RESUMO
La Diabetes del adulto de inicio juvenil, es un subtipo hereditario poco común que se manifiesta a una edad temprana, relacionado con mutaciones en genes específicos que principalmente afectan la función de las células beta pancreática. Un diagnóstico preciso es fundamental para un tratamiento efectivo, aunque puede ser desafiante debido a la variabilidad en sus características clínicas y moleculares. Esta revisión analiza la evidencia disponible sobre estas características y los métodos de diagnóstico utilizados en laboratorio. Se realizó una búsqueda exhaustiva en bases de datos científicas, seleccionando estudios relevantes según criterios específicos. Se analizaron características clínicas, hallazgos moleculares y métodos de diagnóstico, utilizando tablas, gráficos y síntesis narrativas. Se identificaron mutaciones genéticas asociadas con MODY, así como biomarcadores útiles en el laboratorio clínico. Además, se describieron métodos de diagnóstico molecular, incluyendo la secuenciación de próxima generación (NGS). Esta revisión resalta la importancia del diagnóstico preciso de MODY, subrayando la diversidad de sus características biológicas y moleculares, y la necesidad de una investigación más profunda para mejorar su identificación y manejo clínico
Maturity Onset Diabetes of the Young is a rare hereditary subtype that manifests at an early age, related to mutations in specific genes that primarily affect the function of pancreatic beta cells. An accurate diagnosis is crucial for effective treatment, though it can be challenging due to variability in clinical and molecular characteristics. This review examines available evidence on these characteristics and laboratory diagnostic methods. A comprehensive search was conducted in scientific databases, selecting relevant studies based on specific criteria. Clinical features, molecular findings, and diagnostic methods were analyzed using tables, graphs, and narrative synthesis. Genetic mutations associated with MODY were identified, as well as useful biomarkers in clinical laboratory settings. Additionally, molecular diagnostic methods were described, including next-generation sequencing (NGS). This review emphasizes the importance of precise MODY diagnosis, highlighting the diversity of its biological and molecular characteristics, and the need for further research to enhance its identification and clinical management
A diabetes adulto de início juvenil é um subtipo hereditário raro que se manifesta em uma idade precoce, relacionado a mutações em genes específicos que afetam principalmente a função das células beta do pâncreas. Um diagnóstico preciso é fundamental para um tratamento eficaz, embora possa ser desafiador devido à variabilidade em suas características clínicas e moleculares. Esta revisão analisa a evidência disponível sobre essas características e os métodos de diagnóstico utilizados em laboratório. Foi realizada uma busca abrangente em bases de dados científicas, selecionando estudos relevantes com base em critérios específicos. Características clínicas, descobertas moleculares e métodos de diagnóstico foram analisados utilizando tabelas, gráficos e síntese narrativa. Foram identificadas mutações genéticas associadas ao MODY, assim como biomarcadores úteis em laboratório clínico. Além disso, foram descritos métodos de diagnóstico molecular, incluindo a sequenciação de próxima geração (NGS). Esta revisão enfatiza a importância do diagnóstico preciso do MODY, destacando a diversidade de suas características biológicas e moleculares e a necessidade de uma pesquisa mais aprofundada para melhorar sua identificação e manejo clínico
Assuntos
Revisão SistemáticaRESUMO
La Diabetes del adulto de inicio juvenil, es un subtipo hereditario poco común que se manifiesta a una edad temprana, relacionado con mutaciones en genes específicos que principalmente afectan la función de las células beta pancreática. Un diagnóstico preciso es fundamental para un tratamiento efectivo, aunque puede ser desafiante debido a la variabilidad en sus características clínicas y moleculares. Esta revisión analiza la evidencia disponible sobre estas características y los métodos de diagnóstico utilizados en laboratorio. Se realizó una búsqueda exhaustiva en bases de datos científicas, seleccionando estudios relevantes según criterios específicos. Se analizaron características clínicas, hallazgos moleculares y métodos de diagnóstico, utilizando tablas, gráficos y síntesis narrativas. Se identificaron mutaciones genéticas asociadas con MODY, así como biomarcadores útiles en el laboratorio clínico. Además, se describieron métodos de diagnóstico molecular, incluyendo la secuenciación de próxima generación (NGS). Esta revisión resalta la importancia del diagnóstico preciso de MODY, subrayando la diversidad de sus características biológicas y moleculares, y la necesidad de una investigación más profunda para mejorar su identificación y manejo clínico.
Maturity Onset Diabetes of the Young is a rare hereditary subtype that manifests at an early age, related to mutations in specific genes that primarily affect the function of pancreatic beta cells. An accurate diagnosis is crucial for effective treatment, though it can be challenging due to variability in clinical and molecular characteristics. This review examines available evidence on these characteristics and laboratory diagnostic methods. A comprehensive search was conducted in scientific databases, selecting relevant studies based on specific criteria. Clinical features, molecular findings, and diagnostic methods were analyzed using tables, graphs, and narrative synthesis. Genetic mutations associated with MODY were identified, as well as useful biomarkers in clinical laboratory settings. Additionally, molecular diagnostic methods were described, including next-generation sequencing (NGS). This review emphasizes the importance of precise MODY diagnosis, highlighting the diversity of its biological and molecular characteristics, and the need for further research to enhance its identification and clinical management.
A diabetes adulto de início juvenil é um subtipo hereditário raro que se manifesta em uma idade precoce, relacionado a mutações em genes específicos que afetam principalmente a função das células beta do pâncreas. Um diagnóstico preciso é fundamental para um tratamento eficaz, embora possa ser desafiador devido à variabilidade em suas características clínicas e moleculares. Esta revisão analisa a evidência disponível sobre essas características e os métodos de diagnóstico utilizados em laboratório. Foi realizada uma busca abrangente em bases de dados científicas, selecionando estudos relevantes com base em critérios específicos. Características clínicas, descobertas moleculares e métodos de diagnóstico foram analisados utilizando tabelas, gráficos e síntese narrativa. Foram identificadas mutações genéticas associadas ao MODY, assim como biomarcadores úteis em laboratório clínico. Além disso, foram descritos métodos de diagnóstico molecular, incluindo a sequenciação de próxima geração (NGS). Esta revisão enfatiza a importância do diagnóstico preciso do MODY, destacando a diversidade de suas características biológicas e moleculares e a necessidade de uma pesquisa mais aprofundada para melhorar sua identificação e manejo clínico.
RESUMO
PURPOSE: Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract, and its unique location within the small intestine presents difficulties in obtaining tissue samples from the lesions. This limitation hinders the research and development of effective clinical treatment methods. Circulating tumor DNA (ctDNA) analysis holds promise as an alternative approach for investigating SBA and guiding treatment decisions, thereby improving the prognosis of SBA. METHODS: Between January 2017 and August 2021, a total of 336 tissue or plasma samples were obtained and the corresponding mutation status in tissue or blood was evaluated with NGS. RESULTS AND CONCLUSIONS: The study found that in SBA tissues, the most commonly alternated genes were TP53, KRAS, and APC, and the most frequently affected pathways were RTK-RAS-MAPK, TP53, and WNT. Notably, the RTK-RAS-MAPK pathway was identified as a potential biomarker that could be targeted for treatment. Then, we validated the gene mutation profiling of ctDNA extracted from SBA patients exhibited the same characteristics as tissue samples for the first time. Subsequently, we applied ctDNA analysis on a terminal-stage patient who had shown no response to previous chemotherapy. After detecting alterations in the RTK-RAS-MAPK pathway in the ctDNA, the patient was treated with MEK + EGFR inhibitors and achieved a tumor shrinkage rate of 76.33%. Our study utilized the largest Chinese SBA cohort to uncover the molecular characteristics of this disease, which might facilitate clinical decision making for SBA patients.
Assuntos
Adenocarcinoma , DNA Tumoral Circulante , Neoplasias Intestinais , Mutação , Humanos , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Biomarcadores Tumorais/genética , Intestino Delgado/patologia , Adulto , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética , Proteína da Polipose Adenomatosa do Colo/genética , China , Prognóstico , População do Leste AsiáticoRESUMO
The present study describes Coccomyxa bragantinensis n. sp., which was found parasitising the gallbladder of the Coco Sea catfish, Bagre bagre, captured off Ajuruteua beach, in the region of Bragança in Pará state, northern Brazil. Most (77.5%) of the 40 fish specimens examined (31/40) had myxospores floating in the bile liquid. These spores are partially ellipsoid, with a tapering anterior extremity and a rounded, elongated posterior extremity with a single piriform polar capsule containing a helicoidal polar filament, with 5-6 coils. A partial sequence of 957 bp of the SSU rDNA gene was obtained from the specimens and deposited in GenBank (xxx). The new species described here - Coccomyxa bragantinensis n. sp. - is phylogenetically similar to Coccomyxa morovi, although it differs from all the other Coccomyxa species and is the first species of this genus to be described from Brazil on the basis of molecular evidence.
Assuntos
Peixes-Gato , Cnidários , Doenças dos Peixes , Myxozoa , Doenças Parasitárias em Animais , Animais , Cnidários/genética , Filogenia , Brasil , Doenças Parasitárias em Animais/epidemiologia , DNA Ribossômico/genéticaRESUMO
Hydrochar is a carbon-based material that can be used as soil amendment. Since the physical-chemical properties of hydrochar are mainly assigned to process parameters, we aimed at evaluating the organic fraction of different hydrochars through 13C-NMR and off-line TMAH-GC/MS. Four hydrochars produced with sugarcane bagasse, vinasse and sulfuric or phosphoric acids were analyzed to elucidate the main molecular features. Germination and initial growth of maize seedlings were assessed using hydrochar water-soluble fraction to evaluate their potential use as growth promoters. The hydrochars prepared with phosphoric acid showed larger amounts of bioavailable lignin-derived structures. Although no differences were shown about the percentage of maize seeds germination, the hydrochar produced with phosphoric acid promoted a better seedling growth. For this sample, the greatest relative percentage of benzene derivatives and phenolic compounds were associated to hormone-like effects, responsible for stimulating shoot and root elongation. The reactions parameters proved to be determinant for the organic composition of hydrochar, exerting a strict influence on molecular features and plant growth response.
Assuntos
Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Carvão Vegetal/química , Carvão Vegetal/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Desenvolvimento Vegetal/efeitos dos fármacos , Compostos de Amônio Quaternário/química , Água/química , Bioensaio , Raízes de Plantas/anatomia & histologia , Raízes de Plantas/efeitos dos fármacos , Brotos de Planta/anatomia & histologia , Brotos de Planta/efeitos dos fármacos , Sementes/efeitos dos fármacos , Zea mays/efeitos dos fármacos , Zea mays/crescimento & desenvolvimentoRESUMO
The epidemiology and clonality of methicillin-resistant Staphylococcus aureus (MRSA) has not been investigated, as not much research or surveillance has been undertaken to identify and characterize the circulating MRSA strains in Barbados. Prevalence rates, molecular characteristics and antimicrobial susceptibility pattern of MRSA infections in hospitalized and nonhospitalized patients were investigated. A total of 293 isolates were included in the study, with 100 from the hospital and 193 from the public health laboratory. Isolates were collected over a period of 1 (2015-2016) and 3 years (2013-2016) respectively. MRSA was identified using standard microbiologic techniques and was further analysed by multiplex PCR for the presence of the spa, mec gene complex typing and PVL genes (lukS-PV and lukF-PV). A prevalence rate of 19.7% was calculated for those hospitalized. All hospital isolates were sensitive to vancomycin, rifampin, linezolid and cotrimoxazole (trimethoprim/sulfamethoxazole), whilst 82% were sensitive to clindamycin. The PVL gene was detected in 76% of hospital isolates. In the community isolates, resistance was observed in erythromycin (100%), ciprofloxacin (97.4%), clindamycin (13%) and cotrimoxazole (5.7%). There was no resistance to vancomycin. The PVL gene was detected in 97.9% of the isolates, the mecA gene in only 2.1% and the mecC gene in 0%. Most MRSA isolates were community acquired in both settings, and the antimicrobial susceptibility profile was similar, suggesting transmission of community-associated MRSA into the hospital environment. Further harmonization of antimicrobial policy for the treatment of MRSA (and by extension other pathogens) should be implemented to quell ongoing transmission. We found that 93.4% of MRSA in Barbados treated in the primary healthcare system were sensitive to cotrimoxazole. By typing MRSA isolates and drawing interferences on transmission on the basis of genetic relatedness, transmission pathways may be tracked. Further studies must be performed for this high level of comprehensiveness so that with the surveillance of MRSA, effective strategies may be developed to prevent or limit transmission.
RESUMO
Several Sarcocystis spp. have carnivores as definitive host and sarcocysts are common in muscles of herbivores (intermediate host). However, sarcocysts have been found in muscles of wild and domestic carnivores suggesting they are intermediate host for some Sarcocystis spp. Here, we report mature sarcocysts in the muscles of Pampas fox (Lycalopex gymnocercus). A total of 36 free-living foxes were analyzed. Different skeletal muscles were assessed by microscopic and molecular methods. Cysts and/or DNA of Sarcocystis sp. were detected in 61.1% (22/36) foxes. Histopathology revealed the presence of sarcocysts in 52.8% (19/36) foxes. The tongue and masseter were the muscles more frequently infected. Of all the samples processed by homogenization of pooled muscles of each animal, 45.4% (10/22) evidenced muscle cysts and 68.2% (15/22) resulted positives by PCR. Individual cysts obtained from the ten positive samples in direct microscopic examination were all positive by PCR. Five amplicons from individual cysts from different samples were selected for sequencing together with four PCR products obtained from the pooled muscles. All nine sequences shared a high identity among them (99.8-100%) and showed the highest identity by BLAST (99%) with a S. svanai sequence (KM362428) from a North American dog. By transmission electron microscopy, the sarcocyst wall was thin (<1µm), had minute undulations, with tiny evaginations and without evident villar protrusions. The cyst wall type is referred as "type 1". Sarcocystis svanai infects L. gymnocercus with a high prevalence and the presence of mature sarcocysts suggests the role of the Pampas fox as natural intermediate host. The definitive host of S. svanai remains unknown.
Assuntos
Raposas/parasitologia , Músculo Esquelético/parasitologia , Sarcocystis/isolamento & purificação , Sarcocystis/fisiologia , Sarcocistose/veterinária , Animais , Raposas/anatomia & histologia , Microscopia Eletrônica de Transmissão , Filogenia , Reação em Cadeia da Polimerase , RNA Ribossômico 18S/genética , Sarcocystis/genética , Sarcocystis/ultraestrutura , Sarcocistose/parasitologia , Sarcocistose/fisiopatologia , Sarcocistose/transmissão , América do Sul , Língua/parasitologiaRESUMO
The human calcium- and integrin-binding protein (CIB) family is composed of CIB1, CIB2, CIB3, and CIB4 proteins and the CIB4 gene affects fertility. Kermani sheep is one of the most important breeds of Iranian sheep breeds. The aim of this study was to analyze for the first time molecular characteristics of the CIB4 gene and protein in Kermani sheep. Different tissues were collected from the Kermani sheep and real time PCR was performed. The PCR products were sequenced, comparative analyses of the nucleotide sequences were performed, a phylogenetic tree was constructed, and different characteristics of CIB4 proteins were predicted. Real time PCR results showed that the CIB4 gene is expressed only in testis of Kermani sheep. The cDNA nucleotide sequence was identical with small tail Han sheep, cattle, goat, camel, horse, dog, mouse and human, respectively 100, 99, 99, 98, 98, 96, 96, and 96%. Hence, it can be suggested that the CIB4 gene plays a role in male fertility. Based on the phylogenetic analysis, sheep CIB4 gene has a close relationship with goat and cattle first, and then with camel and whale. Although we demonstrated that CIB4 is a testis-specific gene, expressed only in the testis and it interacts with other proteins, the mechanisms by which CIB4 expression is regulated need to be elucidated.
Assuntos
Animais , Masculino , Feminino , Proteínas de Ligação ao Cálcio/análise , Proteínas de Ligação ao Cálcio/genética , Ovinos/genética , Sequência de Aminoácidos , Sequência de Bases , Eletroforese/veterinária , Filogenia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Valores de ReferênciaRESUMO
Los componentes glicosilados de la envoltura de Mycobacterium tuberculosis tienen un papel importante en la inmunopatogénesis de la tuberculosis. Permiten la adhesión, penetración y persistencia de la micobacteria en el macrófago; de igual manera, participan en los mecanismos de activación de estas células y la producción de citocinas relevantes durante la respuesta inmune. En esta revisión, examinamos las características de las principales estructuras sacarídicas de la superficie de la micobacteria y su relación con la modulación de la respuesta inmune.
The glycosylated compounds of Mycobacterium tuberculosis envelope play an important role in the immunopathogenesis of tuberculosis. These molecules are involved in the binding to the host cell surface followed by their internalization and persistence in macrophages; likewise they take part in the macrophage's activation and the production of cytokines that are relevant during the immune response against mycobacteria. In this review we examine the molecular characteristics of the main mycobacterial cell surface saccharide structures and their relation with the modulation of the immune response to tuberculosis.