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1.
Comput Struct Biotechnol J ; 23: 473-482, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38261868

RESUMO

TRP channels are important pharmacological targets in physiopathology. TRPV2 plays distinct roles in cardiac and neuromuscular function, immunity, and metabolism, and is associated with pathologies like muscular dystrophy and cancer. However, TRPV2 pharmacology is unspecific and scarce at best. Using in silico similarity-based chemoinformatics we obtained a set of 270 potential hits for TRPV2 categorized into families based on chemical nature and similarity. Docking the compounds on available rat TRPV2 structures allowed the clustering of drug families in specific ligand binding sites. Starting from a probenecid docking pose in the piperlongumine binding site and using a Gaussian accelerated molecular dynamics approach we have assigned a putative probenecid binding site. In parallel, we measured the EC50 of 7 probenecid derivatives on TRPV2 expressed in Pichia pastoris using a novel medium-throughput Ca2+ influx assay in yeast membranes together with an unbiased and unsupervised data analysis method. We found that 4-(piperidine-1-sulfonyl)-benzoic acid had a better EC50 than probenecid, which is one of the most specific TRPV2 agonists to date. Exploring the TRPV2-dependent anti-hypertensive potential in vivo, we found that 4-(piperidine-1-sulfonyl)-benzoic acid shows a sex-biased vasodilator effect producing larger vascular relaxations in female mice. Overall, this study expands the pharmacological toolbox for TRPV2, a widely expressed membrane protein and orphan drug target.

2.
Front Cell Infect Microbiol ; 13: 1239700, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37743860

RESUMO

Despite global efforts to assess the early response and persistence of SARS-CoV-2 antibodies in patients infected with or recovered from COVID-19, our understanding of the factors affecting its dynamics remains limited. This work aimed to evaluate the early and convalescent immunity of outpatients infected with SARS-CoV-2 and to determine the factors that affect the dynamics and persistence of the IgM and IgG antibody response. Seropositivity of volunteers from Mexico City and the State of Mexico, Mexico, was evaluated by ELISA using the recombinant receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein for 90 days, at different time points (1, 15, 45, 60, and 90 days) after molecular diagnosis (RT-qPCR). Gender, age range, body mass index (BMI), comorbidities, and clinical spectrum of disease were analyzed to determine associations with the dynamics of anti-SARS-CoV-2 antibodies. On 90 days post-infection, individuals with moderate and asymptomatic disease presented the lowest levels of IgM, while for IgG, at the same time, the highest levels occurred with mild and moderate disease. The IgM and IgG levels were related to the clinical spectrum of disease, BMI, and the presence/absence of comorbidities through regression trees. The results suggest that the dynamics of anti-SARS-CoV-2 IgM and IgG antibodies in outpatients could be influenced by the clinical spectrum of the disease. In addition, the persistence of antibodies against SARS-CoV-2 could be related to the clinical spectrum of the disease, BMI, and the presence/absence of comorbidities.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Anticorpos Antivirais , Imunoglobulina G , Imunoglobulina M , Imunidade
3.
Int J Mol Sci ; 24(14)2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37511519

RESUMO

This review of human amoebiasis is based on the most current knowledge of pathogenesis, diagnosis, treatment, and Entamoeba/microbiota interactions. The most relevant findings during this last decade about the Entamoeba parasite and the disease are related to the possibility of culturing trophozoites of different isolates from infected individuals that allowed the characterization of the multiple pathogenic mechanisms of the parasite and the understanding of the host-parasite relationship in the human. Second, the considerable advances in molecular biology and genetics help us to analyze the genome of Entamoeba, their genetic diversity, and the association of specific genotypes with the different amoebic forms of human amoebiasis. Based on this knowledge, culture and/or molecular diagnostic strategies are now available to determine the Entamoeba species and genotype responsible for invasive intestinal or extraintestinal amoebiasis cases. Likewise, the extensive knowledge of the immune response in amoebiasis with the appearance of new technologies made it possible to design diagnostic tools now available worldwide. Finally, the understanding of the interaction between the Entamoeba species and the intestinal microbiota aids the understanding of the ecology of this parasite in the human environment. These relevant findings will be discussed in this review.


Assuntos
Amebíase , Disenteria Amebiana , Entamoeba histolytica , Entamoeba , Humanos , Entamoeba histolytica/genética , Ecossistema , Amebíase/diagnóstico , Amebíase/terapia , Amebíase/parasitologia , Disenteria Amebiana/diagnóstico , Disenteria Amebiana/terapia , Disenteria Amebiana/parasitologia , Intestinos , Entamoeba/genética
4.
Clin Ophthalmol ; 17: 1729-1737, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37361692

RESUMO

Significance: The need for early identification and treatment of young children's refractive error needs has become a public health concern. The UCSD Eyemobile for Children (EyeMobile) provides vision screenings and comprehensive eye exams on the Eyemobile among a population of underserved, predominantly Hispanic preschool and elementary school children. The program also provides spectacles for children who fail eye exams due to refractive error. Methods: We performed a retrospective cross-sectional analysis of all children screened from 2011 to 2017 by the Eyemobile across 10 San Diego elementary schools. We examined demographics, distance and near visual acuity, autorefraction, stereopsis, and color vision. To measure compliance to our spectacle program, we checked if children who were prescribed spectacles were wearing them, as instructed, at the following year's screening. Differences between compliance measures with respect to school, age, ethnicity, and gender were determined using chi-square analysis, while all other measures were fit to a binary logistic regression to determine statistically significant factors. Results: A total of 12,176 elementary school children were screened between 2011 and 2017. Of these children, 5269 (43.3%) were referred for a comprehensive eye examination. Across six years, 3163 (60.0%) of the children referred completed their eye examinations. There was a significant increase (p < 0.001) in exam completion in the successive years. Exam completion was significantly higher in ten-year-olds (p = 0.0278) and in 3 of the 10 schools (p < 0.0001, p = 0.0027, and p = 0.0309). A total of 1089 (8.9% of screened) children were prescribed spectacles. Of the 409 children that were recorded with the compliance method, 342 (83.6%) were found to be fully compliant and wearing their spectacles as prescribed. Conclusion: The Eyemobile program demonstrated high levels of compliance for both eye examination completion and prescribed spectacle wear in underserved populations in the San Diego region, compared to similar national programs.

5.
Front Cell Infect Microbiol ; 12: 967724, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118018

RESUMO

Blastocystis spp. is a unicellular organism that resides in digestive tract of various vertebrates, with a worldwide distribution and a variable prevalence. For many years, Blastocystis spp. was considered a cyst of a flagellate, a fungus, or a saprophyte yeast of the digestive tract; in 1996, it is placed in the group of stramenopiles (heterokonts). Since its new classification, many questions have arisen around this protist about its role as a pathogen or non-pathogen organism. Recent evidence indicates that Blastocystis spp. participates in the immune inflammatory response in the intestinal microbiome generating an anti-inflammatory response, showing a lower concentration of fecal inflammatory markers in infected human hosts. Here, we review recent findings on the regulatory function of Blastocystis spp. in the immune inflammatory response to comprehend the purpose of Blastocystis spp. in health and disease, defining if Blastocystis spp. is really a pathogen, a commensal or even a mutualist in the human gut microbiome.


Assuntos
Infecções por Blastocystis , Blastocystis , Microbioma Gastrointestinal , Animais , Anti-Inflamatórios , Infecções por Blastocystis/epidemiologia , Fezes/microbiologia , Humanos
6.
J Bacteriol ; 204(7): e0012022, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35657707

RESUMO

Live-cell fluorescence imaging of methanogenic archaea has been limited due to the strictly anoxic conditions required for growth and issues with autofluorescence associated with electron carriers in central metabolism. Here, we show that the fluorescence-activating and absorption-shifting tag (FAST) complexed with the fluorogenic ligand 4-hydroxy-3-methylbenzylidene-rhodanine (HMBR) overcomes these issues and displays robust fluorescence in Methanococcus maripaludis. We also describe a mechanism to visualize cells under anoxic conditions using a fluorescence microscope. Derivatives of FAST were successfully applied for protein abundance analysis, subcellular localization analysis, and determination of protein-protein interactions. FAST fusions to both formate dehydrogenase (Fdh) and F420-reducing hydrogenase (Fru) displayed increased fluorescence in cells grown on formate-containing medium, consistent with previous studies suggesting the increased abundance of these proteins in the absence of H2. Additionally, FAST fusions to both Fru and the ATPase associated with the archaellum (FlaI) showed a membrane localization in single cells observed using anoxic fluorescence microscopy. Finally, a split reporter translationally fused to the alpha and beta subunits of Fdh reconstituted a functionally fluorescent molecule in vivo via bimolecular fluorescence complementation. Together, these observations demonstrate the utility of FAST as a tool for studying members of the methanogenic archaea. IMPORTANCE Methanogenic archaea are important members of anaerobic microbial communities where they catalyze essential reactions in the degradation of organic matter. Developing additional tools for studying the cell biology of these organisms is essential to understanding them at a mechanistic level. Here, we show that FAST, in combination with the fluorogenic ligand HMBR, can be used to monitor protein dynamics in live cells of M. maripaludis. The application of FAST holds promise for future studies focused on the metabolism and physiology of methanogenic archaea.


Assuntos
Formiato Desidrogenases , Mathanococcus , Archaea/metabolismo , Formiato Desidrogenases/metabolismo , Ligantes , Mathanococcus/metabolismo , Imagem Óptica
7.
mSphere ; 6(4): e0008321, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34406855

RESUMO

An estimated 3.5 billion people are colonized by intestinal parasites worldwide. Intestinal parasitic eukaryotes interact not only with the host but also with the intestinal microbiota. In this work, we studied the relationship between the presence of multiple enteric parasites and the community structures of gut bacteria and eukaryotes in an asymptomatic mother-child cohort from a semirural community in Mexico. Fecal samples were collected from 46 mothers and their respective children, with ages ranging from 2 to 20 months. Mothers and infants were found to be multiparasitized by Blastocystis hominis, Entamoeba dispar, Endolimax nana, Chilomastix mesnili, Iodamoeba butshlii, Entamoeba coli, Hymenolepis nana, and Ascaris lumbricoides. Sequencing of bacterial 16S rRNA and eukaryotic 18S rRNA genes showed a significant effect of parasite exposure on bacterial beta-diversity, which explained between 5.2% and 15.0% of the variation of the bacterial community structure in the cohort. Additionally, exposure to parasites was associated with significant changes in the relative abundances of multiple bacterial taxa, characterized by an increase in Clostridiales and decreases in Actinobacteria and Bacteroidales. Parasite exposure was not associated with changes in intestinal eukaryote relative abundances. However, we found several significant positive correlations between intestinal bacteria and eukaryotes, including Oscillospira with Entamoeba coli and Prevotella stercorea with Entamoeba hartmanni, as well as the co-occurrence of the fungus Candida with Bacteroides and Actinomyces, Bifidobacterium, and Prevotella copri and the fungus Pichia with Oscillospira. The parasitic exposure-associated changes in the bacterial community structure suggest effects on microbial metabolic routes, host nutrient uptake abilities, and intestinal immunity regulation in host-parasite interactions. IMPORTANCE The impact of intestinal eukaryotes on the prokaryotic microbiome composition of asymptomatic carriers has not been extensively explored, especially in infants and mothers with multiple parasitic infections. In this work, we studied the relationship between protist and helminth parasite colonization and the intestinal microbiota structure in an asymptomatic population of mother-child binomials from a semirural community in Mexico. We found that the presence of parasitic eukaryotes correlated with changes in the bacterial gut community structure in the intestinal microbiota in an age-dependent way. Parasitic infection was associated with an increase in the relative abundance of the class Clostridia and decreases of Actinobacteria and Bacteroidia. Parasitic infection was not associated with changes in the eukaryote community structure. However, we observed strong positive correlations between bacterial and other eukaryote taxa, identifying novel relationships between prokaryotes and fungi reflecting interkingdom interactions within the human intestine.


Assuntos
Bactérias/genética , Fezes/parasitologia , Microbioma Gastrointestinal/genética , Helmintos/fisiologia , Enteropatias Parasitárias/epidemiologia , Parasitos/fisiologia , Adolescente , Adulto , Animais , Bactérias/classificação , Estudos de Coortes , Feminino , Microbioma Gastrointestinal/fisiologia , Helmintos/genética , Interações Hospedeiro-Parasita , Humanos , Lactente , México/epidemiologia , Pessoa de Meia-Idade , Modelos Estatísticos , Mães , Parasitos/classificação , Parasitos/genética , RNA Ribossômico 16S/genética , População Rural/estatística & dados numéricos , Adulto Jovem
8.
J Biomech ; 115: 110130, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33257007

RESUMO

Estimation of ground reaction forces in runners has been limited to laboratory environments by means of instrumented treadmills, in-ground force plates and optoelectronic systems. Recent advances in estimation techniques using wearable sensors for kinematic analysis and sports performance could enable estimation outside the laboratory. This paper proposes a state-input-parameter estimation framework to continuously estimate the vertical ground reaction force waveform during running. By modeling a runner as a single degree of freedom mass-spring-damper with acceleration measurements at the sacrum a state-space formulation can be applied using Newtonian methods. A dual-Kalman filter is employed to estimate the unmeasured system input which feeds through to an unscented Kalman filter to estimate system dynamics and unknown model parameters (e.g. spring stiffness). For validation, 14 subjects performed three one-minute running trials at three different speeds (self-selected slow, comfortable, and fast) on a pressure-sensor-instrumented treadmill. The estimated vertical ground reaction force waveform parameters; peak vertical ground reaction force (RMSE=6.1-7.2%,ρ=0.95-0.97), vertical impulse (RMSE=8.5-13.0%,ρ=0.50-0.60), loading rate (RMSE=24.6-39.4%,ρ=0.85-0.93), and cadence RMSE<1%,ρ=1.00 were compared against the instrumented treadmill measurements. The proposed state-input-parameter estimation framework could monitor personalized vertical ground reaction force metrics for potential biofeedback applications. The feedback mechanism could provide information about the vertical ground reaction force characteristics to the runner as they are running to provide knowledge of both desirable and undesirable loading characteristics experienced.


Assuntos
Corrida , Fenômenos Biomecânicos , Teste de Esforço , Fadiga , Humanos , Fenômenos Mecânicos
9.
Microorganisms ; 8(10)2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33050280

RESUMO

The etiological agent of human amoebiasis is the protozoan parasite E. histolytica; the disease is still an endemic infection in some countries and the outcome of infection in the host infection can range from asymptomatic intestinal infection to intestinal or liver invasive forms of the disease. The invasive character of this parasite is multifactorial and mainly due to the differential expression of multiple pathogenic genes. The aim of the present work was to measure the differential expression of some genes in different specimens of patients with amoebic liver abscess (ALA) and specimens of genital amoebiasis (AG) by RT-qPCR. Results show that the expression of genes is different in both types of samples. Almost all studied genes were over expressed in both sets of patients; however, superoxide dismutase (Ehsod), serine threonine isoleucine rich protein (Ehstirp), peroxiredoxin (Ehprd) and heat shock protein 70 and 90 (Ehhsp-70, EHhsp-90) were higher in AG biopsies tissue. Furthermore, cysteine proteinases 5 and 2 (Ehcp5, Ehcp2), lectin (Ehgal/galnaclectin) and calreticulin (Ehcrt) genes directly associate with pathogenic mechanisms of E. histolytica had similar over expression in both AG and ALA samples. In summary the results obtained show that trophozoites can regulate the expression of their genes depending on stimuli or environmental conditions, in order to regulate their pathogenicity and ensure their survival in the host.

10.
Cell Signal ; 72: 109636, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32283254

RESUMO

The Wnt signaling pathway is a crucial regulator of the intestinal epithelium homeostasis and is altered in most colon cancers. While the role of aberrant canonical, ß-catenin-dependent Wnt signaling has been well established in colon cancer promotion, much less is known about the role played by noncanonical, ß-catenin-independent Wnt signaling in this type of cancer. This work aimed to characterize the noncanonical signal transduction pathway in colon cancer cells. To this end, we used the prototype noncanonical ligand, Wnt5a, in comparison with Wnt3a, the prototype of a canonical ß-catenin activating ligand. The analysis of the expression profile of Wnt receptors in colon cancer cell lines showed a clear increase in both level expression and variety of Frizzled receptor types expressed in colon cancer cells compared with non-malignant cells. We found that Wnt5a activates a typical Wnt/Ca++ - noncanonical signaling pathway in colon malignant cells, inducing the hyperphosphorylation of Dvl1, Dvl2 and Dvl3, promoting Ca++ mobilization as a result of phospholipase C (PLC) activation via pertussis toxin-sensitive G-protein, and inducing PLC-dependent cell migration. We also found that while the co-receptor Ror2 tyrosine kinase activity is not required for Ca++ mobilization-induced by Wnt5a, it is required for the inhibitory effects of Wnt5a on the ß-catenin-dependent transcriptional activity. Unexpectedly, we found that although the prototype canonical Wnt3a ligand was unique in stimulating the ß-catenin-dependent transcriptional activity, it also simultaneously activated PLC, promoted Ca++ mobilization, and induced Rho kinase and PLC-dependent cell migration. Our data indicate, therefore, that a Wnt ligand can activate at the same time the so-called Wnt canonical and noncanonical pathways inducing the formation of complex signaling networks to integrate both pathways in colon cancer cells.


Assuntos
Neoplasias do Colo/metabolismo , Proteínas Wnt/metabolismo , Via de Sinalização Wnt , Animais , Cálcio/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Neoplasias do Colo/patologia , Proteínas de Ligação ao GTP/metabolismo , Humanos , Ligantes , Camundongos , Modelos Biológicos , Toxina Pertussis/farmacologia , Fosforilação/efeitos dos fármacos , Isoformas de Proteínas/metabolismo , Estabilidade Proteica/efeitos dos fármacos , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Receptores Wnt/metabolismo , Fatores de Tempo , Transcrição Gênica/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-30406037

RESUMO

Calreticulin (CRT) is a highly conserved protein in the endoplasmic reticulum that plays important roles in the regulation of key cellular functions. Little is known about the participation of E. histolytica CRT (EhCRT) in the processes of pathogenicity or in the modulation of the host immune response. The aim of this study was to evaluate the role of CRT in the proliferation and the cytokine profile in peripheral blood mononuclear cells (PBMCs) from patients with amebic liver abscess (ALA) during the acute phase (AP-ALA) of the disease compared to patients during the resolution phase (R-ALA). The PBMCs from each participant were cocultured with EhCRT and tested by the colorimetric method to evaluate their proliferation index (PI). The supernatants were subjected to an enzyme-linked immunosorbent assay (ELISA) to evaluate the concentration of cytokines. The mean values of all groups were compared using the independent t-test. When the PIs of individuals without diagnosis of liver abscess (NEG) were compared, there were no statistically significant differences in the proliferation of PBMCs between patients with AP-ALA and R-ALA when stimulated with EhCRT or concanavalin A (ConA). However, the levels of interleukins [IL-6, IL-10, granulocyte colony stimulating factor (GCSF), and transforming growth factor ß1 (TGFß1)] were higher in patients with AP-ALA, whereas in patients with R-ALA, higher levels of interferon gamma (IFNγ) were detected. These results suggest that EhCRT acts as a mitogen very similar to the activity of ConA. In addition, EhCRT is an excellent immunogen for the specific activation of PBMCs, inducing the differential expression of ILs depending on the outcome of disease, determining the type of immune response: a Th2 cytokine profile during the acute phase and a Th1 profile during the resolution phase.


Assuntos
Calreticulina/metabolismo , Citocinas/biossíntese , Entamoeba histolytica/crescimento & desenvolvimento , Entamoeba histolytica/imunologia , Interações Hospedeiro-Patógeno , Leucócitos Mononucleares/parasitologia , Abscesso Hepático Amebiano/parasitologia , Calreticulina/imunologia , Células Cultivadas , Técnicas de Cocultura , Meios de Cultura/química , Entamoeba histolytica/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Humanos , Leucócitos Mononucleares/imunologia , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/metabolismo
14.
Med Microbiol Immunol ; 207(5-6): 287-296, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29936564

RESUMO

An outbreak of nosocomial infections due to Streptococcus pyogenes (Group A Streptococcus; GAS) occurred in a post-surgery oncology unit and concerned more than 60 patients and lasted 20 months despite enhanced infection control and prophylaxis measures. All GAS strains were characterized (emm genotype, toxin gene profile and pulse-field gel electrophoresis subtype). Selected strains were sequenced and phylogenetic relationship established. Capacity to form biofilm and interaction with human pulmonary epithelial cells and macrophages were determined. Twenty-six GAS strains responsible for invasive infections (II) and 57 for non-II or colonization were isolated from patients (n = 66) or healthcare workers (n = 13). Seventy strains shared the same molecular markers and 69 the same PFGE pattern; 56 were sequenced. They all belonged to the emerging emm89 clade 3; all but 1 were clonal. Whole genome sequencing identified 43 genetic profiles with sporadic mutations in regulatory genes and acquired mutations in 2 structural genes. Except for two regulatory gene mutants, all strains tested had the same biofilm formation capacity and displayed similar adherence and invasion of pulmonary epithelial cells and phagocytosis and survival in human macrophages. This large outbreak of GAS infection in a post-surgery oncology unit, a setting that contains highly susceptible patients, arose from a strain of the emergent emm89 clade. No relationship between punctual or acquired mutations, invasive status, and strain phenotypic characteristics was found. Noteworthy, the phenotypic characteristics of this clone account for its emergence and its remarkable capacity to elicit outbreaks.


Assuntos
Surtos de Doenças , Genótipo , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes/classificação , Streptococcus pyogenes/isolamento & purificação , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Toxinas Bacterianas/análise , Biofilmes/crescimento & desenvolvimento , Eletroforese em Gel de Campo Pulsado , Células Epiteliais/microbiologia , Feminino , França , Técnicas de Genotipagem , Humanos , Macrófagos/microbiologia , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Neoplasias/cirurgia , Filogenia , Análise de Sequência de DNA , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/genética , Streptococcus pyogenes/crescimento & desenvolvimento , Infecção da Ferida Cirúrgica/microbiologia , Adulto Jovem
15.
Biomed Res Int ; 2018: 3916263, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29744356

RESUMO

Blastocystis subtype 3 (ST3) is a parasitic protist found in the digestive tract of symptomatic and asymptomatic humans around the world. While this parasite exhibits a high prevalence in the human population, its true geographic distribution and global genetic diversity are still unknown. This gap in knowledge limits the understanding of the spread mechanisms, epidemiology, and impact that this parasite has on human populations. Herein, we provided new data on the geographical distribution and genetic diversity of Blastocystis ST3 from a rural human population in Mexico. To do so, we collected and targeted the SSU-rDNA region in fecal samples from this population and further compared its genetic diversity and structure with that previously observed in populations of Blastocystis ST3 from other regions of the planet. Our analyses reveled that diversity of Blastocystis ST3 showed a high haplotype diversity and genetic structure to the world level; however, they were low in the Morelos population. The haplotype network revealed a common widespread haplotype from which the others were generated recently. Finally, our results suggested a recent expansion of the diversity of Blastocystis ST3 worldwide.


Assuntos
Infecções por Blastocystis/genética , Blastocystis/genética , DNA Ribossômico/genética , Variação Genética , Adolescente , Adulto , Blastocystis/patogenicidade , Infecções por Blastocystis/epidemiologia , Infecções por Blastocystis/parasitologia , Criança , Pré-Escolar , DNA de Protozoário , Fezes/parasitologia , Feminino , Trato Gastrointestinal/parasitologia , Trato Gastrointestinal/patologia , Haplótipos/genética , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Filogenia , População Rural , Adulto Jovem
16.
Sci Rep ; 8(1): 6104, 2018 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-29666399

RESUMO

NK cells are important in innate immunity for their capacity to kill infected or cancer cells. The killer cell immunoglobulin-like receptors (KIR) are a family of polymorphic genes with inhibitory and activating functions. The main driving force for gastric cancer (GC) development is a chronic response, which causes an increase of NK cells in the gastric mucosa. The aim of this work was to study polymorphisms in KIR genes in patients with either GC or non-atrophic gastritis (NAG). We studied 242 patients (130 with NAG and 112 with GC) and contrasted with 146 asymptomatic individuals. We analyzed diversity in the content and localization of KIR genes in the different clinical groups studied. Four activating and one inhibitory genes were associated with GC: 2DS1 (OR 3.41), 2DS3 (OR 4.66), 2DS5 (OR 2.25), 3DS1 (OR 3.35) and 2DL5 (OR 3.6). The following were also found as risk factors for GC: Bx genotype (OR 4.2), Bx-Bx centromere-telomere (OR 2.55), cA01|cB03 (OR 36.39) and tB01|tB01 (OR 7.55) gene content and three B motifs (OR 10.9). Polymorphisms in KIR genes were associated with GC and suggest that mutated NK cells may contribute to GC development by increasing gastric mucosa inflammation, leading to constant tissue damage.


Assuntos
Polimorfismo Genético , Receptores KIR/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Feminino , Frequência do Gene , Genótipo , Humanos , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/patologia
17.
Curr Eye Res ; 43(5): 654-658, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29424565

RESUMO

PURPOSE: To compare the performance of the PlusoptiX S12 mobile photoscreener and the Retinomax K+3 Autorefractor as screening devices in preschool children. METHODS: Children ranging from 3 to 5 years of age from 11 San Diego County preschools underwent vision screening in their schools where ambient light could not always be controlled using both the Retinomax and the PlusoptiX. Cycloplegic refraction on the consented children was subsequently performed on the UCSD EyeMobile for children on-site at the school locations. RESULTS: A total of 321 children were screened with the PlusoptiX and Retinomax. The PlusoptiX referred 22% of children, of whom 70% of the referrals were read as "unable". The Retinomax referred 13% and there were no "unables". Similar results occurred in the cycloplegic-refracted 182 consented children-64% of the PlusoptiX referrals were read as "unable" . Only one third of these "unables" required glasses. Both devices referred the four children with amblyopia and one case of strabismus. However, PlusoptiX's 3 false negatives had amblyopia risk factors (ARFs) while the one Retinomax's false negative did not have ARFs. The Retinomax screening had 95% sensitivity and 94% specificity. The PlusoptiX screening had 86% sensitivity and 84% specificity. CONCLUSION: In this preschool population and environment, the PlusoptiX referred 63% more than the Retinomax in addition to a lower specificity and sensitivity. Adjusting PlusoptiX referral criteria might not substantially improve the specificity of the PlusoptiX due to the high numbers of "unables".


Assuntos
Ambliopia/diagnóstico , Erros de Refração/diagnóstico , Seleção Visual/instrumentação , Pré-Escolar , Reações Falso-Negativas , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Retinoscopia , Sensibilidade e Especificidade
18.
PLoS One ; 12(8): e0181962, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28771523

RESUMO

We sought to establish an ex vivo model for examining the interaction of E. histolytica with human tissue, using precision-cut liver slices (PCLS) from donated organs. E. histolytica- or E. dispar-infected PCLS were analyzed at different post-infection times (0, 1, 3, 24 and 48 h) to evaluate the relation between tissue damage and the expression of genes associated with three factors: a) parasite survival (peroxiredoxin, superoxide dismutase and 70 kDa heat shock protein), b) parasite virulence (EhGal/GalNAc lectin, amoebapore, cysteine proteases and calreticulin), and c) the host inflammatory response (various cytokines). Unlike E. dispar (non-pathogenic), E. histolytica produced some damage to the structure of hepatic parenchyma. Overall, greater expression of virulence genes existed in E. histolytica-infected versus E. dispar-infected tissue. Accordingly, there was an increased expression of EhGal/GalNAc lectin, Ehap-a and Ehcp-5, Ehcp-2, ehcp-1 genes with E. histolytica, and a decreased or lack of expression of Ehcp-2, and Ehap-a genes with E. dispar. E. histolytica-infected tissue also exhibited an elevated expression of genes linked to survival, principally peroxiredoxin, superoxide dismutase and Ehhsp-70. Moreover, E. histolytica-infected tissue showed an overexpression of some genes encoding for pro-inflammatory interleukins (ILs), such as il-8, ifn-γ and tnf-α. Contrarily, E. dispar-infected tissue displayed higher levels of il-10, the gene for the corresponding anti-inflammatory cytokine. Additionally, other genes were investigated that are important in the host-parasite relationship, including those encoding for the 20 kDa heat shock protein (HSP-20), the AIG-1 protein, and immune dominant variable surface antigen, as well as for proteins apparently involved in mechanisms for the protection of the trophozoites in different environments (e.g., thioredoxin-reductase, oxido-reductase, and 9 hypothetical proteins). Some of the hypothetical proteins evidenced interesting overexpression rates, however we should wait to their characterization. This finding suggest that the present model could be advantageous for exploring the complex interaction between trophozoites and hepatocytes during the development of ALA, particularly in the initial stages of infection.


Assuntos
Entamoeba histolytica/genética , Entamoeba/genética , Entamebíase/parasitologia , Abscesso Hepático Amebiano/etiologia , Proteínas de Protozoários/genética , Adolescente , Adulto , Idoso , Animais , Citocinas/metabolismo , Entamoeba/patogenicidade , Entamoeba histolytica/patogenicidade , Entamebíase/complicações , Feminino , Interações Hospedeiro-Parasita , Humanos , Abscesso Hepático Amebiano/metabolismo , Abscesso Hepático Amebiano/patologia , Masculino , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , Prevalência , Virulência
19.
Managua; s.n; ago. 2017. 67 p. tab, graf.
Tese em Espanhol | LILACS | ID: biblio-1007768

RESUMO

OBJETIVO: Caracterizar pacientes con indicación de cesárea atendidas en el servicio de ginecología y obstetricia de la clínica médica previsional Asunción ­ MINSA, Juigalpa Chontales, Nicaragua ,2016. DISEÑO: Estudio descriptivo, cuantitativo de corte transversal. Está constituido por 161 mujeres que se les practicó cirugía vía cesárea, se recolectó la información de expedientes clínicos médico legales, del departamento de archivo, que cumplieròn los criterios de inclusión correspondientes. RESULTADOS: El 86.96%se trataba de mujeres en el rango de edad entre 20-35 años, en un 72.05% de educación universitaria, el 54.04% laboraban de acuerdo a su formación profesional, 58.39% eran casadas y el 75.78% procedían del área urbana. De acuerdo a los factores gineco - obstétricos, las pacientes en el estudio no tenían antecedentes personales no patológicos hasta en un 96.89%, con embarazos de término hasta en 83.23%, 42.24% tenían cesáreas anteriores y hasta 72.05% no tenían antecedentes patológicos personales, el 100% recibió atención prenatal, el 86.34% recibió más de 4 atenciones prenatales. 43.48% no presentarón factores de riesgo durante su embarazo y 91.93% no tuvierón factores de riesgo durante el parto. La principal indicación de cesárea hasta en 36.65% precisamente fue cesárea anterior. CONCLUSIONES: Con respecto a las características sociodemográficas, todos estos factores no favorecierón a indicación absoluta de cesárea, no presentarón factores ginecológicos y obstétricos de relevancia que hayan favorecido su indicación absoluta de cesárea, la cual fue la principal causa de indicación para realizar interrupción del embarazo vía alta actual


Assuntos
Humanos , Feminino , Gravidez , Unidade Hospitalar de Ginecologia e Obstetrícia , Cesárea
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