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The cytosolic enzymes N-Acetyl Transferases 1 and 2 (NATs) transfer an acetyl group from acetyl-CoA to a xenobiotic substrate. NATs are regulated at the genetic and epigenetic levels by deacetylase enzymes such as sirtuins. The enzymatic expression of NAT1, NAT2, and SIRT1 was evaluated by flow cytometry, as well as the enzymatic activity of NATs by cell culture and HPLC analysis. Six SNPs were determined through genotyping. T2D patients (n = 29) and healthy subjects (n = 25) with a median age of 57 and 50, respectively, were recruited. An increased enzyme expression and a diminished NAT2 enzymatic activity were found in cells of T2D patients compared to the control group, while NAT1 was negatively correlated with body fat percentage and BMI. In contrast, Sirtuin inhibition increased NAT2 activity, while Sirtuin agonism decreased its activity in both groups. The analysis of NAT2 SNPs showed a higher frequency of rapid acetylation haplotypes in T2D patients compared to the control group, possibly associated as a risk factor for diabetes. The enzymatic expression of CD3+NAT2+ cells was higher in the rapid acetylators group compared to the slow acetylators group. The levels and activity of NAT1 were associated with total cholesterol and triglycerides. Meanwhile, CD3+NAT2+ cells and NAT2 activity levels were associated with HbA1c and glucose levels. The results indicate that NAT2 could be involved in metabolic processes related to the development of T2D, due to its association with glucose levels, HbA1c, and the altered SIRT-NAT axis. NAT1 may be involved with dyslipidaemias in people who are overweight or obese.
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24-year-old man with positive HIV, with a giant exofitic anal condyloma, with a clinical presentation of a painfull suppurative anal condyloma with a pathology report of an in situ squamous cell carcinoma. The purpose of the investigation is a case report and the procedure was observational. The finding was a Buschke-Lowenstein tumor.
Varón de 24 años, con infección por el virus de la inmunodeficiencia humana, que presenta una tumoración exofítica, dolorosa y supurativa, con reporte positivo de virus de papiloma humano y reporte histopatológico de carcinoma espinocelular sin evidencia de diseminación (in situ). El propósito de la investigación es un reporte de caso y el procedimientos fue observacional. El hallazgo fue un tumor de Buschke-Lowenstein.
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Tumor de Buschke-Lowenstein , Carcinoma de Células Escamosas , Condiloma Acuminado , Masculino , Humanos , Tumor de Buschke-Lowenstein/cirurgia , Tumor de Buschke-Lowenstein/patologia , Condiloma Acuminado/complicações , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/cirurgia , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/cirurgia , Canal AnalRESUMO
(1) Background: Parkinson's disease (PD) is a relatively common and complex pathology, and some of its mechanisms remain to be elucidated. Change in host microbiota is related to the pathophysiology of numerous diseases. This systematic review aims to gather existing data on the occidental hemisphere, compare it, and search for any significant association between Parkinson's disease and gut microbiota dysbiosis. (2) Methods: Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) and Meta-analyses Of Observational Studies in Epidemiology (MOOSE) protocols were used for this systematic review. PubMed was used as the database search engine. Of the 166 studies found, only 10 were used, as they met our inclusion criteria: case-control studies, studies that assessed the correlation of PD and gut microbiome, studies that took place in occidental regions, and studies that were performed on humans and were written in English. The Newcastle-Ottawa Scale was used as the assessment tool for overall risk of bias in this systematic review. (3) Results: The studies analyzed were divided into three geographic areas: Region 1: United States of America and Canada; Region 2: Germany, Ireland, and Finland; and Region 3: Italy; based on geographical similarities among these populations. The following statistically significant results were described in PD patients, compared with non-PD controls. In the first region, a significant increase in the following bacteria was seen: 1. Phylum: Actinobacteriota and its Genus: Bifidobacterium; 2. Phylum: Verrucomicrobiota and its Genus: Akkermansia; 3. Genus: Enterococcus, Hungatella, Lactobacillus, and Oscillospira of the Phylum: Firmicutes; 4. Family: Ruminococcaceae of Phylum: Firmicutes; 5. Phylum: Bacteroidetes and its Genus: Bacteroides; 6. Phylum: Proteobacteria. A significant decrease was described in the Family: Lachnospiraceae and its Genus: Blautia, Coprococcus, and Roseburia, which belong to the Phylum: Firmicutes. In the second region, a raised number of: 1. Phylum: Verrucomicrobiota, its Genus: Akkermansia, and its Species: Akkermansia muciniphila; 2. Family: Verrucomicrobiaceae of the Phylum: Verrucomicrobiota; 3. Genus: Lactobacillus and Roseburia of the Phylum: Firmicutes; 4. Family: Lactobacillaceae of the Phylum: Firmicutes; 5. Family: Barnesiellaceae of the Phylum: Bacteroidetes; 6. Genus: Bifidobacterium of the Phylum: Actinobacteriota; 7. Species: Bilophila wadsworthia of the Phylum: Thermodesulfobacteriota, was identified. Only one Genus: Prevotella of the Phylum: Bacteroidetes was decreased. In the third and last region, an augmented number of these bacteria were found: 1. Phylum: Verrucomicrobiota and its Genus: Akkermansia; 2. Family: Bifidobacteriaceae and Coriobacteriaceae of the Phylum: Actinobacteriota; 3. Phylum: Firmicutes and its Family: Christensenellaceae and Lactobacillaceae; 4. Family: Enterococcaceae and its Genus: Enterococcus, of the Phylum: Firmicutes; 5. Genus: Lactococcus and Oscillospira, of the Phylum: Firmicutes; 6. Phylum: Proteobacteria, its Family: Enterobacteriaceae, and the Genus: Citrobacter, Klebsiella, Salmonella, and Shigella; 7. Genus: ParaBacteroides of the Phylum: Bacteroidetes. In contrast, a significant decrease in 1. Phylum: Firmicutes, its Family: Lachnospiraceae, and its Genus: Roseburia and 2. Genus: Ruminococcus of the Phylum: Firmicutes, was described. (4) Conclusion: A significant gut dysbiosis, involving multiple bacterial taxa, was found in PD patients compared to healthy people in the occidental regions. However, more studies are needed to find the precise pathophysiologic involvement of other groups of pathogens, such as fungi and parasites, in the development and progression of PD.
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BACKGROUND/AIM: Arylamine N-acetyltransferase 1 and 2 (NAT1 and NAT2) are drug-metabolizing enzymes that play a key role in the development of acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: This study evaluated NAT1 and NAT2 mRNA and protein expression and their enzymatic activity in peripheral blood mononuclear cells (PBMC) from patients with ALL (n=20) and healthy children (n=19) and explored the mechanisms that regulate these enzymes in ALL such as microRNAs (miR-1290, miR-26b) and SNPs. RESULTS: PBMC from patients with ALL showed a decrease in NAT1 mRNA and protein expression. In addition, NAT1 enzymatic activity was decreased in patients with ALL. There was no influence of SNP 559 C>T or 560 G>A on low NAT1 activity. The lower expression of NAT1 might be related to the loss of acetylated histone H3K14 in the NAT1 gene promoter in patients with ALL and the higher relative expression of miR-1290 in the plasma of patients with relapsed ALL compared with healthy controls. There were significantly fewer CD3+/NAT1+ double-positive cells in patients who relapsed compared with control subjects. Based on a t-distributed stochastic neighbor embedding algorithm, CD19+ cells that reappeared in patients with relapse showed low NAT1 expression. In contrast, for NAT2, there were no significant results. CONCLUSION: The expression and function of NAT1 and miR-1290 levels could be involved in modulating immune cells altered in ALL.
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Arilamina N-Acetiltransferase , MicroRNAs , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Leucócitos Mononucleares/metabolismo , Projetos Piloto , Arilamina N-Acetiltransferase/genética , Arilamina N-Acetiltransferase/metabolismo , MicroRNAs/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , RNA MensageiroRESUMO
Background: Breast cancer (BC) is the malignant tumour that has been most frequently diagnosed, being the second most common cancer worldwide and the most frequent in women. Objective: To analyse the probability of 5-year overall survival according to age, stage of disease, immunohistochemical subtype, histological grade and histological type in patients with BC. Methodology: Operational research that used a cohort design of patients diagnosed with BC at the SOLCA Núcleo de Loja-Ecuador Hospital from 2009 to 2015 and with follow-up until December 2019. Survival was estimated with the actuarial method and Kaplan-Meier method, and, for multivariate analysis, the proportional hazards model or Cox regression was used to estimate the adjusted Hazard Ratios (HRs). Results: Two hundred and sixty-eight patients were studied. Mean overall survival was 4.35 years (95% confidence interval (95% CI): 40.20-4.51) and 66% survived to 5 years. The main predictors of survival were advanced stage of disease (III-IV) (HR = 7.03; 95% CI: 3.81-12.9); patients human epidermal growth factor receptor 2-neu (HER2-neu) overexpressed (HR = 2.26; 95% CI = 1.31-4.75) and triple negative (HR = 2.57; 95% CI = 1.39-4.75). The other variables were not significant. Conclusions: The results show a higher mortality associated with higher clinical stage, more aggressive histological grades and immunohistochemical subtype HER2-neu overexpressed and triple negative tumours.
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A putative xanthorhodopsin-encoding gene, XR34, was found in the genome of the moderately halophilic gammaproteobacterium Salinivibrio socompensis S34, isolated from modern stromatolites found on the shore of Laguna Socompa (3570 m), Argentina Puna. XR-encoding genes were clustered together with genes encoding X-carotene, retinal (vitamin-A aldehyde), and carotenoid biosynthesis enzymes while the carotene ketolase gene critical for the salinixanthin antenna compound was absent. To identify its functional behavior, we herein overexpressed and characterized this intriguing microbial rhodopsin. Recombinant XR34 showed all the salient features of canonical microbial rhodopsin and covalently bound retinal as a functional chromophore with λmax = 561 nm (εmax ca. 60,000 M-1 cm-1). Two canonical counterions with pK values of around 6 and 3 were identified by pH titration of the recombinant protein. With a recovery time of approximately half an hour in the dark, XR34 shows light-dark adaptation shifting the absorption maximum from 551 to 561 nm. Laser-flash induced photochemistry at pH 9 (deprotonated primary counterion) identified a photocycle starting with a K-like intermediate, followed by an M-state (λmax ca. 400 nm, deprotonated Schiff base), and a final long wavelength-absorbing N- or O-like intermediate before returning to the parental 561 nm-state. Initiating the photocycle at pH 5 (protonated counterion) yields only bathochromic intermediates, due to the lacking capacity of the counterion to accept the Schiff base proton. Illumination of the membrane-embedded protein yielded a capacitive transport current. The presence of the M-intermediate under these conditions was demonstrated by a blue light-induced shunt process.
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Bacteriorodopsinas , Bases de Schiff , Bases de Schiff/química , Carotenoides/metabolismo , Retinaldeído/química , Rodopsinas Microbianas/genética , Rodopsinas Microbianas/química , Rodopsinas Microbianas/metabolismo , Concentração de Íons de HidrogênioRESUMO
Modern non-lithifying stromatolites on the shore of the volcanic lake Socompa (SST) in the Puna are affected by several extreme conditions. The present study assesses for the first time light utilization and functional metabolic stratification of SST on a millimeter scale through shotgun metagenomics. In addition, a scanning-electron-microscopy approach was used to explore the community. The analysis on SST unveiled the profile of a photosynthetic mat, with cyanobacteria not directly exposed to light, but placed just below a high-UV-resistant community. Calvin-Benson and 3-hydroxypropinate cycles for carbon fixation were abundant in upper, oxic layers, while the Wood-Ljungdahl pathway was dominant in the deeper anoxic strata. The high abundance of genes for UV-screening and oxidant-quenching pigments and CPF (photoreactivation) in the UV-stressed layers could indicate that the zone itself works as a UV shield. There is a remarkable density of sequences associated with photoreceptors in the first two layers. Also, genetic evidence of photosynthesis split in eukaryotic (layer 1) and prokaryotic (layer 2). Photoheterotrophic bacteria, aerobic photoautotrophic bacteria, and anaerobic photoautotrophic bacteria coexist by selectively absorbing different parts of the light spectrum (blue, red, and IR respectively) at different positions of the mat. Genes for oxygen, nitrogen, and sulfur metabolism account for the microelectrode chemical data and pigment measurements performed in previous publications. We also provide here an explanation for the vertical microbial mobility within the SST described previously. Finally, our study points to SST as ideal modern analogues of ancient ST.
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Altitude , Cianobactérias , Cianobactérias/genética , Cianobactérias/metabolismo , Fotossíntese , Luz , Lagos/microbiologiaRESUMO
Introducción: Infecciones moderadas, severas y/o profundas del territorio maxilofacial (ITM) constituyen un desafío de gran relevancia en los centros hospitalarios de alta complejidad. Objetivo: Actualizar esta epidemiología de resolución quirúrgica bajo anestesia general, en pabellón central tratado en el Hospital de Urgencia Asistencia Pública (HUAP) durante el período comprendido entre diciembre de 2014 a diciembre de 2019 y compararla con la realidad de otros centros hospitalarios de alta complejidad en Chile y en el extranjero. Materiales y Método: Estudio retrospectivo que analizó los protocolos operatorios de los pacientes intervenidos quirúrgicamente por ITM, en pabellón central, bajo anestesia general, en un período de 60 meses. Las variables analizadas fueron edad, género, espacio anatómico comprometido y presentación clínica. Resultados: Se realizaron 291 procedimientos quirúrgicos, para 452 infecciones. La edad promedio de los pacientes fue 38 años, con predominio del sexo masculino (57,3%); el rango de edad más afectado fue entre los 30-39 años (26,1%); el espacio submandibular fue el más comprometido (29,5%). Discusión: Los resultados expuestos concuerdan con estudios a nivel nacional e internacional. Conclusión: Resulta necesario continuar la investigación epidemiológica para establecer políticas de prevención y tratamiento eficientes en relación a cada servicio y en conjunto a nivel de salud pública.
Introduction: Moderate, severe or deep infections of the maxillofacial territory (IMT) are a relevant problem in hospital centres. Objective: To demonstrate and update the epidemiology of IMT´s with surgical resolution under general Anesthesia in mayor operating rooms at the Public Assistance Emergency Hospital (HUAP) during the period from December 2014 to December 2019, and to compare it with the epidemiological reality of other hospital centres in Chile and abroad. Materials and Method: A retrospective study analyzed the operative protocols of patients for 60 months. Studied variables were age, sex, compromised anatomical space and clinical presentation. Results: 291 surgical procedures were performed to resolve 452 infections. The average age of the operated patients was 38 years, with a slight predominance of the male gender (57.3%); the most affected age range was between 30 and 39 years (26.1%); the submandibular space was the most compromised (29.5%). Discussion: The exposed results agree with studies carried out at national and international level. Conclusion: It is necessary to continue an epidemiological investigation in order to establish efficient prevention and treatment policies for each service and altogether to unify public health statistics.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Assistência Pública , Cirurgia Bucal , Epidemiologia , Serviços Médicos de EmergênciaRESUMO
Since their discovery, arylamine N-acetyltransferases 1 and 2 (NAT1 and NAT2, respectively) have been associated with the metabolism of xenobiotics. NAT2 is the main factor in the therapeutic success of tuberculosis treatment due to its role in the biotransformation of isoniazid. However, researchers have started to investigate the possible participation of NAT1 and NAT2 (NATs) in carcinogenesis, although the mechanisms have not been elucidated fully. NATs enzymatic activity is essential in some types of cancer, such as breast cancer and acute lymphoblastic leukemia. Whether NAT1 and/or NAT2 participate in insulin resistance level in diabetes mellitus or in the immune system remains to be explored. Therefore, it is clear that its role in cell physiology has more implications than just metabolizing compounds.
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Arilamina N-Acetiltransferase , Acetiltransferases , Arilamina N-Acetiltransferase/genética , Arilamina N-Acetiltransferase/metabolismo , Sistema Imunitário/metabolismoRESUMO
In Alzheimer´s disease (AD) there is a reduction in hippocampal neurogenesis that has been associated to cognitive deficits. Previously we showed that Andrographolide (ANDRO), the main bioactive component of Andrographis paniculate, induces proliferation in the hippocampus of the APPswe/PSEN1ΔE9 (APP/PS1) mouse model of AD as assessed by staining with the mitotic marker Ki67. Here, we further characterized the effect of ANDRO on hippocampal neurogenesis in APP/PS1 mice and evaluated the contribution of this process to the cognitive effect of ANDRO. Treatment of 8-month-old APP/PS1 mice with ANDRO for 4 weeks increased proliferation in the dentate gyrus as evaluated by BrdU incorporation. Although ANDRO had no effect on neuronal differentiation of newborn cells, it strongly increased neural progenitors, neuroblasts and newborn immature neurons, cell populations that were decreased in APP/PS1 mice compared to age-matched wild-type mice. ANDRO had no effect on migration or in total dendritic length, arborization and orientation of immature neurons, suggesting no effects on early morphological development of newborn neurons. Finally, ANDRO treatment improved the performance of APP/PS1 mice in the object location memory task. This effect was not completely prevented by co-treatment with the anti-mitotic drug TMZ, suggesting that other effects of ANDRO in addition to the increase in neurogenesis might underlie the observed cognitive improvement. Altogether, our data indicate that in APP/PS1 mice ANDRO stimulates neurogenesis in the hippocampus by inducing proliferation of neural precursor cells and improves spatial memory performance.