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PIK3CA-related overgrowth spectrum (PROS) encompasses different clinical entities caused by somatic activating mutations in PIK3CA. Among PROS, CLOVES syndrome represents a severe phenotype with poor survival rate. We present the case of a 4-month-old girl with CLOVES syndrome successfully treated with alpelisib, a PIKC3A inhibitor.

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Colorectal cancer is a widespread neoplasia with high ratios of chemoresistance. Phytochemicals in plant-based extracts could be useful to treat colorectal cancer, and/or reduce chemoresistance. Methanolic extract of avocado mesocarp (MEAM) has demonstrated antitumoral properties, depending on the fruit ripening stage (RS). The aim of this study was to analyze the effects of methanolic extracts of "Hass" avocado fruit at different RS on cytotoxicity, antioxidative, anti-inflammatory, anti-invasive, cell cycle, and epithelial-mesenchymal transition inhibition in colorectal adenocarcinoma cell line HT29. The MEAM showed an increasing concentration of total phenolic compounds as the RS progressed, which was correlated with antioxidant capacity measured by the Ferric Reducing Antioxidant Power assay but not with the 2.2-diphenyl-1-picrylhydrazyl assay. The specific phenolic compounds of MEAM were determined by high-performance liquid chromatography, and it was found that concentrations of epicatechin decreased while concentrations of chlorogenic acid increased as the RS progressed. The HT29 cell line was treated with MEAM for 48 h, and all MEAM had a cytotoxic effect, reported by MTT assay, nevertheless, the strongest effect was associated with the presence of chlorogenic acid. MEAM induced apoptosis and cell cycle arrest in phase G0/G1, reported by flow cytometry. Moreover, MEAM inhibited cell migration evidenced by the wound healing assay. On the other hand, MEAM significantly reduced expression of mRNA of tumor necrosis factor-alpha and cyclooxygenase 2. These effects comprise important inhibition of some hallmarks of cancer. This, in turn, may provide interesting guidelines for developing antitumoral intervention agents.

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El maltrato infantil (MI) es un problema multidimensional. El estrés crónico producido por dicho fenómeno afecta el desarrollo cerebral de niños, niñas y adolescentes (NNA), incidiendo negativamente en la evolución de diversos aspectos del desarrollo, condicionando su vida futura. El objetivo de este estudio es analizar el desempeño sociocognitivo de NNA que han vivenciado MI, mediante el análisis de las funciones del neurodesarrollo, evaluado con subpruebas de la NEPSY II. Se analizan funciones ejecutivas y percepción social, bases del razonamiento y adaptación social. Se estudia el desempeño de 14 de NNA pertenecientes a un Programa de la Fundación Súmate, cuya Misión es la recuperación de la escolaridad NNA que han visto alterado el curso de su desarrollo por MI. Los resultados dan cuenta de alteraciones cerebrales asociadas al MI, las que se evidencian en un deficitario desarrollo funcional de las variables estudiadas. Existe grave descenso en los procesos y subprocesos del funcionamiento ejecutivo. En relación con la percepción social, la muestra estudiada presenta un mejor desarrollo, el que desciende a medida que aumenta la edad. Las funciones estudiadas tienen directa relación con el razonamiento cognitivo y desarrollo socio adaptativo, bases sobre las que se estructura el desarrollo académico. Los hallazgos, refuerzan la urgencia de abordar esta sensible realidad desde la práctica médica en la atención primaria y especializada. Los resultados también son de utilidad para orientar el desarrollo de políticas públicas que efectivamente contribuyan al progreso de nuestro país.

Abstract. Child maltreatment (MI) is a multidimensional problem. The chronic stress produced by this phenomenon affects the brain development of children and adolescents (NNA), negatively affecting the evolution of various aspects of development, conditioning their future life. The objective of this study is to analyze the sociocognitive performance of children and adolescents who have experienced IM, through the analysis of the performance of neurodevelopmental functions, evaluated through subtests of the NEPSY II. Executive functions and social perception, reasoning bases and social adaptation are studied. The performance of 14 NNA belonging to a Fundación Súmate Program is studied, whose mission is the recovery of NNA schooling that has seen the course of their development altered by IM. The results show brain alterations associated with MI, evidenced in a deficient functional development of the variables studied. There is a serious decline in the processes and threads of executive functioning. In relation to social perception, the studied sample presents a better development, which decreases as age increases. The functions studied are directly related to cognitive reasoning and socio-adaptive development, based on which academic development is structured. The findings reinforce the urgency of addressing this sensitive reality from medical practice in primary and specialized care. The results are also useful to guide the development of public policies that effectively contribute to the progress of our country.

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Store-operated calcium entry (SOCE) is an important process in calcium signaling. Its role in physiological and pathological events is well recognized. However, in cancerous systems, the importance of SOCE in relation to the degree of cancer aggressiveness, as well as its regulation by ligands such as purinergic molecules, are not well documented. This study aimed to characterize a differential effect of the P2Y2 receptor (promoted by UTP of 10 µM and inhibited by ARC118925XX of 1 µM) on intracellular calcium response between metastatic (SKOV-3) and non-metastatic (CAOV-3) ovarian cell lines in conditions of normal (1.5 mM) and zero extracellular calcium concentration. The sustained calcium influx observed exclusively in SKOV-3 cells was associated with the presence of SOCE (promoted by thapsigargin (74.81 ± 0.94 ΔF) and sensitive to 2-APB (20.60 ± 0.85 ΔF)), whereas its absence in CAOV-3 cells (26.2 ± 6.1 ΔF) was correlated with a low expression of ORAI1. The relevance of SOCE in metastatic SKOV-3 cells was further corroborated when 2-APB significantly inhibited (40.4 ± 2.8% of covered area) UTP-induced cell migration (54.6 ± 3.7% of covered area). In conclusion, our data suggest that SOCE activation elicited by the P2Y2 receptor is involved in the aggressiveness of ovarian cancer cells.

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We describe the demographic, clinical, radiological, and laboratory findings relating them also to the severity and clinical outcome of 129 children (0-18 years) who were admitted to a tertiary care pediatric hospital in Mexico City due to severe acute respiratory syndrome coronavirus 2 infection between April 1, 2020 and March 31, 2021. The infection was confirmed using reverse transcription-polymerase chain reaction Fever (82.2%), tachypnea (72.1%), and cough (71.3%) were the most reported signs at the moment of hospitalization. The most frequent radiological pattern that stood out was the interstitial pattern (66.7%). History of oncologic pathology (25.6%) was the most frequent past medical history. Non-steroidal anti-inflammatory drugs (93%), antibiotics (57.4%), and steroids (40.3%) were the most common medication given. The average hospitalization stay was 14.2 days, and 21.7% of the total patients required transfer to the intensive care unit. At discharge, 20.2% required oxygen on an outpatient basis, and unfortunately, 7.0% of the patients who were admitted to the institute for COVID-19 died. Our findings confirm that COVID-19 in children has a mild presentation except for patients with hematologic/oncologic comorbidities who had severe presentations.

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Inflammation mediated by the innate immune system is a physiopathological response to diverse detrimental circumstances such as microbe infections or tissular damage. The molecular events that underlie this response involve the assembly of multiprotein complexes known as inflammasomes. These assemblages are essentially formed by a stressor-sensing protein, an adapter protein and a non-apoptotic caspase (1 or 11). The coordinated aggregation of these components mediates the processing and release of pro-inflammatory interleukins (IL-ß and IL-18) and cellular death by pyroptosis induction. The inflammatory response is essential for the defense of the organism; for example, it triggers tissue repair and the destruction of pathogen microbe infections. However, when inflammation is activated chronically, it promotes diverse pathologies in the lung, liver, brain and other organs. The nervous system is one of the main tissues where the inflammatory process has been characterized, and its implications in health and disease are starting to be understood. Thus, the regulation of inflammasomes in specific cellular types of the central nervous system needs to be thoroughly understood to innovate treatments for diverse pathologies. In this review, the presence and participation of inflammasomes in pathological conditions in different types of glial cells will be discussed.

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The purinergic system is fundamental in the tumor microenvironment, since it regulates tumor cell interactions with the immune system, as well as growth and differentiation in autocrine-paracrine responses. Here, we investigated the role of the adenosine A2B receptor (A2BR) in ovarian carcinoma-derived cells' (OCDC) properties. From public databases, we documented that high A2BR expression is associated with a better prognostic outcome in ovarian cancer patients. In vitro experiments were performed on SKOV-3 cell line to understand how A2BR regulates the carcinoma cell phenotype associated with cell migration. RT-PCR and Western blotting revealed that the ADORA2B transcript (coding for A2BR) and A2BR were expressed in SKOV-3 cells. Stimulation with BAY-606583, an A2BR agonist, induced ERK1/2 phosphorylation, which was abolished by the antagonist PSB-603. Pharmacological activation of A2BR reduced cell migration and actin stress fibers; in agreement, A2BR knockdown increased migration and enhanced actin stress fiber expression. Furthermore, the expression of E-cadherin, an epithelial marker, increased in BAY-606583-treated cells. Finally, cDNA microarrays revealed the pathways mediating the effects of A2BR activation on SKOV-3 cells. Our results showed that A2BR contributed to maintaining an epithelial-like phenotype in OCDC and highlighted this purinergic receptor as a potential biomarker.

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Tissue engineering has been able to develop novel decellularization-recellularization techniques, which facilitates the research for the generation of functional organs. This is based in the initial obtention of the organ's extracellular matrix (ECM). Therefore, any improvement in the decellularization process would have a positive impact in the results of the recellularization process. Nevertheless, commonly the methods and equipment employed for this process are expensive and thus limit the access of this technique to various research groups globally. To develop a decellularization technique with the exclusive use of hydrostatic pressure of detergent solutions, to have an easily accessible and low-cost technique that meets the basic requirements of acellularity and functionality of the ECM. This experimental study was performed in 10 male Wistar rats, obtaining the liver to carry out serial washes, with 1%, 2%, and 3% Triton X-100 solutions and 0.1% SDS. The washes were performed by using a gravity perfusion system (GPS), which assured us a continuous hydrostatic pressure of 7.5 mmHg. The obtained ECM was processed using stains and immunostaining to determine the residual cell content and preservation of its components. The staining showed a removal of cellular and nuclear components of approximately 97% of the acellular ECM, with an adequate three-dimensional pattern of collagen and proteoglycans. Furthermore, the acellular ECM allowed the viability of a primary hepatocyte culture. The use of the GPS decellularization technique allowed us to obtain an acellular and functional ECM, drastically reducing experimentation costs.

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Gastric cancer (GC) is a major health concern worldwide, presenting a complex pathophysiology that has hindered many therapeutic efforts so far. In this context, purinergic signaling emerges as a promising pathway for intervention due to its known role in cancer cell proliferation and migration. In this work, we explored in more detail the role of purinergic signaling in GC with several experimental approaches. First, we measured extracellular ATP concentrations on GC-derived cell lines (AGS, MKN-45, and MKN-74), finding higher levels of extracellular ATP than those obtained for the non-tumoral gastric cell line GES-1. Next, we established the P2Y2 and P2X4 receptors (P2Y2R and P2X4R) expression profile on these cells and evaluated their role on cell proliferation and migration after applying overexpression and knockdown strategies. In general, a P2Y2R overexpression and P2X4R downregulation pattern were observed on GC cell lines, and when these patterns were modified, concomitant changes in cell viability were observed. These modifications on gene expression also modified transepithelial electrical resistance (TEER), showing that higher P2Y2R levels decreased TEER, and high P2X4R expression had the opposite effect, suggesting that P2Y2R and P2X4R activation could promote and suppress epithelial-mesenchymal transition (EMT), respectively. These effects were confirmed after treating AGS cells with UTP, a P2Y2R-agonist that modified the expression patterns towards mesenchymal markers. To further characterize the effects of P2Y2R activation on EMT, we used cDNA microarrays and observed that UTP induced important transcriptional changes on several cell processes like cell proliferation induction, apoptosis inhibition, cell differentiation induction, and cell adhesion reduction. These results suggest that purinergic signaling plays a complex role in GC pathophysiology, and changes in purinergic balance can trigger tumorigenesis in non-tumoral gastric cells.

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In this article, we show an alternative low-cost fabrication method to obtain poly(dimethyl siloxane) (PDMS) microfluidic devices. The proposed method allows the inscription of micron resolution channels on polystyrene (PS) surfaces, used as a mold for the wanted microchip's production, by applying a high absorption coating film on the PS surface to ablate it with a focused low-power visible laser. The method allows for obtaining micro-resolution channels at powers between 2 and 10 mW and can realize any two-dimensional polymeric devices. The effect of the main processing parameters on the channel's geometry is presented.