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Vibrios, a group of bacteria that are among the most abundant in marine environments, include several species such as Vibrio cholerae and Vibrio parahaemolyticus, which can be pathogenic to humans. Some species of Vibrio contain prophages within their genomes. These prophages can carry genes that code for toxins, such as the zonula occludens toxin (Zot), which contribute to bacterial virulence. Understanding the association between different Vibrio species, prophages and Zot genes can provide insights into their ecological interactions. In this study, we evaluated 4619 Vibrio genomes from 127 species to detect the presence of prophages carrying the Zot toxin. We found 2030 potential prophages with zot-like genes in 43 Vibrio species, showing a non-random association within a primarily modular interaction network. Some prophages, such as CTX or Vf33, were associated with specific species. In contrast, prophages phiVCY and VfO3K6 were found in 28 and 20 Vibrio species, respectively. We also identified six clusters of Zot-like sequences in prophages, with the ZOT2 cluster being the most frequent, present in 34 Vibrio species. This analysis helps to understand the distribution patterns of zot-containing prophages across Vibrio genomes and the potential routes of Zot-like toxin dissemination.
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Endotoxinas , Genoma Bacteriano , Prófagos , Vibrio , Proteínas de Bactérias/genética , Filogenia , Prófagos/genética , Vibrio/genética , Vibrio/virologia , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/virologiaRESUMO
Vibrio parahaemolyticus is an important human pathogen that is currently the leading cause of shellfish-borne gastroenteritis in the world. Particularly, the pandemic strain has the capacity to induce cytotoxicity and enterotoxicity through its Type 3 Secretion System (T3SS2) that leads to massive cell death. However, the specific mechanism by which the T3SS2 induces cell death remains unclear and its contribution to mitochondrial stress is not fully understood. In this work, we evaluated the contribution of the T3SS2 of V. parahaemolyticus in generating mitochondrial stress during infection in human intestinal HT-29 cells. To evaluate the contribution of the T3SS2 of V. parahaemolyticus in mitochondrial stress, infection assays were carried out to evaluate mitochondrial transition pore opening, mitochondrial fragmentation, ATP quantification, and cell viability during infection. Our results showed that the Δvscn1 (T3SS2+) mutant strain contributes to generating the sustained opening of the mitochondrial transition pore. Furthermore, it generates perturbations in the ATP production in infected cells, leading to a significant decrease in cell viability and loss of membrane integrity. Our results suggest that the T3SS2 from V. parahaemolyticus plays a role in generating mitochondrial stress that leads to cell death in human intestinal HT-29 cells. It is important to highlight that this study represents the first report indicating the possible role of the V. parahaemolyticus T3SS2 and its effector proteins involvement in generating mitochondrial stress, its impact on the mitochondrial pore, and its effect on ATP production in human cells.
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Vibrio anguillarum is a pathogen for several fish and shellfish species. Its ecology is influenced by diverse factors, including bacteriophages. Here, we identify and characterize a new temperate bacteriophage (Valp1) of V. anguillarum. Valp1 is a myovirus with a 60 nm head and a 90 nm contractile tail. Its double-stranded DNA genome of 42,988 bp contains 68 genes, including a protelomerase gene, typical of telomeric phages. Valp1 inhibits the growth of the virulent strain of V. anguillarum PF4, while the derived lysogenic strain P1.1 presents a slight reduction in its growth but is not affected by the presence of Valp1. Both strains present similar virulence in a larval zebrafish (Danio rerio) model, and only slight differences have been observed in their biochemical profile. Co-culture assays reveal that PF4 and P1.1 can coexist for 10 h in the presence of naturally induced Valp1, with the proportion of PF4 ranging between 28% and 1.6%. By the end of the assay, the phage reached a concentration of ~108 PFU/mL, and all the non-lysogenic PF4 strains were resistant to Valp1. This equilibrium was maintained even after five successive subcultures, suggesting the existence of a coexistence mechanism between the lysogenic and non-lysogenic populations of V. anguillarum in conjunction with the phage Valp1.
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In recent studies, emphasis has been placed on the zonula occludens toxin (Zot) from the non-toxigenic Vibrio parahaemolyticus strain PMC53.7 as an agent inducing alterations in the actin cytoskeleton of infected Caco-2 cells and which appears as a relevant virulence factor. Universal zot primers were designed by the alignment of different types of zot gene and identification of conserved sequences to investigate the presence in diverse environmental and clinical V. parahaemolyticus isolates, in co-occurrence with virulence factors, such a hemolysins and secretion systems. The study screened a total of 390 isolates from environmental sources from Chile and Italy and 95 Chilean clinical isolates. The results revealed that around 37.2% of Chilean environmental strains and 25.9% of Italian strains, and 24.2% of clinical isolates carried the zot gene. The Zot-C2 cluster was present in 71.4% of Chilean environmental strains but absent in clinical isolates, while the Zot-C4 cluster was identified in 28.6% of environmental and 100% of clinical isolates. Understanding the role of zot in V. parahaemolyticus virulence is crucial, especially considering the risk associated with consuming diverse isolates from bivalves and the co-occurrence with virulence factors such as TDH, TRH or T3SS2.
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The gut-brain axis is an essential communication pathway between the central nervous system (CNS) and the gastrointestinal tract. The human microbiota is composed of a diverse and abundant microbial community that compasses more than 100 trillion microorganisms that participate in relevant physiological functions such as host nutrient metabolism, structural integrity, maintenance of the gut mucosal barrier, and immunomodulation. Recent evidence in animal models has been instrumental in demonstrating the possible role of the microbiota in neurodevelopment, neuroinflammation, and behavior. Furthermore, clinical studies suggested that adverse changes in the microbiota can be considered a susceptibility factor for neurological disorders (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). In this review, we will discuss evidence describing the role of gut microbes in health and disease as a relevant risk factor in the pathogenesis of neurodegenerative disorders, including AD, PD, HD, and ALS.
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Doença de Alzheimer , Esclerose Lateral Amiotrófica , Microbioma Gastrointestinal , Doença de Huntington , Doenças Neurodegenerativas , Doença de Parkinson , Animais , Humanos , Eixo Encéfalo-Intestino , Microbioma Gastrointestinal/fisiologia , Doenças Neurodegenerativas/patologia , Sistema Nervoso Central , Doença de Parkinson/patologia , Doença de Huntington/patologiaRESUMO
The bacterial community of the intestinal microbiota influences many host functions, and similar effects have been recently reported for the fungal community (mycobiota). Cobia is a tropical fish that has been studied for its potential in marine aquaculture. However, the study of its bacterial community has been underreported and the mycobiota has not been investigated. We analyzed the gut bacterial and fungal profile present in the intestinal mucosa of reared adult cobias fed two diets (frozen fish pieces (FFPs) and formulated feed (FF)) for 4 months by sequencing the 16S rRNA (V3-V4) and internal transcribed spacer-2 (ITS2) regions using Illumina NovaSeq 6000. No significant differences in the alpha diversity of the bacterial community were observed, which was dominated by the phyla Proteobacteria (~96%) and Firmicutes (~1%). Cobia fed FF showed higher abundance of 10 genera, mainly UCG-002 (Family Oscillospiraceae) and Faecalibacterium, compared to cobia fed FFPs, which showed higher abundance of 7 genera, mainly Methylobacterium-Methylorubrum and Cutibacterium. The inferred bacterial functions were related to metabolism, environmental information processing and cellular processes; and no differences were found between diets. In mycobiota, no differences were observed in the diversity and composition of cobia fed the two diets. The mycobiota was dominated by the phyla Ascomycota (~88%) and Basidiomycota (~11%). This is the first study to describe the gut bacterial and fungal communities in cobia reared under captive conditions and fed on different diets and to identify the genus Ascobulus as a new member of the core fish mycobiota.
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The 2019 coronavirus disease (COVID-19) pandemic has affected different human populations since March 2020 and challenged healthcare systems, especially in chronic non-communicable diseases such as cancer. The present study aimed to evaluate the mortality, risk factors, and symptoms of cancer patients and control subjects, diagnosed with COVID-19 and admitted to intensive care unit (ICU). This retrospective, observational, non-randomized, controlled study of patients admitted to ICU was conducted between March and August 2020 in an Ecuadorian oncology center. Patient information collected from electronic medical records included sociodemographic information, clinical history, symptoms, laboratory test results, COVID-19 treatment, and discharge status. For patients with neoplasia, diagnosis, type, and status of cancer, as well as antineoplastic treatment received over the past month was also recorded. Descriptive statistics and multiple logistic regression were used to analyze the data. Statistical analysis was performed with SPSS (version 22.0) and R (version 4.1.3). In total, 79 adult COVID-19 patients were studied (40 with cancer and 39 controls). The total mean time until COVID-19 symptoms onset was 6.2â ±â 3.5 days (5.3â ±â 3.2 days in the cancer group vs 7.2â ±â 3.6 days in the control group; Pâ =â .016) but no difference was observed in reported symptoms. All patients received an antibiotic treatment, but only 70% of the cancer group had antivirals (Pâ <â .001). Cancer patients had lower hemoglobin levels than controls (10.7â ±â 2.8 vs 13.3â ±â 1.7 g/dL; Pâ <â .001). In terms of mortality, not statistically significance difference was reported between groups. The study showed that high ferritin (Absolute Odds Ratio of 3.9; 95% CI 1.1-14.6) and mechanical ventilation (Absolute Odds Ratio of 4.9; 95% CI 1.3-18.6) were independent COVID-19 mortality risk factors. COVID-19 infection did not represent an increased risk of mortality in cancer patients, but elevated ferritin levels and the need for mechanical ventilation were identified as mortality risk factors.
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COVID-19 , Neoplasias , Adulto , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Equador/epidemiologia , Estudos Retrospectivos , Tratamento Farmacológico da COVID-19 , Respiração Artificial , Neoplasias/epidemiologia , Fatores de Risco , FerritinasRESUMO
The COVID-19 pandemic has both highlighted and worsened existing health inequities among communities of color and structurally vulnerable populations. Community Health Workers, inclusive of Community Health Representatives (CHW/Rs) have entered the spotlight as essential to COVID-19 prevention and control. To learn about community experiences and perspectives related to COVID-19 and inform CHW/R workforce capacity building efforts, a series of focus groups were conducted with CHW/Rs throughout Arizona at two time points in 2021. Throughout the data collection and analysis process, researchers and community partners engaged in ongoing and open dialogue about what CHW/Rs on the ground were reporting as priority community concerns, needs, and challenges. Thus, CHW/Rs informed the development of culturally and linguistically relevant health education messages, materials, and training for CHW/Rs. In this community case study, we detail the efforts of partnership between a statewide CHW professional association and an academic research team that facilitated rapid decision-making and knowledge sharing to create community-grounded tools and resources supportive of CHW/R workforce capacity building in the context of the COVID-19 pandemic.
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COVID-19 , Humanos , Agentes Comunitários de Saúde , Fortalecimento Institucional , Arizona , Pandemias , Recursos HumanosRESUMO
Despite extensive work on both insect disease and plant reproduction, there is little research on the intersection of the two. Insect-infecting pathogens could disrupt the pollination process by affecting pollinator population density or traits. Pathogens may also infect insect herbivores and change herbivory, potentially altering resource allocation to plant reproduction. We conducted a meta-analysis to (1) summarize the literature on the effects of pathogens on insect pollinators and herbivores and (2) quantify the extent to which pathogens affect insect traits, with potential repercussions for plant reproduction. We found 39 articles that fit our criteria for inclusion, extracting 218 measures of insect traits for 21 different insect species exposed to 25 different pathogens. We detected a negative effect of pathogen exposure on insect traits, which varied by host function: pathogens had a significant negative effect on insects that were herbivores or carried multiple functions but not on insects that solely functioned as pollinators. Particular pathogen types were heavily studied in certain insect orders, with 7 of 11 viral pathogen studies conducted in Lepidoptera and 5 of 9 fungal pathogen studies conducted in Hymenoptera. Our results suggest that most studies have focused on a small set of host-pathogen pairs. To understand the implications for plant reproduction, future work is needed to directly measure the effects of pathogens on pollinator effectiveness.
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Shikimic acid-derived polyoxygenated cyclohexene natural products commonly occurring in several species of the Uvaria represent natural products with promising biological activities. While a number of derivatives have been reported from Uvaria grandiflora (U. grandiflora), further studies are needed to discover additional bioactive congeners, particularly derivatives with multi-protein target inhibitory properties implicated in diseases such as diabetes and obesity. In this paper, isolation and identification of a new highly oxygenated cyclohexene, uvagrandol (1), along with the known compound (-)-zeylenone (2) from the DCM sub-extract of U. grandiflora following in vitro and in silico assessment of their enzyme inhibitory properties against α-glucosidase, dipeptidyl peptidase IV, porcine lipase, and human recombinant monoacylglycerol lipase are reported. The structure of 1 was elucidated using 1D and 2D NMR data analysis. The absolute configuration of 1 was established by quantum chemical calculations via the Gauge-Independent Atomic Orbital (GIAO) NMR method followed by TDDFT-Electronic Circular Dichroism (ECD) calculations. The structures of the eight possible stereoisomers were optimized by means of DFT calculations (B3LYP/6-31+G[d,p] in vacuum), and then their isotropic shielding tensors were obtained using the GIAO method at mPW1PW91/6-31G(d,p) in chloroform. Through DP4+, the isomer of configuration (1S,2S,3R,6R) for 1 was predicted with 96.3% probability. Compounds 1 and 2 significantly inhibited the four target enzymes in vitro. Binding studies through molecular docking simulations showed strong binding affinities for (-)-zeylenone (2), thus validating the in vitro results. Our findings suggest the potential of polyoxygenated cyclohexenes, in particular (-)-zeylenone (2), in anti-diabetic and anti-obesity drug discovery.
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Introducción: Las enfermedades reumáticas se caracterizan por la presencia de manifestaciones articulares y extraarticulares. Entre estas últimas, uno de los sistemas menos estudiados es el reproductor. Objetivo: Caracterizar las manifestaciones ginecológicas que con mayor frecuencia se presentan en el curso de las enfermedades reumáticas. Métodos: Se realizó una investigación básica, no experimental, descriptiva y longitudinal que incluyó un total de 117 pacientes femeninas con diagnóstico de varias enfermedades reumáticas según los criterios del Colegio Americano de Reumatología. La muestra quedó conformada por 108 pacientes. Durante la realización del estudio se identificó la incidencia de manifestaciones ginecológicas en las pacientes reumáticas y el tipo de manifestación que se notifica con mayor frecuencia. Resultados: Pacientes con un promedio de edad de 61,19 años, predominio de procedencia urbana (61,11 por ciento) y con diagnóstico de artritis reumatoide (61,11 por ciento). El 39,81 por ciento de ellas refirió tiempo de evolución de la enfermedad entre 3 y 5 años. El 62,04 por ciento de las pacientes presentó algún tipo de manifestación extraarticular ginecológica. La secreción vaginal (50,75 por ciento), vulvovaginitis (25,37 por ciento), cervicitis (20,90 por ciento) y la dispareunia (14,92 por ciento) fueron las de mayor frecuencia de presentación. Conclusiones: Las manifestaciones ginecológicas son frecuentes en las pacientes con enfermedades reumáticas. Las manifestaciones ginecológicas de origen inflamatorio fueron las de mayor presentación y fueron más frecuente en la artritis reumatoide y el lupus eritematoso. En la esclerosis sistémica las manifestaciones neoplásicas fueron las más frecuentes(AU)
Introduction: Rheumatic diseases are characterized by the presence of articular and extra-articular manifestations. Within the latter, one of the least studied systems. Objective: To characterize the gynecological manifestations that most frequently occur in the course of rheumatic diseases. Methods: A basic, non-experimental, descriptive and longitudinal research was carried out that included a total of 117 female patients diagnosed with various rheumatic diseases according to the criteria of the American College of Rheumatology. The sample was made up of 108 patients. During the study, the incidence of gynecological manifestations in rheumatic patients and the type of manifestation that is most frequently reported were identified. Result: average age of 61.19 years, predominance of patients of urban origin (61.11%) and with a diagnosis of rheumatoid arthritis (61.11 percent). 39.81 percent of the patients reported disease evolution time between three and five years. 62.04% of the patients presented some type of extra-articular gynecological manifestation. Vaginal secretion (50.75 percent), vulvovaginitis (25.37 percent), cervicitis (20.90 percent) and dyspareunia (14.92 percent) were the ones with the highest frequency of presentation. Conclusions: Gynecological manifestations are frequently found in patients with rheumatic diseases. Gynecological manifestations of inflammatory origin were those with the highest frequency of presentation and were more frequent in rheumatoid arthritis and lupus erythematosus. In systemic sclerosis, neoplastic manifestations were the most frequent(AU)
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Humanos , FemininoRESUMO
Laying the groundwork on preliminary structure-activity relationship study relating to the disruptive activity of cytochalasan derivatives on mammalian cell actin cytoskeleton, we furthered our study on the cytochalasans of the Dothideomycetes fungus, Sparticola triseptata. A new cytochalasan analog triseptatin (1), along with the previously described cytochalasans deoxaphomin B (2) and cytochalasin B (3), and polyketide derivatives cis-4-hydroxy-6-deoxyscytalone (4) and 6-hydroxymellein (5) were isolated from the rice culture of S. triseptata. The structure of 1 was elucidated through NMR spectroscopic analysis and high-resolution mass spectrometry (HR-ESI-MS). The relative and absolute configurations were established through analysis of NOESY spectroscopic data and later correlated with experimental electronic circular dichroism and time-dependent density functional theory (ECD-TDDFT) computational analysis. Compounds 1 and 2 showed cytotoxic activities against seven mammalian cell lines (L929, KB3.1, MCF-7, A549, PC-3, SKOV-3, and A431) and antiproliferative effects against the myeloid leukemia K-562 cancer cell line. Both 1 and 2 were shown to possess properties inhibiting the F-actin network, prompting further hypotheses that should to be tested in the future to enable a well-resolved concept of the structural implications determining the bioactivity of the cytochalasin backbone against F-actin.
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Anthropogenic pollution has a huge impact on the water quality of marine ecosystems. Heavy metals and antibiotics are anthropogenic stressors that have a major effect on the health of the marine organisms. Although heavy metals are also associate with volcanic eruptions, wind erosion or evaporation, most of them come from industrial and urban waste. Such contamination, coupled to the use and subsequent misuse of antimicrobials in aquatic environments, is an important stress factor capable of affecting the marine communities in the ecosystem. Bivalves are important ecological components of the oceanic environments and can bioaccumulate pollutants during their feeding through water filtration, acting as environmental sentinels. However, heavy metals and antibiotics pollution can affect several of their physiologic and immunological processes, including their microbiome. In fact, heavy metals and antibiotics have the potential to select resistance genes in bacteria, including those that are part of the microbiota of bivalves, such as Vibrio spp. Worryingly, antibiotic-resistant phenotypes have been shown to be more tolerant to heavy metals, and vice versa, which probably occurs through co- and cross-resistance pathways. In this regard, a crucial role of heavy metal resistance genes in the spread of mobile element-mediated antibiotic resistance has been suggested. Thus, it might be expected that antibiotic resistance of Vibrio spp. associated with bivalves would be higher in contaminated environments. In this review, we focused on co-occurrence of heavy metal and antibiotic resistance in Vibrio spp. In addition, we explore the Chilean situation with respect to the contaminants described above, focusing on the main bivalves-producing region for human consumption, considering bivalves as potential vehicles of antibiotic resistance genes to humans through the ingestion of contaminated seafood.
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Bivalves , Metais Pesados , Microbiota , Agricultura , Animais , Antibacterianos/farmacologia , Bactérias/genética , ChileRESUMO
Kelps or brown algae are a wide group of marine macroalgae that play an important role in aquatic ecosystems and generally have high commercial value. To facilitate brown algal studies, we report the complete genome sequence of the largest kelp Macrocystis pyrifera. The whole genome is â¼428 Mb in size, comprises 44,307 scaffolds with an average GC content of 47%, and is predicted to contain a total of 24,778 genes. 18S sequence-based phylogenetic analysis revealed that littoral brown seaweed Scytosiphon lomentaria is the closest species of M. pyrifera. Numerous genes identified in this dataset are involved in genetic information processing, signaling, and cellular processes, carbohydrate metabolism, and terpenoids biosynthesis.
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Axenic fermentation on solid rice of the saprobic fungus Sparticola junci afforded two new highly oxidized naphthalenoid polyketide derivatives, sparticatechol A (1) and sparticolin H (2) along with sparticolin A (3). The structures of 1 and 2 were elucidated on the basis of their NMR and HR-ESIMS spectroscopic data. Assignment of absolute configurations was performed using electronic circular dichroism (ECD) experiments and Time-Dependent Density Functional Theory (TDDFT) calculations. Compounds 1-3 were evaluated for COX inhibitory, antiproliferative, cytotoxic and antimicrobial activities. Compounds 1 and 2 exhibited strong inhibitory activities against COX-1 and COX-2. Molecular docking analysis of 1 conferred favorable binding against COX-2. Sparticolin H (2) and A (3) showed a moderate antiproliferative effect against myelogenous leukemia K-562 cells and weak cytotoxicity against HeLa and mouse fibroblast cells.
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Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Ascomicetos/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Fibroblastos/efeitos dos fármacos , Policetídeos/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Cultura Axênica/métodos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular/métodos , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/isolamento & purificação , Fermentação , Fibroblastos/metabolismo , Células HeLa , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular/métodos , Estrutura Molecular , Policetídeos/química , Policetídeos/isolamento & purificaçãoRESUMO
Quimioterapia neoadyuvante (NAC) en cáncer de mama permite conocer la sensibilidad del tumor al tratamiento, alcanzar respuesta patológica completa (pRC), está asociada a mejor supervivencia en cáncer de mama localmente avanzado. El objetivo de este estudio fue conocer el impacto de la pRC en la supervivencia en una cohorte de pacientes tratadas con NAC y cirugía. Se realizo un estudio de diseño observacional de tipo retrospectivo, correlacional, con un seguimiento promedio de 90 meses, de una cohorte de pacientes tratadas con NAC y cirugía desde enero del 2009 a diciembre del 2011. El análisis de datos se realizó mediante el software estadístico SPSS v22.0, para el análisis de supervivencia se utilizó el método de Kaplan Meier, para comparar supervivencias se consideró significativa una p<0,05. Entre las características principales de 199 pacientes, se destacan: edad joven a la presentación, elevado índice de proliferación y alta frecuencia del tipo inflamatorio. pRC ocurrió en el 14,1% de pacientes y la supervivencia global (SG) de acuerdo con la respuesta patológica se comparó entre aquellas pacientes que obtuvieron pRC, con las que tuvieron enfermedad residual, con una SG del 71,4% vs 45% respectivamente, con una diferencia significativa (p:0.009). En esta cohorte de pacientes la pRC impactó en la supervivencia en todos los subtipos clínico-patológicos, sobre todo en el subtipo triple negativo. Evaluar los datos en el entorno real es importante para definir estrategias y mejorar los resultados.
Neoadjuvant chemotherapy (NAC) in breast cancer allows knowing the sensitivity of the tumor to treatment, achieving pathological response complete (pRC), and is associated with better survival in locally advanced breast cancer. The objective of this study was to determine the impact of pRC on survival in a cohort of patients treated with NAC and surgery. A retrospective, correlational observational design study was carried out, with an average follow-up of 90 months, of a cohort of patients treated with NAC and surgery from January 2009 to December 2011. Data analysis was performed using the software SPSS v22.0 statistic, for the survival analysis the Kaplan Meier method was used, to compare survivals a p <0.05 was considered significant. Among the main characteristics of 199 patients, the following stand out: young age at presentation, high proliferation index and high frequency of the inflammatory type. pRC occurred in 14.1% of patients and overall survival (OS) according to the pathological response was compared between those patients who obtained pRC, with those who had residual disease, with an OS of 71.4% vs 45% respectively, with a significant difference (p: 0.009). In this cohort of patients, pRC impacted on survival in all clinicopathological subtypes, especially in the triple negative subtype. Evaluating data in the real environment is important to define strategies and improve results.
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Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/métodos , Terapia Neoadjuvante/métodos , Prognóstico , Taxa de Sobrevida , Estudos Retrospectivos , Resultado do Tratamento , Correlação de DadosRESUMO
The host microbiome plays an essential role in health and disease. Microbiome modification by pathogens or probiotics has been poorly explored especially in the case of probiotic yeasts. Next-generation sequencing currently provides the best tools for their characterization. Debaryomyces hansenii 97 (D. hansenii 97) and Yarrowia lipolytica 242 (Y. lipolytica 242) are yeasts that protect wildtype zebrafish (Danio rerio) larvae against a Vibrio anguillarum (V. anguillarum) infection, increasing their survival rate. We investigate the effect of these microorganisms on the microbiome and neutrophil response (inflammation) in zebrafish larvae line Tg(Bacmpx:GFP) i114. We postulated that preinoculation of larvae with yeasts would attenuate the intestinal neutrophil response and prevent modification of the larval microbiome induced by the pathogen. Microbiome study was performed by sequencing the V3-V4 region of the 16S rRNA gene and prediction of metabolic pathways by Piphillin in conventionally raised larvae. Survival and the neutrophil response were both evaluated in conventional and germ-free conditions. V. anguillarum infection resulted in higher neutrophil number in the intestinal area compared to non-infected larvae in both conditions. In germ-free conditions, infected larvae pre-inoculated with yeasts showed fewer neutrophil numbers than infected larvae. In both conditions, only D. hansenii 97 increased the survival of infected larvae. Beta diversity of the microbiota was modified by V. anguillarum and both yeasts, compared to non-inoculated larvae. At 3 days post-infection, V. anguillarum modified the relative abundance of 10 genera, and pre-inoculation with D. hansenii 97 and Y. lipolytica 242 prevented the modification of 5 and 6 of these genera, respectively. Both yeasts prevent the increase of Ensifer and Vogesella identified as negative predictors for larval survival (accounting for 40 and 27 of the variance, respectively). In addition, yeast pre-inoculation prevents changes in some metabolic pathways altered by V. anguillarum's infection. These results suggest that both yeasts and V. anguillarum can shape the larval microbiota configuration in the early developmental stage of D. rerio. Moreover, modulation of key taxa or metabolic pathways of the larval microbiome by yeasts can be associated with the survival of infected larvae. This study contributes to the understanding of yeast-pathogen-microbiome interactions, although further studies are needed to elucidate the mechanisms involved.
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Sparticols A (1) and B (2), two catechol-bearing naphthalenedioxy derivatives, were isolated from the submerged culture of the Spanish broom inhabiting Dothideomycetes fungus, Sparticola junci. The structures of 1 and 2 were established by NMR spectroscopic analysis and high-resolution mass spectrometry. The 8S absolute configuration of their ß-hydroxy functionalities was determined by ECD-TDDFT. Both compounds exhibited inhibitory activity against Staphylococcus aureus with an MIC value of 66.6 µg/mL. Polyketides 1 and/or 2 may be associated with pathways cascading to seco-spirodioxynapthalene derivatives.
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Antibacterianos/farmacologia , Ascomicetos/química , Catecóis/farmacologia , Policetídeos/farmacologia , Antibacterianos/isolamento & purificação , Catecóis/isolamento & purificação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Policetídeos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Short-chain fatty acids (SCFAs) are carboxylic acids produced as a result of gut microbial anaerobic fermentation. They activate signaling cascades, acting as ligands of G-protein-coupled receptors, such as GPR41, GPR43, and GPR109A, that can modulate the inflammatory response and increase the intestinal barrier integrity by enhancing the tight junction proteins functions. These junctions, located in the most apical zone of epithelial cells, control the diffusion of ions, macromolecules, and the entry of microorganisms from the intestinal lumen into the tissues. In this sense, several enteric pathogens secrete diverse toxins that interrupt tight junction impermeability, allowing them to invade the intestinal tissue and to favor gastrointestinal colonization. It has been recently demonstrated that SCFAs inhibit the virulence of different enteric pathogens and have protective effects against bacterial colonization. Here, we present an overview of SCFAs production by gut microbiota and their effects on the recovery of intestinal barrier integrity during infections by microorganisms that affect tight junctions. These properties make them excellent candidates in the treatment of infectious diseases that cause damage to the intestinal epithelium.
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Vibrio parahaemolyticus is the leading cause of seafood-associated bacterial gastroenteritis worldwide. Although different studies have focused on its pattern of variation over time, knowledge about the environmental factors driving the dynamics of this pathogen, within the Chilean territory, is still lacking. This study determined the prevalence of total and pathogenic V. parahaemolyticus strains (tdh and/or trh genes) in mussels (Mytilus chilensis) collected from two natural growing areas between 2017 and 2018, using selective agar and PCR analysis. V. parahaemolyticus was detected in 45.6% (93/204) of pooled samples from the Valdivia River Estuary. The pathogenic strains carrying the tdh and/or trh gene were detected in 11.8% (24/204): tdh in 9.8% (20/204), trh in 0.5% (1/204), and 1.5% (3/204) presented both genes. In Reloncaví Fjord, V. parahaemolyticus was detected in 14.4% (30/209) of the samples, pathogenic V. parahaemolyticus carrying the trh gene was detected in 0.5% (1/209) of the samples, while the tdh gene was not detected in the samples from this area. The total count of mauve-purple colonies typical of V. parahaemolyticus on CHROMagar was positively associated by multivariate analysis with area, water temperature, and salinity. Similarly, V. parahaemolyticus detection rates by PCR had a positive correlation with the area and water temperature. The chances of detecting total V. parahaemolyticus in the Valdivia River Estuary are significantly higher than in the Reloncaví Fjord, but inversely, during spring-summer months, the interaction factor between the area and temperature indicated that the chances of detecting V. parahaemolyticus are higher in the Reloncaví Fjord. Interestingly, this period coincides with the season when commercial and natural-growing shellfish are harvested. On the other hand, pathogenic V. parahaemolyticus tdh+ was significantly correlated with an increase of water temperature. These environmental parameters could be used to trigger a warning on potential hazard, which would influence human health and economic losses in aquaculture systems.