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Advances in methodologies to evaluate biomaterials brought an explosive growth of data, ensuing computational challenges to better analyzing them and allowing for high-throughput profiling of biological systems cost-efficiently. In this sense, we have applied bioinformatics tools to better understand the biological effect of different sintering temperatures of hydroxyapatite (abbreviated HA; at 1100, 1150, and 1250°C) on osteoblast performance. To do, we have better analyzed an earlier deposited study, in which the access code is E-MTAB-7219, which the authors have explored different in silico tools on this purpose. In this study, differential gene expression analyses were performed using the gene set variation analysis (GSVA) algorithm from the transcriptomes respecting the thermal changes of HA, which were validated using exclusively in vitro strategies. Furthermore, in silico approaches elected biomarkers during cell behavior in response to different sintering temperatures of HA, and it was further validated using cell culture and qPCR technologies. Altogether, the combination of those strategies shows the capacity of sintered HA at 1250°C to present a better performance in organizing an adequate microenvironment favoring bone regeneration, angiogenesis and material resorption stimulus once it has promoted higher involvement of genes such as CDK2, CDK4 (biomarkers of cell proliferation), p15, Osterix gene (related with osteogenic differentiation), RANKL (related with osteoclastogenesis), VEGF gene (related with angiogenesis), and HIF1α (related with hypoxia microenvironment). Altogether, the combination of in silico and cell culture strategies shows the capacity of sintered HA at 1250°C in guaranteeing osteoblast differentiation and it can be related in organizing an adequate microenvironment favoring bone regeneration, angiogenesis, and material resorption stimulus.
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Materiales Biocompatibles , Durapatita , Materiales Biocompatibles/farmacología , Durapatita/farmacología , Temperatura , Osteogénesis , Proliferación Celular , Técnicas de Cultivo de Célula , BiomarcadoresRESUMEN
This study estimated biomass and carbon from components, future carbon values ââand to obtain economic productive value of carbon fixation of a Seasonal Semideciduous Forest. Biomass and carbon were estimated using adjusted equations and selected using regression statistics. The prognosis of the diametric distribution was performed using the movement ratio method. In the economic evaluation, it was estimated productive value of the stand, referring to the current and future carbon fixation capacity. The coefficients of determination (adjusted R²) of the equations ranged from 0.11 to 0.90 and the standard error of the estimate (Syx) ranged from 41.53% to 141.89% for the biomass of the components, and from 0.03 to 0.87 for adjusted R² and from 46.20% to 143.64% for the error, for stored carbon in the components. The total biomass of the tree component estimated was 56.25 t ha-1 and 25.88 t ha-1 of total carbon. Using the future distributions by the method of the ratio of movements, total stored carbon (aerial + roots) estimated was 14.44 t. ha-1 over the 20-year period. The productive value for the fragment reached R$ 299.95 per ha. year-1.
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Carbono , Bosques , Biomasa , Carbono/análisis , Brasil , Estaciones del Año , ÁrbolesRESUMEN
The DFNA58 locus contains a genomic duplication involving three protein-coding genes (CNRIP1, PLEK, and PPP3R1's exon 1) and other uncharacterized lncRNA genes (LOC101927723, LOC107985892 and LOC102724389). To clarify the role of these genes in hearing and precisely determine their role in hearing loss, four iPSC lines were generated from two carriers and two noncarriers of the duplication.
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Pérdida Auditiva , Células Madre Pluripotentes Inducidas , Humanos , Leucocitos Mononucleares , Pérdida Auditiva/genética , Audición , ExonesRESUMEN
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.
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COVID-19 , SARS-CoV-2 , Humanos , Linfocitos T CD8-positivos , Linfocitos T Colaboradores-Inductores , PulmónRESUMEN
It is important to understand whether endothelial cells are epigenetically affected by titanium-enriched media when angiogenesis is required during bone development and it is expected to be recapitulated during osseointegration of biomaterials. To better address this issue, titanium-enriched medium was obtained from incubation of titanium discs for up to 24 h as recommended by ISO 10993-5:2016, and further used to expose human umbilical vein endothelial cells (HUVECs) for up to 72 h, when the samples were properly harvested to allow molecular analysis and epigenetics. In general, our data show an important repertoire of epigenetic players in endothelial cells responding to titanium, reinforcing protein related to the metabolism of acetyl and methyl groups, as follows: Histone deacetylases (HDACs) and NAD-dependent deacetylase sirtuin-1 (Sirt1), DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) methylcytosine dioxygenases, which in conjunction culminate in driving chromatin condensation and the methylation profile of DNA strands, respectively. Taking our data into consideration, HDAC6 emerges as important player of this environment-induced epigenetic mechanism in endothelial cells, while Sirt1 is required in response to stimulation of reactive oxygen species (ROS) production, as its modulation is relevant to vasculature surrounding implanted devices. Collectively, all these findings support the hypothesis that titanium keeps the surrounding microenvironment dynamically active and so affects the performance of endothelial cells by modulating epigenetics. Specifically, this study shows the relevance of HDAC6 as a player in this process, possibly correlated with the cytoskeleton rearrangement of those cells. Furthermore, as those enzymes are druggable, it opens new perspectives to consider the use of small molecules to modulate their activities as a biotechnological tool in order to improve angiogenesis and accelerate bone growth with benefits of a fast recovery time for patients.
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BACKGROUND: Acid sphingomyelinase deficiency (ASMD) is a lysosomal disorder caused by deficiency of acid sphingomyelinase (ASM) leading to the accumulation of sphingomyelin (SM) in a variety of cell types. Lysosphingomyelin (LysoSM) is the de-acetylated form of SM and it has been shown as a biomarker for ASMD in tissues, plasma, and dried blood spots (DBS) and lysosphingomyelin-509 (LysoSM509) is the carboxylated analogue of LysoSM. High levels of Lysosphingomyelin 509 (LysoSM509) have also been shown in ASMD patients. In this study, we report the utility of the quantification of LysoSM and LysoSM509 in DBS of patients from Latin America with ASMD by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). RESULTS: DBS samples from 14 ASMD patients were compared with 15 controls, and 44 general newborns. All patients had their diagnosis confirmed by the quantification of ASM and the measurement of the activity of chitotriosidase. All patients had significantly higher levels of lysoSM and lysoSM509 compared to controls and general newborns. CONCLUSIONS: The quantification of lysosphingolipids in DBS is a valuable tool for the diagnosis of ASMD patients and lysoSM can be useful in the differential diagnosis with NPC. This method is also valuable in the ASMD newborn screening process.
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Enfermedad de Niemann-Pick Tipo A , Enfermedades de Niemann-Pick , Recién Nacido , Humanos , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Esfingomielina FosfodiesterasaRESUMEN
Visceral adiposity is a risk factor for severe COVID-19, and a link between adipose tissue infection and disease progression has been proposed. Here we demonstrate that SARS-CoV-2 infects human adipose tissue and undergoes productive infection in fat cells. However, susceptibility to infection and the cellular response depends on the anatomical origin of the cells and the viral lineage. Visceral fat cells express more ACE2 and are more susceptible to SARS-CoV-2 infection than their subcutaneous counterparts. SARS-CoV-2 infection leads to inhibition of lipolysis in subcutaneous fat cells, while in visceral fat cells, it results in higher expression of pro-inflammatory cytokines. Viral load and cellular response are attenuated when visceral fat cells are infected with the SARS-CoV-2 gamma variant. A similar degree of cell death occurs 4-days after SARS-CoV-2 infection, regardless of the cell origin or viral lineage. Hence, SARS-CoV-2 infects human fat cells, replicating and altering cell function and viability in a depot- and viral lineage-dependent fashion.
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COVID-19 , SARS-CoV-2 , Tejido Adiposo , Enzima Convertidora de Angiotensina 2 , Citocinas , HumanosRESUMEN
BACKGROUND: Prior epidemiologic studies on the association between diabetes and gastric cancer risk provided inconclusive findings, while traditional, aggregate data meta-analyses were characterized by high between-study heterogeneity. OBJECTIVE: To investigate the association between type 2 diabetes and gastric cancer using data from the 'Stomach Cancer Pooling (StoP) Project', an international consortium of more than 30 case-control and nested case-control studies, which is large and provides harmonized definition of participants' characteristics across individual studies. The data have the potential to minimize between-study heterogeneity and provide greater statistical power for subgroup analysis. METHODS: We included 5592 gastric cancer cases and 12 477 controls from 14 studies from Europe, Asia, North America, and South America in a two-stage individual-participant data meta-analysis. Random-effect models were used to estimate summary odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) by pooling study-specific ORs. RESULTS: We did not find an overall association between diabetes and gastric cancer (pooled OR = 1.01, 95% CI, 0.94-1.07). However, the risk of cardia gastric cancer was significantly higher among individuals with type 2 diabetes (OR = 1.16, 95% CI, 1.02-1.33). There was no association between diabetes and gastric cancer risk in strata of Helicobacter pylori infection serostatus, age, sex, BMI, smoking status, alcohol consumption, fruit/vegetable intake, gastric cancer histologic type, and source of controls. CONCLUSION: This study provides additional evidence that diabetes is unrelated to gastric cancer overall but may be associated with excess cardia gastric cancer risk.
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Diabetes Mellitus Tipo 2 , Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/patología , Humanos , Factores de Riesgo , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/etiologíaRESUMEN
Objective@#To report an unusual presentation of thyroglossal duct cyst causing airway obstruction in an elderly man. @*Methods@# Design: Case Report Setting: Tertiary Government Training Hospital Patient: One @*Results@#A 71-year-old man with an anterior neck mass was brought to the Emergency Room due to progressive difficulty of breathing. A smooth, non-ulcerating right supraglottic mass obstructed the airway. Following an emergency high tracheotomy, contrast computed tomography scan of the neck revealed a hypodense mass with peripheral rim enhancement in the right supraglottis and an extralaryngeal component. Intra-operatively, a dumbbell- shaped cystic mass with a tract connected to the hyoid bone led to a Sistrunk procedure. Final histopathology findings were consistent with thyroglossal duct cyst. @*Conclusion@#It is possible for an elderly patient with impending upper airway obstruction, dysphonia, and neck mass to still have a benign and congenital thyroglossal duct cyst with intralaryngeal extension.
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Quiste Tirogloso , Obstrucción de las Vías AéreasRESUMEN
The Acinetobacter baumannii RND efflux pump AdeABC is regulated by the 2-component regulator AdeRS. In this study, we compared the regulation and expression of AdeABC of the reference strains ATCC 17978 and ATCC 19606. A clearly stronger efflux activity was demonstrated for ATCC 19606. An amino acid substitution at residue 172 of adeS was identified as a potential cause for differential expression of the pump. Therefore, we recommend caution with exclusively using single reference strains for research.
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Acinetobacter baumannii , Acinetobacter baumannii/genética , Acinetobacter baumannii/metabolismo , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Farmacorresistencia Bacteriana/genética , Farmacorresistencia Bacteriana Múltiple/genética , Proteínas de Transporte de Membrana/genética , Pruebas de Sensibilidad MicrobianaRESUMEN
A homozygous mutation in the inositol monophosphatase 1 (IMPA1) gene was recently identified in nine individuals with severe intellectual disability (ID) and disruptive behavior. These individuals belong to the same family from Northeastern Brazil, which has 28 consanguineous marriages and 59 genotyped family members. IMPA1 is responsible for the generation of free inositol from de novo biosynthesis and recycling from inositol polyphosphates and participates in the phosphatidylinositol signaling pathway. To understand the role of IMPA1 deficiency in ID, we generated induced pluripotent stem cells (iPSCs) from patients and neurotypical controls and differentiated these into hippocampal dentate gyrus-like neurons and astrocytes. IMPA1-deficient neuronal progenitor cells (NPCs) revealed substantial deficits in proliferation and neurogenic potential. At low passage NPCs (P1 to P3), we observed cell cycle arrest, apoptosis, progressive change to a glial morphology and reduction in neuronal differentiation. These observations were validated by rescuing the phenotype with myo-inositol supplemented media during differentiation of patient-derived iPSCs into neurons and by the reduction of neurogenic potential in control NPCs-expressing shIMPA1. Transcriptome analysis showed that NPCs and neurons derived from ID patients have extensive deregulation of gene expression affecting pathways necessary for neurogenesis and upregulation of gliogenic genes. IMPA1 deficiency did not affect cell cycle progression or survival in iPSCs and glial progenitor cells or astrocyte differentiation. Therefore, this study shows that the IMPA1 mutation specifically affects NPC survival and neuronal differentiation.
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Discapacidad Intelectual , Neurogénesis , Monoéster Fosfórico Hidrolasas , Diferenciación Celular/genética , Humanos , Discapacidad Intelectual/genética , Mutación , Neurogénesis/genética , Monoéster Fosfórico Hidrolasas/genéticaRESUMEN
Intake of heterocyclic amines (HCAs) and other mutagenic compounds formed during cooking has been hypothesized to be responsible for the positive association observed between red meat and colorectal cancer. We evaluated whether well-done/very well-done preferences for various meat and fish items, higher intakes of meat and fish, and meat-derived and fish-derived HCA are associated with the risk of colorectal adenoma (CRA) in a Japanese-Brazilian population. We selected 302 patients with adenoma and 403 control individuals who underwent total colonoscopy between 2007 and 2013, and collected information on aspects of meat intake using a detailed questionnaire. We also estimated HCA intake of the study participants using an HCA database that matched the cooking methods of this population. Latent class analysis on the basis of response to doneness preferences for different cooking methods of commonly consumed meat and fish items identified four distinct subgroups. Compared with the subgroup characterized by a preference for rare/medium well-done cooking for most meat and fish items, the odds ratio of CRA for the well-done/very well-done preference subgroup was 1.19 (95% confidence interval: 0.51-2.75). High intake of mixed-meat dishes was suggestively associated inversely with CRA, whereas a high intake of poultry was associated positively with CRA. No clear association with intake of total or specific HCAs and no effect modification by N-acetyltransferase 2 acetylation genotype were observed. We found no statistically significant associations between meat and HCA intake and CRA. These findings do not support a positive association between meat and meat-derived HCA intake and the risk of CRA.
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Adenoma/epidemiología , Aminas/administración & dosificación , Arilamina N-Acetiltransferasa/genética , Carcinógenos/administración & dosificación , Neoplasias Colorrectales/epidemiología , Culinaria/estadística & datos numéricos , Adenoma/genética , Adulto , Anciano , Aminas/efectos adversos , Aminas/metabolismo , Pueblo Asiatico/estadística & datos numéricos , Brasil/epidemiología , Carcinógenos/metabolismo , Estudios de Casos y Controles , Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/genética , Comportamiento del Consumidor/estadística & datos numéricos , Culinaria/métodos , Conducta Alimentaria , Femenino , Productos Pesqueros/efectos adversos , Predisposición Genética a la Enfermedad , Calor/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Carne Roja/efectos adversos , Factores de RiesgoRESUMEN
Low socioeconomic position (SEP) is a strong risk factor for incidence and premature mortality from several cancers. Our study aimed at quantifying the association between SEP and gastric cancer (GC) risk through an individual participant data meta-analysis within the "Stomach cancer Pooling (StoP) Project". Educational level and household income were used as proxies for the SEP. We estimated pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) across levels of education and household income by pooling study-specific ORs through random-effects meta-analytic models. The relative index of inequality (RII) was also computed. A total of 9,773 GC cases and 24,373 controls from 25 studies from Europe, Asia and America were included. The pooled OR for the highest compared to the lowest level of education was 0.60 (95% CI, 0.44-0.84), while the pooled RII was 0.45 (95% CI, 0.29-0.69). A strong inverse association was observed both for noncardia (OR 0.39, 95% CI, 0.22-0.70) and cardia GC (OR 0.47, 95% CI, 0.22-0.99). The relation was stronger among H. pylori negative subjects (RII 0.14, 95% CI, 0.04-0.48) as compared to H. pylori positive ones (RII 0.29, 95% CI, 0.10-0.84), in the absence of a significant interaction (p = 0.28). The highest household income category showed a pooled OR of 0.65 (95% CI, 0.48-0.89), while the corresponding RII was 0.40 (95% CI, 0.22-0.72). Our collaborative pooled-analysis showed a strong inverse relationship between SEP indicators and GC risk. Our data call for public health interventions to reduce GC risk among the more vulnerable groups of the population.
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Escolaridad , Disparidades en el Estado de Salud , Infecciones por Helicobacter/epidemiología , Neoplasias Gástricas/epidemiología , Adulto , Anciano , Asia/epidemiología , Estudios de Casos y Controles , Conjuntos de Datos como Asunto , Europa (Continente)/epidemiología , Femenino , Mucosa Gástrica/microbiología , Helicobacter pylori/aislamiento & purificación , Humanos , Incidencia , Renta/estadística & datos numéricos , Masculino , Persona de Mediana Edad , América del Norte/epidemiología , Medición de Riesgo , Factores de Riesgo , Poblaciones Vulnerables/estadística & datos numéricosRESUMEN
Calcium/Calmodulin-dependent Protein Kinase Kinase 2 (CAMKK2) acts as a signaling hub, receiving signals from various regulatory pathways and decoding them via phosphorylation of downstream protein kinases - such as AMPK (AMP-activated protein kinase) and CAMK types I and IV. CAMKK2 relevance is highlighted by its constitutive activity being implicated in several human pathologies. However, at present, there are no selective small-molecule inhibitors available for this protein kinase. Moreover, CAMKK2 and its closest human homolog, CAMKK1, are thought to have overlapping biological roles. Here we present six new co-structures of potent ligands bound to CAMKK2 identified from a library of commercially-available kinase inhibitors. Enzyme assays confirmed that most of these compounds are equipotent inhibitors of both human CAMKKs and isothermal titration calorimetry (ITC) revealed that binding to some of these molecules to CAMKK2 is enthalpy driven. We expect our results to advance current efforts to discover small molecule kinase inhibitors selective to each human CAMKK.
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Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/química , Inhibidores de Proteínas Quinasas/química , Animales , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/antagonistas & inhibidores , Descubrimiento de Drogas , Humanos , Ligandos , Conformación Molecular , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Unión Proteica , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Recombinantes , Relación Estructura-ActividadRESUMEN
The liver is responsible for many metabolic, endocrine and exocrine functions. Approximately 2 million deaths per year are associated with liver failure. Modern 3D bioprinting technologies allied with autologous induced pluripotent stem cells (iPS)-derived grafts could represent a relevant tissue engineering approach to treat end stage liver disease patients. However, protocols that accurately recapitulates liver's epithelial parenchyma through bioprinting are still underdeveloped. Here we evaluated the impacts of using single cell dispersion (i.e. obtained from conventional bidimensional differentiation) of iPS-derived parenchymal (i.e. hepatocyte-like cells) versus using iPS-derived hepatocyte-like cells spheroids (i.e. three-dimensional cell culture), both in combination with non-parenchymal cells (e.g. mesenchymal and endothelial cells), into final liver tissue functionality. Single cell constructs showed reduced cell survival and hepatic function and unbalanced protein/amino acid metabolism when compared to spheroid printed constructs after 18 days in culture. In addition, single cell printed constructs revealed epithelial-mesenchymal transition, resulting in rapid loss of hepatocyte phenotype. These results indicates the advantage of using spheroid-based bioprinting, contributing to improve current liver bioprinting technology towards future regenerative medicine applications and liver physiology and disease modeling.
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Bioimpresión , Células Madre Pluripotentes Inducidas/citología , Hígado/citología , Esferoides Celulares/citología , Bioimpresión/instrumentación , Bioimpresión/métodos , Diferenciación Celular , Proliferación Celular , Supervivencia Celular , Femenino , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Hígado/metabolismo , Masculino , Impresión Tridimensional , Esferoides Celulares/metabolismo , Ingeniería de TejidosRESUMEN
BACKGROUND: Liver organoid technology holds great promises to be used in large-scale population-based drug screening and in future regenerative medicine strategies. Recently, some studies reported robust protocols for generating isogenic liver organoids using liver parenchymal and non-parenchymal cells derived from induced pluripotent stem cells (iPS) or using isogenic adult primary non-parenchymal cells. However, the use of whole iPS-derived cells could represent great challenges for a translational perspective. METHODS: Here, we evaluated the influence of isogenic versus heterogenic non-parenchymal cells, using iPS-derived or adult primary cell lines, in the liver organoid development. We tested four groups comprised of all different combinations of non-parenchymal cells for the liver functionality in vitro. Gene expression and protein secretion of important hepatic function markers were evaluated. Additionally, liver development-associated signaling pathways were tested. Finally, organoid label-free proteomic analysis and non-parenchymal cell secretome were performed in all groups at day 12. RESULTS: We show that liver organoids generated using primary mesenchymal stromal cells and iPS-derived endothelial cells expressed and produced significantly more albumin and showed increased expression of CYP1A1, CYP1A2, and TDO2 while presented reduced TGF-ß and Wnt signaling activity. Proteomics analysis revealed that major shifts in protein expression induced by this specific combination of non-parenchymal cells are related to integrin profile and TGF-ß/Wnt signaling activity. CONCLUSION: Aiming the translation of this technology bench-to-bedside, this work highlights the role of important developmental pathways that are modulated by non-parenchymal cells enhancing the liver organoid maturation.
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Regulación de la Expresión Génica , Células Madre Pluripotentes Inducidas/citología , Hígado/crecimiento & desarrollo , Organoides/crecimiento & desarrollo , Factor de Crecimiento Transformador beta/metabolismo , Proteínas Wnt/metabolismo , Adulto , Diferenciación Celular , Células Endoteliales/citología , Células Endoteliales/metabolismo , Femenino , Humanos , Hígado/metabolismo , Masculino , Organoides/metabolismo , Tejido Parenquimatoso/crecimiento & desarrollo , Tejido Parenquimatoso/metabolismo , Proteoma/análisis , Adulto JovenRESUMEN
BACKGROUND: Helicobacter pylori (H. pylori) infection is more frequent among men, though the magnitude of the association might be inaccurate due to potential misclassification of lifetime infection and publication bias. Moreover, infection is common, and most studies are cross-sectional. Thus, prevalence ratios (PRs) may be easier to interpret than odds ratios (ORs). AIM: The aim of this study was to quantify the association between sex and H. pylori infection using controls from 14 studies from the Stomach Cancer Pooling (StoP) Project. PARTICIPANTS AND METHODS: H. pylori infection was defined based on IgG serum antibody titers or multiplex serology. Participants were also classified as infected if gastric atrophy was present, based on histological examination or serum pepsinogen (PG) levels (PG I≤70 and PG I/II ratio≤3). Summary ORs and PRs, adjusted for age, social class and smoking, and corresponding 95% confidence intervals (CIs), were estimated through random-effects meta-analysis. RESULTS: Men had significantly higher OR (OR: 1.33, 95% CI: 1.04-1.70) and PR (PR: 1.05, 95% CI: 1.00-1.10) of infection, with stronger associations among hospital-based or older controls. Results were similar when considering the presence of gastric atrophy to define infection status, particularly among participants older than 65 years. CONCLUSION: This collaborative pooled-analysis supports an independent effect of sex on the prevalence of H. pylori infection, while minimizing misclassification of lifetime infection status and publication bias.
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Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Anciano , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Atrofia , Femenino , Gastritis Atrófica/diagnóstico , Gastritis Atrófica/epidemiología , Gastritis Atrófica/microbiología , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/inmunología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo , Factores de Riesgo , Pruebas Serológicas , Factores Sexuales , Estómago/microbiología , Estómago/patologíaRESUMEN
BACKGROUND: Physical activity (PA) is recommended as adjuvant therapy to control blood pressure (BP). The effectiveness of simple recommendations is not clear. We aimed to assess the agreement between self-report of adherence to PA in clinical routine and International Physical Activity Questionnaire (IPAQ) interview and its association with BP control. METHODS: A cross-sectional study was conducted with hypertensive outpatients. Adherence to recommendation to PA was assessed by the physician and IPAQ interview. A cutoff of 150 minutes/week was used to classify active or nonactive patients. High sitting time was considered >4 hours/day. A total of 127 individuals (SBP 144.9±24.4 mmHg/DBP 82.0±12.8 mmHg) were included. RESULTS: A total of 69 subjects (54.3%) reported to be active to their physician, whereas 81 (63.8%) were classified as active by IPAQ (6.3% active in leisure time PA). Kappa test was 0.22 (95% CI, 0.06-0.37). The rate of BP control was 45.7%. There was no association with the reported PA assessed by both methods nor with sitting time. Our results demonstrated poor agreement between self-report adherence and IPAQ interview, and neither evaluation was associated with BP control. CONCLUSION: Our findings underpin evidences that a simple PA recommendation has low association with BP control in clinical settings.
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Smoking has been associated with acquisition and increased persistence of Helicobacter pylori infection, as well as with lower effectiveness of its eradication. A greater prevalence of infection among smokers could contribute to the increased risk for gastric cancer. We aimed to estimate the association between smoking and seropositivity to H. pylori through an individual participant data pooled analysis using controls from 14 case-control studies participating in the Stomach Cancer Pooling Project. Summary odds ratios and prevalence ratios (PRs), adjusted for age, sex and social class, and the corresponding 95% confidence intervals (CIs) were estimated through random-effects meta-analysis. Heterogeneity was quantified using the I statistic and publication bias with Egger's test. There was no significant association between smoking (ever vs. never) and H. pylori seropositivity (adjusted odds ratio = 1.08; 95% CI: 0.89-1.32; adjusted PR = 1.01; 95% CI: 0.98-1.05). The strength of the association did not increase with the intensity or duration of smoking; stratified analyses according to sex, age, region or type of sample did not yield a consistent pattern of variation or statistically significant results, except for participants younger than 55 years and who had been smoking for more than 30 years (adjusted PR = 1.08; 95% CI: 1.02-1.15). This is the first collaborative analysis providing pooled estimates for the association between smoking and H. pylori seropositivity, based on detailed and uniform information and adjusting for major covariates. The results do not support an association between smoking and H. pylori infection.
Asunto(s)
Infecciones por Helicobacter/epidemiología , Helicobacter pylori/aislamiento & purificación , Fumadores/estadística & datos numéricos , Neoplasias Gástricas/prevención & control , Fumar Tabaco/epidemiología , Adulto , Factores de Edad , Anciano , Estudios de Casos y Controles , Femenino , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/patogenicidad , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Fumar Tabaco/efectos adversosRESUMEN
Repeats in coding and non-coding regions have increasingly been associated with many human genetic disorders, such as Richieri-Costa-Pereira syndrome (RCPS). RCPS, mostly characterized by midline cleft mandible, Robin sequence and limb defects, is an autosomal-recessive acrofacial dysostosis mainly reported in Brazilian patients. This disorder is caused by decreased levels of EIF4A3, mostly due to an increased number of repeats at the EIF4A3 5'UTR. EIF4A3 5'UTR alleles are CG-rich and vary in size and organization of three types of motifs. An exclusive allelic pattern was identified among affected individuals, in which the CGCA-motif is the most prevalent, herein referred as "disease-associated CGCA-20nt motif." The origin of the pathogenic alleles containing the disease-associated motif, as well as the functional effects of the 5'UTR motifs on EIF4A3 expression, to date, are entirely unknown. Here, we characterized 43 different EIF4A3 5'UTR alleles in a cohort of 380 unaffected individuals. We identified eight heterozygous unaffected individuals harboring the disease-associated CGCA-20nt motif and our haplotype analyses indicate that there are more than one haplotype associated with RCPS. The combined analysis of number, motif organization and haplotypic diversity, as well as the observation of two apparently distinct haplotypes associated with the disease-associated CGCA-20nt motif, suggest that the RCPS alleles might have arisen from independent unequal crossing-over events between ancient alleles at least twice. Moreover, we have shown that the number and sequence of motifs in the 5'UTR region is associated with EIF4A3 repression, which is not mediated by CpG methylation. In conclusion, this study has shown that the large number of repeats in EIF4A3 does not represent a dynamic mutation and RCPS can arise in any population harboring alleles with the CGCA-20nt motif. We also provided further evidence that EIF4A3 5'UTR is a regulatory region and the size and sequence type of the repeats at 5'UTR may contribute to clinical variability in RCPS.