الملخص
Abstract Background Neurofibromatosis type 1 (NF1) is a rare genetic disorder with a wide range of clinical manifestations, notably neurocutaneous features, that can lead to emotional and physical consequences. Objectives This study assessed the influence of sociodemographic factors and clinical features of the disease on the quality of life of Brazilian individuals with NF1. Methods This is a descriptive cross-sectional study. Data were collected from 101 individuals with NF1 using the Brazilian version of the Impact of NF1 on Quality of Life Questionnaire (INF1-QoL), a form with information on sociodemographic characteristics, and an NF1 visibility self-evaluation scale. The relationship between variables was evaluated through statistical testing, and the significance level was defined as 0.05. Results The study included 101 adults with NF1 aged 18 to 59 years, with a mean age of 35.54 years (±9.63) and a female predominance (n = 84, 83.17%). The mean total INF1-QoL score was 10.62 (±5.63), with a median of 10, minimum value of 0, and maximum of 31 points. Two characteristics of the participants were significantly associated with the quality of life: educational level (p = 0.003) and familial history of NF1 (p = 0.019). There was a statistically significant correlation between the INF1-QoL score and the degree of disease visibility (rho = 0.218; p = 0.028). Study limitations Cross-sectional study, conducted with a convenience sample and using self-reported measures. Conclusions The findings support the significant impact of NF1 on quality of life. The authors recommend multidisciplinary follow-up for patients, with adherence to anticipatory clinical care measures, adequate pain control, psychological assistance, and genetic counseling.
الملخص
Se presenta el caso de un lactante de 2 meses que fue llevado a consulta varias veces por llanto problemático, inicialmente interpretado como de causa gastrointestinal. Dado que el síntoma persistía, se sospechó de una fractura debido a su asociación con la movilización de los miembros y la palpación de una tumoración en la cara anterior de la tibia derecha. Las radiografías mostraron compromiso poliostótico diafisario y lesiones compatibles con compromiso cortical de huesos largos. Se realizó el diagnóstico operativo de síndrome de Caffey-De Toni-Silverman y se inició el tratamiento con antiinflamatorios no esteroideos, lo que resultó en una remisión sintomática. Posteriormente, se confirmó el diagnóstico mediante la identificación de la variante patogénica COL1A1 en estado heterocigota. Se trata de una patología rara de la cual se estima una incidencia de 48/100 000 y hay menos de 150 casos descritos al momento.
Here we describe the case of a 2-month-old infant who consulted several times due to excessive crying, initially interpreted as having a gastrointestinal cause. Since the symptom persisted, a fracture was suspected due to its association with mobilization of the limbs and palpation of a mass on the anterior aspect of the right tibia. X-rays showed diaphyseal polyostotic involvement and lesions compatible with cortical involvement of long bones. Caffey-De Toni-Silverman syndrome was diagnosed and treatment with nonsteroidal anti-inflammatory drugs was initiated, resulting in symptom remission. Subsequently, the diagnosis was confirmed by the identification of the pathogenic heterozygous variant COL1A1. This is a rare condition with an estimated incidence of 48/100 000 individuals, and less than 150 cases have been described to date.
الموضوعات
Humans , Male , Infant , Crying , Hyperostosis, Cortical, Congenital/diagnosis , Collagen Type I/genetics , Collagen Type I, alpha 1 Chainالملخص
Introducción. La pandemia por COVID-19 afectó la atención de pacientes con diabetes mellitus tipo 1 (DM1). Además, se reportó un aumento de cetoacidosis diabética (CAD) como forma de diagnóstico. Objetivos. Evaluar si durante la pandemia por COVID-19 se modificaron el tiempo de evolución de síntomas, las causas de hospitalización por DM1 y la proporción de formas graves, y describir la infección por SARS-CoV-2 en estos pacientes. Población y métodos. Estudio transversal que incluyó pacientes menores de 19 años hospitalizados por DM1 en un centro pediátrico de referencia de marzo de 2018 a agosto de 2019 (prepandemia) y de marzo de 2020 a agosto de 2021 (pandemia). Resultados. Se analizaron 231 internaciones, 135 prepandemia y 96 en pandemia. Los pacientes con debut diabético presentaron menor tiempo de evolución de síntomas en pandemia que en prepandemia (18,8 ± 10,2 vs. 52,1 ±12,1 días, respectivamente; p <0,001). Las hospitalizaciones por todas las formas de debut diabético y el debut con CAD fueron más frecuentes en pandemia que en prepandemia (59,4 % vs. 39,3 %; OR 2,3; IC95% 1,3-3,8; p = 0,003); y (40,6 % vs. 20,7 %; OR 2,6; IC95% 1,4-5,2; p = 0,006) respectivamente. La proporción de formas graves de CAD no se modificó entre ambos períodos (48,1 % vs. 59,9 %; p = 0,3). Solo 6 pacientes presentaron infección por SARS-CoV-2; 3 fueron formas graves. Conclusión. Durante la pandemia, disminuyó el tiempo de evolución de síntomas y aumentó la frecuencia de hospitalizaciones por debut de DM1, con mayor proporción de CAD. No se modificó la proporción de formas graves de CAD
Introduction. The COVID-19 pandemic impacted on the health care of patients with type 1 diabetes mellitus (DM1). An increase in diabetic ketoacidosis (DKA) as a form of diagnosis was reported. Objectives. To assess whether there were changes in the time from symptom onset, the causes of hospitalization due to DM1, and the proportion of severe forms, and to describe SARS-CoV-2 infection in these patients. Population and methods. Cross-sectional study in patients younger than 19 years hospitalized due to DM1 from March 2018 to August 2019 (pre-pandemic) and from March 2020 to August 2021 (pandemic). Results. The assessment included 135 hospitalizations in the pre-pandemic period and 96 during the pandemic. The time from symptom onset during the pandemic in those with debutof diabetes was shorter than in the pre-pandemic period (18.8 ± 10.2 versus 52.1 ± 12.1 days, respectively; p < 0.001). Hospitalizations due to all forms of diabetes debut and debut with DKA were more common during the pandemic than before it (59.4% versus 39.3%; odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.33.8; p = 0.003 and 40.6% versus 20.7%; OR: 2.6; 95% CI: 1.45.2; p = 0.006, respectively). Severe forms of DKA did not change between both periods (48.1% versus 59.9%; p = 0.3). Only 6 patients developed SARS-CoV-2 infection; 3 were severe. Conclusion. During the pandemic, the time from symptom onset decreased and the frequency of hospitalizations due to debut of DM1 increased. The proportion of severe forms of DKA did not change.
الموضوعات
Humans , Male , Female , Child, Preschool , Child , Adolescent , Diabetic Ketoacidosis/diagnosis , Diabetic Ketoacidosis/epidemiology , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , Hospitalization/statistics & numerical data , Time Factors , Cross-Sectional Studiesالملخص
SUMMARY: Glucose has an essential role in the proliferation and survival of testicular tissue. Glucose transporters (GLUTs) are responsible for glucose uptake across cell membranes. In the present work, two main isoforms GLUT1 and GLUT3 were investigated in the testes of Laboratory mouse (BALB/c), Lesser Egyptian jerboa (Jaculus jaculus), Golden hamster (Mesocricetus auratus), and Desert Hedgehog (Paraechinus aethiopicus). Immunofluorescent localization of GLUT1 and GLUT3 showed considerable species differences. The lowest expression of GLUT1 and GLUT3 was localized in the testis of Laboratory mouse (BALB/c), the highest GLUT1 localization was detected in the testis of Lesser Egyptian jerboa (Jaculus jaculus), and the highest GLUT3 immunofluorescent localization was observed in the testis of Hedgehog (Paraechinus aethiopicus). The results imply that GLUT3 is the principal glucose transporter in the studied testes, which is related to species differences. The different immunolocalization of GLUT in examined testes suggests using various transport systems for energy gain in different species.
La glucosa tiene un papel esencial en la proliferación y supervivencia del tejido testicular. Los transportadores de glucosa (GLUT) son responsables de la absorción de glucosa a través de las membranas celulares. En el presente trabajo, se investigaron dos isoformas principales GLUT1 y GLUT3 en los testículos de un ratón de laboratorio (BALB/c), un jerbo egipcio menor (Jaculus jaculus), un hámster dorado (Mesocricetus auratus) y un erizo del desierto (Paraechinus aethiopicus). La localización inmunofluorescente de GLUT1 y GLUT3 mostró diferencias considerables entre especies. La expresión más baja de GLUT1 y GLUT3 se localizó en el testículo del ratón de laboratorio (BALB/c), la localización más alta de GLUT1 se detectó en el testículo del jerbo egipcio menor (Jaculus jaculus) y la localización inmunofluorescente de GLUT3 más alta se observó en el testículo de Erizo (Paraechinus aethiopicus). Los resultados implican que GLUT3 es el principal transportador de glucosa en los testículos estudiados, lo que está relacionado con diferencias entre especies. La diferente inmunolocalización de GLUT en los testículos examinados sugiere el uso de varios sistemas de transporte para ganar energía en diferentes especies.
الملخص
Resumen Introducción : El endofenotipo de cáncer de mama triple negativo (TNBC) es uno de los menos frecuentes y sin diana terapéutica, por tanto, se plantea estudiar la correlación del punto de control inmunológico PD-L1 con el establecimiento de microambiente tumoral evaluado por la infiltración linfocitaria intratumoral estromal (TILs) y su importancia en la práctica clínica. Métodos : Se realizó un estudio retrospectivo de casos y controles, con 31 casos de carcinoma infiltrante de la mama triple negativo y 57 controles no pareados de endofenotipo Luminal A, Luminal B y HER-2 atendidos en un año. Se evaluaron las variables: tipo y grado his tológico, expresión PD-L1 con el clon 22C3, TILs, invasión linfovascular, tamaño tumoral, compromiso de ganglios linfáticos y metástasis. El análisis estadístico se ejecutó con la prueba de chi cuadrado y prueba de coeficiente de correlación de Spearman. Resultados : Se encontró una correlación negativa estadísticamente significativa entre TILs y PD-L1 (rho - 0.106, p 0.025), indicando que a mayor expresión de PD-L1, es menor la infiltración linfocitaria intratumo ral. En los grupos de TILs B (10-40% TILs) y C (40-90% TILs) donde se presenta marcado infiltrado inflamatorio intratumoral se evidenció mayor número de pacientes negativos para PD-L1 (CPS <10) con 16 y 10 casos res pectivamente. Para los casos TNBC se logró identificar un coeficiente de asociación negativa (rho -0.378) y con significancia estadística (p 0.01). Discusión : Se estableció la asociación de TNBC, TILs y expresión de PDL1, lo cual es importante para la instau ración de terapias diana y el desarrollo de la medicina de precisión.
Abstract Introduction : Triple negative breast cancer endophe notype (TNBC) is one of the least frequent and without therapeutic target; therefore we propose to study the correlation of PD-L1 immune checkpoint with the es tablishment of tumor microenvironment assessed by intratumoral stromal lymphocyte infiltration (TILS) and its importance in clinical practice. Methods : A retrospective case-control study was performed, with 31 cases of triple-negative infiltrat ing breast carcinoma and 57 unmatched controls of Luminal A, Luminal B and HER-2 endophenotype seen in one year. The following variables were evaluated: histologic type and grade, PD-L1 expression with clone 22C3, TILS, lymphovascular invasion, tumor size, lymph node involvement and metastasis. Statistical analysis was performed with the chi-square test and Spearman correlation coefficient test. Results : a statistically significant negative correlation was found between TILS and PD-L1 (rho - 0.106, p 0.025), indicating that the higher the expression of PD-L1, the lower the intratumoral lymphocytic infiltration. In the TILS B (10-40% TILS) and C (40-90% TILS) groups where there was a marked intratumoral inflammatory infiltrate, a greater number of patients were negative for PD-L1 (CPS <10) with 16 and 10 cases, respectively. For TNBC cases a negative association coefficient was identified (rho -0.378) with statistical significance (p 0.01). Discussion : The association between TNBC, TILS and PDL1 expression was established, which is important for the establishment of target therapies and the develop ment of precision medicine.
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SUMMARY: Hypoxic preconditioning is known to induce neuroprotection, but its effects and pathways in chronic brain pathology still unknown. The aim was to establish an involvement of a7 subunit of nicotinic acetylcholine receptors (a7nAchRs), and sirtuins of 1 (SIRT1) and 3 (SIRT3) types in the effects of hypoxic hypobaric preconditioning on brain damage in mice with chronic cerebral hypoperfusion caused by the left common carotid artery occlusion. The male C57/6j (C57, wild type) and a7nAchRs(-/-) mice were divided to six experimental groups (10 mice per group): sham-operated C57, C57 with chronic cerebral hypoperfusion, C57 with hypoxic hypobaric preconditioning and chronic cerebral hypoperfusion, sham-operated a7nAchRs(-/-) mice, a7nAchRs(-/-) with chronic cerebral hypoperfusion, a7nAchRs(-/-) with hypoxic hypobaric preconditioning and chronic cerebral hypoperfusion. For preconditioning, mice were exposed to hypoxia by "lifting" in barochamber to simulated altitude of 5600 m a.s.l. for 1 h/day on 3 consecutive days before surgical manipulation. Expressions of SIRT1, SIRT3 in brain tissue, and histopathological changes of the hippocampi were examined. It was shown that 8-week chronic hypoperfusion of the brain, caused by unilateral occlusion of the common carotid artery, was accompanied by injury to the neurons of the hippocampi of both hemispheres, which was more pronounced on the side of the occlusion. This damage, as well as the mechanisms of neuroprotection induced by hypoxic preconditioning, were maintained for at least 8 weeks by mechanisms mediated through a7nAChRs. Deficite of a7nAChRs was accompanied with reduction of neuronal damage caused CCH in 8 weeks, as well as preconditioning effects, and lead to compensatory activation of regulatory and protective mechanisms mediated by SIRT1, in normal conditions and in CCH. In wild-type (C57) mice, protective mechanisms in CCH were realized to a greater extent by increased expression of SIRT3 in both hemispheres of the brain.
Se sabe que el precondicionamiento hipóxico induce neuroprotección, pero aún se desconocen sus efectos y vías en la patología cerebral crónica. El objetivo fue establecer la participación de la subunidad a7 de los receptores nicotínicos de acetilcolina (a7nAchR) y las sirtuinas de tipo 1 (SIRT1) y 3 (SIRT3) en los efectos del precondicionamiento hipóxico hipobárico sobre el daño cerebral en ratones con hipoperfusión cerebral crónica causada por la oclusión de la arteria carótida común izquierda. Los ratones macho C57/6j (C57, tipo salvaje) y a7nAchRs(-/-) se dividieron en seis grupos experimentales (10 ratones por grupo): C57 con operación simulada, C57 con hipoperfusión cerebral crónica, C57 con precondicionamiento hipobárico hipóxico y crónica. hipoperfusión cerebral, ratones a7nAchRs(-/-) operados de forma simulada, a7nAchRs(-/-) con hipoperfusión cerebral crónica, a7nAchRs(-/-) con precondicionamiento hipobárico hipóxico e hipoperfusión cerebral crónica. Para el preacondicionamiento, los ratones fueron expuestos a hipoxia "levantándolos" en una cámara de barro a una altitud simulada de 5600 m s.n.m. durante 1 h/día durante 3 días consecutivos antes de la manipulación quirúrgica. Se examinaron las expresiones de SIRT1, SIRT3 en tejido cerebral y los cambios histopatológicos de los hipocampos. Se demostró que la hipoperfusión cerebral crónica de 8 semanas, causada por la oclusión unilateral de la arteria carótida común, se acompañaba de lesión de las neuronas del hipocampo de ambos hemisferios y que era más pronunciada en el lado de la oclusión. Este daño, así como los mecanismos de neuroprotección inducidos por el precondicionamiento hipóxico, se mantuvieron durante al menos 8 semanas mediante mecanismos mediados por a7nAChR. El déficit de a7nAChR se acompañó de una reducción del daño neuronal causado por CCH en 8 semanas, así como de efectos de precondicionamiento, y condujo a una activación compensatoria de mecanismos reguladores y protectores mediados por SIRT1, en condiciones normales y en CCH. En ratones de tipo salvaje (C57), los mecanismos de protección en CCH se realizaron en mayor medida mediante una mayor expresión de SIRT3 en ambos hemisfe- rios del cerebro.
الموضوعات
Animals , Mice , Brain Ischemia , Sirtuin 1/metabolism , Sirtuin 3/metabolism , alpha7 Nicotinic Acetylcholine Receptor/metabolism , Hypoxia , Cerebrovascular Circulation , Blotting, Western , Carotid Stenosisالموضوعات
Humans , Neurofibromatosis 1 , Nerve Sheath Neoplasms , Sarcoma , Soft Tissue Neoplasms , Surgical Oncology , Neural Crestالملخص
Abstract Objectives: Clinical-laboratory comparison of a population of children and adolescents with DM1 followed at a Brazilian outpatient university clinic, at two different periods (2014 and 2020), regarding changes made both to the insulin therapy scheme and to the nutritional approach to carbohydrate counting. Methods: The data of patients with DM1 aged 0-19 years enrolled in the service in 2014 and 2020 were collected. Student's t-test was performed to compare the means of HbA1c and the variables of interest. Results: NPH + regular insulin was predominantly used in 2014 (49.1%), while in 2020, the predominance shifted to insulin analogs (48.4%). Pump use tripled from 1.3% in 2014 to 4.4% in 2020, and the percentage of patients performing carbohydrate counting reduced from 28.3% to 17.8%. Regarding HbA1c, the 2014 group of patients had a mean of 9.8%, while the 2020 group had a mean of 9.6% (p = 0.49). Conclusion: The change in treatments between 2014 and 2020 did not result in a significant improvement in HbA1c levels. However, it was identified the importance of carbohydrate counting and the use of insulin analogs to improve metabolic control in this population at both times.
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SUMMARY: The objective of this study was to observe the clinical efficacy of apatinib (AP) combined with 131I in the treatment of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and the prognostic significance of MIP-1α after treatment, and to provide reference and guidance for future treatment and disease assessment of RAIR-DTC. One hundred and six patients with RAIR- DTC admitted to our hospital from January 2019 to October 2020 were selected for the study. All the patients were treated with TC surgery with 131I at our hospital, and 58 of them were subsequently transferred to AP treatment, which was considered as the research group; the other 48 patients were transferred to thyroid stimulating hormone (TSH) suppression treatment, which was considered as the control group. The clinical efficacy of the research group was better than that of the control group (P 0.05). After treatment, Tg, TL, maximum diameter of C/B lymph nodes, number of lymph nodes and number of calcified spots were lower in the research group than in the control group (P < 0.05). ROC analysis revealed that the predictive sensitivity of MIP-1α for prognosis of 3-year RAIR-DTC death in the research group of patients was 84.63 % and the specificity was 72.16 %. AP combined with 131I is effective in the treatment of RAIR-DTC and is worth using in the clinical practice. In addition, elevated levels of MIP-1α predicted a poor prognosis for patients with RAIR-DTC.
El objetivo de este estudio fue observar la eficacia clínica de apatinib (AP) combinado con 131I en el tratamiento del cáncer de tiroides diferenciado refractario al yodo radiactivo (RAIR-DTC) y la importancia pronóstica de MIP-1α después del tratamiento, y proporcionar referencia y orientación para futuros tratamientos y enfermedades. Evaluación de RAIR- DTC. Se seleccionaron para el estudio 106 pacientes con RAIR- DTC ingresados en nuestro hospital desde enero de 2019 hasta octubre de 2020. Todos los pacientes fueron tratados con cirugía CT con 131I, y 58 de ellos fueron trasladados posteriormente a tratamiento AP, los que fueron considerados como grupo de investigación; los otros 48 pacientes fueron transferidos a tratamiento de supresión de la hormona estimulante de la tiroides (TSH), que se consideró como grupo de control. La eficacia clínica del grupo de investigación fue mejor que la del grupo de control (P 0,05). Después del tratamiento, Tg, TL, diámetro máximo de los linfonodos C/B, número linfonodos y número de manchas calcificadas fueron menores en el grupo de investigación que en el grupo de control (P <0,05). El análisis ROC reveló que la sensibilidad predictiva de MIP-1α para el pronóstico de muerte por RAIR-DTC a 3 años en el grupo de pacientes de investigación fue del 84,63 % y la especificidad fue del 72,16 %. AP combinado con 131I es eficaz en el tratamiento del RAIR-DTC y vale la pena utilizarlo en la práctica clínica. Además, los niveles elevados de MIP-1α predijeron un mal pronóstico para los pacientes con RAIR- DTC.
الموضوعات
Humans , Pyridines/therapeutic use , Thyroid Neoplasms/therapy , Iodine Radioisotopes/therapeutic use , Antineoplastic Agents/therapeutic use , Prognosis , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/radiotherapy , Treatment Outcome , Combined Modality Therapy , Macrophage Inflammatory Proteinsالملخص
SUMMARY: Despite comprehensive studies and reports about the properties of dental pulp stem cells (DPSCs) in vitro, we still need to confirm whether these in vitro characteristics coincide with the nature of DPSCs in situ. The anatomical location of DPSCs populations in the dental pulp has yet to be investigated. Moreover, the mesenchymal DPSCs have been much more studied than the neural crest-derived DPSCs. In this study, well-recognized neural/neural crest stem cell markers NCAM1, Nestin, SNAIL/SLUG, SOX9, and S100 are being investigated by immunohistochemistry to localize the precise location of these populations of DPSCs within the human adult dental pulp.All previously mentioned markers were expressed in the dental pulp, and their intensity and location of expression were reported.
A pesar de estudios e informes exhaustivos sobre las propiedades de las células madre de la pulpa dental (DPSC) in vitro, todavía necesitamos confirmar si estas características in vitro coinciden con la naturaleza de las DPSC in situ. La ubicación anatómica de las poblaciones de DPSC en la pulpa dental aún no se ha investigado. Además, las DPSC mesenquimales han sido mucho más estudiadas que las DPSC derivadas de la cresta neural. En este estudio, se están investigando mediante inmunohisto química marcadores de células madre de la cresta neural/ neural NCAM1, Nestin, SNAIL/SLUG, SOX9 y S100 para localizar la ubicación precisa de estas poblaciones de DPSC dentro de la pulpa dental humana adulta. Todos los marcadores mencionados anteriormente se expresaron en la pulpa dental y se informó su intensidad y ubicación de expresión.
الموضوعات
Humans , Adolescent , Young Adult , Stem Cells/metabolism , Dental Pulp/cytology , Neural Crest/cytology , Immunohistochemistry , S100 Proteins , CD56 Antigen , SOX9 Transcription Factor , Nestinالملخص
SUMMARY: Overexpression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in various tumor tissues and cell lines was found to promote tumor cell proliferation, migration, and invasion. However, the role of MALAT1 in gastric cancer (GC) is still unclear. We aimed to investigate the correlation between long-chain non-coding RNAs (lncRNAs), MALAT1, MicroRNAs (miRNA) and vascular endothelial growth factor A (VEGFA) in gastric cancer and to disclose underlying mechanism. The correlation between MALAT1 levels and clinical features was analyzed by bioinformatics data and human samples. The expression of MALAT1 was down regulated in AGS cells to detect the cell proliferation, migration, and invasion characteristics, as well as the effects on signal pathways. Furthermore, we validated the role of MALAT1/miR-330-3p axis in GC by dual luciferase reporter gene assays. Expression of MALAT1 was higher in cancer tissues than in para-cancerous tissues. The high MALAT1 level predicted malignancy and worse prognosis. Down-regulation of MALAT1 expression in AGS cells inhibited cell proliferation, migration, and invasion by targeting VEGFA. By dual luciferase reporter gene assay and miR-330-3p inhibitor treatment, we demonstrate that MALAT1 sponged miR-330-3p in GC, leading to VEGFA upregulation and activation of the mTOR signaling pathway. The MALAT1/miR-330-3p axis regulates VEGFA through the mTOR signaling pathway and promotes the growth and metastasis of gastric cancer.
Se descubrió que la sobreexpresión del transcrito 1 de adenocarcinoma de pulmón asociado a metástasis (MALAT1) en varios tejidos tumorales y líneas celulares promueve la proliferación, migración e invasión de células tumorales. Sin embargo, el papel de MALAT1 en el cáncer gástrico (CG) aún no está claro. Nuestro objetivo fue investigar la correlación entre los ARN no codificantes de cadena larga (lncRNA), MALAT1, los microARN (miARN) y el factor de crecimiento endotelial vascular A (VEGFA) en el cáncer gástrico y revelar el mecanismo subyacente. La correlación entre los niveles de MALAT1 y las características clínicas se analizó mediante datos bioinformáticos y muestras humanas. La expresión de MALAT1 se reguló negativamente en las células AGS para detectar las características de proliferación, migración e invasión celular, así como los efectos sobre las vías de señales. Además, validamos el papel del eje MALAT1/miR- 330-3p en GC mediante ensayos de genes indicadores de luciferasa dual. La expresión de MALAT1 fue mayor en tejidos cancerosos que en tejidos paracancerosos. El alto nivel de MALAT1 predijo malignidad y peor pronóstico. La regulación negativa de la expresión de MALAT1 en células AGS inhibió la proliferación, migración e invasión celular al apuntar a VEGFA. Mediante un ensayo de gen indicador de luciferasa dual y un tratamiento con inhibidor de miR-330-3p, demostramos que MALAT1 esponjaba miR-330-3p en GC, lo que lleva a la regulación positiva de VEGFA y la activación de la vía de señalización mTOR. El eje MALAT1/miR-330-3p regula VEGFA a través de la vía de señalización mTOR y promueve el crecimiento y la metástasis del cáncer gástrico.
الموضوعات
Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Vascular Endothelial Growth Factor A , TOR Serine-Threonine Kinases , RNA, Long Noncoding , RNA/genetics , Signal Transduction , Gene Expression Regulation, Neoplastic , Cell Movement , Blotting, Western , Apoptosis , Genes, Reporter , Cell Proliferation , Real-Time Polymerase Chain Reaction , Neoplasm Invasivenessالملخص
La tuberculosis es una infección de alta incidencia en Latinoamérica. Su presentación como infección activa está determinada por factores de riesgo del hospedero. Comunicamos el caso clínico de una mujer joven que presentó una forma grave de tuberculosis pulmonar. Al explorar sus factores de riesgo se confirmó un estado de inmunosupresión profundo, causado por un linfoma de células T, asociada a una co-infección por virus linfotrópico T humano tipo 1. Se destacan los aspectos microbiológicos y de pronóstico de la co-infección de Mycobacterium tuberculosis y HTLV-1
Tuberculosis is a high-incidence infection in Latin America. Its presentation as an active infection is determined by risk factors in the host. We report the case of a young woman who presented a severe form of pulmonary tuberculosis. When exploring her risk factors, a profound state of immunosuppression was found, caused by T-cell lymphoma, associated with co-infection with human lymphotropic virus. Microbiological and prognostic aspects of Mycobacterium tuberculosis and HTLV-1 co-infection are highlighted.
الموضوعات
Humans , Female , Middle Aged , Tuberculosis, Pulmonary/complications , HTLV-I Infections/complications , Tuberculosis, Pulmonary/diagnostic imaging , Human T-lymphotropic virus 1 , HTLV-I Infections/diagnostic imaging , Leukemia, T-Cell/complications , Immunocompromised Host , Fatal Outcome , Coinfection , Mycobacterium tuberculosisالملخص
El tumor neuroectodérmico maligno del tracto gastrointestinal es una neoplasia rara con pocos casos reportados en la literatura, especialmente en América Latina. Descrito por primera vez en 2003, se trata de una entidad sin tratamiento estandarizado y de pobre pronóstico. Se presenta el caso de una paciente de 22 años de edad que acude a la consulta por dolor abdominal, anemia y masa abdominal palpable. Luego de estudios pertinentes se decide la conducta resectiva y el posterior tratamiento oncológico. (AU)
Malignant gastrointestinal neuroectodermal tumor (GNET), formerly known as clear cell sarcoma of the gastrointestinal tract, is an extremely rare tumor of mesenchymal origin, which presents great microscopic and molecular similarity to clear cell sarcoma found in other parts of the body, such as tendons and aponeurosis. It is characterized by its rapid evolution, high recurrence rate and frequent diagnosis as metastatic disease.1,2 (AU)
الموضوعات
Humans , Female , Young Adult , Sarcoma, Clear Cell/pathology , Neuroectodermal Tumors/pathology , Gastrointestinal Neoplasms/diagnosis , Digestive System Surgical Procedures/methods , Immunohistochemistry , S100 Proteins/analysis , Gastrointestinal Neoplasms/surgery , Ileum/surgeryالملخص
A neurofibromatose tipo 1 (NF1) é um distúrbio neurocutâneo hereditário no qual se formam tumores no sistema nervoso (neurofibromas). Os neurofibromas são os tumores benignos mais comuns na NF1. O tipo, o tamanho, o número e a localização dos neurofibromas devem ser considerados para a escolha do tratamento. Apresentamos um caso de NF1, no qual foi realizada uma ampla ressecção do couro cabeludo devido à presença de múltiplos neurofibromas. Associado a isso, a reconstrução foi realizada com retalhos de avanço mais autoenxerto de pele parcial, com resultados favoráveis e boa cobertura das áreas onde os tumores foram removidos.
Neurofibromatosis type 1 (NF1) is an inherited neurocutaneous disorder in which tumors form in the nervous system (neurofibromas). Neurofibromas are the most common benign tumors in NF1. The type, size, number, and location of the neurofibromas should be considered for the choice of treatment. We present a case of NF1, in which a wide scalp resection was performed due to the presence of multiple neurofibromas. Associated with this, reconstruction was performed with advancement flaps plus partial skin autograft with favorable results and good coverage of the areas where the tumors were removed.
الملخص
Abstract The aim of this study was to explore the association between differential percentages of dendritic cell (DC) subsets in peripheral blood and malignancy (grade and lymph node metastasis) of peritoneal adenocarcinoma patients and the frequencies of dendritic cell subsets in the normal controls. The peripheral blood of 30 patients with peritoneal adenocarcinoma and 12 healthy controls were collected for multicolor flow cytometry analysis. Peritoneal adenocarcinoma patients were grouped according to the malignant degree (grade and lymph node metastasis). Percentages of myeloid DCs (mDCs) and its subsets MDC1 and MDC2 in DCs were lower in peripheral blood of patients with peritoneal adenocarcinoma than in normal controls. The percentages of plasmacytoid dendritic cells (pDCs) and CD16+mDCs in DCs were higher than in normal controls. Compared with poor differentiation grade, patients with well/moderate differentiation grade had an increased percentage of CD16+mDCs. Contrary to CD16+mDCs, the percentage of MDC1 was lower in the well/moderate differentiation grade group. In patients with no lymph node metastasis, pDCs and CD16+mDCs levels were higher compared with patients with lymph node metastasis. mDCs and MDC1 levels had opposite results. pDCs were positively correlated with CD16+mDCs in peripheral blood of peritoneal patients, as was mDCs and MDC1. CD16+mDCs were negatively correlated with MDC1. The percentages of pDCs and CD16+mDCs in DCs were positively correlated with CD3+CD8+T cells, and pDCs also positively correlated with CD8+PD-1+T cells. Our results revealed that DCs subsets correlated with peritoneal adenocarcinoma malignancy. Dendritic cells play an independent role in the immune function of peritoneal adenocarcinoma.
الملخص
SUMMARY: Senile osteoporosis is mainly caused by reduced osteoblast differentiation and has become the leading cause of fractures in the elderly worldwide. Natural organics are emerging as a potential option for the prevention and treatment of osteoporosis. This study was designed to study the effect of resveratrol on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in osteoporosis mice. A mouse model of osteoporosis was established by subcutaneous injection of dexamethasone and treated with resveratrol administered by gavage. In vivo and in vitro, we used western blot to detect protein expression, and evaluated osteogenic differentiation of BMSCs by detecting the expression of osteogenic differentiation related proteins, calcium deposition, ALP activity and osteocalcin content. Resveratrol treatment significantly increased the body weight of mice, the level of serum Ca2+, 25(OH)D and osteocalcin, ration of bone weight, bone volume/total volume, trabecular thickness, trabecular number, trabecular spacing and cortical thickness in osteoporosis mice. In BMSCs of osteoporosis mice, resveratrol treatment significantly increased the expression of Runx2, osterix (OSX) and osteocalcin (OCN) protein, the level of calcium deposition, ALP activity and osteocalcin content. In addition, resveratrol treatment also significantly increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT in BMSCs of osteoporosis mice. In vitro, resveratrol increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT, Runx2, OSX and OCN protein, the level of calcium deposition, ALP activity and osteocalcin content in BMSCs in a concentration-dependent manner, while SIRT1 knockdown significantly reversed the effect of resveratrol. Resveratrol can attenuate osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells, and the mechanism may be related to the regulation of SIRT1/PI3K/AKT pathway.
La osteoporosis senil es causada principalmente por una diferenciación reducida de osteoblastos y se ha convertido en la principal causa de fracturas en las personas mayores en todo el mundo. Los productos orgánicos naturales están surgiendo como una opción potencial para la prevención y el tratamiento de la osteoporosis. Este estudio fue diseñado para estudiar el efecto del resveratrol en la diferenciación osteogénica de las células madre mesenquimales de la médula ósea (BMSC) en ratones con osteoporosis. Se estableció un modelo de osteoporosis en ratones mediante inyección subcutánea de dexametasona y se trató con resveratrol administrado por sonda. In vivo e in vitro, utilizamos Western blot para detectar la expresión de proteínas y evaluamos la diferenciación osteogénica de BMSC detectando la expresión de proteínas relacionadas con la diferenciación osteogénica, la deposición de calcio, la actividad de ALP y el contenido de osteocalcina. El tratamiento con resveratrol aumentó significativamente el peso corporal de los ratones, el nivel sérico de Ca2+, 25(OH)D y osteocalcina, la proporción de peso óseo, el volumen óseo/ volumen total, el espesor trabecular, el número trabecular, el espaciado trabecular y el espesor cortical en ratones con osteoporosis. En BMSC de ratones con osteoporosis, el tratamiento con resveratrol aumentó significativamente la expresión de las proteínas Runx2, osterix (OSX) y osteocalcina (OCN), el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina. Además, el tratamiento con resveratrol también aumentó significativamente la expresión de SIRT1, p-PI3K/PI3K y p-AKT/AKT en BMSC de ratones con osteoporosis. In vitro, el resveratrol aumentó la expresión de las proteínas SIRT1, p-PI3K/PI3K y p- AKT/AKT, Runx2, OSX y OCN, el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina en BMSC de manera dependiente de la concentración, mientras que La caída de SIRT1 revirtió significativamente el efecto del resveratrol. El resveratrol puede atenuar la osteoporosis al promover la diferenciación osteogénica de las células madre mesenquimales de la médula ósea, y el mecanismo puede estar relacionado con la regulación de la vía SIRT1/PI3K/AKT.
الموضوعات
Animals , Male , Mice , Osteoporosis/drug therapy , Resveratrol/administration & dosage , Osteogenesis/drug effects , Cell Differentiation/drug effects , Blotting, Western , Disease Models, Animal , Sirtuin 1 , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Resveratrol/pharmacology , Mice, Inbred C57BLالملخص
Abstract The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.
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Abstract Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.
الملخص
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/REF-1) is a multifunctional protein acting on cellular signaling pathways, including DNA repair and redox activities. APE1/REF-1 has emerged as a target for cancer therapy, and its role in breast cancer models would reveal new strategies for cancer therapy. APX2009 is a specific APE1/REF-1 redox inhibitor whose anticancer properties have not been described in breast cancer cells. Here, we investigated the effect of the APX2009 treatment in the breast cancer cell lines MDA-MB-231 and MCF-7. Breast cancer cell lines were cultured, and WST1 and colony formation assays were performed to evaluate cell proliferation. Annexin V-FITC/7-AAD and LDH-Glo™ assays were performed to evaluate cell death. The wound healing assay and Matrigel transwell assay were performed after APX2009 treatment to evaluate the cellular migration and invasion processes, respectively. Our findings demonstrated that APX2009 treatment decreased breast cancer cell proliferative, migratory, and invasive properties. Furthermore, it induced apoptosis in both cell lines. Our study is the first to show the effects of APX2009 treatment on apoptosis in a breast cancer cell. Therefore, this study suggested that APX2009 treatment is a promising anticancer molecule for breast cancer.
الملخص
Forkhead Box O1 (FOXO1) has been reported to play important roles in many tumors. However, FOXO1 has not been studied in pan-cancer. The purpose of this study was to reveal the roles of FOXO1 in pan-cancer (33 cancers in this study). Through multiple public platforms, a pan-cancer analysis of FOXO1 was conducted to obtained FOXO1 expression profiles in various tumors to explore the relationship between FOXO1 expression and prognosis of these tumors and to disclose the potential mechanism of FOXO1 in these tumors. FOXO1 was associated with the prognosis of multiple tumors, especially LGG (low grade glioma), OV (ovarian carcinoma), and KIRC (kidney renal clear cell carcinoma). FOXO1 might play the role of an oncogenic gene in LGG and OV, while playing the role of a cancer suppressor gene in KIRC. FOXO1 expression had a significant correlation with the infiltration of some immune cells in LGG, OV, and KIRC. By combining FOXO1 expression and immune cell infiltration, we found that FOXO1 might influence the overall survival of LGG through the infiltration of myeloid dendritic cells or CD4+ T cells. Functional enrichment analysis and gene set enrichment analysis showed that FOXO1 might play roles in tumors through immunoregulatory interactions between a lymphoid and a non-lymphoid cell, TGF-beta signaling pathway, and transcriptional misregulation in cancer. FOXO1 was associated with the prognosis of multiple tumors, especially LGG, OV, and KIRC. In these tumors, FOXO1 might play its role via the regulation of the immune microenvironment.