Thymoquinone Potentially Modulates the Expression of Key Onco- and Tumor Suppressor miRNAs in Prostate and Colon Cancer Cell Lines: Insights from PC3 and HCT-15 Cells.

Prostate cancer (PC) and colon cancer significantly contribute to global cancer-related morbidity and mortality. Thymoquinone (TQ), a naturally occurring phytochemical found in black cumin, has shown potential as an anticancer compound. This study aimed to investigate the effects of TQ on the expression profile of key tumor suppressor and onco-suppressor miRNAs in PC3 prostate cancer cells and HCT-15 colon cancer cells. Cell viability assays revealed that TQ inhibited the growth of both cell lines in a dose-dependent manner, with IC50 values of approximately 82.59 µM for HCT-15 and 55.83 µM for PC3 cells. Following TQ treatment at the IC50 concentrations, miRNA expression analysis demonstrated that TQ significantly downregulated miR-21-5p expression in HCT-15 cells and upregulated miR-34a-5p, miR-221-5p, miR-17-5p, and miR-21-5p expression in PC3 cells. However, no significant changes were observed in the expression levels of miR-34a-5p and miR-200a-5p in HCT-15 cells. The current findings suggest that TQ might exert its antiproliferative effects by modulating specific tumor suppressor and onco-suppressor miRNAs in prostate and colon cancer cells. Further investigations are warranted to elucidate the precise underlying mechanisms and to explore the therapeutic potential of TQ in cancer treatment. To the best of our knowledge, this is the first report regarding the effect of TQ on the miRNA expression profile in colon and prostate cancer cell lines.

Fetal Goiter Diagnosed in a Euthyroid Patient: An Unusual Presentation of the Fetal Thyroid Disease.

Fetal thyroid disease is rare, and the disease is mostly contextualized in the setting of a treated maternal thyroid disease. The presentation of thyroid disease in the fetus of a euthyroid mother is unusual. This paper presents the case of a 21-week pregnant woman with an incidental finding from a detailed anatomy ultrasound and evaluates available diagnostic and therapeutic management options. There is no consensus with sufficient evidence given the unusual presentation of this type of pathology. In most cases, the evidence is in the etiology of a mother with previous thyroid pathology that modifies the fetal outcome. Hence, it is important to describe cases to accumulate and, at some point, sufficient evidence of different treatments, with the intention of improving the quality of the recommendations. The management of fetal euthyroid goiter is a complex challenge. Most specialists manage the information on a case-by-case basis, with the same general goals as in patients with other thyroid pathologies.

Exploring the Potential Role of Circulating microRNAs as Biomarkers for Predicting Clinical Response to Neoadjuvant Therapy in Breast Cancer.

Breast cancer (BC) is a leading cause of cancer-related deaths among women worldwide. Neoadjuvant therapy (NAT) is increasingly being used to reduce tumor burden prior to surgical resection. However, current techniques for assessing tumor response have significant limitations. Additionally, drug resistance is commonly observed, raising a need to identify biomarkers that can predict treatment sensitivity and survival outcomes. Circulating microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have been shown to play a significant role in cancer progression as tumor inducers or suppressors. The expression of circulating miRNAs has been found to be significantly altered in breast cancer patients. Moreover, recent studies have suggested that circulating miRNAs can serve as non-invasive biomarkers for predicting response to NAT. Therefore, this review provides a brief overview of recent studies that have demonstrated the potential of circulating miRNAs as biomarkers for predicting the clinical response to NAT in BC patients. The findings of this review will strengthen future research on developing miRNA-based biomarkers and their translation into medical practice, which could significantly improve the clinical management of BC patients undergoing NAT.

Regulatory mechanisms of microRNAs in endocrine disorders and their therapeutic potential.

MicroRNAs (miRNAs) are small endogenous non-coding RNA molecules capable of regulating gene expression at the post-transcriptional level either by translational inhibition or mRNA degradation and have recently been importantly related to the diagnosis and prognosis of the most relevant endocrine disorders. The endocrine system comprises various highly vascularized ductless organs regulating metabolism, growth and development, and sexual function. Endocrine disorders constitute the fifth principal cause of death worldwide, and they are considered a significant public health problem due to their long-term effects and negative impact on the patient's quality of life. Over the last few years, miRNAs have been discovered to regulate various biological processes associated with endocrine disorders, which could be advantageous in developing new diagnostic and therapeutic tools. The present review aims to provide an overview of the most recent and significant information regarding the regulatory mechanism of miRNAs during the development of the most relevant endocrine disorders, including diabetes mellitus, thyroid diseases, osteoporosis, pituitary tumors, Cushing's syndrome, adrenal insufficiency and multiple endocrine neoplasia, and their potential implications as disease biomarkers.

Recent insights into the microRNA and long non-coding RNA-mediated regulation of stem cell populations.

Stem cells are undifferentiated cells that have multi-lineage differentiation. The transition from self-renewal to differentiation requires rapid and extensive gene expression alterations. Since different stem cells exhibit diverse non-coding RNAs (ncRNAs) expression profiles, the critical roles of ncRNAs in stem cell reprogramming, pluripotency maintenance, and differentiation have been widely investigated over the past few years. Hence, in this current review, the two main categories of ncRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are discussed. While the primary way by which miRNAs restrict mRNA transcription is through miRNA-mRNA interaction, lncRNAs have a wide range of effects on mRNA functioning, including interactions with miRNAs. Both of these ncRNAs participate in the post-transcriptional regulation of crucial biological mechanisms, such as cell cycle regulation, apoptosis, aging, and cell fate decisions. These findings shed light on a previously unknown aspect of gene regulation in stem cell fate determination and behavior. Overall, we summarized the key roles of miRNAs (including exosomal miRNAs) and lncRNAs in the regulation of stem cell populations, such as cardiac, hematopoietic, mesenchymal, neural, and spermatogonial, as well ncRNAs' influence on malignancy through modulating cancer stem cells, which might significantly contribute to clinical stem cell therapy and in regenerative medicine.

MicroRNA-mediated regulation of key signaling pathways in hepatocellular carcinoma: A mechanistic insight.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. The molecular pathogenesis of HCC varies due to the different etiologies and genotoxic insults. The development of HCC is characterized by complex interactions between several etiological factors that result in genetic and epigenetic changes in proto-onco and/or tumor suppressor genes. MicroRNAs (miRNAs) are short non-coding RNAs that also can act as oncomiRs or tumor suppressors regulating the expression of cancer-associated genes post-transcriptionally. Studies revealed that several microRNAs are directly or indirectly involved in cellular signaling, and dysregulation of those miRNAs in the body fluids or tissues potentially affects key signaling pathways resulting in carcinogenesis. Therefore, in this mini-review, we discussed recent progress in microRNA-mediated regulation of crucial signaling networks during HCC development, concentrating on the most relevant ones such as PI3K/Akt/mTOR, Hippo-YAP/TAZ, and Wnt/ß-catenin, which might open new avenues in HCC management.

A Brief Review on the Regulatory Roles of MicroRNAs in Cystic Diseases and Their Use as Potential Biomarkers.

miRNAs are small endogenous conserved non-coding RNA molecules that regulate post-transcriptional gene expression through mRNA degradation or translational inhibition, modulating nearly 60% of human genes. Cystic diseases are characterized by the presence of abnormal fluid-filled sacs in the body, and though most cysts are benign, they can grow inside tumors and turn malignant. Recent evidence has revealed that the aberrant expression of a number of miRNAs present in extracellular fluids, including plasma or serum, urine, saliva, follicular fluid, and semen, contribute to different cystic pathologies. This review aims to describe the role of different miRNAs in three worldwide relevant cystic diseases: polycystic ovarian syndrome (PCOS), polycystic kidney disease (PKD), and pancreatic cyst tumors (PCTs), as well as their potential use as novel biomarkers.

The role of microRNAs in solving COVID-19 puzzle from infection to therapeutics: A mini-review.

Nowadays, one of the major global health concerns is coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though numerous treatments and vaccines to combat this virus are currently under development, the detailed molecular mechanisms underlying the pathogenesis of this disease are yet to be elucidated to design future therapeutic tools against SARS-CoV-2 variants. MicroRNAs (miRNAs) are small (20-24 nucleotides), non-coding RNA molecules that regulate post-transcriptional gene expression. Recently, it has been demonstrated that both host and viral-encoded miRNAs are crucial for the successful infection of SARS-CoV-2. For instance, dysregulation of miRNAs that modulate multiple genes expressed in COVID-19 patients with comorbidities (e.g., type 2 diabetes, lung adenocarcinoma, and cerebrovascular disorders) could affect the severity of the disease. Thus, altered expression levels of circulating miRNAs might be helpful to diagnose this illness and forecast whether a COVID-19 patient could develop a severe state of the disease. Besides, researchers have found a number of miRNAs could inhibit the expression of proteins, such as ACE2, TMPRSS2, spike, and Nsp12, involved in the life cycle of SARS-CoV-2. Accordingly, miRNAs represent potential biomarkers and therapeutic targets for this devastating viral disease. Therefore, in this current review, we present the recent discoveries regarding the clinical relevance and biological roles of miRNAs in COVID-19.

Phytochemicals mediated modulation of microRNAs and long non-coding RNAs in cancer prevention and therapy.

MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are two main categories of noncoding RNAs (ncRNAs) that can influence essential biological functions in various ways, as well as their expression and function are tightly regulated in physiological homeostasis. Additionally, the dysregulation of these ncRNAs seems to be crucial to the pathogenesis of human diseases. The latest findings indicate that ncRNAs execute vital roles in cancer initiation and progression, and the cancer phenotype can be reversed by modulating their expression. Available scientific discoveries suggest that phytochemicals such as polyphenols, alkaloids, terpenoids, and organosulfur compounds can significantly modulate multiple cancer-associated miRNAs and lncRNAs, thereby inhibiting cancer initiation and development. However, despite promising outcomes of experimental research, only a few clinical trials are currently being conducted to evaluate the therapeutic effectiveness of these compounds. Nevertheless, understanding phytochemical-mediated ncRNA regulation in cancer and the underlying molecular mechanisms on tumor pathophysiology can aid in the development of novel therapeutic strategies to combat this deadly disease.

Human microRNAs in host-parasite interaction: a review.

MicroRNAs (miRNAs) are a group of small noncoding RNA molecules with significant capacity to regulate the gene expression at the post-transcriptional level in a sequence-specific manner either through translation repression or mRNA degradation triggering a fine-tuning biological impact. They have been implicated in several processes, including cell growth and development, signal transduction, cell proliferation and differentiation, metabolism, apoptosis, inflammation, and immune response modulation. However, over the last few years, extensive studies have shown the relevance of miRNAs in human pathophysiology. Common human parasitic diseases, such as Malaria, Leishmaniasis, Amoebiasis, Chagas disease, Schistosomiasis, Toxoplasmosis, Cryptosporidiosis, Clonorchiasis, and Echinococcosis are the leading cause of death worldwide. Thus, identifying and characterizing parasite-specific miRNAs and their host targets, as well as host-related miRNAs, are important for a deeper understanding of the pathophysiology of parasite-specific diseases at the molecular level. In this review, we have demonstrated the impact of human microRNAs during host-parasite interaction as well as their potential to be used for diagnosis and prognosis purposes.

[Prevalence in birth defects diagnosed by ultrasound: three years experience in university maternal fetal medicine unit]. / Prevalencia de malformaciones congénitas diagnosticadas por ultrasonido: tres años de experiencia en una unidad de medicina materno fetal universitaria.

OBJECTIVE: To establish the prevalence of congenital malformations diagnosed in Maternal-Fetal Medicine Unit of Hospital de San José, Bogotá-Colombia and comparing them to national and international reports. MATERIALS AND METHODS: Retrospective, descriptive observational where the quantification of all malformed fetuses diagnosed in Maternal-Fetal Medicine Unit from June 2010 to June 2013 was performed. RESULTS: 236 malformed fetuses, a total of 11,914 births, for a prevalence of 1.98% were included at a mean gestational age at diagnosis of 26.7 weeks (SD 7.1 weeks). The most common congenital malformations were at the level of Central Nervous System (CNS) 88 (37%) in total and within them, the most prevalent was ventriculomegaly 16 (7%). Of the 236 malformed fetuses, 165 fetuses (70.2%) had only one affected system 29 (12.3%) 2 compromised systems and 42 (17.5%) over 3 affected systems. Karyotyping was offered to all antenatal patients, however, accepted only 63 (26.7%), and 39 (62%) with normal results and the other aneuploidies were found, having Trisomy 21 as the most common. It was possible to establish a concordance of 86% between the antenatal and postnatal diagnosis. The perinatal mortality found in this study was 34.7%, mainly in fetuses with congenital diaphragmatic hernia 16 cases (88.8%), fetal non-immune hydrops 8 cases (80%), cardiovascular abnormalities 31 cases (46.2%) genitourinary and 13 cases (24%), and fetuses with CNS malformations such as sequence acranea-anencefalia, holoprosencephaly and encephalocele mortality occurred in 100%. CONCLUSION: In this study the prevalence of congenital anomalies was found comparable to that reported at local and global levels, which were diagnosed and adequately characterized by more than two-thirds by obstetrical ultrasound performed by trained personnel in prenatal diagnosis. Perinatal morbidity and mortality remain high thoracic, cardiovascular, renal and non-immune hydrops congenital anomalies.

Employing laparoscopic surgery for endometriosis.

Endometriosis is a chronic, multifactorial disease, which can impact significantly on a women's quality of life. It is associated with pelvic pain, dyspareunia and intestinal disorders, and can lead to infertility. The use of laparoscopic surgery in the management of endometriosis is well documented; however, the optimal management of women with deep infiltrating disease remains controversial. This review describes the different surgical strategies for the treatment of endometriosis.

Tratamiento del cáncer de laringe experiencia en el Instituto Oncológico Doctor Luis Razetti / Laryngeal cancer treatment experience in the Oncology Institute Doctor Luis Razetti

El cáncer de laringe representa un 20%-25% de los carcinomas de cabeza y cuello. Actualmente su tratamiento incluye diversas modalidades, desde cirugía para enfermedad localizada hasta esquemas concurrentes de quimioterapia y radioterapia para estadios avanzados. Evaluar los resultados del tratamiento del carcinoma laríngeo en nuestra institución en el período 2000-2009; por lo que se realizó un estudio retrospectivo analítico basado en las historias clínicas de pacientes con diagnóstico histopatológico de carcinoma laríngeo, en estadios precoces y avanzados no metastásicos. El objetivo primario del estudio es evaluar la supervivencia global, según el estadiaje y/o las modalidades terapéuticas. Los objetivos secundarios incluyen supervivencia libre de enfermedad y supervivencia libre de laringectomía. Un total de 187 pacientes, la sobrevida global fue significativamente mayor en estadios precoces comparado a estadios avanzados (P=0,023). La sobrevida global en estadios avanzados no presentó diferencias estadísticamente significativas independientemente de la modalidad de tratamiento aplicado. La sobrevida libre de laringectomía y libre de enfermedad muestra una tendencia preliminar a favor del tratamiento concurrente definitivo en estadios avanzados. La sobrevida global y libre de enfermedad en estadios precoces no presentó variación de acuerdo a la modalidad del tratamiento definitivo (P=0,086). La radioterapia ofrece una eficacia comparable a la cirugía en estadios precoces, el tratamiento multimodal de estadios avanzados permite una mayor sobrevida libre de laringectomía y libre de enfermedad sin impacto aparente en la sobrevida global en relación con la cirugía radical.

The laryngeal cancer accounts for 20%- 25% of all the head and neck carcinomas. The current treatment includes various forms ranging from surgery for localized disease to concurrent schemes chemotherapy and radiotherapy for the advanced stages. The purpose of this study is to evaluate the results of the treatment of laryngeal carcinoma at our institution in the period 2000-2009. For what was done a retrospective study based on medical records of patients with histopathological diagnosis of laryngeal carcinoma, stage early and in advanced non-metastatic. The primary objective is to evaluate overall survival, according to the staging and or therapeutic modalities we used. The secondary end points included disease free survival, laringectomy free survival. For a total of 187 patients, the overall survival was significantly higher in early stages compared to advanced stages (P=0.023). The global survival in advanced stages did not differ statistically significant regardless of the type of treatment we applied. The free laringectomy survival and the disease free survival show atrend in favor of the preliminary final concurrent treatment in the advanced stages. The overall survival and disease free survival in early stages did not present variation according to the definitive treatment modality (P= 0.086). Radiotherapy offers comparable efficacy to surgery in early stages, multimodal treatment for advanced stages allows greater laringectomy free survival and disease free survival without apparent impact on overall free survival in relation to the radical surgery.

Tratamiento adyuvante en cáncer de colon: nuestra experiencia / Adjuvant treatment for colon cancer: our experience

El cáncer de colon es uno de los tumores más frecuentes en nuestro país. Posterior a cirugía, la quimioterapia adyuvante ha mostrado beneficios para los pacientes de alto riesgo y ganglios positivos, por lo que es considerada estándar. De este estudio, es evaluar la experiencia de nuestra institución en lo que a esta modalidad de tratamiento se refiere durante cinco años. De manera preliminar, se evaluaron un total de 118 pacientes. La distribución por género fue igual. Los tumores de colon izquierdo ocuparon el mayor porcentaje (45,76%), la histología más frecuente fue adenocarcinoma. En cuanto al TNM, el T más frecuente fue el T3 (53.1%) y el N el NO (46,9%). El 63,2% de pacientes recibió quimioterapia adyuvante, siendo los esquemas más utilizados, Folfox 4 62,5% seguido de Xelos 18,1% y Capecitabina 13,9. El 66,7% presentó eventos adversos. siendo las más frecuentes diarreas, nauseas, vómitos, y neuropatía periférica, todos G1/2 en la mayoría de los casos. No hubo muerte asociada al tratamiento. El 100% de los pacientes tuvieron seguimiento y para el año 2009 el 55,93% se encontraban vivos. La sobrevida global fue mayor en el grupo que recibió adyuvancia sin llegar a significancia estadística (P=0,098) ya que hasta la fecha no se ha alcanzado la mediana de sobrevida global. La sobrevida libre de enfermedad, fue mayor en el grupo que recibió quimioterapia, alcanzado significancia estadística (P=0,045).

Colon cancer is one of the most common tumors in our country. Following surgery, adjuvant chemotherapy has shown benefit for patients at high risk and node-positive, so it is considered standard modality. The aim of this study is to evaluate the experience of our institution as far as this treatment modality, referred for five years. Preliminary we evaluated total of 118 patients, the gender distribution was equal. Left colon tumors, occupied the highest percentage (45.76%) and the most common histology was adenocarcinoma. With regard to TNM, T3 was the most frequent (53.1%) and N0 also (46.9%). Of the sample assessed, 63.2% received adjuvant che motherapy, being the most widely used schemes, Folfox 4 62.5 %, Xelox18.1% and Capecitabine 13.9%. 66.7% of patients had adverse events, being the most frequent diarrhea, nausea, vomiting, and peripheral neuropathy, all G1/2 in most cases. There were no treatment-related deaths. 100% of patients had follow-up, for the year 2009, 55.93% of them were alive. The OS was greater in the group that received adjuvant treatment with regard to that it did not receive it, without statistics significant (P=0.098) since up to the date there has not been reached the median of global survival. Similar results were obtained with regard to the DFS, being this major in the group that received chemotherapy, versus the group that did not receive it, reached significant statistics (P=0.045).

Embarazo ectópico en la cicatriz uterina: reporte de un caso y revisión de la literatura / Ectopic pregnancy in the uterine scar: a case report and literature review

Introducción: el embarazo ectópico en la cicatriz uterina se presenta en 1:1.800 a 1:2.216 embarazos y representa 6,1% de los embarazos ectópicos en pacientes con antecedente de cesárea.Objetivo: revisar el manejo y el diagnóstico del embarazo ectópico en la cicatriz uterina a partir del caso de una paciente con esta patología. Presentación del caso: una paciente de 24 años con antecedente de cesárea, asistió a consulta en el Hospital Universitario de Santander con dolor en el hemiabdomen inferior. A partir de estos síntomas, se le realizó ecografía y Doppler interpretados como de alta probabilidad de embarazo ectópico en la cicatriz uterina. Posteriormente, se inició terapia con metotrexato combinado con ácido folínico. Finalmente, se hizo control con evolución favorable de la paciente. Discusión: el embarazo ectópico en la cicatriz uterina es una complicación a largo plazo de la cesárea. Su diagnóstico debe ser considerado en toda mujer con antecedente de cesárea que consulte por hemorragia en la primera mitad del embarazo antes de la décima semana de gestación. En estos casos, el diagnóstico ecográfico inicial puede ser difícil pero se puede llegar a un diagnóstico certero con ecografías repetidas. Por otra parte, el tratamiento puede ser médico o quirúrgico y depende básicamente del tiempo de gestación en que se haga el diagnóstico.

Introduction: ectopic pregnancy in the uterine scar occurs in 1:1,800 to 1:2,216 of pregnancies and accounts for 6.1% of ectopic pregnancies in the group of patients having had prior cesarean section. Objective: in order to review the management and diagnosis of this condition, the case of a patient having an ectopic pregnancy in the uterine scar is presented. Case presentation: a 24-year-old patient having had a previous cesarean section consulted the Santander teaching hospital suffering from lower abdominal pain. Doppler ultrasound suggested a high probability of ectopic pregnancy in the uterine scar. Methotrexate and folinic acid therapy was thus begun. Controls were made with favorable results. Discussion: ectopic pregnancy in the uterine scar is a long-term complication of cesarean section; it is a diagnosis which should be considered in any female having a history of previous cesarean consulting for hemorrhage during the first half of pregnancy before 10 weeks' gestation. Initial ultrasound diagnosis can be difficult; however, diagnosis can be made with repeated scans. Treatment may be medical or surgical and will mainly depend on the gestation time when diagnosis is made.