The molecular pathogenesis of craniopharyngiomas.

Research from the last 20 years has provided important insights into the molecular pathogenesis of craniopharyngiomas (CPs). Besides the well-known clinical and histological differences between the subtypes of CPs, adamantinomatous (ACP) and papillary (PCP) craniopharyngiomas, other molecular differences have been identified, further elucidating pathways related to the origin and development of such tumors. The present minireview assesses current knowledge on embryogenesis and the genetic, epigenetic, transcriptomic, and signaling pathways involved in the ACP and PCP subtypes, revealing the similarities and differences in their profiles. ACP and PCP subtypes can be identified by the presence of mutations in CTNNB1 and BRAF genes, with prevalence around 60% and 90%, respectively. Therefore, ß-catenin accumulates in the nucleus-cytoplasm of cell clusters in ACPs and, in PCPs, cell immunostaining with specific antibody against the V600E-mutated protein can be seen. Distinct patterns of DNA methylation further differentiate ACPs and PCPs. In addition, research on genetic and epigenetic changes and tumor microenvironment specificities have further clarified the development and progression of the disease. No relevant transcriptional differences in ACPs have emerged between children and adults. In conclusion, ACPs and PCPs present diverse genetic signatures and each subtype is associated with specific signaling pathways. A better understanding of the pathways related to the growth of such tumors is paramount for the development of novel targeted therapeutic agents.

The molecular pathogenesis of craniopharyngiomas

ABSTRACT Research from the last 20 years has provided important insights into the molecular pathogenesis of craniopharyngiomas (CPs). Besides the well-known clinical and histological differences between the subtypes of CPs, adamantinomatous (ACP) and papillary (PCP) craniopharyngiomas, other molecular differences have been identified, further elucidating pathways related to the origin and development of such tumors. The present minireview assesses current knowledge on embryogenesis and the genetic, epigenetic, transcriptomic, and signaling pathways involved in the ACP and PCP subtypes, revealing the similarities and differences in their profiles. ACP and PCP subtypes can be identified by the presence of mutations in CTNNB1 and BRAF genes, with prevalence around 60% and 90%, respectively. Therefore, β-catenin accumulates in the nucleus-cytoplasm of cell clusters in ACPs and, in PCPs, cell immunostaining with specific antibody against the V600E-mutated protein can be seen. Distinct patterns of DNA methylation further differentiate ACPs and PCPs. In addition, research on genetic and epigenetic changes and tumor microenvironment specificities have further clarified the development and progression of the disease. No relevant transcriptional differences in ACPs have emerged between children and adults. In conclusion, ACPs and PCPs present diverse genetic signatures and each subtype is associated with specific signaling pathways. A better understanding of the pathways related to the growth of such tumors is paramount for the development of novel targeted therapeutic agents.

The Contribution of JAK2 46/1 Haplotype in the Predisposition to Myeloproliferative Neoplasms.

Haplotype 46/1 (GGCC) consists of a set of genetic variations distributed along chromosome 9p.24.1, which extend from the Janus Kinase 2 gene to Insulin like 4. Marked by four jointly inherited variants (rs3780367, rs10974944, rs12343867, and rs1159782), this haplotype has a strong association with the development of BCR-ABL1-negative myeloproliferative neoplasms (MPNs) because it precedes the acquisition of the JAK2V617F variant, a common genetic alteration in individuals with these hematological malignancies. It is also described as one of the factors that increases the risk of familial MPNs by more than five times, 46/1 is associated with events related to inflammatory dysregulation, splenomegaly, splanchnic vein thrombosis, Budd-Chiari syndrome, increases in RBC count, platelets, leukocytes, hematocrit, and hemoglobin, which are characteristic of MPNs, as well as other findings that are still being elucidated and which are of great interest for the etiopathological understanding of these hematological neoplasms. Considering these factors, the present review aims to describe the main findings and discussions involving the 46/1 haplotype, and highlights the molecular and immunological aspects and their relevance as a tool for clinical practice and investigation of familial cases.

Epidemiology and Characterization of Shiga Toxin-Producing Escherichia Coli of Hemolytic Uremic Syndrome in Argentina.

Argentina has one of the highest prevalence in Shiga toxin-producing Escherichia coli (STEC) and the high rate of hemolytic uremic syndrome (HUS) in the world. Though preventive steps such as food safety have been implemented as a way to reduce STEC infections, these have proven to be insufficient. STEC's pathogenesis, virulence factors, relationship with the environment, and emerging strains have been studied in the past few years in the country. Many factors that contribute to the morbidity and mortality of STEC infections include the expression of pathologic genes, alternative characteristics (inhibition of phagocytosis, invasion, cytotoxicity, and bacterial attachment), and host factors (age, immune status, treatments, medical history). However, research studies in combination with epidemiological data suggest trends of the prognosis, with the relationship between and genetic combinations of adherence, Shiga toxin (Stx) genes, and virulence genes, which significantly influence disease outcomes. This review explains the characteristics and epidemiology of STEC in Argentina. All these facts show that the application of molecular subtyping techniques in real-time is essential for detecting and controlling outbreaks. Applying molecular subtyping techniques in hemorrhagic diarrhea can avoid severe consequences caused by progression to HUS, and help the epidemiological analysis of the outbreak.

Molecular pathways and potential biomarkers in gallbladder cancer: A comprehensive review.

The most common malignancy of the biliary tract, gallbladder cancer (GBC) often has a dismal prognosis. The aggressive nature of the tumor, delayed diagnosis at advanced stages of the disease, and lack of effective treatment options are some of the factors that contribute to a poor outcome. Early detection and accurate assessment of disease burden is critical to optimize management and improve long-term survival, as well as identify patients for adjuvant therapy and clinical trials. With recent advances in the understanding of the molecular pathogenesis of GBC, several specific diagnostic and biomarkers have been proposed as being of diagnostic and prognostic importance. Indeed, identification of novel diagnostic and prognostic markers has an important role in early diagnosis and development of targeted therapies among patients with GBC. Next-generation sequencing technology and genomewide data analysis have provided novel insight into understanding the molecular pathogenesis of biliary tract cancers, thereby identifying potential biomarkers for clinical use. We herein review available GBC biomarkers and the potential clinical implications in the management of GBC.

Tropism and molecular pathogenesis of canine distemper virus.

BACKGROUND: Canine distemper virus (CDV), currently termed Canine morbillivirus, is an extremely contagious disease that affects dogs. It is identified as a multiple cell tropism pathogen, and its host range includes a vast array of species. As a member of Mononegavirales, CDV has a negative, single-stranded RNA genome, which encodes eight proteins. MAIN BODY: Regarding the molecular pathogenesis, the hemagglutinin protein (H) plays a crucial role both in the antigenic recognition and the viral interaction with SLAM and nectin-4, the host cells' receptors. These cellular receptors have been studied widely as CDV receptors in vitro in different cellular models. The SLAM receptor is located in lymphoid cells; therefore, the infection of these cells by CDV leads to immunosuppression, the severity of which can lead to variability in the clinical disease with the potential of secondary bacterial infection, up to and including the development of neurological signs in its later stage. CONCLUSION: Improving the understanding of the CDV molecules implicated in the determination of infection, especially the H protein, can help to enhance the biochemical comprehension of the difference between a wide range of CDV variants, their tropism, and different steps in viral infection. The regions of interaction between the viral proteins and the identified host cell receptors have been elucidated to facilitate this understanding. Hence, this review describes the significant molecular and cellular characteristics of CDV that contribute to viral pathogenesis.

Management of an internal root resorption on a permanent tooth: a case report / Manejo de una reabsorción radicular interna en una pieza permanente: reporte de caso

Internal root resorption (IRR) is a rare pulp disease. Its etiology involves late pulpal inflammations and trauma, among others. IRR may also show some symptoms, and is usually detected by X-rays. However, its diagnosis is significantly improved by the use of cone beam computed tomography (CBCT). The objective of this case report was to account for the diagnosis and management of an internal root resorption without perforation. The patient, a 26-year-old male, went to the School of Dentistry at Universidad Andres Bello, Concepción, without having symptoms in the tooth 1.1. Anamnesis revealed the presence of previous symptoms. CBCT examination showed absence of bowl-shaped calcified dentin tissue on the inner walls of the root canal with apical lesion but without perforation of surrounding tissues. Endodontic treatment was performed using the following methods: irrigation of the root canal with 2 percent chlorhexidine (CHX) using a Max-i-probe cannula and simultaneous cavitation of the irrigant Then calcium hydroxide (CH) was applied as intracanal medication for a week and Schilder’s technique for vertical compaction was used. The patient was checked after one week and then after six months. He did not have any symptoms. Early diagnosis using modern imaging equipment, appropriate use of ultrasound for chemomechanical debridement and thermoplastic filling techniques contribute to a more favorable prognosis of patients with internal root resorption...

La reabsorción radicular interna (RRI) es una condición pulpar poco común, cuyo origen etiológico incluye procesos inflamatorios tardíos de la pulpa, traumatismos, entre otros; por otra parte ésta podría presentar sintomatología. Generalmente es detectada por hallazgo radiográfico, sin embargo, requiere de un mejor método de diagnóstico por imagen como es la tomografía computarizada cone beam (TCCB). El objetivo de este reporte de caso fue detallar el diagnóstico y manejo de una reabsorción radicular interna sin perforación. El paciente de sexo masculino, 26 años de edad acudió a la Facultad de Odontología de la Universidad Andrés Bello sede Concepción, sin presentar síntomas en el diente 1.1. La anamnesis refirió presencia de sintomatología con anterioridad. La evaluación mediante la TCCB demostró ausencia de tejido dentinario calcificado en forma de cuenco en las paredes internas del conducto radicular con presencia de lesión apical sin evidenciar perforación hacia tejidos circundantes. Se realizó el tratamiento endodóntico, usando los siguientes métodos: el conducto radicular se irrigó con Clorhexidina (CHX) al 2 por ciento usando cánula Max-i-probe y simultáneamente fue realizada la cavitación del irrigante, luego se colocó Hidróxido de Calcio (HC) como medicación intraconducto por una semana. Se usó la técnica de compactación vertical de Schilder más un control del paciente a la semana y a los 6 meses. El paciente no presentó sintomatología. El diagnóstico temprano mediante herramientas imaginológicas contemporáneas, la utilización del ultrasonido para el desbridamiento químico-mecánico y las técnicas de obturación termoplásticas usadas acorde al caso hacen que las piezas con reabsorción radicular interna tengan un pronóstico más favorable...