Investigation of the molecular genetic causes of non-syndromic primary ovarian ınsufficiency by next generation sequencing analysis

ABSTRACT Objective: The aim of this study is to investigate the molecular genetic causes of non-syndromic primary ovarian insufficiency (POI) cases with the gene panel based on next generation sequencing analysis and to establish the relationship between genotype and phenotype. Subjects and methods: Twenty three cases aged 14-40 years followed up with POI were included. Patients with a karyotype of 46, XX, primary or secondary amenorrhea before the age of 40, with elevated FSH (>40 IU/mL) and low AMH levels (<0.03 ng/mL) were included in the study. Molecular genetic analyzes were performed by the next generation sequencing analysis method targeted with the TruSightTM Exome panel. Results: Median age of the cases was 17.8 (14.0-24.3) years, and 12 (52%) cases admitted before the age of 18. Fifteen (65%) patients had consanguineous parents. In 2 (8.6%) cases, variants detected were in genes that have been previously proven to cause POI. One was homozygous variant in FIGLA gene and the other was homozygous variant in PSMC3IP gene. Heterozygous variants were detected in PROK2, WDR11 and CHD7 associated with hypogonadotropic hypogonadism, but these variants are insufficient to contribute to the POI phenotype. Conclusion: Genetic panels based on next generation sequencing analysis technologies can be used to determine the molecular genetic diagnosis of POI, which has a highly heterogeneous genetic basis.

Multiple copy number variation in a patient with Kleefstra syndrome / Múltiplas variações de número de cópias em paciente com síndrome de Kleefstra

ABSTRACT Objective: To report a rare case of a patient with a molecular diagnosis of Kleefstra syndrome (KS) who has four other chromosomal alterations involving pathogenic variants. Case description: Male patient, two years old, with global delay, including in neuropsychomotor development, ocular hypertelorism, broad forehead, brachycephaly, hypotonia, ligament laxity, unilateral single palmar crease and arachnoid cyst. The microarray-based comparative genomic hybridization (a-CGH) identified copy number variations (CNVs) in five regions: 9q34.3, 6p22.1, Yq11.223, Yp11.23, and 2q24.1. The heterozygous microdeletion in 9q34.3 involving the EHMT1 gene confirms the diagnosis of KS. Comments: The presence of pathogenic CNVs and/or those of uncertain significance, located on chromosomes 2, 6 and Y, may be contributing to a variability in the patient's clinical condition (arachnoid cyst, single palmar fold and ligament laxity), compared to other individuals with only KS genetic alteration, making the dignosis of the disease harder.

RESUMO Objetivo: Relatar um caso raro de paciente com diagnóstico molecular de síndrome de Kleefstra (SK) que apresenta quatro outras alterações cromossômicas envolvendo variantes patogênicas. Descrição do caso: Paciente masculino, dois anos de idade, com atraso global de desenvolvimento neuropsicomotor, hipertelorismo ocular, fronte ampla, braquicefalia, hipotonia, frouxidão ligamentar, prega palmar única unilateral e cisto aracnoide. Exame de hibridização genômica comparativa (a-CGH) identificou variações de número de cópias (CNV) em cinco regiões: 9q34.3, 6p22.1, Yq11.223, Yp11.23 e 2q24.1. A microdeleção heterozigótica em 9q34.3 confirma o diagnóstico de síndrome de Kleefstra. Comentários: A presença das CNV patogênicas e/ou de significado incerto, localizadas nos cromossomos 2, 6 e Y, pode estar contribuindo para uma variabilidade no quadro clínico do paciente (cisto aracnoide, prega palmar única e frouxidão ligamentar) em relação a outros indivíduos somente com alteração genética da SK, dificultando o diagnóstico da doença.

Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells

Background Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection. Results Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimer:monomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimer:monomer ratio. These effects were prevented by combined administration of IFN-β, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimer:monomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimer:monomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimer:monomer equilibrium. Conclusions Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related biological response which partakes in the suppression of viral replication. Further studies are needed to replicate our findings in neuronal cells as well as animal models, and to ascertain the nature of such α-syn conformations.

Molecular characterization of Aeromonas hydrophila isolates from diseased fishes in district Kasur, Punjab, Pakistan / Caracterização molecular de isolados de Aeromonas hydrophila de peixes doentes no distrito de Kasur, Punjab, Paquistão

Abstract Pakistan is an agricultural country and fisheries play a very important role in the economic development of the country. Different diseases are prevalent in Pakistani fish but information related to the causative agents is not well-known. Keeping in view the significance of bacterial pathogens as the causative agents of multiple fish diseases, the present study was conducted for identification, characterization and analysis of virulence genes of Aeromonas spp. isolated from diseased fishes. A total of fifty fish samples having multiple clinical indications were collected from different fish farms of district Kasur, Punjab Pakistan. For isolation of Aeromonas spp. samples were enriched and inoculated on Aeromonas isolation medium. Isolates were identified and characterized by different biochemical tests, Analytical Profile Index (API) 20E kit and Polymerase Chain Reaction (PCR) assays. All isolates were screened for three putative virulence genes including aerolysin (aer), haemolysin (hyl) and heat labile cytotonic enterotoxin (alt). Seven isolates of Aeromonas (A.) hydrophila were retrieved and identified based on API 20E. These isolates were further confirmed as A. hydrophila on the basis of PCR assays. Three isolates were detected positive for the presence of virulence genes (alt and hyl). Whereas aerolysin (aer) gene was not present in any of A. hydrophila isolates. The present study confirmed A. hydrophila as the causative agent of epizootic ulcerative syndrome and motile Aeromonas septicemia in fish farms of district Kasur, Punjab Pakistan. Moreover, detection of two virulence genes (alt and hyl) in A. hydrophila isolates is a threat for fish consumers of study area.

Resumo O Paquistão é um país agrícola, onde a pesca desempenha um papel muito importante para o desenvolvimento econômico. Diferentes doenças são prevalentes em peixes do Paquistão, mas as informações relacionadas aos agentes causadores não são bem conhecidas. Tendo em vista a importância dos patógenos bacterianos como agentes causadores de múltiplas doenças em peixes, o presente estudo foi conduzido para identificação, caracterização e análise de genes de virulência de isolados de Aeromonas spp. de peixes doentes. Foram coletadas 50 amostras de peixes com múltiplas indicações clínicas em diferentes fazendas do distrito de Kasur, Punjab, Paquistão. Para isolar Aeromonas spp., as amostras foram enriquecidas e inoculadas em meio de isolamento. Os isolados foram identificados e caracterizados por diferentes testes bioquímicos, kit Analytical Profile Index (API) 20E, e ensaios de reação em cadeia da polimerase (PCR). Todos os isolados foram selecionados para três genes de virulência putativos, incluindo aerolisina (aer), hemolisina (hyl) e enterotoxina citotônica termolábil (alt). Sete isolados de Aeromonas hydrophila foram recuperados e identificados com base no API 20E. Esses isolados foram posteriormente confirmados como A. hydrophila de acordo com ensaios de PCR. Três isolados indicaram a presença de genes de virulência (alt e hyl), enquanto o gene aerolisina (aer) não esteve presente em nenhum dos isolados de A. hydrophila. O presente estudo confirmou A. hydrophila como o agente causador da síndrome ulcerativa epizoótica e septicemia móvel por Aeromonas em fazendas de peixes, no distrito de Kasur, Punjab, Paquistão. Além disso, a detecção de dois genes de virulência (alt e hyl) em isolados de A. hydrophila é uma ameaça para os consumidores de peixes da área de estudo.

Analysis of Germin-like protein genes family in Vitis vinifera (VvGLPs) using various in silico approaches / Análise da família de genes de proteínas semelhantes a germin em Vitis vinifera (VvGLPs) usando várias abordagens in silico

Germin-like proteins (GLPs) play an important role against various stresses. Vitis vinifera L. genome contains 7 GLPs; many of them are functionally unexplored. However, the computational analysis may provide important new insight into their function. Currently, physicochemical properties, subcellular localization, domain architectures, 3D structures, N-glycosylation & phosphorylation sites, and phylogeney of the VvGLPs were investigated using the latest computational tools. Their functions were predicted using the Search tool for the retrieval of interacting genes/proteins (STRING) and Blast2Go servers. Most of the VvGLPs were extracellular (43%) in nature but also showed periplasmic (29%), plasma membrane (14%), and mitochondrial- or chloroplast-specific (14%) expression. The functional analysis predicted unique enzymatic activities for these proteins including terpene synthase, isoprenoid synthase, lipoxygenase, phosphate permease, receptor kinase, and hydrolases generally mediated by Mn+ cation. VvGLPs showed similarity in the overall structure, shape, and position of the cupin domain. Functionally, VvGLPs control and regulate the production of secondary metabolites to cope with various stresses. Phylogenetically VvGLP1, -3, -4, -5, and VvGLP7 showed greater similarity due to duplication while VvGLP2 and VvGLP6 revealed a distant relationship. Promoter analysis revealed the presence of diverse cis-regulatory elements among which CAAT box, MYB, MYC, unnamed-4 were common to all of them. The analysis will help to utilize VvGLPs and their promoters in future food programs by developing resistant cultivars against various biotic (Erysiphe necator and in Powdery Mildew etc.) and abiotic (Salt, drought, heat, dehydration, etc.) stresses.

As proteínas do tipo germin (GLPs) desempenham um papel importante contra vários estresses. O genoma de Vitis vinifera L. contém 7 GLPs; muitos deles são funcionalmente inexplorados. No entanto, a análise computacional pode fornecer informações importantes sobre sua função. Atualmente, as propriedades físico-químicas, localização subcelular, arquitetura de domínio, estruturas 3D, sítios de N-glicosilação e fosforilação e estudos filogenéticos dos VvGLPs foram conduzidos usando as ferramentas computacionais mais recentes. Suas funções foram previstas usando a ferramenta Search para recuperação de genes/proteínas em interação (STRING) e servidores Blast2Go. A maioria dos VvGLPs são extracelulares (43%) na natureza, mas também mostraram expressão periplasmática (29%), na membrana plasmática (14%) e específica para mitocôndrias ou cloroplastos (14%). A análise funcional previu atividades enzimáticas únicas para essas proteínas, incluindo terpeno sintase, isoprenoide sintase, lipoxigenase, fosfato permease, receptor quinase e hidrolases geralmente mediadas por cátion Mn +. VvGLPs mostraram similaridade na estrutura geral, forma e posição do domínio cupin. Funcionalmente, os VvGLPs controlam e regulam a produção de metabólitos secundários para lidar com vários estresses. Filogeneticamente, VvGLP1, -3, -4, -5 e VvGLP7 mostraram maior similaridade devido à duplicação, enquanto VvGLP2 e VvGLP6 revelaram uma relação distante. A análise do promotor revelou a presença de diversos elementos cis-reguladores, entre os quais CAAT box, MYB, MYC, sem nome-4, sendo comum a todos eles. A análise ajudará a utilizar VvGLPs e seus promotores em programas alimentares futuros, desenvolvendo cultivares resistentes contra vários estresses bióticos (Erysiphe necator e no oídio, etc.) e abióticos (sal, seca, calor, estresse hídrico, etc.).

Screening and bioinformatics analysis of key autophagy-related genes in alcoholic hepatitis / 器官移植

Objective To screen key autophagy-related genes in alcoholic hepatitis (AH) and investigate potential biomarkers and therapeutic targets for AH. Methods Two AH gene chips in Gene Expression Omnibus (GEO) and autophagy-related data sets obtained from MSigDB and GeneCards databases were used, and the key genes were verified and obtained by weighted gene co-expression network analysis (WGCNA). The screened key genes were subject to gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) and immune infiltration analyses. Messenger RNA (mRNA)- microRNA (miRNA) network was constructed to analyze the expression differences of key autophagy-related genes during different stages of AH, which were further validated by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) in the liver tissues of AH patients and mice. Results Eleven autophagy-related genes were screened in AH (EEF1A2, CFTR, SOX4, TREM2, CTHRC1, HSPB8, TUBB3, PRKAA2, RNASE1, MTCL1 and HGF), all of which were up-regulated. In the liver tissues of AH patients and mice, the relative expression levels of SOX4, TREM2, HSPB8 and PRKAA2 in the AH group were higher than those in the control group. Conclusions SOX4, TREM2, HSPB8 and PRKAA2 may be potential biomarkers and therapeutic targets for AH.

Molecular characterization of Aeromonas hydrophila isolates from diseased fishes in district Kasur, Punjab, Pakistan

Abstract Pakistan is an agricultural country and fisheries play a very important role in the economic development of the country. Different diseases are prevalent in Pakistani fish but information related to the causative agents is not well-known. Keeping in view the significance of bacterial pathogens as the causative agents of multiple fish diseases, the present study was conducted for identification, characterization and analysis of virulence genes of Aeromonas spp. isolated from diseased fishes. A total of fifty fish samples having multiple clinical indications were collected from different fish farms of district Kasur, Punjab Pakistan. For isolation of Aeromonas spp. samples were enriched and inoculated on Aeromonas isolation medium. Isolates were identified and characterized by different biochemical tests, Analytical Profile Index (API) 20E kit and Polymerase Chain Reaction (PCR) assays. All isolates were screened for three putative virulence genes including aerolysin (aer), haemolysin (hyl) and heat labile cytotonic enterotoxin (alt). Seven isolates of Aeromonas (A.) hydrophila were retrieved and identified based on API 20E. These isolates were further confirmed as A. hydrophila on the basis of PCR assays. Three isolates were detected positive for the presence of virulence genes (alt and hyl). Whereas aerolysin (aer) gene was not present in any of A. hydrophila isolates. The present study confirmed A. hydrophila as the causative agent of epizootic ulcerative syndrome and motile Aeromonas septicemia in fish farms of district Kasur, Punjab Pakistan. Moreover, detection of two virulence genes (alt and hyl) in A. hydrophila isolates is a threat for fish consumers of study area.

Resumo O Paquistão é um país agrícola, onde a pesca desempenha um papel muito importante para o desenvolvimento econômico. Diferentes doenças são prevalentes em peixes do Paquistão, mas as informações relacionadas aos agentes causadores não são bem conhecidas. Tendo em vista a importância dos patógenos bacterianos como agentes causadores de múltiplas doenças em peixes, o presente estudo foi conduzido para identificação, caracterização e análise de genes de virulência de isolados de Aeromonas spp. de peixes doentes. Foram coletadas 50 amostras de peixes com múltiplas indicações clínicas em diferentes fazendas do distrito de Kasur, Punjab, Paquistão. Para isolar Aeromonas spp., as amostras foram enriquecidas e inoculadas em meio de isolamento. Os isolados foram identificados e caracterizados por diferentes testes bioquímicos, kit Analytical Profile Index (API) 20E, e ensaios de reação em cadeia da polimerase (PCR). Todos os isolados foram selecionados para três genes de virulência putativos, incluindo aerolisina (aer), hemolisina (hyl) e enterotoxina citotônica termolábil (alt). Sete isolados de Aeromonas hydrophila foram recuperados e identificados com base no API 20E. Esses isolados foram posteriormente confirmados como A. hydrophila de acordo com ensaios de PCR. Três isolados indicaram a presença de genes de virulência (alt e hyl), enquanto o gene aerolisina (aer) não esteve presente em nenhum dos isolados de A. hydrophila. O presente estudo confirmou A. hydrophila como o agente causador da síndrome ulcerativa epizoótica e septicemia móvel por Aeromonas em fazendas de peixes, no distrito de Kasur, Punjab, Paquistão. Além disso, a detecção de dois genes de virulência (alt e hyl) em isolados de A. hydrophila é uma ameaça para os consumidores de peixes da área de estudo.

Analysis of Germin-like protein genes family in Vitis vinifera (VvGLPs) using various in silico approaches

Abstract Germin-like proteins (GLPs) play an important role against various stresses. Vitis vinifera L. genome contains 7 GLPs; many of them are functionally unexplored. However, the computational analysis may provide important new insight into their function. Currently, physicochemical properties, subcellular localization, domain architectures, 3D structures, N-glycosylation & phosphorylation sites, and phylogeney of the VvGLPs were investigated using the latest computational tools. Their functions were predicted using the Search tool for the retrieval of interacting genes/proteins (STRING) and Blast2Go servers. Most of the VvGLPs were extracellular (43%) in nature but also showed periplasmic (29%), plasma membrane (14%), and mitochondrial- or chloroplast-specific (14%) expression. The functional analysis predicted unique enzymatic activities for these proteins including terpene synthase, isoprenoid synthase, lipoxygenase, phosphate permease, receptor kinase, and hydrolases generally mediated by Mn+ cation. VvGLPs showed similarity in the overall structure, shape, and position of the cupin domain. Functionally, VvGLPs control and regulate the production of secondary metabolites to cope with various stresses. Phylogenetically VvGLP1, -3, -4, -5, and VvGLP7 showed greater similarity due to duplication while VvGLP2 and VvGLP6 revealed a distant relationship. Promoter analysis revealed the presence of diverse cis-regulatory elements among which CAAT box, MYB, MYC, unnamed-4 were common to all of them. The analysis will help to utilize VvGLPs and their promoters in future food programs by developing resistant cultivars against various biotic (Erysiphe necator and in Powdery Mildew etc.) and abiotic (Salt, drought, heat, dehydration, etc.) stresses.

Resumo As proteínas do tipo germin (GLPs) desempenham um papel importante contra vários estresses. O genoma de Vitis vinifera L. contém 7 GLPs; muitos deles são funcionalmente inexplorados. No entanto, a análise computacional pode fornecer informações importantes sobre sua função. Atualmente, as propriedades físico-químicas, localização subcelular, arquitetura de domínio, estruturas 3D, sítios de N-glicosilação e fosforilação e estudos filogenéticos dos VvGLPs foram conduzidos usando as ferramentas computacionais mais recentes. Suas funções foram previstas usando a ferramenta Search para recuperação de genes/proteínas em interação (STRING) e servidores Blast2Go. A maioria dos VvGLPs são extracelulares (43%) na natureza, mas também mostraram expressão periplasmática (29%), na membrana plasmática (14%) e específica para mitocôndrias ou cloroplastos (14%). A análise funcional previu atividades enzimáticas únicas para essas proteínas, incluindo terpeno sintase, isoprenoide sintase, lipoxigenase, fosfato permease, receptor quinase e hidrolases geralmente mediadas por cátion Mn +. VvGLPs mostraram similaridade na estrutura geral, forma e posição do domínio cupin. Funcionalmente, os VvGLPs controlam e regulam a produção de metabólitos secundários para lidar com vários estresses. Filogeneticamente, VvGLP1, -3, -4, -5 e VvGLP7 mostraram maior similaridade devido à duplicação, enquanto VvGLP2 e VvGLP6 revelaram uma relação distante. A análise do promotor revelou a presença de diversos elementos cis-reguladores, entre os quais CAAT box, MYB, MYC, sem nome-4, sendo comum a todos eles. A análise ajudará a utilizar VvGLPs e seus promotores em programas alimentares futuros, desenvolvendo cultivares resistentes contra vários estresses bióticos (Erysiphe necator e no oídio, etc.) e abióticos (sal, seca, calor, estresse hídrico, etc.).

Development of the Goose Tongue Filiform Papillae: Could it be Tooth-Like Sense Organs? / Desarrollo de las Papilas Filiformes de la Lengua de Ganso: ¿Podrían ser Órganos Sensoriales Parecidos a los Dientes?

SUMMARY: The geese's tongue filiform papillae are particularly long, and exhibit the same morphology of a tooth, evoking the lingual teeth of several fishes. In adult animals, they contain numerous mechanical Herbst's corpuscles but no taste buds. In the embryo, they appear since stage 38 and acquire their definitive shape between stages 38 and 42. They express several proteins associated with mammalian tooth development (BMP4, β-catenin, SHH, PITX2, PAX9), also known to be linked to parrot's pseudoteeth and goose's denticulations development. Neurofilaments are early present in the papillae primordia, and appear particularly numerous in adult papillae. Our results suggest that these papillae constitute a mechanical organ with a « tooth shape » derived from ancestral odontodes, whose development is controlled by numerous genes involved in classical odontogenesis.

Las papilas filiformes de la lengua de los gansos son particularmente largas y exhiben la morfología de un diente, evocando los dientes linguales presentes en varios peces. En los animales adultos, contienen numerosos corpúsculos de Herbst mecánicos, aunque una ausencia de papilas gustativas. En el embrión, aparecen a partir del estadio 38 y adquieren su forma definitiva entre los estadios 38 y 42. Expresan varias proteínas asociadas al desarrollo dentario de los mamíferos (BMP4, β-catenina, SHH, PITX2, PAX9), también conocidas por estar asociadas al desarrollo de pseudodientes en el loro y denticulaciones en el ganso. Los neurofilamentos están presentes tempranamente en los primordios de las papilas y aparecen particularmente numerosos en las papilas adultas. Nuestros resultados sugieren que estas papilas constituyen un órgano mecánico con «forma de diente» derivado de odontoides ancestrales, cuyo desarrollo está controlado por numerosos genes implicados en la odontogénesis clásica.

Genética y genómica de la longevidad y el envejecimiento / Genetics and genomics of longevity and aging

El envejecimiento y la longevidad son procesos que involucran una serie de factores genéticos, bioquímicos y ambientales. En esta revisión se tratan algunas cuestiones sobre estos dos procesos biológicos y epigenéticos. Se presentan los genes más importantes en estos procesos, así como se ejemplifican enfermedades que presentan un aceleramiento o falla en la longevidad y el envejecimiento. Se usa el análisis inteligente de datos para hallar interacciones de proteínas/genes que expliquen estos dos fenómenos biológicos.

Aging and longevity are processes that involve a series of genetic, biochemical and environmental factors. This review addresses some issues about these two biological and epigenetic processes. The most important genes in these processes are presented, as well as diseases that present an acceleration or failure in longevity and aging. Intelligent data analysis is used to find protein/gene interactions that explain these two biological phenomena.

Current Insights on Neoplasms and Adequate Dental Care for Patients with Oral Cancer / Actualización sobre Neoplasmas y su Correcta Atención Odontológica en Pacientes con Cancer Oral

The present study aimed to review the literature on the main complications of antineoplastic therapies and the degree of knowledge of dental surgeons about these complications. A bibliographic search was conducted in the main health databases PUBMED (www.pubmed.gov) and Scholar Google (www.scholar.google.com.br), in which studies published from 1987 to 2023 were collected. Laboratory studies, case reports, systematic and literature reviews, which were developed in living individuals, about the main neoplastic genes and their relationship with the cells of individuals affected by neoplasms in the head and neck region, and studies on the care with this group of patients, were included. Therefore, articles that did not deal with neoplasm and the main complications of antineoplastic therapies were excluded. Neoplasm is a clonal disorder, caused by mutations, resulting from changes in the genetic structure of cells. Each healthy cell has instructions on how to grow and divi de. In the presence of any error in these instructions (mutation), it can result in a diseased cell that, when proliferating, may cause a tumor. Countless knowledge has been accumulated over the years on the main characteristics of neoplasms, whether they are cancer cell biology, carcinogenesis mechanism, neoplasms of the maxillofacial system and sequels of antineoplastic treatments. In this context, methods have been developed that offer a better quality of life for patients diagnosed with this pathology, as well as preventive vaccine models that may, in the not too distant future, contribute to this goal to be successfully achieved.

El presente estudio tuvo como objetivo revisar la literatura sobre las principales complicaciones de las terapias antineoplásicas y el grado de conocimiento de los odontólogos sobre este abordaje. Se realizó una búsqueda bibliográfica en las principales bases de datos de salud PUBMED (www.pubmed.gov) y Scholar Google (www.scholar.google.com.br), en la que se recopilaron estudios publicados entre 1987 y 2023. Fueron incluidos estudios de laboratorio, relatos de casos, revisiones de la literatura y revisiones sistemáticas, desarrolladas en individuos vivos, que incluyeran los principales genes neoplásicos y su relación con las células de individuos afectados por neoplasias en la cabeza y el cuello. También, se tuvieron en cuenta estudios relacionados con la atención a este grupo de pacientes. La neoplasia es un trastorno clonal, causado por mutaciones, como resultado de cambios en la estructura genética de las células. Cada célula sana tiene instrucciones sobre cómo crecer y dividirse. En presencia de cualquier error en estas instrucciones (mutación), puede provocar una célula alterada que, al proliferar, puede causar un tumor. Se han acumulado innumerables conocimientos a lo largo de los años sobre las principales características de las neoplasias, ya sea sobre biología de células cancerosas, el mecanismo de la carcinogénesis, la neoplasias del sistema maxilofacial y las diferentes secuelas de tratamientos antineoplásicos. En este contexto, se han desarrollado métodos que ofrecen una mejor calidad de vida para los pacientes diagnosticados con esta patología, así como modelos de vacunas preventivas que, en un futuro no muy lejano, pueden contribuir a alcanzar este objetivo con éxito.

Tumor desmoplásico de células redondas / Desmoplastic round cell tumor

Resumen El tumor desmoplásico de células pequeñas y redon das es una neoplasia poco frecuente y muy agresiva que forma parte de la familia de los "tumores de célu las pequeñas, redondas y azules". Presenta una mayor incidencia en el sexo masculino en la segunda década de la vida. Se debe a la translocación t(11;22) (p13;q12). Se puede localizar tanto en el abdomen como en el re troperitoneo caracterizándose por presentar síntomas inespecíficos. El tratamiento es muy variado y no se ha detectado todavía aquel que garantice la cura total del paciente. El objetivo del presente estudio es exponer un caso clínico de tumor desmoplásico como enfermedad abdo minal infrecuente y su expresión imagenológica.

Abstract Desmoplastic small round cell tumor is a rare and very aggressive neoplasm that belongs to the family of "small round blue cell tumors". It has a higher incidence in males in the second decade of life. It is due to trans location t(11;22) (p13;q12). It can be located both in the abdomen and in the retroperitoneum and is character ized by nonspecific symptoms. The treatment is very varied and the one that guarantees the total cure of the patient has not yet been detected. The objective of this study is to expose a clinical case of desmoplastic tumor as an rare abdominal disease and its imaging expression.

The association of BRAF V600E gene mutation with proliferative activity and histopathological characteristics of congenital melanocytic nevi in children

Abstract Background: A lot of congenital melanocytic nevi (CMN) carry the somatic mutation in the oncogene BRAF V600E. But the detailed histopathologic characteristics and the proliferative activity of CMN with BRAF V600E gene mutation have not been systematically documented. Objective: To identify the proliferative activity and histopathological features correlating them with BRAF V600E gene mutation status in CMN. Methods: CMN were retrospectively identified from the laboratory reporting system. Mutations were determined by Sanger sequencing. The CMN were divided into a mutant group and control group according to whether there was BRAF gene mutation and were strictly matched according to gender, age, nevus size, and location. Histopathological analysis, analysis of Ki67 expression by immunohistochemistry and laser confocal fluorescence microscopy were performed. Results: The differences in Ki67 index, the depth of nevus cell involvement and the number of nevus cell nests between the mutant group and the control group was statistically significant, with p-values of 0.041, 0.002 and 0.007, respectively. Compared with BRAFV600E negative nevi, BRAF V600E positive nevi often exhibited predominantly nested intraepidermal melanocytes, and larger junctional nests, but the difference in this datasets were not statistically significant. The number of nests (p = 0.001) was positively correlated with the proportion of Ki67 positive cells. Study limitations: A small sample of patients were included and there was no follow-up. Conclusions: BRAF V600E gene mutations were associated with high proliferative activity and distinct histopathological features in congenital melanocytic nevi.

Mecanismos moleculares de la esquizofrenia / Molecular mechanisms of schizophrenia / Mecanismos moleculares da esquizofrenia

La etiología de la esquizofrenia no está totalmente dilucidada. Se conocen más de 100 diferentes loci de genes relacionados con esquizofrenia, la mayoría de los cuales codifican moléculas asociados a los sistemas de neurotransmisores o al neurodesarrollo. Las primeras abarcan receptores de los neurotransmisores como dopamina, GABA o glutamato y de otros neurotransmisores con menor relación, como la serotonina y la acetilcolina. También están implicadas diversas enzimas relacionadas con el metabolismo, cotransportadores y algunas proteínas intracelulares involucradas en la degradación o síntesis de dichos neurotransmisores. Entre las moléculas que intervienen en el neurodesarrollo están los factores neurotróficos (BDNF, DISC1, NRG1) y las proteínas del complemento C3 y C4, que median la respuesta inflamatoria y la poda sináptica durante el desarrollo temprano. Los productos de la producción genética involucrados en la etiología de la esquizofrenia aportan a la vulnerabilidad selectiva o al proceso de lesión que se instaura o progresa en el paciente, por tanto, su estudio es de relevancia para la comprensión de los fenómenos clínicos propios de la enfermedad.

The etiology of schizophrenia is not fully elucidated. More than 100 different gene loci related to schizophrenia are known, most of which encode molecules associated with neurotransmitter systems or neurodevelopment. These include receptors for neurotransmitters such as dopamine, GABA, or glutamate, as well as other neurotransmitters with less direct relevance, such as serotonin and acetylcholine. Various enzymes involved in metabolism, cotransporters, and intracellular proteins involved in the degradation or synthesis of said neurotransmitters are also implicated. Among the molecules involved in neurodevelopment are neurotrophic factors (BDNF, DISC1, NRG1) and complement proteins C3 and C4, which mediate the inflammatory response and synaptic pruning during early development. The genetic products involved in the etiology of schizophrenia contribute to selective vulnerability or the process of injury that is established or progresses in the patient. Therefore, their study is relevant to the understanding of the clinical phenomena associated with the disease.

A etiologia da esquizofrenia não está totalmente elucidada. Mais de 100 diferentes loci de genes relacionados à esquizofrenia são conhecidos, a maioria dos quais codifica moléculas associadas a sistemas de neurotransmissores ou neurodesenvolvimento. O primeiro inclui receptores para neurotransmissores como dopamina, GABA ou glutamato e outros neurotransmissores menos relacionados, como serotonina e acetilcolina. Também estão envolvidas várias enzimas relacionadas com o metabolismo, cotransportadores e algumas proteínas intracelulares envolvidas na degradação ou síntese dos referidos neurotransmissores. Entre as moléculas envolvidas no neurodesenvolvimento estão os fatores neurotróficos (BDNF, DISC1, NRG1) e as proteínas do complemento C3 e C4, que medeiam a resposta inflamatória e a poda sináptica durante o desenvolvimento inicial. Os produtos da produção genética envolvidos na etiologia da esquizofrenia contribuem para a vulnerabilidade seletiva ou para o processo de lesão que se instala ou progride no paciente, portanto, seu estudo é relevante para a compreensão dos fenômenos clínicos da esquizofrenia

Use of topical colistin in bacterial keratitis caused by extensively drug-resistant Pseudomonas Aeruginosa: a case report / Uso de colistina tópica em ceratite bacteriana causada por Pseudomonas Aeruginosa extensivamente resistente a medicamentos: relato de caso

ABSTRACT Bacterial keratitis caused by multidrug-resistant strains of Pseudomonas aeruginosa is a therapeutic challenge due to a limited number of active antimicrobials and rapid progression to corneal necrosis and perforation. To report the use of topical colistin and surgical tarsorrhaphy in a case of keratitis caused by extensively drug-resistant Pseudomonas aeruginosa in a patient with severe coronavirus disease-2019 (COVID-19) pneumonia. A 56-year-old male was admitted to the intensive care unit with clinical symptoms of severe COVID-19 pneumonia. During his stay in the unit, he developed rapidly progressive keratitis with Pseudomonas aeruginosa resistant to all drugs except for colistin on culture. Due to incomplete lid closure, a temporary tarsorrhaphy was performed, and a regimen of descending-dose topical colistin was initiated. After five weeks, keratitis resolved completely. Extensively drug-resistant Pseudomonas aeruginosa is an unusual cause of bacterial keratitis. We describe the safe and effective use of topical colistin in a case with severe corneal involvement.

RESUMO A ceratite bacteriana causada por cepas multirresistentes de Pseudomonas aeruginosa é um desafio terapêutico, devido à disponibilidade limitada de antimicrobianos e à rápida progressão para necrose e perfuração da córnea. O objetivo deste artigo é relatar o uso de colistina tópica e tarsorrafia cirúrgica em um caso de ceratite por Pseudomonas aeruginosa amplamente resistente a medicamentos em um paciente com pneumonia grave por COVID19. Um homem de 56 anos foi internado em uma unidade de terapia intensiva com sintomas clínicos de pneumonia grave por COVID19. Durante sua permanência na unidade de terapia intensiva, o paciente desenvolveu uma ceratite rapidamente progressiva, cuja cultura foi positiva para Pseudomonas aeruginosa resistente a todos os antimicrobianos, exceto colistina. Devido ao fechamento incompleto da pálpebra, foi realizada uma tarsorrafia temporária e foi instituído um esquema de colistina tópica em doses decrescentes. Após cinco semanas, a resolução completa da ceratite foi alcançada. Pseudomonas aeruginosa amplamente resistente a medicamentos é uma causa incomum de ceratite bacteriana. Este relato descreve o uso seguro e eficaz da colistina tópica em um caso com comprometimento corneano grave.

Aspectos histológicos, genéticos y moleculares de las lesiones preneoplásicas de la mucosa gástrica / Histological, genetic and molecular aspects of preneoplastic lesions of the gastric mucosa

Siendo el cáncer gástrico la 3ª causa de muerte por cáncer en Chile, y existiendo estrategias de tamizaje consistentes en pesquisa de lesiones preneoplásicas de la mucosa gástrica, es relevante conocer los aspectos genéticos y moleculares que puedan ser aplicados, en la optimización de dichas estrategias a grupos de mayor riesgo. El objetivo de este manuscrito fue revisar la evidencia actual en los aspectos señalados, y de la inmunohistoquímica de 4 marcadores (p53, CDX2, MUC2 y S100A9) en la mucosa gástrica normal y en las lesiones preneoplásicas de la misma.

SUMMARY: Since gastric cancer is the 3rd leading cause of death from cancer in Chile, and there are screening strategies consisting of screening for preneoplastic lesions of the gastric mucosa, it is important to know certain genetic and molecular aspects that can be applied in optimizing these strategies for higher risk groups. The aim of this manuscript was to review the current evidence on the aforementioned aspects, and on the immunohistochemistry of 4 markers (p53, CDX2, MUC2 and S100A9) in normal gastric mucosa and in its preneoplastic lesions.

Human beta-defensin 1 circulating level and gene polymorphism in non-segmental vitiligo Egyptian patients

Abstract Background: Vitiligo is an acquired depigmented skin disorder. It has a genetic and autoimmune background. Human beta defensin-1(HBD-1) plus its gene polymorphism were linked to some autoimmune disorders. Objectives: To elucidate the possible role of HBD-1 in the pathogenesis of non-segmental vitiligo (NSV) through evaluation of HBD-1 serum levels and its single nucleotide polymorphism (SNP) in patients having NSV, in addition, to correlating the results with the extent of vitiligo in those patients. Methods: A current case-control study included 50 patients having NSV and 50 controls. The authors used Vitiligo Area Scoring Index (VASI) score to assess vitiligo severity and laboratory investigations to assess serum HBD-1 level using ELISA and defensin-beta1 (DEFB1) SNP using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: There were significantly lower HBD-1 serum levels in NSV cases than in controls (p < 0.001). There was a significant predominance of GG DEFB1 genotype and G allele in NSV patients in comparison to controls (p < 0.001). The levels of serum HBD-1 and DEFB1 genotypes were not associated or correlated significantly with any of the personal and clinical parameters of vitiligo patients. Study limitations: The small sample size. Conclusions: DEFB1 gene polymorphism (GG genotype and G allele) may modulate vitiligo risk and contribute to vitiligo development in Egyptian populations. Decreased circulating HBD-1 levels might have an active role in vitiligo etiopathogenesis that could be mediated through its possible anti-inflammatory effects.

Lactic Acid Inhibits the Cytotoxicity of NK-92 Cells via Activating the Lactate Receptor GPR81

Aims: Lactate acid functions as not only an energy source but a signaling molecule through the lactate receptor GPR81 under physiological conditions. However, the pathological role of lactic acid in the tumor microenvironment remains unclear, particularly for immune cells. Methodology: NK-92 cells were treated with L-lactic acid solutions at final concentrations of 10, 20, 30, and 40 mM, and its cell viability and cytotoxicity on A549 cells and A375 cells were evaluated by CCK8 assay and crystal violet assay, respectively. Furthermore, qPCR was used to assess the expression of GPR81 and cytotoxicity-related genes in NK-92 cells treated with antagonist and agonist. And their relationship between lactate/GPR81 pathway and cytotoxicity-related genes were analyzed by Pearson’s correlation. Results: The viability of NK-92 cells was inhibited by L-lactic acid with increasing concentration. Additionally, the cytotoxic activity against tumor cells of NK-92 cells treated with L-lactic acid decreased with increasing concentration. Moreover, qPCR results demonstrated that GPR81 can be activated by lactic acid or agonist (3,5-DHBA) and downregulate the expression cytotoxicity-related genes which included FASLG gene(Fas Ligand),TNF-? gene(Tumor necrosis factor-?), INFG gene (Interferon-?), RPF1 gene (Perforin 1), GZMA gene (Granzyme A), GZMB gene (Granzyme B), GZMH gene (Granzyme H), GAMK gene (Granzyme K) and GZMM gene (Granzyme M). And the expression of GPR81 returned to near-control level when treated with L-lactic acid in the presence of antagonist (3-OBA), the expression of cytotoxicity-related genes did as well. Pearson’s correlation analysis of cytotoxicity-related genes with GPR81 revealed that their correlation coefficient seems negative. Conclusion: Lactic acid can activate the GPR81 to downregulate the expression of cytotoxicity-related genes, subsequently lower the cytotoxicity of NK-92 cells.

VIH/sida y epigenética / HIV/AIDS and epigenetic

Resumen Desde 1981, el virus de la inmunodeficiencia humana ha afectado a más de 75 millones de personas en el mundo. La prevención, el diagnóstico temprano y, ante todo el empleo de la terapia antirretroviral, ha disminuido su morbimortalidad. Sin embargo, su cura y el desarrollo de una vacuna efectiva aún son objetivos no alcanzables a corto plazo. Una de las barreras para obtener su control es la persistencia crónica de los virus o sus subproductos en los denominados reservorios celulares, lo que induce un proceso inflamatorio crónico complejo que se manifiesta clínicamente como enfermedad cardiovascular, diversos tipos de cáncer, envejecimiento precoz, entre otras patologías. Los procesos intrínsecos que llevan a estos trastornos han estado siendo investigados a profundidad en los últimos años y la epigenética, definida como el estudio de las modificaciones que afectan de manera directa la expresión de los genes, pero sin cambios en la secuencia del ácido desoxirribonuncleico, puede ayudar a desentrañar estos retos. En esta revisión se analizan los mecanismos epigenéticos, como la metilación del ácido desoxirribonuncleico, las modificaciones en histonas y el ácido ribonucleico no codificante, como posibles blancos en el diagnóstico y tratamiento de la inflamación crónica y sus consecuencias clínicas asociadas al virus de inmunodeficiencia humana/sida.

Abstract Since 1981, over 75 million people have been infected with human immunodeficiency virus. The survival rate of patients with this infection has dramatically increased with the use of antiretroviral therapy, and this therapy significantly reduced the incidence of AIDS defining events. Despite recent progress, neither a cure nor a preventive vaccine against human immunodeficiency virus infection is likely to become available soon. Epigenetics is defined as the study of chemical modifications of intrinsic and extrinsic factors of the genetic code regulating gene expression. Three types of epigenetic markers have been found: DNA methylation, post-translational histone modifications, and non-coding RNA (ncRNA). In this review, we analyzed recent research about the relation between epigenetic mechanisms, the persistence of HIV in host cells, the chronic inflammatory response evoked, the cardiovascular diseases associated and premature aging in this population.

Potenciales biomarcadores moleculares de infiltración a sistema nervioso central en leucemia linfoblástica aguda / Central nervous system potential molecular biomarkers in acute lymphoblastic leukemia

Resumen La leucemia linfoblástica aguda es el tipo de leucemia más frecuente en niños entre los 2 y 3 años. A nivel internacional la población hispana es reportada como la más prevalente. En México se carece de información reciente, sin embargo, se conoce que es uno de los cánceres más frecuentes en niños. La infiltración de células linfoblásticas a sistema nervioso central es una complicación de pronóstico ominoso que puede presentarse en los pacientes con leucemia linfoblástica aguda, actualmente el diagnóstico se establece mediante citología de líquido cefalorraquídeo, sin embargo, es una prueba operador dependiente y que es afectada por el número de punciones realizadas en la toma de líquido cefalorraquídeo, con potencial contaminación con sangre. En distintos estudios se han caracterizado 6 genes que presentan una sobreexpresión en líquido cefalorraquídeo cuando se presenta dicha infiltración, en esta revisión analizamos estos nuevos marcadores y su potencial como herramientas de diagnóstico oportuno.

Abstract Acute lymphoblastic leukemia is the most common type of leukemia in children between 2 and 3 years of age. Internationally, hispanic population is reported as the most prevalent. In Mexico there is few recent information, however, it is known that it is one of the most frequent cancers in children. Infiltration of lymphoblastic cells into the central nervous system is an ominous prognostic complication that can occur in patients with acute lymphoblastic leukemia. Currently, diagnosis is established by cerebrospinal fluid cytology, however, this technique is affected by the number of punctions done while obtaining the fluid. In several research studies, 6 genes have been identified to be overexpressed in cerebrospinal fluid when infiltration occurs. In this review we analyzed these new molecular biomarkers and their potential as tools for timely diagnosis.