RESUMO
Extracellular vesicles (EVs) represent an attractive source of biomarkers due to their biomolecular cargo. The aim of this study was to identify candidate protein biomarkers from plasma-derived EVs of patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Plasma-derived EVs from healthy participants (HP), LC, and HCC patients (eight samples each) were subjected to label-free quantitative proteomic analysis using LC-MS/MS. A total of 248 proteins were identified, and differentially expressed proteins (DEPs) were obtained after pairwise comparison. We found that DEPs mainly involve complement cascade activation, coagulation pathways, cholesterol metabolism, and extracellular matrix components. By choosing a panel of up- and down-regulated proteins involved in cirrhotic and carcinogenesis processes, TGFBI, LGALS3BP, C7, SERPIND1, and APOC3 were found to be relevant for LC patients, while LRG1, TUBA1C, TUBB2B, ACTG1, C9, HP, FGA, FGG, FN1, PLG, APOB and ITIH2 were associated with HCC patients, which could discriminate both diseases. In addition, we identified the top shared proteins in both diseases, which included LCAT, SERPINF2, A2M, CRP, and VWF. Thus, our exploratory proteomic study revealed that these proteins might play an important role in the disease progression and represent a panel of candidate biomarkers for the prognosis and diagnosis of LC and HCC.
Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular , Vesículas Extracelulares , Cirrose Hepática , Neoplasias Hepáticas , Proteômica , Humanos , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/metabolismo , Vesículas Extracelulares/metabolismo , Cirrose Hepática/sangue , Cirrose Hepática/metabolismo , Proteômica/métodos , Biomarcadores Tumorais/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem , Proteoma/metabolismo , Cromatografia Líquida , Biomarcadores/sangueRESUMO
Liver diseases preceding the occurrence of hepatocellular carcinoma (HCC) play a crucial role in the progression and establishment of HCC, a malignancy ranked as the third deadliest cancer worldwide. Late diagnosis, alongside ineffective treatment, leads patients to a poor survival rate. This scenario argues for seeking novel alternatives for detecting liver alterations preceding the early occurrence of HCC. Experimental studies have reported that ABCC3 protein increases within HCC tumors but not in adjacent tissue. Therefore, we analyzed ABCC3 expression in public databases and investigated the presence of ABCC3 and its isoforms in plasma, urine and its release in extracellular vesicles (EVs) cargo from patients bearing cirrhosis and HCC. The UALCAN and GEPIA databases were used to analyze the expression of ABCC3 in HCC. The results were validated in a case-control study including 41 individuals bearing cirrhosis and HCC, and the levels of ABCC3 in plasma and urine samples, as well as EVs, were analyzed by ELISA and western blot. Our data showed that ABCC3 expression was higher in HCC tissues than in normal tissues and correlated with HCC grade and stage. ABCC3 protein levels were highly increased in both plasma and urine and correlated with liver disease progression and severity. The isoforms MRP3A and MRP3B of ABCC3 were significantly increased in both EVs and plasma/urine of patients bearing HCC. ABCC3 expression gradually increases in HCC tissues, and its protein levels are increased in both plasma and urine of patients with cirrhosis and HCC. MRP3A and MRP3B isoforms have the potential to be prognostic biomarkers of HCC.
RESUMO
Systemic candidiasis are high mortality infections caused by yeasts of the genus Candida, affecting patients with numerous risk factors. Nowadays, candidemia produced by "non-albicans" species has increased considerably. Timely diagnosis and subsequent treatment substantially improve patients' survival. Our objectives are to study the frequency, distribution, and antifungal susceptibility profiles of candidemia isolates in our hospital. We conducted a descriptive, cross-sectional study. Positive blood cultures were recorded from January 2018 to December 2021. Positive Candida genus blood cultures were selected, classified, and analyzed on their susceptibility profile for amphotericin B, fluconazole and caspofungin using AST-YS08® card for VITEK 2 Compact® to determine minimum inhibitory concentration (MIC) and CLSI M60 2020 2nd Edition to determine breakpoints. 3862 positive blood cultures were obtained, 113 (2.93%) presented growth of Candida spp., corresponding to 58 patients. 55.2% came from the Hospitalization Ward and Emergency Services and 44.8% from the Intensive Care Unit. The species were distributed as follows: Nakaseomyces glabratus (Candida glabrata) (32.74%), Candida albicans (27.43%), Candida parapsilosis (23.01%), Candida tropicalis (7.08%) and others (9.73%). Most species were found to be susceptible to most antifungals, except for C. parapsilosis, presenting 4 isolates with resistance to fluconazole and N. glabratus (C. glabrata), whose clinical susceptibility data remains insufficient to provide accurate breakpoints. The percentage of recorded positive blood cultures of Candida spp. was 2.93%, these results were consistent with those reported at a regional level. A predominance of "non-albicans" species was observed. It is essential to know the prevalence, epidemiology, and susceptibility profiles of candidemia in our country, as well as being updated on its subsequent changes, maintaining epidemiological surveillance. This allows professionals to map out early and effective therapeutic strategies, staying alert of possible multi-resistant strains.
Assuntos
Antifúngicos , Candidemia , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Candidemia/microbiologia , Fluconazol/farmacologia , Uruguai/epidemiologia , Estudos Transversais , Candida , Candida glabrata , Hospitais Universitários , Candida parapsilosis , Testes de Sensibilidade Microbiana , Farmacorresistência FúngicaRESUMO
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by parenchymal scarring, leading progressively to alveolar architecture distortion, respiratory failure, and eventually death. Currently, there is no effective treatment for IPF. Previously, 3'5-dimaleamylbenzoic acid (3'5-DMBA), a maleimide, demonstrated pro-apoptotic, anti-inflammatory, and anti-cancer properties; however, its potential therapeutic effects on IPF have not been addressed. Bleomycin (BLM) 100 U/kg was administered to CD1 mice through an osmotic minipump. After fourteen days of BLM administration, 3'5-DMBA (6 mg/kg or 10 mg/kg) and its vehicle carboxymethylcellulose (CMC) were administered intragastrically every two days until day 26. On day 28, all mice were euthanized. The 3'5-DMBA effect was assessed by histological and immunohistochemical staining, as well as by RT-qPCR. The redox status on lung tissue was evaluated by determining the glutathione content and the GSH/GSSG ratio. 3'5-DMBA treatment re-established typical lung histological features and decreased the expression of BLM-induced fibrotic markers: collagen, α-SMA, and TGF-ß1. Furthermore, 3'5-DMBA significantly reduced the expression of genes involved in fibrogenesis. In addition, it decreased reduced glutathione and increased oxidized glutathione content without promoting oxidative damage to lipids, as evidenced by the decrease in the lipid peroxidation marker 4-HNE. Therefore, 3'5-DMBA may be a promising candidate for IPF treatment.
Assuntos
Bleomicina , Fibrose Pulmonar Idiopática , Animais , Anti-Inflamatórios/farmacologia , Bleomicina/efeitos adversos , Colágeno/metabolismo , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Fator de Crescimento Transformador beta1/metabolismoRESUMO
We compiled an updated database of all Agave species found in Mexico and analyzed it with specific criteria according to their biological parameters to evaluate the conservation and knowledge status of each species. Analyzing the present status of all Agave species not only provides crucial information for each species, but also helps determine which ones require special protection, especially those which are heavily used or cultivated for the production of distilled beverages. We conducted an extensive literature review search and compiled the conservation status of each species using mainstream criteria by IUCN. The information gaps in the database indicate a lack of knowledge and research regarding specific Agave species and it validates the need to conduct more studies on this genus. In total, 168 Agave species were included in our study, from which 89 are in the subgenus Agave and 79 in the subgenus Littaea. Agave lurida and A. nizandensis, in the subgenus Agave and Littaea, respectively, are severely endangered, due to their endemism, lack of knowledge about pollinators and floral visitors, and their endangered status according to the IUCN Red List. Some species are at risk due to the loss of genetic diversity resulting from production practices (i.e., Agave tequilana), and others because of excessive and unchecked overharvesting of wild plants, such as A. guadalajarana, A. victoriae-reginae, A. kristenii, and others. Given the huge economic and ecological importance of plants in the genus Agave, our review will be a milestone to ensure their future and continued provision of ecosystem services for humans, as well as encouraging further research in Agave species in an effort to enhance awareness of their conservation needs and sustainable use, and the implementation of eco-friendly practices in the species management.
RESUMO
A previously healthy 12-year-old boy had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related multisystem inflammatory syndrome (MIS-C) that was rapidly fatal. Autopsy revealed the presence of a large intracardiac thrombus. SARS-CoV-2 spike protein was detected in intestinal cells, supporting the hypothesis that viral presence in the gut may be related to the immunologic response of MIS-C.
Assuntos
COVID-19 , Intestinos , Glicoproteína da Espícula de Coronavírus , COVID-19/complicações , COVID-19/patologia , Criança , Evolução Fatal , Humanos , Intestinos/virologia , Masculino , SARS-CoV-2 , Síndrome de Resposta Inflamatória SistêmicaRESUMO
PURPOSE: Gestational diabetes mellitus (GDM) induces cardiovascular and metabolic disturbances in offspring. However, the effects of GDM in pain processing in offspring and whether male and female offspring are equally affected is not well known. Thus, we determined: i) whether GDM in mice affects offspring hindpaw mechanical sensitivity, capsaicin-induced spontaneous pain-like behaviors, and epidermal nerve fiber density (ENFD); and ii) whether there is sexual dimorphism in these parameters in offspring from GDM dams. METHODS: GDM was induced in pregnant ICR mice via i.p. streptozotocin (STZ). Then, glucose levels from dams and offspring were determined. Male and female offspring 2-3 months of age were evaluated for: a) baseline mechanical sensitivity of the hind paw by using von Frey filaments; b) number of flinches and time spent guarding induced by intraplantar capsaicin (0.1%); and c) density of PGP-9.5 and CGRP axons in the epidermis from the hind paw glabrous skin. RESULTS: Prepartum levels of glucose in STZ-treated dams were significantly increased compared to vehicle-treated dams; however, GDM or vehicle offspring displayed normal and similar blood glucose levels. Male and female GDM offspring showed significantly greater mechanical sensitivity and capsaicin-induced pain behaviors compared to vehicle offspring. Male GDM offspring displayed a slightly more intense nociceptive phenotype in the capsaicin test. PGP-9.5 and CGRP ENFD in hind paw glabrous skin were greater in male and female GDM offspring versus their controls. Sexual dimorphism was generally not observed in GDM offspring in most of the studied parameters. CONCLUSION: These results suggest GDM induced greater pain-like behaviors in adult offspring regardless of sex along with an increased ENFD of PGP-9.5 and CGRP in the hind paw glabrous skin. We show that GDM peripheral neuropathy differs from diabetic peripheral neuropathy acquired in adulthood and set the foundation to further study this in human babies exposed to GDM.
RESUMO
BACKGROUND: The occlusal surface of the first permanent molar is the most frequently affected site by dental caries. AIM: To assess the caries-free survival of first permanent molars in children participating in a community-based oral health preventive program. DESIGN: This was a retrospective study conducted on 426 children under 12 years of age, beneficiaries of a preventive program from 2009 to 2015, in El Cedro, Colombia. The program offered oral health care education, supervised brushing and mouth washing, and application of topical fluoride. By using parametric survival models for interval-censored data, primary and secondary caries-free survival of any first permanent molar was estimated and analyzed. RESULTS: Before program implementation, dental caries lesions presented at an average age, adjusted by age of eruption, of 8.3 years for primary caries lesion and 9.3 years for secondary caries lesion. After 7 years of the program, the estimated average age for presenting primary dental caries lesion was delayed by 4.6 years and by 5.3 years for secondary caries. CONCLUSION: The implementation of the oral health program led to improved caries-free survival of first permanent molars.
Assuntos
Cárie Dentária , Criança , Pré-Escolar , Colômbia , Seguimentos , Humanos , Dente Molar , Saúde Bucal , Serviços Preventivos de Saúde , Estudos RetrospectivosRESUMO
Resumen: El pénfigo es una enfermedad autoinmunitaria y crónica de incidencia y prevalencia bajas; sin embargo, puede alcanzar mortalidad de incluso 75% sin tratamiento. Existen dos variedades principales: el pénfigo vulgar y el foliáceo, que en términos clínicos se distinguen por la aparición de ampollas en la piel, con afección de las mucosas en los pacientes con pénfigo vulgar. En esta revisión se detalla la epidemiología, causas, fisiopatología y tratamiento de esta enfermedad, con insistencia en la importancia de los esteroides como piedra angular del tratamiento de estos pacientes.
Abstract: Pemphigus is an autoimmune and chronic disease with low incidence and preva- lence. Nevertheless it could reach a 75% mortality rate without treatment. There are two principal types: vulgar pemphigus and foliaceus pemphigus, which are clinically characterized by skin blister appearance, with mucosal affection in patients with pemphigus vulgaris. This review details the epidemiology, etiology, physiopathology and treatment of this disease, remarking the steroid importance as the cornerstone in the management of these patients.
RESUMO
Introducción: Las enfermedades transmitidas por alimentos (ETA) son consideradas como un problema de salud pública por el daño físico y económico que genera. Objetivo: Describir las características epidemiológicas y clínicas de los brotes de ETA en el Paraguay entre el 2015 y 2016. Metodología: Estudio descriptivo de corte transversal, con datos secundarios de la Dirección General de Vigilancia de la Salud. MSPyBS. Se calcularon frecuencias, medidas de tendencia central y proporción. Resultados: 14 brotes involucraron a 231personas, 56% mujeres (2015: 47%; 2016: 64%), 52% entre 5-14 años (2015: 57%; 2016: 47,5%). Las regiones sanitarias afectadas en 2015: Asunción (73%) y Central (19,8%), en tanto que en 2016: Caaguazú (42,5%) y Asunción (34,2%). En ambos años, se registran brotes en domicilios (2015: 14,4%; 2016: 5,8%) e instituciones educativas (2015: 4,5%; 2016: 35%). En un 62,8% (2015-2016) no se identifica el alimento sospechoso ingerido. El vómito fue síntoma más referido en 2015 (54,1%); en 2016 fue dolor abdominal (67,9%). El 44% de los casos se registraron en la semana epidemiológica (SE) 49 (2015) y el 42% en la SE 32 (2016). Conclusión: Para ambos periodos fueron similares las características de edad y sexo. Asunción se encuentra entre los primeros sitios de mayor notificación, identificándose como lugar de ingesta el domicilio o institución educativa en ambos periodos. Se observa deficiencias en cuanto al registro del alimento sospechoso y variaciones en cuanto a las manifestaciones clínicas y el periodo de tiempo en el que registraron el mayor número de casos (2015: verano; 2016: invierno) Palabras-clave: brote; enfermedades transmitidas por alimentos; vigilancia; Paraguay.
Introduction: Food borne diseases (ETA) is considered a public health problem due to the physical and economic damage it causes. Objective: To describe the epidemiological and clinical characteristics of ETA outbreaks in Paraguay between 2015 and 2016. Methodology: Cross-section descriptive study, with secondary data from the General Directorate of Health Surveillance. MSPyBS. Frequencies, measures of central tendency and proportion were calculated. Results: 14 outbreaks involved 231 people, 56% women (2015: 47%, 2016: 64%), 52% between 5-14 years (2015: 57%, 2016: 47.5%). The health regions affected in 2015: Asunción (73%) and Central (19.8%), while in 2016: Caaguazú (42.5%) and Asunción (34.2%). In both years, outbreaks were recorded in homes (2015: 14.4%, 2016: 5.8%) and educational institutions (2015: 4.5%, 2016: 35%). In 62.8% (2015-2016) the suspected ingested food is not identified. Vomiting was the most referred symptom in 2015 (54.1%); in 2016 it was abdominal pain (67.9%). 44% of the cases were registered in the epidemiological week (SE) 49 (2015) and 42% in EW 32 (2016). Conclusion: For both periods, the characteristics of age and sex were similar. Asunción is among the first sites of greater notification, identifying as place of intake the address or educational institution in both periods. Deficiencies are observed in the registration of suspect food and variations in clinical manifestations and the period of time in which they recorded the highest number of cases (2015: summer, 2016: winter) Key words: outbreak; foodborne diseases; surveillance; Paraguay