating this process.

Endolysosomal two-pore channel 2 plays opposing roles in primary and metastatic malignant melanoma cells.

The ion channel two-pore channel 2 (TPC2), localised on the membranes of acidic organelles such as endo-lysosomes and melanosomes, has been shown to play a role in pathologies including cancer, and it is differently expressed in primary versus metastatic melanoma cells. Whether TPC2 plays a pro- or anti-oncogenic role in different tumour conditions is a relevant open question which we have explored in melanoma at different stages of tumour progression. The behaviour of primary melanoma cell line B16F0 and its metastatic subline B16F10 were compared in response to TPC2 modulation by silencing (by small interfering RNA), knock-out (by CRISPR/Cas9) and overexpression (by mCherry-TPC2 transfected plasmid). TPC2 silencing increased cell migration, epithelial-to-mesenchymal transition and autophagy in the metastatic samples, but abated them in the silenced primary ones. Interestingly, while TPC2 inactivation failed to affect markers of proliferation in both samples, it strongly enhanced the migratory behaviour of the metastatic cells, again suggesting that in the more aggressive phenotype TPC2 plays a specific antimetastatic role. In line with this, overexpression of TPC2 in B16F10 cells resulted in phenotype rescue, that is, a decrease in migratory ability, thus collectively resuming traits of the B16F0 primary cell line. Our research shows a novel role of TPC2 in melanoma cells that is intriguingly different in initial versus late stages of cancer progression.

Fast and portable fluorescence lifetime analysis for early warning detection of micro- and nanoplastics in water.

The presence of plastic fragments in aquatic environments, particularly at the micro- and nano-scale, has become a significant global concern. However, current detection methods are limited in their ability to reveal the presence of such particles in liquid samples. In this study, we propose the use of a fluorescence lifetime analysis system for the detection of micro- and nanoplastics in water. This approach relies on the inherent endogenous fluorescence of plastic materials and involves the collection of single photons emitted by plastic fragments upon exposure to a pulsed laser beam. Briefly, a pulsed laser beam (repetition frequency = 40 MHz) shines onto a sample solution, and the emitted light is filtered, collected, and used to trace the time distributions of the photons with high temporal resolution. Finally, the fluorescence lifetime was measured using fitting procedures and a phasor analysis. Phasor analysis is a fit-free method that allows the measurement of the fluorescence lifetime of a sample without any assumptions or prior knowledge of the sample decay pattern. The developed instrument was tested using fluorescence references and validated using unlabelled micro- and nano-scale particles. Our system successfully detected polystyrene particles in water, achieving a remarkable sensitivity with a detection limit of 0.01 mg/mL, without the need for sample pre-treatment or visual inspection. Although further studies are necessary to enhance the detection limit of the technique and distinguish between different plastic materials, this proof-of-concept study suggests the potential of the fluorescence lifetime-based approach as a rapid, robust, and cost-effective method for early warning detection and identification of plastic contaminants in aquatic environments.

Manejo de analgésicos en ortodoncia / Analgesic management in orthodontics

Antecedentes: El dolor y el miedo al dolor durante el tratamiento odontológico son frecuentes tanto en la práctica general como en la especialidad de la ortodoncia. El dolor de variada intensidad se presenta en 94% de los pacientes durante el primer día del tratamiento ortodóncico y todavía al sexto día lo padece aproximadamente 50%. Sin embargo, en muchas ocasiones los pacientes no reciben una receta médica o medicamentos para el alivio del dolor y esto puede conducir a la automedicación. Objetivos: El propósito de este estudio fue determinar el manejo del dolor que el ortodoncista realiza durante el tratamiento dental. Material y métodos: Este estudio es de tipo transversal mediante una encuesta de respuesta inmediata a 51 odontólogos especialistas en ortodoncia egresados de diferentes universidades y en diferentes tiempos. Asimismo, fueron entrevistados 100 pacientes ortodóncicos portadores de brackets a quienes se les realizaron preguntas relacionadas con la percepción de dolor y el manejo farmacológico de éste durante la cementación de brackets, cambio del arco de alambre o activación de sus aparatos. Resultados: 35.3% (n = 18/51) de los ortodoncistas prescriben analgésicos de manera habitual, mientras que 64.7% (n = 33/51) no lo hacen y 29.4% (n = 15/51) los indican con horario fijo. El analgésico de elección fue el paracetamol (64.7%; n = 33/51). 51% (n = 26/51) de los ortodoncistas refieren que no emplean analgésicos porque no existe dolor durante el tratamiento dental, o si lo hay, es leve, transitorio y tolerable. 52% (n = 52/100) recibió la instrucción verbal de tomar analgésicos en caso de ser necesario, mientras que al resto no se le dio tal indicación. Del total de pacientes sólo 4% (n = 4/100) no percibió dolor durante el tratamiento, en tanto que el resto presentó dolor leve (19%), moderado (57%) y severo (20%). La frecuencia de días con dolor posterior a la cementación o activación de los brackets fue de 1-3 días (56%). El principal trastorno ocasionado por el tratamiento fue la alteración de la masticación, es decir, la incapacidad y/o dolor durante la masticación se presentó en 86%, y 42% se adaptó a la presencia de los brackets en su boca en un tiempo de entre dos a cuatro semanas. Conclusiones: La mayoría de los ortodoncistas encuestados afirman que el dolor producido por las fuerzas ortodóncicas es de baja intensidad y el paciente lo tolera muy bien, por lo que la administración de analgésicos es innecesaria y cuando tienen que recetar algún medicamento, el de su preferencia es el paracetamol; sin embargo, no lo recetan con dosis y horario fijo. La afirmación de parte de 51% de los ortodoncistas respecto a que el paciente no presenta dolor durante el tratamiento ortodóncico no se cumple, ya que se encontró que 77% de los pacientes presentaron dolor entre moderado y severo durante al menos 1-3 días posteriores a la cementación o activación de los aparatos (AU)

Background: Pain and fear of suffering during the orthodontic treatment, are still frequent in both general and specialty dental practice, including the orthodontics. The pain with different intensity, it is shown in the 94% of the patient, during the 1st day of the orthodontic treatment but still, during the 6th day, it appears to the 50% of the patients. Nevertheless, on many occasions, the patients do not receive any prescription or pain relief medication and this may lead to self-medication. Objectives: The purpose of this study was to determine the pain management that the orthodontist performs during dental treatment. Material and methods: This cross-sectional study was carried out by an immediate response survey to 51 orthodontic dentists graduated from different universities and at different times. We also interviewed 100 orthodontic patients who were asked questions related to their perception of pain and its pharmacological management during the activation of the devices. Results: 35.3% (n = 18/51) of orthodontists usually prescribe analgesics while the 64.7% (n = 33/51) they won't give any prescriptions; 29.4% (n = 15/51) indicating a specific time. The analgesic choice was paracetamol (64.7%; n = 33/51). 51% (n = 26/51) of the orthodontist they said that most of the time they won't give any prescription because there was no pain during the dental treatment, or in case that exists, they comment that is transitory or is a tolerated pain. The 52% (n = 52/100) they received the indication of taking analgesics in case they needed it, whereas the rest weren't receiving any indication. Of all patients only 4% (n = 4/100) did not feel pain during their treatment; meanwhile, the 19% felt a mild pain; 57% felt a moderate pain and 20% severe pain. The frequency with pain after the cementation or activation of the devices it is about 1 to 3 days (56%). The main disorder by the treatment was the chewing alteration (86%), and the 42% adapted to their braces in a time of 2-4 weeks. Conclusions: The majority of orthodontists enrolled, they had commented that the pain produced by the force of the braces is a low intensity and that the patient will tolerate without any problem, and because of that, there isn't a need to give them any prescription, and when there's a need the one of their preference is paracetamol, nevertheless they don't give the prescription with time and required doses. The affirmation from the 51% of the orthodontist about the patient that does not suffer any pain during their orthodontic treatment it's not according to the 77% who felt pain between moderate and severe during at least 1-3 days after the cementation or activation of devices (AU)