ABSTRACT
Chlorpyrifos (CPF) is a widely used organophosphate insecticide that has been linked to detrimental health effects that range from neurological impacts to respiratory disease. The objective of this study was to assess respiratory symptoms associated with CPF exposure throughout the application season. Urine samples were collected from Egyptian adolescent applicators (n = 206) and non-applicators (n = 72) to assess 3,5,6-trichloro-2-pyridinol (TCPy), a biomarker for CPF exposure, along with spirometry measures to determine lung ventilatory function. Samples were collected over 7 months in 2016. Logistic regression was used to model the odds of reporting wheeze symptoms based on urinary TCPy concentrations while controlling for age and smoking in the household. Ordinal multinomial logistic regression was used to model the percent reference for forced expiratory volume in one second (rFEV1) based on urinary TCPy concentration (µg/g creatinine). Wheezing increased with increasing pesticide exposure (OR = 1.74 (1.32 - 2.31)). There was no statistically significant relationship between rFEV1 and TCPy concentration. Efforts to reduce pesticide exposure should be implemented to prevent the potential onset or exacerbation of any linked respiratory complications in adolescents.
ABSTRACT
The Brazil nut is an excellent source of selenium (Se), an essential micronutrient for human health. In this study, we hypothesized that Brazil nut intake modulates circulating microRNAs (miRNAs) in obese women and aimed to evaluate the effects of this nut intake on circulating miRNAs in women with obesity or metabolic syndrome (MetS). A randomized controlled clinical trial was conducted on 54 subjects recruited from the Clinical Hospital in São Paulo, Brazil. Patients were randomly assigned to 2 groups: a Brazil nut group (BN group, nâ¯=â¯29) and a control group (CO group, nâ¯=â¯25); both were monitored for 2â¯months. BN group members were instructed to consume 1 Brazil nut (approximately 1261⯵g/Se) per day; CO group members were instructed not to consume any. Biochemical parameters related to Se status and 25 circulating miRNAs in plasma were evaluated in all patients both at baseline and after 2â¯months. Expression levels of 2 miRNAs (miR-454-3p and miR-584-5p) were significantly increased after Brazil nut intake. To investigate the effect of MetS on circulating miRNAs at baseline, we performed comparisons between women with MetS (nâ¯=â¯23) and women without MetS (others, nâ¯=â¯31). Circulating miR-375 levels were significantly lower (Pâ¯=â¯.012) in women with MetS. In conclusion, our findings suggested that a daily intake of 1 Brazil nut increased circulating miR-454-3p and miR-584-5p expression levels in obese women, and our network analysis indicated a link between Se intake, vitamin D metabolism, and calcium homeostasis.
Subject(s)
Bertholletia/metabolism , Diet/methods , MicroRNAs/blood , Nuts/metabolism , Obesity/blood , Adult , Biomarkers/blood , Brazil , Female , Humans , Obesity/metabolismABSTRACT
OBJECTIVE: Increased inflammatory response is an important factor in the pathophysiology of obesity. The mineral selenium (Se), of which one of the main food sources is the Brazil nut, has important antioxidant and anti-inflammatory functions through the action of selenoproteins. Thus, the evaluation of the influence of this micronutrient in this context is of great relevance. The aim of this study was to evaluate the effects of Brazil nut intake with high Se concentrations on inflammatory biomarkers and its relation to Se status in obese women. METHODS: A randomized controlled clinical trial was carried out with 55 women recruited at Clinical Hospital in São Paulo, Brazil. Patients were randomly assigned to either the Brazil nut group (BN) or the control group (CO) and followed up for 2 mo. The BN group consumed 1 unit/d of Brazil nuts (â¼ 1261 µg/Se); the CO group did not receive any intervention. At baseline and after 2 mo, analysis of biochemical parameters related to Se status, oxidative stress, and inflammatory biomarkers were performed. RESULTS: At baseline, both groups did not present Se deficiency. In the BN group, a significant increase (P < 0.05) in all Se biomarkers and in gene expression of several proinflammatory parameters (interleukin-6, tumor necrosis factor-α, and Toll-like receptors 2 and 4) were observed after the intervention period. No changes were observed for the CO group. CONCLUSION: Although there were no changes in plasma inflammatory biomarkers levels, a significant increase in gene expression may be an indication of a proinflammatory stimulus in obesity, induced by the consumption of Brazil nuts with high Se levels.
Subject(s)
Bertholletia , Diet/adverse effects , Inflammation Mediators/blood , Obesity/blood , Selenium/blood , Adult , Bertholletia/chemistry , Biomarkers/blood , Diet/methods , Eating/physiology , Female , Humans , Inflammation , Middle Aged , Obesity/physiopathology , Selenium/administration & dosage , Young AdultABSTRACT
The purpose of this retrospective study was to determine survival times and prognostic factors of dogs with visceral hemangiosarcoma (HSA) treated with surgery alone or surgery and doxorubicin. Medical records from 2 hospitals from 2005 to 2014 were searched for dogs with histopathologically confirmed visceral HSA. Data relevant to patient demographics, tumor characteristics, and outcomes were abstracted. The most common primary organ affected was the spleen; however, primary tumor location had no influence on prognosis. Twenty-three dogs were treated with surgery alone, while 14 dogs were treated with surgery and doxorubicin. There was a significant difference in survival times between dogs treated with surgery alone and with surgery followed by doxorubicin (66 days versus 274 days). Dogs with stage I tumors (196 days) had a longer median survival time (MST) than dogs with stage II (117 days) and stage III (23 days) disease. The overall MST was 179 days with a 1-year survival rate of 29.2%.
Hémangiosarcome viscéral canin traité par la chirurgie seule et la doxorubicine : 37 cas (20052014). Le but de cette étude rétrospective consistait à déterminer les temps de survie et les facteurs de pronostic des chiens atteints d'un hémangiosarcome (HSE) viscéral traités à l'aide de la chirurgie seule ou de la chirurgie et de la doxorubicine. Les dossiers médicaux de deux cliniques de 2005 à 2014 ont été fouillés pour trouver des chiens avec un HSE viscéral confirmé par histopathologie. Les données pertinentes pour les données démographiques du patient, les caractéristiques de la tumeur et les résultats ont été extraits des dossiers. L'organe primaire le plus couramment affecté était la rate. Cependant, l'emplacement primaire de la tumeur n'avait aucune influence sur le pronostic. Vingt-trois chiens ont été traités par la chirurgie seule, tandis que 14 chiens ont été traités par la chirurgie et la doxorubicine. Il y avait une différence importante dans les temps de survie entre les chiens traités par la chirurgie seule et la chirurgie suivie de la doxorubicine (66 jours contre 274 jours). Les chiens ayant des tumeurs de stade I (196 jours) avaient un temps de survie médian (TSM) plus long que les chiens atteints d'une maladie de stade II (117 jours) et de stade III (23 jours). Le TSM général était de 179 jours avec un taux de survie après 1 an de 29,2 %.(Traduit par Isabelle Vallières).
Subject(s)
Antineoplastic Agents/therapeutic use , Dog Diseases/drug therapy , Dog Diseases/surgery , Doxorubicin/therapeutic use , Hemangiosarcoma/veterinary , Animals , Dogs , Female , Hemangiosarcoma/drug therapy , Hemangiosarcoma/surgery , Male , Retrospective Studies , Splenic Neoplasms/drug therapy , Splenic Neoplasms/surgery , Splenic Neoplasms/veterinary , Treatment OutcomeABSTRACT
Successful fertilization requires that sperm are activated prior to contacting an oocyte. In C. elegans, this activation process, called spermiogenesis, transforms round immobile spermatids into motile, fertilization-competent spermatozoa. We describe the phenotypic and genetic characterization of spe-43, a new component of the spe-8 pathway, which is required for spermiogenesis in hermaphrodites; spe-43 hermaphrodites are self-sterile, while spe-43 males show wild-type fertility. When exposed to Pronase to activate sperm in vitro, spe-43 spermatids form long rigid spikes radiating outward from the cell periphery instead of forming a motile pseudopod, indicating that spermiogenesis initiates but is not completed. Using a combination of recombinant and deletion mapping and whole genome sequencing, we identified F09E8.1 as spe-43. SPE-43 is predicted to exist in two isoforms; one isoform appears to be a single-pass transmembrane protein while the other is predicted to be a secreted protein. SPE-43 can bind to other known sperm proteins, including SPE-4 and SPE-29, which are known to impact spermiogenesis. In summary, we have identified a membrane protein that is present in C. elegans sperm and is required for sperm activation via the hermaphrodite activation signal.
Subject(s)
Caenorhabditis elegans Proteins/genetics , Spermatogenesis/genetics , Spermatozoa/metabolism , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/metabolism , Fertility/genetics , Male , Mutation , Phenotype , Polymorphism, Single Nucleotide , Reverse Transcriptase Polymerase Chain Reaction , Spermatogenesis/physiology , Spermatozoa/physiology , Whole Genome SequencingABSTRACT
O carcinoma hepatocelular (HCC) é uma neoplasia primária com mau prognóstico e alta taxa de recorrência. Estudos recentes demostram que o HCC pode ser classificado em três subtipos segundo o perfil molecular. Destes subtipos, o HCC pouco diferenciado apresenta pior prognostico. Neste sentido, torna-se de particular interesse o estudo de compostos com efeitos diferenciadores e citotóxicos nas células destas neoplasias pouco diferenciadas. O butirato, um ácido graxo de cadeia curta produzido pela fermentação microbiana da fibra alimentar no intestino, tem demonstrado atividade anti-neoplásica e capacidade moduladora da diferenciação celular em diversos tipos celulares, incluindo linhagens de HCC humano e células progenitoras hepáticas. Assim, objetivou-se neste estudo, caracterizar o efeito do butirato de sódio (NaBu) em duas linhagens de células neoplásicas de rato: uma pouco diferenciada (GP7TB) e a outra, uma linhagem derivada de um HCC diferenciado (JM-1). A linhagem GP7TB mostrou maior resistência ao NaBu (ED50= 7,7 mM) do que as células JM-1 (ED50= 5,2 mM). A redução na viabilidade celular após 72 h de tratamento com NaBu esteve relacionada com a diminuição na proliferação celular e no caso das células GP7TB, de um aumento na apoptose. O tratamento com NaBu induziu alterações morfológicas nas duas linhagens celulares, porém apenas nas células do tipo GP7TB, essas alterações sugerem um processo de diferenciação/transdiferenciação celular. O aumento na expressão de genes envolvidos no controle da pluripotência de células tronco, assim como de alguns marcadores de células tronco, sugere que o NaBu induziu uma reprogramação profunda das células GP7TB. Por outro lado, a redução na expressão de genes relacionados com migração e plasticidade celular assim como de proliferação celular apontam que estas células diminuíram seu potencial invasivo e a capacidade de autorenovação. Embora sejam necessárias análises adicionais para confirmar o efeito observado nos perfis de expressão gênica, os resultados deste estudo sugerem que o NaBu apresenta efeito antineoplásico por meio da redução da proliferação, aumento da apoptose e modulação da expressão de genes associados com a transição epitéliomesenquimal em células com características tronco tumorais
Hepatocellular carcinoma (HCC) is a primary neoplasia with poor prognosis and high recurrence rate. Recent evidence suggests that HCC can be classified in three different subtypes based on their molecular profile. Among these subtypes, the poorlydifferentiated HCC has the worst prognosis. Therefore, the study of compounds with pro-differentiating and cytotoxic effects on poorly-differentiated neoplastic cells represents a matter of primary concern. Butyrate which is a short-chain fatty acid produced by microbial fermentation in the intestine, has demonstrated anti-neoplastic activity and pro-differentiating potential in several cell types, including, human HCC cell lines and liver progenitor cells. In this study, we aimed to characterize the effect of sodium butyrate (NaBu) on two neoplastic cell lines derived from rats: a poorlydifferentiated cell line (GP7TB) and, a cell line derived from a well-differentiated HCC. GP7TB showed increased resistance to NaBu treatment (ED50= 7.7 mM) compared to JM-1 (ED50= 5.2 mM). The reduction in cell viability observed after 72 h of treatment was explained by a reduction in cell proliferation and, in the case of GP7TB, by increased levels of apoptosis. The NaBu treatment induced morphological alterations in both cell lines. However, only in the case of GP7TB cells, the alterations suggested a differentiation/transdifferentiation process. The up-regulation of genes involved in pluripotency and genes expressing stem cell markers indicated that NaBu triggered a deep reprogramming of GP7TB cells. Besides, a down-regulation in the expression of genes related with cell migration and plasticity suggested that these cells reduced their invasive potential and their self-renewal capacity. Additional analyses are necessary to confirm the observed effect on gene expression profiles. However, the results of this study suggest that NaBu exert anti-neoplastic effects through apoptosis, reduction of cell proliferation and downregulation of genes associated with epithelial-mesenchymal transition of cancer stem-like cells
Subject(s)
Animals , Rats , Butyrates/analysis , Carcinoma, Hepatocellular/prevention & control , Antineoplastic Agents/adverse effects , Neoplastic Stem Cells , Cell Line , Data Interpretation, Statistical , Immunophenotyping/instrumentation , Butyric Acid , Flow Cytometry/methodsABSTRACT
MicroRNAs (miRNAs) are post-transcriptional gene expression regulators which expression is frequently altered in hepatocellular carcinoma (HCC). ß-ionone (ßI) is noted for its ability to inhibit persistent preneoplastic lesions (pPNLs) in liver rats. We evaluated the expression of miRNAs involved in carcinogenesis and possible targets modulated by ßI, in pPNLs and surrounding of microdissected tissues. Rats subjected to resistant hepatocyte model were treated during promotion stage with ßI (16 mg/100 g body weight) or corn oil (CO; 0.25 mL/100 g body weight; controls). Five animals receive no treatment (NT). In CO group, 38 and 29 miRNAs showed reduced expression relative to NT (P < 0.05) in pPNLs and surrounding, respectively. No miRNAs showed increased expression in surrounding of the CO compared to NT group; however, 30 miRNAs showed increased expression (P ≤ 0.05) in pPNLs of the CO group. There was no difference between ßI and CO groups (P > 0.05) in the expression of miRNAs in surrounding. In pPNLs ßI increased expression of miR-122 and miR-34a (P ≤ 0.05) and reduced of Igf2 (P ≤ 0.05), target of the latter, compared to CO. Additionally, ßI decreased the expression of miR-181c and its target Gdf2 (P ≤ 0.05). ßI reduced the expression of miR-181b and miR-708 (P ≤ 0.05) and increased the expression of their respective target mRNAs Timp3 and Mtss1 (P ≤ 0.05), relative to CO group. Modulation of miRNAs target genes by ßI was confirmed in vitro. ßI is a promising chemopreventive agent in the initial stages of hepatocarcinogenesis, as it modulates the expression of the miRNAs and target genes that can alter the metastatic phenotype of HCC. © 2016 Wiley Periodicals, Inc.
Subject(s)
Anticarcinogenic Agents/therapeutic use , Carcinoma, Hepatocellular/prevention & control , Gene Expression Regulation, Neoplastic/drug effects , Liver Neoplasms/prevention & control , Liver/drug effects , MicroRNAs/genetics , Norisoprenoids/therapeutic use , Animals , Carcinogenesis/drug effects , Carcinogenesis/metabolism , Carcinogenesis/pathology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Humans , Liver/metabolism , Liver/pathology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , Precancerous Conditions/genetics , Precancerous Conditions/pathology , Precancerous Conditions/prevention & control , Rats , Rats, WistarABSTRACT
UNLABELLED: Human astrovirus (HAstV) is a leading cause of viral diarrhea in infants and young children worldwide. HAstV is a nonenveloped virus with a T=3 capsid and a positive-sense RNA genome. The capsid protein (CP) of HAstV is synthesized as a 90-kDa precursor (VP90) that can be divided into three linear domains: a conserved N-terminal domain, a hypervariable domain, and an acidic C-terminal domain. Maturation of HAstV requires proteolytic processing of the astrovirus CP both inside and outside the host cell, resulting in the removal of the C-terminal domain and the breakdown of the rest of the CP into three predominant protein species with molecular masses of â¼34, 27/29, and 25/26 kDa, respectively. We have now solved the crystal structure of VP90(71-415) (amino acids [aa] 71 to 415 of VP90) of human astrovirus serotype 8 at a 2.15-Å resolution. VP90(71-415) encompasses the conserved N-terminal domain of VP90 but lacks the hypervariable domain, which forms the capsid surface spikes. The structure of VP90(71-415) is comprised of two domains: an S domain, which adopts the typical jelly-roll ß-barrel fold, and a P1 domain, which forms a squashed ß-barrel consisting of six antiparallel ß-strands similar to what was observed in the hepatitis E virus (HEV) capsid structure. Fitting of the VP90(71-415) structure into the cryo-electron microscopy (EM) maps of HAstV produced an atomic model for a continuous, T=3 icosahedral capsid shell. Our pseudoatomic model of the human HAstV capsid shell provides valuable insights into intermolecular interactions required for capsid assembly and trypsin-mediated proteolytic maturation needed for virus infectivity. Such information has potential applications in the development of a virus-like particle (VLP) vaccine as well as small-molecule drugs targeting astrovirus assembly/maturation. IMPORTANCE: Human astrovirus (HAstV) is a leading cause of viral diarrhea in infants and young children worldwide. As a nonenveloped virus, HAstV exhibits an intriguing feature in that its maturation requires extensive proteolytic processing of the astrovirus capsid protein (CP) both inside and outside the host cell. Mature HAstV contains three predominant protein species, but the mechanism for acquired infectivity upon maturation is unclear. We have solved the crystal structure of VP90(71-415) of human astrovirus serotype 8. VP90(71-415) encompasses the conserved N-terminal domain of the viral CP. Fitting of the VP90(71-415) structure into the cryo-EM maps of HAstV produced an atomic model for the T=3 icosahedral capsid. Our model of the HAstV capsid provides valuable insights into intermolecular interactions required for capsid assembly and trypsin-mediated proteolytic maturation. Such information has potential applications in the development of a VLP vaccine as well as small-molecule drugs targeting astrovirus assembly/maturation.
Subject(s)
Capsid Proteins/chemistry , Mamastrovirus/chemistry , Crystallography, X-Ray , Humans , Models, Molecular , Molecular ConformationABSTRACT
Los tumores del estroma gastrointestinal localizados en el duodeno, constituyen la localización más compleja para el tratamiento de esta neoplasia, es relativamente infrecuente, con una prevalencia de 5 por ciento a 7 por ciento de todos los tumores del estroma gastrointestinal tratados quirúrgicamente. La mayoría de los reportes publicados sobre estos tumores son reportes de casos. Las manifestaciones clínicas, el diagnóstico radiológico, el tratamiento quirúrgico y los factores pronósticos constituyen materia de controversia. Los tumores del estroma gastrointestinal malignos son generalmente de gran tamaño (>5 cm), con índice mitótico alto, y pueden dar metástasis a hígado y peritoneo. Se reporta el caso de un hombre de 41 años con dolor abdominal de comienzo súbito. El estudio ecográfico demostró lesión compleja que ocupaba el hemiabdomen superior derecho. La tomografía abdominal masa sólida, heterogénea, hipercaptante, en íntimo contacto con el duodeno. Se realizó laparotomía con tumor de 20 cm en íntimo contacto con la primera porción del duodeno, realizando exéresis del mismo. El estudio anatomopatológico reveló un tumor de bajo grado con células características del estroma intestinal. La inmunohistoquímica confirmó la estirpe estromal intestinal del tumor. Se completa resección quirúrgica(AU)
The tumors of the gastrointestinal stroma located in the duodenum are the most complex location for this neoplasia treatment; they are relatively infrequent, with a prevalence of 5-7 percent of all the stromal gastrointestinal tumors surgically treated. Most of the reports published on these tumors are case reports. The clinical manifestations, the radiological diagnosis, the surgical treatment and the predictive factors are controversial matters. The malignant stromal gastrointestinal tumors are, in general, of great size (>5 cm), with a high mitotic index, and could give metastasis to the liver and peritoneum. We report the case of a man aged 41 years with abdominal pain of sudden beginning. The echographic study showed complex lesion occupying the upper right hemi abdomen. The abdominal tomography showed an increased uptake, heterogeneous, solid mass, in intimate contact with the duodenum. A laparotomy was carried out with a 20-cm tumor in intimate contact with the first duodenal portion, excising it. The anatomopathological study revealed a low grade tumor with intestinal stroma characteristic cells. The surgical resection was completed(AU)
Subject(s)
Humans , Male , Adult , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors , Duodenal Diseases , Case ReportsABSTRACT
Los tumores del estroma gastrointestinal localizados en el duodeno, constituyen la localización más compleja para el tratamiento de esta neoplasia, es relativamente infrecuente, con una prevalencia de 5% a 7% de todos los tumores del estroma gastrointestinal tratados quirúrgicamente. La mayoría de los reportes publicados sobre estos tumores son reportes de casos. Las manifestaciones clínicas, el diagnóstico radiológico, el tratamiento quirúrgico y los factores pronósticos constituyen materia de controversia. Los tumores del estroma gastrointestinal malignos son generalmente de gran tamaño (>5 cm), con índice mitótico alto, y pueden dar metástasis a hígado y peritoneo. Se reporta el caso de un hombre de 41 años con dolor abdominal de comienzo súbito. El estudio ecográfico demostró lesión compleja que ocupaba el hemiabdomen superior derecho. La tomografía abdominal masa sólida, heterogénea, hipercaptante, en íntimo contacto con el duodeno. Se realizó laparotomía con tumor de 20 cm en íntimo contacto con la primera porción del duodeno, realizando exéresis del mismo. El estudio anatomopatológico reveló un tumor de bajo grado con células características del estroma intestinal. La inmunohistoquímica confirmó la estirpe estromal intestinal del tumor. Se completa resección quirúrgica.
The tumors of the gastrointestinal stroma located in the duodenum are the most complex location for this neoplasia treatment; they are relatively infrequent, with a prevalence of 5 - 7 % of all the stromal gastrointestinal tumors surgically treated. Most of the reports published on these tumors are case reports. The clinical manifestations, the radiological diagnosis, the surgical treatment and the predictive factors are controversial matters. The malignant stromal gastrointestinal tumors are, in general, of great size (>5 cm), with a high mitotic index, and could give metastasis to the liver and peritoneum. We report the case of a man aged 41 years with abdominal pain of sudden beginning. The echographic study showed complex lesion occupying the upper right hemi abdomen. The abdominal tomography showed an increased uptake, heterogeneous, solid mass, in intimate contact with the duodenum. A laparotomy was carried out with a 20-cm tumor in intimate contact with the first duodenal portion, excising it. The anatomopathological study revealed a low grade tumor with intestinal stroma characteristic cells. The surgical resection was completed.
ABSTRACT
UNLABELLED: Astroviruses are small, nonenveloped viruses with a single-stranded positive-sense RNA genome causing acute gastroenteritis in children and immunocompromised patients. Since positive-sense RNA viruses have frequently been found to replicate in association with membranous structures, in this work we characterized the replication of the human astrovirus serotype 8 strain Yuc8 in Caco-2 cells, using density gradient centrifugation and free-flow zonal electrophoresis (FFZE) to fractionate cellular membranes. Structural and nonstructural viral proteins, positive- and negative-sense viral RNA, and infectious virus particles were found to be associated with a distinct population of membranes separated by FFZE. The cellular proteins associated with this membrane population in infected and mock-infected cells were identified by tandem mass spectrometry. The results indicated that membranes derived from multiple cell organelles were present in the population. Gene ontology and protein-protein interaction network analysis showed that groups of proteins with roles in fatty acid synthesis and ATP biosynthesis were highly enriched in the fractions of this population in infected cells. Based on this information, we investigated by RNA interference the role that some of the identified proteins might have in the replication cycle of the virus. Silencing of the expression of genes involved in cholesterol (DHCR7, CYP51A1) and fatty acid (FASN) synthesis, phosphatidylinositol (PI4KIIIß) and inositol phosphate (ITPR3) metabolism, and RNA helicase activity (DDX23) significantly decreased the amounts of Yuc8 genomic and antigenomic RNA, synthesis of the structural protein VP90, and virus yield. These results strongly suggest that astrovirus RNA replication and particle assembly take place in association with modified membranes potentially derived from multiple cell organelles. IMPORTANCE: Astroviruses are common etiological agents of acute gastroenteritis in children and immunocompromised patients. More recently, they have been associated with neurological diseases in mammals, including humans, and are also responsible for different pathologies in birds. In this work, we provide evidence that astrovirus RNA replication and virus assembly occur in contact with cell membranes potentially derived from multiple cell organelles and show that membrane-associated cellular proteins involved in lipid metabolism are required for efficient viral replication. Our findings provide information to enhance our knowledge of astrovirus biology and provide information that might be useful for the development of therapeutic interventions to prevent virus replication.
Subject(s)
Astroviridae/genetics , Intracellular Membranes/metabolism , RNA, Viral/metabolism , Viral Proteins/genetics , Virus Replication/genetics , Adenosine Triphosphate/biosynthesis , Astroviridae/metabolism , Caco-2 Cells , Cell Fractionation , DEAD-box RNA Helicases/genetics , DEAD-box RNA Helicases/metabolism , Fatty Acid Synthase, Type I/genetics , Fatty Acid Synthase, Type I/metabolism , Fatty Acids/biosynthesis , Gene Expression Regulation , Host-Pathogen Interactions , Humans , Inositol 1,4,5-Trisphosphate Receptors/genetics , Inositol 1,4,5-Trisphosphate Receptors/metabolism , Intracellular Membranes/chemistry , Intracellular Membranes/virology , Molecular Sequence Annotation , Oxidoreductases Acting on CH-CH Group Donors/genetics , Oxidoreductases Acting on CH-CH Group Donors/metabolism , Phosphotransferases (Alcohol Group Acceptor)/genetics , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Protein Interaction Mapping , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , RNA, Viral/genetics , Signal Transduction , Sterol 14-Demethylase/genetics , Sterol 14-Demethylase/metabolism , Viral Proteins/metabolismABSTRACT
CD4+ type 1 T regulatory (Tr1) cells have a crucial role in inducing tolerance. Immune regulation by these cells is mainly mediated through the secretion of high amounts of IL-10. Several studies have suggested that this regulatory population may be involved in tumor-mediated immune-suppression. However, direct evidence of a role for Tr1 cells in human solid tumors is lacking. Using ex vivo isolated cells from individuals with hepatocellular carcinoma (HCC; n = 39) or liver metastases from colorectal cancer (LM-CRC; n = 60) we identify a CD4+FoxP3-IL-13-IL-10+ T cell population in tumors of individuals with primary or secondary liver cancer that is characterized as Tr1 cells by the expression of CD49b and the lymphocyte activation gene 3 (LAG-3) and strong suppression activity of T cell responses in an IL-10 dependent manner. Importantly, the presence of tumor-infiltrating Tr1 cells is correlated with tumor infiltration of plasmacytoid dendritic cells (pDCs). pDCs exposed to tumor-derived factors enhance IL-10 production by Tr1 cells through up-regulation of the inducible co-stimulatory ligand (ICOS-L). These findings suggest a role for pDCs and ICOS-L in promoting intra-tumoral immunosuppression by Tr1 cells in human liver cancer, which may foster tumor progression and which might interfere with attempts of immunotherapeutic intervention.
ABSTRACT
No disponible
Subject(s)
Humans , Mental Disorders/epidemiology , Diagnostic Techniques and Procedures/instrumentation , Diagnosis, Differential , Diagnostic ErrorsABSTRACT
Introducción: Las granulaciones aracnoideas se consideran gigantes cuando su tamaño excede un centímetro. Son hallazgos poco frecuentes y se pueden confundir con diversas afecciones de los senos de la duramadre.Caso clínico: Se reporta un paciente masculino, de 44 años de edad, con dos años en remisión de un linfoma no Hodgkin, con manifestaciones de cefalea primaria tipo tensional, sin signos de alarma ni focalización neurológica en el examen físico y con un estudio de imágenes de resonancia magnética de cráneo que sólo mostró una estructura alargada de bordes bien definidos en el interior del seno transverso derecho, de 20 mm de longitud y 5 de grosor; hipointensa en secuencias potenciadas en T1 y FLAIR e hiperintensa en T2, en correspondencia con las intensidades de señales del líquido cefalorraquídeo.Conclusiones: Se estableció el diagnóstico de granulación aracnoidea gigante, como hallazgo incidental no relacionado con la cefalea, ni con los antecedentes de enfermedad maligna del paciente. Una adecuada correlación clínico-imágenes con las diferentes secuencias de intensidades de señales en la resonancia magnética, permite diferenciar las granulacionesaracnoideas gigantes de otras afecciones de los senos durales(AU)
Introduction: Arachnoid granulations are considered as "giants" when they exceed one cm in size and they are uncommon findings that may be mistaken by dural sinuses diseases.Clinical case: A 44 years old male patient is reported with a primary headache of tension type without alarm or focal signs, two years after remission of a non-Hodgkin lymphoma. Cranial magnetic resonance images just revealed a 20 per 5 millimeters well defined structure within the right transverse sinus, which showed T1 and FLAIR-weighted images hypointensity and T2 hyperintensity, in correspondence with the characteristics of cerebrospinal fluid at the same weighted images.Conclusions: A giant arachnoid granulation was diagnosed as a casual finding that was not related to the symptoms or to previous history of a malignant disease of the patient. It is possible to differentiate giant arachnoid granulations from dural sinuses diseases when an adequate correlation between clinical manifestations and magnetic resonance images is established(AU)
Subject(s)
Humans , Male , Adult , Cerebrum/anatomy & histology , Cerebrum/physiopathology , Tension-Type Headache/diagnosis , Lymphoma, Non-Hodgkin , Magnetic Resonance Imaging/methods , Cerebrospinal FluidABSTRACT
Human astroviruses (HAstV) are a frequent cause of gastroenteritis in young children and immunocompromised patients. To understand the early steps of HAstV infection in the highly permissive Caco-2 cell line, the binding and entry processes of the virus were characterized. The half-time of virus binding to the cell surface was about 10 min, while virus decapsidation took around 130 min. Drugs affecting clathrin-mediated endocytosis, endosome acidification, and actin filament polymerization, as well as those that reduce the presence of cholesterol in the cell membrane, decreased the infectivity of the virus. The infection was also reduced by silencing the expression of the clathrin heavy chain (CHC) by RNA interference or by overexpression of dominant-negative mutants of dynamin 2 and Eps15. Furthermore, the entry of HAstV apparently depends on the maturation of endosomes, since the infection was reduced by silencing the expression of Rab7, a small GTPase involved in the early- to late-endosome maturation. Altogether, our results suggest that HAstV enters Caco-2 cells using a clathrin-dependent pathway and reaches late endosomes to enter cells. Here, we have characterized the mechanism used by human astroviruses, important agents of gastroenteritis in children, to gain entry into their host cells. Using a combination of biochemical and genetic tools, we found that these viruses enter Caco-2 cells using a clathrin-dependent endocytic pathway, where they most likely need to travel to late endosomes to reach the cytoplasm and begin their replication cycle.
Subject(s)
Mamastrovirus/physiology , Virus Internalization , Adaptor Proteins, Vesicular Transport/genetics , Adaptor Proteins, Vesicular Transport/metabolism , Antiviral Agents/pharmacology , Astroviridae Infections/genetics , Astroviridae Infections/metabolism , Astroviridae Infections/virology , Cell Line , Clathrin/genetics , Clathrin/metabolism , Dynamins/genetics , Dynamins/metabolism , Endoribonucleases/metabolism , Fungal Proteins/metabolism , Gene Silencing , Humans , Mamastrovirus/drug effects , Mutation , Virus Attachment , Virus Release , Virus Replication/drug effects , Virus Uncoating , rab GTP-Binding Proteins/genetics , rab GTP-Binding Proteins/metabolism , rab7 GTP-Binding ProteinsABSTRACT
En el presente artículo, se propone un análisis crítico del modelo anatomoclínico y psicopatológico, se reivindica la autonomía epistemológica, metodológica y tecnológica de la Psicología y de su capacitación profesional para el análisis y solución de los problemas psicológicos. Esta perspectiva debería ser tenida en cuenta en el debate actual sobre los itinerarios formativos de la Psicología Clínica dentro y fuera del ámbito sanitario. Se plantea un itinerario formativo de Master en Psicología Clínica para el ejercicio profesional fuera del sistema sanitario, se plantean las oportunidades y riesgos de los itinerarios formativos del Psicólogo Interno Residente (PIR) y del Psicólogo General Sanitario (PSG) (AU)
In this paper, we propose a critical analysis of the anatomoclinical and psychopathological model, we claim the epistemological, methodological and technological autonomy of Psychology and of the professional training for the analysis and solution of psychological problems. This perspective should be taken into account in the current debate on the training programs of Clinical Psychology within and outside the health field. We propose a training program as Clinical Psychology Master for professional practice outside the health system, we raise the opportunities and risks of the curricula of Internal Resident Psychologist (PIR) and the General Health Psychologist (PSG) (AU)
Subject(s)
Humans , Psychology, Clinical/education , Models, Psychological , Professional Competence , Health Services , Internship and ResidencyABSTRACT
La celulitis orbitaria usualmente ocurre como complicación de infecciones de los senos para nasales, y la etiología es principalmente bacteriana. Para realizar un diagnóstico e implantar terapéutica temprana tiene gran importancia reconocer las manifestaciones clínicas de la sinusitis y las edades más afectadas, pues dada su ubicación anatómica, pueden complicarse también con infecciones del sistema nervioso central, que en la edad pediátrica tienen una connotación especial. Se presentan aquí dos pacientes de 10 y 14 años de edad respectivamente, que desarrollaron celulitis orbitaria en un caso, y celulitis frontal y empiema en el otro; así mismo, se muestran los medios diagnósticos utilizados para identificar signos tempranos de posibles complicaciones, con el objetivo que el pediatra pueda identificarlos, así como la terapéutica implantada para dar solución o evitar estas complicaciones(AU)
Orbital cellulite generally occurs as a complication of paranasal sinus infections and the etiology is mainly bacterial. It is very important to recognize the clinical manifestations of sinusitis and the most affected ages to make a correct diagnosis and to apply early treatment, since its anatomical location may bring complications with central nervous system infections which, at pediatric ages, can acquire special significance. Here are two patients aged 10 and 14 years, who developed orbital cellulitis in one case and frontal cellulitis and empyema in the other. Likewise, the diagnostic means used to identify the early signs of possible complications were presented, in order that a pediatrician can detect them, as well as the treatment to solve or to prevent these complications(AU)
Subject(s)
Humans , Adolescent , Sinusitis/complications , Orbital Cellulitis/etiology , Empyema/etiology , Frontal Sinusitis/etiology , Case ReportsABSTRACT
La celulitis orbitaria usualmente ocurre como complicación de infecciones de los senos para nasales, y la etiología es principalmente bacteriana. Para realizar un diagnóstico e implantar terapéutica temprana tiene gran importancia reconocer las manifestaciones clínicas de la sinusitis y las edades más afectadas, pues dada su ubicación anatómica, pueden complicarse también con infecciones del sistema nervioso central, que en la edad pediátrica tienen una connotación especial. Se presentan aquí dos pacientes de 10 y 14 años de edad respectivamente, que desarrollaron celulitis orbitaria en un caso, y celulitis frontal y empiema en el otro; así mismo, se muestran los medios diagnósticos utilizados para identificar signos tempranos de posibles complicaciones, con el objetivo que el pediatra pueda identificarlos, así como la terapéutica implantada para dar solución o evitar estas complicaciones
Orbital cellulite generally occurs as a complication of paranasal sinus infections and the etiology is mainly bacterial. It is very important to recognize the clinical manifestations of sinusitis and the most affected ages to make a correct diagnosis and to apply early treatment, since its anatomical location may bring complications with central nervous system infections which, at pediatric ages, can acquire special significance. Here are two patients aged 10 and 14 years, who developed orbital cellulitis in one case and frontal cellulitis and empyema in the other. Likewise, the diagnostic means used to identify the early signs of possible complications were presented, in order that a pediatrician can detect them, as well as the treatment to solve or to prevent these complications
Subject(s)
Humans , Child , Orbital Cellulitis/diagnosis , Orbital Cellulitis/therapy , Frontal Sinusitis/epidemiologyABSTRACT
La celulitis orbitaria usualmente ocurre como complicación de infecciones de los senos para nasales, y la etiología es principalmente bacteriana. Para realizar un diagnóstico e implantar terapéutica temprana tiene gran importancia reconocer las manifestaciones clínicas de la sinusitis y las edades más afectadas, pues dada su ubicación anatómica, pueden complicarse también con infecciones del sistema nervioso central, que en la edad pediátrica tienen una connotación especial. Se presentan aquí dos pacientes de 10 y 14 años de edad respectivamente, que desarrollaron celulitis orbitaria en un caso, y celulitis frontal y empiema en el otro; así mismo, se muestran los medios diagnósticos utilizados para identificar signos tempranos de posibles complicaciones, con el objetivo que el pediatra pueda identificarlos, así como la terapéutica implantada para dar solución o evitar estas complicaciones(AU)
Orbital cellulite generally occurs as a complication of paranasal sinus infections and the etiology is mainly bacterial. It is very important to recognize the clinical manifestations of sinusitis and the most affected ages to make a correct diagnosis and to apply early treatment, since its anatomical location may bring complications with central nervous system infections which, at pediatric ages, can acquire special significance. Here are two patients aged 10 and 14 years, who developed orbital cellulitis in one case and frontal cellulitis and empyema in the other. Likewise, the diagnostic means used to identify the early signs of possible complications were presented, in order that a pediatrician can detect them, as well as the treatment to solve or to prevent these complications(AU)
Subject(s)
Humans , Child , Orbital Cellulitis/diagnosis , Orbital Cellulitis/therapy , Frontal Sinusitis/epidemiologyABSTRACT
Autophagy is an important component of the innate immune response, directly destroying many intracellular pathogens. However, some pathogens, including several RNA viruses, subvert the autophagy pathway, or components of the pathway, to facilitate their replication. In the present study, the effect of inhibiting autophagy on the growth of dengue virus was tested using a novel inhibitor, spautin-1 (specific and potent autophagy inhibitor 1). Inhibition of autophagy by spautin-1 generated heat-sensitive, noninfectious dengue virus particles, revealing a large effect of components of the autophagy pathway on viral maturation. A smaller effect on viral RNA accumulation was also observed. Conversely, stimulation of autophagy resulted in increased viral titers and pathogenicity in the mouse. We conclude that the presence of functional autophagy components facilitates viral RNA replication and, more importantly, is required for infectious dengue virus production. Pharmacological inhibition of host processes is an attractive antiviral strategy to avoid selection of treatment-resistant variants, and inhibitors of autophagy may prove to be valuable therapeutics against dengue virus infection and pathogenesis.