MACC1 is post-transcriptionally regulated by miR-218 in colorectal cancer

Metastasis is a multistep molecular network process, which is lethal for more than 90% of the cancer patients. Understanding the regulatory functions of metastasis-inducing molecules is in high demand for improved therapeutic cancer approaches. Thus, we studied the post-transcriptional regulation of the crucial carcinogenic and metastasis-mediating molecule metastasis associated in colon cancer 1 (MACC1). In silico analysis revealed MACC1 as a potential target of miR-218, a tumor suppressor miRNA. Expression of these two molecules inversely correlated in colorectal cancer (CRC) cell lines. In a cohort of CRC patient tissues (n = 59), miR-218 is significantly downregulated and MACC1 is upregulated compared with normal mucosa. Luciferase reporter assays with a construct of the MACC1-3'-UTR harboring either the wild type or the mutated miR-218 seed sequence confirmed the specificity of the targeting. miR-218 inhibited significantly MACC1 protein expression, and consistently, MACC1-mediated migration, invasion and colony formation in CRC cells. Anti-miR-218 enhanced the MACC1-mediated migration, invasion and colony formation. Similar findings were observed in the gastric cancer cell line MKN-45. Further, we performed methylation-specific PCR of the SLIT2 and SLIT3 promoter, where miR-218 is encoded in intronic regions. The SLIT2 and SLIT3 promoters are hypermethylated in CRC cell lines. miR-218 and SLIT2 expressions correlated positively. Methyltransferase inhibitor 5-Azacytidine induced miR-218 expression and inhibited the expression of its target MACC1. We also determined that MACC1 has alternative polyadenylation (APA) sites, which results in different lengths of 3'-UTR variants in a CRC cell line. Taken together, miR-218 is post-transcriptionally inhibiting the MACC1 expression and its metastasis-inducing abilities

Epigenetic silencing of miR-520c leads to induced S100A4 expression and its mediated colorectal cancer progression

The S100 calcium-binding protein A4 (S100A4) induces epithelial mesenchymal transition, migration, invasion, angiogenesis and metastasis. Its induced expression in several cancer types correlates with poor prognosis. Apart from the functional and transcriptional regulatory aspects of S100A4, its post-transcriptional regulation is not yet clearly elucidated. In this study, we show that microRNAs (miR) miR-505-5p and miR-520c-3p target the 3'-UTR of S100A4 and inhibits its expression and its mediated migration and invasion. 5-Aza treatment significantly increased miR-520c-3p expression and reduced the S100A4 protein amounts. The upstream promoter region of miR-520c is hypermethylated irrespective of the metastasis status of colorectal cancer (CRC) patient tissues and in all analyzed CRC cell lines. Moreover, in a cohort of CRC patient specimen (n = 59), miR-520c-3p was significantly downregulated. miR-520c-3p stably expressing HCT116 cells showed a reduced metastasis formation in livers after implanting in mice spleen. Taken together, our findings demonstrate that S100A4 is post-transcriptionally regulated by tumor suppressor miRs, miR-505c-5p and miR-520c-3p, and particularly miR-520c-3p expression is epigenetically silenced in CRC

PELATIHAN PEMILIHAN DAN IDENTIFIKASI JAJANAN SEHAT ANAK

The pandemic phase is not over yet, and nutritional problems have not subsided. Stunting is a nutritional status disorder due to an imbalance in intake of needs. Stunting is influenced by several factors, one of which is nutrient intake. Consumption of adequate nutrients, will meet the needs according to age. To fulfill nutrition, it is necessary to consume 3 main meals and 2 snacks. Snacks can be obtained from processing yourself or buying snacks outside. Children and toddlers are already exposed to snacks from outside. According to the results of testing samples of School Snack Foods (PJAS) taken throughout Indonesia in 2014, PJAS that meet the requirements are 76.18% while the target to be achieved is 90%. Training on the selection and identification of healthy snacks for children aims to increase knowledge and skills regarding the feasibility of healthy snacks which is the main concentration on this problem. The activity was carried out at PAUD Sukamanah Village, Baros District, Serang Regency, Banten. The purpose of holding this community service activity was as a means of socializing knowledge about balanced nutrition and healthy snacks. The method of community service carried out is by means of field observations, interviews, socialization and also training. The results of the implementation of this community service activity, still found short (25%) and very short (10%) nutritional status, most of the targets experienced an increase in knowledge of healthy snacks and balanced nutrition (79.6%), snacks that were often consumed by the target before training is chicki (100%) and sweet drinks (50%), most of the targets consume snacks 2-3 times/day (85%)

High MACC1 expression in combination with mutated KRAS G13 indicates poor survival of colorectal cancer patients

BACKGROUND: The metastasis-associated in colon cancer 1 (MACC1) gene has been identified as prognostic biomarker for colorectal cancer (CRC). Here, we aimed at the refinement of risk assessment by separate and combined survival analyses of MACC1 expression with any of the markers KRAS mutated in codon 12 (KRAS G12) or codon 13 (KRAS G13), BRAF V600 mutation and MSI status in a retrospective study of 99 CRC patients with tumors UICC staged I, II and III. FINDINGS: We showed that only high MACC1 expression (HR: 6.09, 95% CI: 2.50-14.85, P < 0.001) and KRAS G13 mutation (HR: 5.19, 95% CI: 1.06-25.45, P = 0.042) were independent prognostic markers for shorter metastasis-free survival (MFS). Accordingly, Cox regression analysis revealed that patients with high MACC1 expression and KRAS G13 mutation exhibited the worst prognosis (HR: 14.48, 95% CI: 3.37-62.18, P < 0.001). Patients were classified based on their molecular characteristics into four clusters with significant differences in MFS (P = 0.003) by using the SPSS 2-step cluster function and Kaplan-Meier survival analysis. CONCLUSION: According to our results, patients with high MACC1 expression and mutated KRAS G13 exhibited the highest risk for metachronous metastases formation. Moreover, we demonstrated that the “Traditional pathway” with an intermediate risk for metastasis formation can be further subdivided by assessing MACC1 expression into a low and high risk group with regard to MFS prognosis. This is the first report showing that identification of CRC patients at high risk for metastasis is possible by assessing MACC1 expression in combination with KRAS G13 mutation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-015-0316-2) contains supplementary material, which is available to authorized users

Efectividad del yodo-131 en el tratamiento del hipertiroidismo en pacientes adultos atendidos en el Hospital C.A.S.E. - Arequipa durante el periodo 2016-2021

Introducción: El hipertiroidismo es un cuadro clínico comúnmente diagnosticado en el servicio de Endocrinología, dentro de las etiologías más comunes se encuentran la Enfermedad de Graves (GD), el Bocio Multinodular Tóxico (BMT) y el Adenoma Tóxico (AT). El manejo del hipertiroidismo requiere de una colaboración multidisciplinar orientados en la etiología y para conseguir objetivos claros con el fin de mejorar la calidad de vida del paciente. Existen tres modalidades de tratamiento: Medicación antitiroidea (ATD), uso yodo radiactivo (I131) y la cirugía de la tiroides. Siendo la terapia con yodo radiactivo (RAI) un modelo terapéutico seguro, rentable y definitivo para pacientes con hipertiroidismo, ya que una sola dosis con yodo radiactivo suele ser suficiente para curar el hipertiroidismo. Marco Conceptual: Los términos tirotoxicosis e hipertiroidismo no son sinónimos. Tirotoxicosis es definida como una condición donde existe un exceso de hormonas tiroideas independientemente de la fuente, en cambio el hipertiroidismo es una condición caracterizada por la sobreproducción (síntesis y secreción) de hormonas tiroideas por parte de la glándula tiroidea. La terapia con I131 es usada como tratamiento de primera línea para la EG, BMT y AT y su objetivo es controlar el hipertiroidismo llevando al paciente a un estado hipotiroideo. Objetivo: Determinar la efectividad de yodo-131 en el tratamiento del Hipertiroidismo en pacientes adultos atendidos en el Servicio de Medicina Nuclear del Hospital C.A.S.E. - Arequipa durante el periodo Enero 2016 a Enero 2021. Materiales y Métodos: Este estudio observacional analítico incluyó pacientes diagnosticados con hipertiroidismo primario que recibieron terapia RAI entre 2016 y 2021. Los datos fueron adquiridos del sistema de registro médico tanto físico y electrónico del hospital. Previo al tratamiento con RAI se suspendió la medicación antitiroidea. Posterior al tratamiento los pacientes fueron evaluados al 1er, 4to, 6to y 12avo mes después de la terapia y se controló T4 libre y TSH. La cura se definió como el desarrollo de eutiroidismo o hipotiroidismo después de una dosis única fija. Además, se utilizó un análisis multivariado de medidas repetidas para identificar que los cambios producidos en los valores de laboratorio se debieron únicamente a la acción del yodo radiactivo. Resultados: En este estudio se incluyeron un total de 84 pacientes diagnosticados de hipertiroidismo con una edad media de 47 ± 14 años. La mayoría de los pacientes eran mujeres, 72 (85.7%). A los doce meses de terapia RAI 72 (85.8%) pacientes lograron la remisión del estado hipertiroideo (pasando al estado hipotiroideo o eutiroideo). Se muestra que la respuesta tiroidea global después de aplicar el tratamiento con yodo radioactivo presenta diferencias estadísticas significativa vii (p<0.05). Conclusiones: Nuestros datos demuestran que la terapia RAI es efectiva para el hipertiroidismo primario. Obteniéndose remisión con una sola dosis fija en la mayoría de los pacientes. La mayoría de nuestros pacientes se curaron dentro de los doce meses de la terapia RAI

Biochemical and microscopy evidence on adverse effects of nitroxidized human serum albumin

23-32Earlier researches have pointed about the accumulation of peroxynitrite modified proteins and their aggregates in the etiopathogenesis of many age-related neurodegenerative and several autoimmune diseases. Human serum albumin (HSA) is present in abundance in plasma and is susceptible to modification by peroxynitrite. In this study, HSA modified with peroxynitrite (nitroxidized-HSA) formed aggregate besides other gross structural changes. Aggregation or assembly of aberrant proteins is responsible for increase in production of reactive species and is often correlated with toxicity in neurodegenerative diseases. However, lack of literature on the cytotoxicity of aggregated nitroxidized-HSA led us to explore its toxicity using human peripheral blood lymphocytes. Elevated protein carbonyl coupled with decreased protein thiol, and release of antioxidant enzymes and lactate dehydrogenase (LDH) were observed upon incubation of lymphocytes with nitroxidized-HSA. Trypan blue exclusion and MTT assays indicated nitroxidized-HSA induced injury/death of lymphocytes. This may be attributed to the observed reactive oxygen species generation during the interaction of nitroxidized-HSA with lymphocytes. Moreover, the analysis of the cellular morphology by dual staining, fluorescence and confocal microscopy further confirms the cytotoxicity of nitroxidized-HSA. Since various age-related degenerative diseases are characterized by deposition of protein aggregates, the demonstrated toxicity of nitroxidized-HSA may be an important driver in the pathophysiology of neurodegenerative diseases

Rückwärtsschnitt zur geometrischen Kalibrierung einer kamerabasierten Goniometermesstechnik für hochauflösende Lichtstärkeverteilungen

Für die Bestimmung von hochaufgelösten Lichtstärkeverteilungskurven (LVK) mittels kamerabasierter Goniometermesstechnik ist eine geometrische Kalibrierung notwendig. Diese stellt den räumlichen Zusammenhang zwischen den einzelnen Komponenten des Messsystems bestehend aus Kamera, Goniometer und einem weißen Schirm her. Zur Bestimmung der geometrischen Kalibrierung wird im Folgenden mithilfe eines photogrammetrischen Verfahrens die Pose einer Kamera im Raum geschätzt. Hierfür werden geometrisch bekannte Objektpunkte sowie deren Bildpunkte in der Abbildung durch eine Messkamera, welche durch das Lochkameramodell beschrieben wird. Des Weiteren werden die intrinsischen Parameter der Kamera benötigt. Die Berechnung beruht auf den Kollinearitätsgleichungen, welche einen mathematischen Zusammenhang zwischen Punktepaaren und der Kamerapose, zusammengesetzt aus Translation und Rotation, herstellen. Bei der folgenden Validierung des Kalibrieransatzes nimmt eine Kamera die Position der Lichtquelle ein, um so Aussagen über die Anwendbarkeit des Ansatzes treffen zu können

Evolution of Chagas’ disease in Brazil. Epidemiological perspective and challenges for the future: a critical review

Aims: This paper aimed to provide a critical review of the evolution of Chagas’ disease in Brazil, its magnitude, historical development and management, and challenges for the future. Methods: A literature search was performed using PubMed, SciELO and Google Scholar and throughout collected articles’ references. Narrative analysis was structured around five main themes identified: vector transmission, control program, and transfusion, oral and congenital transmission. Results: In Brazil, the Chagas’ disease Control Program was fully implemented in the 1980s, when it reached practically all the endemic areas, and in 1991, the Southern Cone Initiative was created, aiming to eliminate the disease transmission through eliminating the Triatoma infestans and controlling blood banks. As a result, the prevalence of chagasic donors in blood banks reduced from 4.4% in the 80s to 0.2% in 2005. In 2006, PAHO certified the interruption of transmission of Chagas’ disease through this vector in Brazil. However, there are still challenges, such as the domiciliation of new vector species, the need for medical care of the infected individuals, the prevention of alternative mechanisms of transmission, the loss of political concern regarding the disease and, the weakening of the control program. Conclusion: Despite the progress towards control, there are still many challenges ahead to maintain and expand such control and minimise the risk of re-emergence