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Marseilleviruses (MsV) are a group of viruses that compose the Marseilleviridae family within the Nucleocytoviricota phylum. They have been found in different samples, mainly in freshwater. MsV are classically organized into five phylogenetic lineages (A/B/C/D/E), but the current taxonomy does not fully represent all the diversity of the MsV lineages. Here, we describe a novel strain isolated from a Brazilian saltwater sample named Marseillevirus cajuinensis. Based on genomics and phylogenetic analyses, M. cajuinensis exhibits a 380,653-bp genome that encodes 515 open reading frames. Additionally, M. cajuinensis encodes a transfer RNA, a feature that is rarely described for Marseilleviridae. Phylogeny suggests that M. cajuinensis forms a divergent branch within the MsV lineage A. Furthermore, our analysis suggests that the common ancestor for the five classical lineages of MsV diversified into three major groups. The organization of MsV into three main groups is reinforced by a comprehensive analysis of clusters of orthologous groups, sequence identities, and evolutionary distances considering several MsV isolates. Taken together, our results highlight the importance of discovering new viruses to expand the knowledge about known viruses that belong to the same lineages or families. This work proposes a new perspective on the Marseilleviridae lineages organization that could be helpful to a future update in the taxonomy of the Marseilleviridae family. IMPORTANCE: Marseilleviridae is a family of viruses whose members were mostly isolated from freshwater samples. In this work, we describe the first Marseillevirus isolated from saltwater samples, which we called Marseillevirus cajuinensis. Most of M. cajuinensis genomic features are comparable to other Marseilleviridae members, such as its high number of unknown proteins. On the other hand, M. cajuinensis encodes a transfer RNA, which is a gene category involved in protein translation that is rarely described in this viral family. Additionally, our phylogenetic analyses suggested the existence of, at least, three major Marseilleviridae groups. These observations provide a new perspective on Marseilleviridae lineages organization, which will be valuable in future updates to the taxonomy of the family since the current official classification does not capture all the Marseilleviridae known diversity.
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Genoma Viral , Vírus , Brasil , Evolução Molecular , Genômica/métodos , Fases de Leitura Aberta , Filogenia , RNA Viral/genética , Vírus/classificação , Vírus/genéticaRESUMO
Among the most intriguing structural features in the known virosphere are mimivirus surface fibrils, proteinaceous filaments approximately 150 nm long, covering the mimivirus capsid surface. Fibrils are important to promote particle adhesion to host cells, triggering phagocytosis and cell infection. However, although mimiviruses are one of the most abundant viral entities in a plethora of biomes worldwide, there has been no comparative analysis on fibril organization and abundance among distinct mimivirus isolates. Here, we describe the isolation and characterization of Megavirus caiporensis, a novel lineage C mimivirus with surface fibrils organized as "clumps." This intriguing feature led us to expand our analyses to other mimivirus isolates. By employing a combined approach including electron microscopy, image processing, genomic sequencing, and viral prospection, we obtained evidence of at least three main patterns of surface fibrils that can be found in mimiviruses: (i) isolates containing particles with abundant fibrils, distributed homogeneously on the capsid surface; (ii) isolates with particles almost fibrilless; and (iii) isolates with particles containing fibrils in abundance, but organized as clumps, as observed in Megavirus caiporensis. A total of 15 mimivirus isolates were analyzed by microscopy, and their DNA polymerase subunit B genes were sequenced for phylogenetic analysis. We observed a unique match between evolutionarily-related viruses and their fibril profiles. Biological assays suggested that patterns of fibrils can influence viral entry in host cells. Our data contribute to the knowledge of mimivirus fibril organization and abundance, as well as raising questions on the evolution of those intriguing structures. IMPORTANCE Mimivirus fibrils are intriguing structures that have drawn attention since their discovery. Although still under investigation, the function of fibrils may be related to host cell adhesion. In this work, we isolated and characterized a new mimivirus, called Megavirus caiporensis, and we showed that mimivirus isolates can exhibit at least three different patterns related to fibril organization and abundance. In our study, evolutionarily-related viruses presented similar fibril profiles, and such fibrils may affect how those viruses trigger phagocytosis in amoebas. These data shed light on aspects of mimivirus particle morphology, virus-host interactions, and their evolution.
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Mimiviridae , Proteínas do Capsídeo/genética , Genoma Viral , Microscopia Eletrônica , Mimiviridae/genética , Mimiviridae/ultraestrutura , FilogeniaRESUMO
IMPORTANCE: Giant viruses are noteworthy not only due to their enormous particles but also because of their gigantic genomes. In this context, a fundamental question has persisted: how did these genomes evolve? Here we present the discovery of cedratvirus pambiensis, featuring the largest genome ever described for a cedratvirus. Our data suggest that the larger size of the genome can be attributed to an unprecedented number of duplicated genes. Further investigation of this phenomenon in other viruses has illuminated gene duplication as a key evolutionary mechanism driving genome expansion in diverse giant viruses. Although gene duplication has been described as a recurrent event in cellular organisms, our data highlights its potential as a pivotal event in the evolution of gigantic viral genomes.
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Evolução Molecular , Duplicação Gênica , Vírus Gigantes , Genoma Viral , Vírus Gigantes/genética , FilogeniaRESUMO
The discovery of mimivirus in 2003 prompted the search for novel giant viruses worldwide. Despite increasing interest, the diversity and distribution of giant viruses is barely known. Here, we present data from a 2012-2022 study aimed at prospecting for amoebal viruses in water, soil, mud, and sewage samples across Brazilian biomes, using Acanthamoeba castellanii for isolation. A total of 881 aliquots from 187 samples covering terrestrial and marine Brazilian biomes were processed. Electron microscopy and PCR were used to identify the obtained isolates. Sixty-seven amoebal viruses were isolated, including mimiviruses, marseilleviruses, pandoraviruses, cedratviruses, and yaraviruses. Viruses were isolated from all tested sample types and almost all biomes. In comparison to other similar studies, our work isolated a substantial number of Marseillevirus and cedratvirus representatives. Taken together, our results used a combination of isolation techniques with microscopy, PCR, and sequencing and put highlight on richness of giant virus present in different terrestrial and marine Brazilian biomes.
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Vírus Gigantes , Brasil , Vírus Gigantes/isolamento & purificação , Vírus Gigantes/genética , Vírus Gigantes/classificação , Vírus Gigantes/ultraestrutura , Filogenia , Reação em Cadeia da Polimerase , Acanthamoeba castellanii/virologia , Acanthamoeba castellanii/isolamento & purificação , Microbiologia do Solo , Esgotos/virologia , Análise de Sequência de DNA , Água do Mar/virologia , Microbiologia da ÁguaRESUMO
Rigorous evidence reviews must follow specific guidelines designed to improve transparency, reproducibility, and to minimize biases to which traditional reviews are susceptible. While evidence synthesis methods, such as systematic reviews and maps, have been used in several research fields, the majority of reviews published in the realm of chemical engineering are nonsystematic. In this study, we incorporated principles of systematic mapping to conduct a literature review covering research on the synthesis of sugar fatty acid esters (SFAE) with Candida antarctica lipase B (CALB). Our results showed that the simple monosaccharides were the most cited sugars among studies we conducted. The direct use of renewable raw materials and frequently available resources to produce alternative sugar esters (SE) was scarcely reported in our data set. We found that free fatty acids (FFA) were the most commonly cited acyl donors amongst all publications, with lauric, oleic, and palmitic acids accounting for â¼43% of the occurrences. Tertiary alcohols (ter-butyl alcohol (T-but) and 2-methyl-2-butanol (2M2B)) and ionic liquids were the most used solvents to synthesize SE. The co-occurence analysis of keywords involving solvent terms showed that most of the papers evaluated different solvents as reaction media (mostly in the form of a bisolvent system), also investigating the impact of their choice on sugar ester productivities. Given the potential of reviews informing us of research decisions, this article reveals trends and spaces across CALB-catalyzed SE synthesis research, in addition to introducing a new methodological perspective for developing reviews in the field of chemical engineering.
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Ésteres , Proteínas Fúngicas , Lipase , Açúcares , Basidiomycota , Catálise , Esterificação , Proteínas Fúngicas/metabolismo , Lipase/metabolismo , Reprodutibilidade dos Testes , Revisões Sistemáticas como AssuntoRESUMO
INTRODUCTION: The pathogen-associated molecular patterns and the danger-associated molecular patterns are possibly responsible for the activation of the inflammatory process in endometriosis through the activation of toll-like receptors (TLRs). OBJECTIVE: The aim of this systematic review was to critically analyze the findings of published articles on TLRs in endometriosis. METHODS: The keywords used were "endometriosis" and "toll-like" and the search was performed in Pubmed, Scielo and Lilacs databases. This study followed the PRISMA guidelines and the risk of bias of articles was conducted by Newcastle-Ottawa scale (NOS). RESULTS: Overall, the studies analyzed in this review point toward an increased expression of TLRs two, four and nine in women with endometriosis. Among all TLRs, TLR4 was the most cited receptor. CONCLUSION: Despite the evidence demonstrating elevated TLR levels in endometriosis, the relationship with the disease is still unclear and needs to be clarified in further studies about innate immune response.
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Endometriose/metabolismo , Receptores Toll-Like/metabolismo , Feminino , Humanos , Imunidade InataRESUMO
Giant viruses are complex members of the virosphere, exhibiting outstanding structural and genomic features. Among these viruses, the pandoraviruses are some of the most intriguing members, exhibiting giant particles and genomes presenting at up to 2.5 Mb, with many genes having no known function. In this work, we analyzed, by virological and microscopic methods, the replication cycle steps of three new pandoravirus isolates from samples collected in different regions of Brazil. Our data indicate that all analyzed pandoravirus isolates can deeply modify the Acanthamoeba cytoplasmic environment, recruiting mitochondria and membranes into and around the electron-lucent viral factories. We also observed that the viral factories start forming before the complete degradation of the cellular nucleus. Various patterns of pandoravirus particle morphogenesis were observed, and the assembly of the particles seemed to be started either by the apex or by the opposite side. On the basis of the counting of viral particles during the infection time course, we observed that pandoravirus particles could undergo exocytosis after their morphogenesis in a process that involved intense recruitment of membranes that wrapped the just-formed particles. The treatment of infected cells with brefeldin affected particle exocytosis in two of the three analyzed strains, indicating biological variability among isolates. Despite such particle exocytosis, the lysis of host cells also contributed to viral release. This work reinforces knowledge of and reveals important steps in the replication cycle of pandoraviruses.IMPORTANCE The emerging Pandoraviridae family is composed of some of the most complex viruses known to date. Only a few pandoravirus isolates have been described until now, and many aspects of their life cycle remain to be elucidated. A comprehensive description of the replication cycle is pivotal to a better understanding of the biology of the virus. For this report, we describe new pandoraviruses and used different methods to better characterize the steps of the replication cycle of this new group of viruses. Our results provide new information about the diversity and biology of these giant viruses.
Assuntos
Acanthamoeba castellanii/virologia , Vírus de DNA/genética , Liberação de Vírus/fisiologia , Replicação Viral/fisiologia , Brasil , Vírus de DNA/isolamento & purificação , Genoma Viral/genética , Vírus Gigantes/genética , Vírus Gigantes/isolamento & purificaçãoRESUMO
There is increasing interest in the potential of natural compounds to treat diseases, such as endometriosis, a gynecological disorder that affects 10-15% of women of reproductive age, and it is related to severe pelvic pain and infertility. We have evaluated the in vitro effects of rutin and the aqueous bark, roots, and leaf extracts (ABE, ARE, and ALE, respectively) and isolated components of Uncaria guianensis on stromal cells from eutopic endometrium and lesions of patients with endometriosis. Two- and three-dimensional cultures were used to assess the cell death and production of reactive oxygen species (ROS), cytokines and growth factors of cells following exposure to these natural products. The applied treatments did not reduce cellular viability, but ROS production did increase. In addition, significant increases in the levels of interleukin (IL)-15, IL-17A, IL-4, IL-6, tumor necrosis factor-α, and vascular endothelium growth factor were observed when 2D-cells from endometrium of patients with endometriosis were treated with ABE, while exposure to ALE induced significant increases in epidermal growth factor in lesion cells.
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Endometriose/patologia , Extratos Vegetais/farmacologia , Rutina/farmacologia , Uncaria/química , Alcaloides/química , Biomarcadores/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Feminino , Fluorescência , Humanos , Mediadores da Inflamação/metabolismo , Fenóis/química , Espécies Reativas de Oxigênio/metabolismo , Esferoides Celulares/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismoRESUMO
Styphnolobium japonicum (L.) Schott is a popular Asian tree widely used in traditional medicine. The current study explored the potential stress resistance and antioxidant activities of its fruits. Phytochemical profiling of the hydroalcoholic fruit extract was done via high performance liquid chromatography-photodiode array-electrospray ionization-mass/mass (HPLC-PDA-ESI-MS/MS). Twenty four phenolic constituents were tentatively identified in the extract. The Caenorhabditis elegans (C. elegans) nematode model in addition to trimethyltin (TMT)-induced neurotoxicity mouse model were used for in vivo evaluation of its antioxidant properties. The ability of the extract to enhance stress resistance was manifested through increasing survival rate by 44.7% and decreasing basal reactive oxygen species (ROS) levels by 72.3% in C. elegans. In addition, the extract increased the levels of the stress response enzyme superoxide dismutase-3 (Sod-3) by 55.5% and decreased the expression of heat shock protein-16.2 (Hsp-16.2) in nematodes, which had been challenged by juglone, by 21%. Using a mouse model, the extract significantly decreased the expression of the oxidative stress marker malondialdehyde (MDA). Furthermore, an elevation in the levels of the antioxidant marker glutathione (GSH), SOD and heme oxygenase-1 (HO-1) enzymes were observed. Our findings imply that Styphnolobium japonicum has the potential to be used in future studies focusing on diseases associated with oxidative stress.
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Antioxidantes/farmacologia , Fabaceae/química , Frutas/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Animais , Antioxidantes/química , Biomarcadores , Caenorhabditis elegans , Glutationa/metabolismo , Camundongos , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Análise Espectral , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
Uncaria tomentosa (Rubiaceae) has a recognized therapeutic potential against various diseases associated with oxidative stress. The aim of this research was to evaluate the antioxidant potential of an aqueous leaf extract (ALE) from U. tomentosa, and its major alkaloids mitraphylline and isomitraphylline. The antioxidant activity of ALE was investigated in vitro using standard assays (DPPH, ABTS and FRAP), while the in vivo activity and mode of action were studied using Caenorhabditis elegans as a model organism. The purified alkaloids did not exhibit antioxidant effects in vivo. ALE reduced the accumulation of reactive oxygen species (ROS) in wild-type worms, and was able to rescue the worms from a lethal dose of the pro-oxidant juglone. The ALE treatment led to a decreased expression of the oxidative stress response related genes sod-3, gst-4, and hsp-16.2. The treatment of mutant worms lacking the DAF-16 transcription factor with ALE resulted in a significant reduction of ROS levels. Contrarily, the extract had a pro-oxidant effect in the worms lacking the SKN-1 transcription factor. Our results suggest that the antioxidant activity of ALE in C. elegans is independent of its alkaloid content, and that SKN-1 is required for ALE-mediated stress resistance.
Assuntos
Antioxidantes/química , Unha-de-Gato/química , Alcaloides Indólicos/farmacologia , Oxindóis/farmacologia , Alcaloides/química , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Oxindóis/química , Extratos Vegetais/química , Folhas de Planta/química , Espécies Reativas de Oxigênio/metabolismoRESUMO
Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 µg/100g; subsequent doses: 0.125µg/100g, intramuscular, 30days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20µg/dL) were used. Lead blood levels of treated rats attained 21.7±2.38µg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension.
Assuntos
Ciclo-Oxigenase 2/metabolismo , Chumbo/toxicidade , Sistema de Sinalização das MAP Quinases/fisiologia , Músculo Liso Vascular/metabolismo , Estresse Oxidativo/fisiologia , Vasoconstrição/fisiologia , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Chumbo/administração & dosagem , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Vasoconstrição/efeitos dos fármacosRESUMO
The aim of this study was to investigate the in vitro and in vivo efficacy and the tissue reaction of an antibiofilm coating composed of xylitol, triclosan, and polyhexamethylene biguanide. The antimicrobial activity was analyzed by a turbidimetric method. Scanning electron microscopy was used to evaluate the antiadherent property of central venous catheter (CVC) fragments impregnated with an antibiofilm coating (I-CVC) in comparison with noncoated CVC (NC-CVC) fragments. Two in vivo assays using subcutaneous implantation of NC-CVC and I-CVC fragments in the dorsal area of rats were performed. The first assay comprised hematological and microbiological analysis. The second assay evaluated tissue response by examining the inflammatory reactions after 7 and 21 days. The formulation displayed antimicrobial activity against all tested strains. A biofilm disaggregation with significant reduction of microorganism's adherence in I-CVC fragments was observed. In vivo antiadherence results demonstrated a reduction of early biofilm formation of Staphylococcus aureus ATCC 25923, mainly in an external surface of the I-CVC, in comparison with the NC-CVC. All animals displayed negative hemoculture. No significant tissue reaction was observed, indicating that the antibiofilm formulation could be considered biocompatible. The use of I-CVC could decrease the probability of development of localized or systemic infections.
Assuntos
Anti-Infecciosos/farmacologia , Materiais Biocompatíveis/farmacologia , Biofilmes , Cateteres Venosos Centrais , Animais , Aderência Bacteriana , Biofilmes/crescimento & desenvolvimento , Feminino , Ratos , Ratos Wistar , Staphylococcus aureus/efeitos dos fármacosRESUMO
Type-2 diabetes mellitus (DM) is a highly prevalent disease with significant morbidity and mortality around the world. However, there is no universally effective treatment, because response to different treatment regimens can vary widely among patients. In this study, we aimed to investigate whether the use of the powdered dried leaves of Eugenia punicifolia (Kunth) DC. (Myrtaceae) is effective as an adjuvant to the treatment of patients with type-2 DM. Fifteen patients were enrolled in a pilot, non-controlled study, and received E. punicifolia for 3 months. After treatment, we observed a significant decrease in glycosylated hemoglobin, basal insulin, thyroid-stimulating hormone, C-reactive protein, and both systolic and diastolic blood pressure. There were no changes in fasting and postprandial glycemia. The compounds myricetin-3-O-rhamnoside, quercetin-3-O-galactoside, quercetin-3-O-xyloside, quercetin-3-O-rhamnoside, kaempferol-3-O-rhamnoside, phytol, gallic acid, and trans-caryophyllene present in the powdered dried leaves of E. punicifolia may be responsible for the therapeutic effect. In conclusion, the powdered leaves of E. punicifolia are promising as an adjuvant in the treatment of type-2 DM and deserve further investigation.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Fitoterapia , Syzygium/química , Idoso , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Folhas de Planta/químicaRESUMO
Objective: To evaluate the association between clinical and imaging with surgical and pathological findings in patients with suspected neuroendocrine tumor of appendix and/or appendix endometriosis. Methods: Retrospective descriptive study conducted at the Teaching and Research Institute of Hospital Israelita Albert Einstein, in which medical records and databases of patients with suspected neuroendocrine tumor of appendix and/or endometriosis of appendix were analyzed by imaging. Results: Twenty-eight patients were included, all of which had some type of appendix alteration on the ultrasound examination. The pathological outcome of the appendix found 25 (89.3%) lesions compatible with endometriosis and three (10.7%) neuroendocrine tumors. The clinical findings of imaging and surgery were compared with the result of pathological anatomy by means of relative frequency. Conclusion: It was possible to observe a higher prevalence of appendix endometriosis when the patient presented more intense pain symptoms. The image observed on ultrasound obtained a high positive predictive value for appendicular endometriosis.
Assuntos
Apêndice , Endometriose , Tumores Neuroendócrinos , Ultrassonografia , Humanos , Feminino , Endometriose/diagnóstico por imagem , Estudos Retrospectivos , Adulto , Tumores Neuroendócrinos/diagnóstico por imagem , Apêndice/diagnóstico por imagem , Apêndice/patologia , Pessoa de Meia-Idade , Diagnóstico Diferencial , Adulto Jovem , Neoplasias do Apêndice/diagnóstico por imagem , Neoplasias do Apêndice/patologia , Doenças do Ceco/diagnóstico por imagemRESUMO
Bacterial ubiquitous Toxin-Antitoxin (TA) systems are considered to be important survival mechanisms during stress conditions. In regular environmental conditions, the antitoxin blocks the toxin, whereas during imbalanced conditions, the antitoxin concentration decreases, exposing the bacteria cell to a range of toxic events. The most evident consequence of this disequilibrium is cell growth arrest, which is the reason why TAs are generally described as active in the function of bacterial growth kinetics. Virulence-associated proteins B and C (VapBC) are a family of type II TA system, in which VapC is predicted to display the toxic ribonuclease activity while VapB counteracts this activity. Previously, using in silico data, we designated four VapBC TA modules in Leptospira interrogans serovar Copenhageni, the main etiological agent of human leptospirosis in Brazil. The present study aimed to obtain the proteins and functionally characterize the VapBC-1 module. The expression of the toxin gene vapC in E. coli did not decrease the cell growth rate in broth culture, as was expected to happen within active TA modules. However, interestingly, when the expression of the toxin was compared to that of the complexed toxin and antitoxin, cell viability was strongly affected, with a decrease of three orders of magnitude in colony forming unity (CFU). The assumption of the affinity between the toxin and the antitoxin was confirmed in vivo through the observation of their co-purification from cultivation of E. coli co-expressing vapB-vapC genes. RNAse activity assays showed that VapC-1 cleaves MS2 RNA and ribosomal RNA from L. interrogans. Our results indicate that the VapBC-1 module is a potentially functional TA system acting on targets that involve specific functions. It is very important to emphasize that the common attribution of the functionality of TA modules cannot be defined based merely on their ability to inhibit bacterial growth in a liquid medium.
RESUMO
Context: Congenital hypopituitarism is a genetically heterogeneous condition. Whole exome sequencing (WES) is a promising approach for molecular diagnosis of patients with this condition. Objectives: The aim of this study is to conduct WES in a patient with congenital hypopituitarism born to consanguineous parents, CDH2 screening in a cohort of patients with congenital hypopituitarism, and functional testing of a novel CDH2 variant. Design: Genomic DNA from a proband and her consanguineous parents was analyzed by WES. Copy number variants were evaluated. The genetic variants were filtered for population frequency (ExAC, 1000 genomes, gnomAD, and ABraOM), in silico prediction of pathogenicity, and gene expression in the pituitary and/or hypothalamus. Genomic DNA from 145 patients was screened for CDH2 by Sanger sequencing. Results: One female patient with deficiencies in growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone and ectopic posterior pituitary gland contained a rare homozygous c.865G>A (p.Val289Ile) variant in CDH2. To determine whether the p.Val289Ile variant in CDH2 affects cell adhesion properties, we stably transfected L1 fibroblast lines, labeled the cells with lipophilic dyes, and quantified aggregation. Large aggregates formed in cells expressing wildtype CDH2, but aggregation was impaired in cells transfected with variant CDH2 or non-transfected. Conclusion: A homozygous CDH2 allelic variant was found in one hypopituitarism patient, and the variant impaired cell aggregation function in vitro. No disease-causing variants were found in 145 other patients screened for CDH2 variants. Thus, CDH2 is a candidate gene for hypopituitarism that needs to be tested in different populations. Significance statement: A female patient with hypopituitarism was born from consanguineous parents and had a homozygous, likely pathogenic, CDH2 variant that impairs cell aggregation in vitro. No other likely pathogenic variants in CDH2 were identified in 145 hypopituitarism patients.
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Seven day exposure to a low concentration of lead acetate increases nitric oxide bioavailability suggesting a putative role of K+ channels affecting vascular reactivity. This could be an adaptive mechanism at the initial stages of toxicity from lead exposure due to oxidative stress. We evaluated whether lead alters the participation of K+ channels and Na+/K+)-ATPase (NKA) on vascular function. Wistar rats were treated with lead (1st dose 4 µg/100 g, subsequent doses 0.05 µg/100g, im, 7 days) or vehicle. Lead treatment reduced the contractile response of aortic rings to phenylephrine (PHE) without changing the vasodilator response to acetylcholine (ACh) or sodium nitroprusside (SNP). Furthermore, this treatment increased basal O2â» production, and apocynin (0.3 µM), superoxide dismutase (150 U/mL) and catalase (1000 U/mL) reduced the response to PHE only in the treated group. Lead also increased aortic functional NKA activity evaluated by K+-induced relaxation curves. Ouabain (100 µM) plus L-NAME (100 µM), aminoguanidine (50 µM) or tetraethylammonium (TEA, 2 mM) reduced the K+-induced relaxation only in lead-treated rats. When aortic rings were precontracted with KCl (60 mM/L) or preincubated with TEA (2 mM), 4-aminopyridine (4-AP, 5 mM), iberiotoxin (IbTX, 30 nM), apamin (0.5 µM) or charybdotoxin (0.1 µM), the ACh-induced relaxation was more reduced in the lead-treated rats. Additionally, 4-AP and IbTX reduced the relaxation elicited by SNP more in the lead-treated rats. Results suggest that lead treatment promoted NKA and K+ channels activation and these effects might contribute to the preservation of aortic endothelial function against oxidative stress.
Assuntos
Aorta/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Compostos Organometálicos/toxicidade , Canais de Potássio/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos , Acetilcolina/farmacologia , Animais , Aorta/patologia , Endotélio Vascular/patologia , Masculino , Nitroprussiato/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Oxigênio/metabolismo , Fenilefrina/farmacologia , Canais de Potássio/metabolismo , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismo , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced.
Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/patologia , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/patologia , Mercúrio/toxicidade , Animais , Transporte Biológico/efeitos dos fármacos , Exposição Ambiental , Humanos , Legislação como AssuntoRESUMO
BACKGROUND: The aging population is growing faster than any other age group worldwide. Associated with aging, the prevalence of overweight and obesity is a potential risk factor for the development and aggravation of numerous pathologies. A genetic factor often associated with obesity is the fat mass and obesity-associated (FTO) (rs9939609) gene polymorphism, which has been extensively investigated in children, young, and adults. However, few studies have been carried out on the older population. This review aimed to verify the influence of the FTO (rs9939609) gene polymorphism on the body composition of the older population. METHODS: We conducted a systematic review and meta-analysis on PubMed, Scielo, and LILACS databases. Statistical analysis for meta-analysis was performed using mean values of Body Mass Index (BMI) and standard deviations. RESULTS: The results did not show significant differences between FTO genotypes and BMI values (-0.32, 95% CI -0.45 to -0.19, I2 = 0%, p = 0.52). However, 59% of the studies identified some influence on body composition, obesity, or comorbidities. CONCLUSION: Few publications verify FTO polymorphism effects on specific groups of the older population, suggesting a reduction in the influence of this gene on the BMI with advancing age. However, we believe that more controlled studies in older populations should be performed.
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato , Predisposição Genética para Doença , Idoso , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Composição Corporal/genética , Índice de Massa Corporal , Genótipo , Humanos , Obesidade/epidemiologia , Obesidade/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
INTRODUCTION: Endometriosis is an inflammatory disease that affects women of reproductive age, causing pain and the possibility of infertility. Endometriosis was associated to low life quality and research shows the impact of endometriosis in several areas of life, justifying how these patients are more likely to develop depression, anxiety, and stress. OBJECTIVE: The aim of the present systematic review was to explore the field of psychology in endometriosis, identifying studies that used the cognitive behavioral therapy technique as a treatment for endometriosis and chronic pelvic pain. METHODS: The keywords used were Endometriosis and Behavioral Therapy; Behavioral Disciplines and Activities; Cognitive Behavioral Therapy; Mental Health; Psychological Techniques; Psychology; Psychotherapy; Mental Health Services; and the search was performed in the following databases: PubMed/Medline, Scielo, Lilacs, and Capes. The study followed the PRISMA guidelines and all studies whose intervention strategy used was related to cognitive-behavioral therapy were considered. RESULTS: Of the 129 articles found, only 5 were selected, and it was possible to identify that the psychological intervention whose approach brought cognitive-behavioral therapy techniques promoted a decrease in the sensation of pain, improvements in the scores of depression and stress, and significant changes in aspects of quality of life such as vitality, physical and social functioning, emotional well-being, control, and autonomy. CONCLUSION: Cognitive-behavioral therapy can be very promising to take care of the emotional side of those who have endometriosis However, the present systematic review highlights the need to develop more structured studies with consistent, clear and replicable methods to reach a psychological intervention protocol for patients who live with this gynecological-physical-emotional condition.
INTRODUçãO: A endometriose é uma doença inflamatória que afeta mulheres em idade reprodutiva, causando dor e possibilidade de infertilidade. A endometriose foi associada a baixa qualidade de vida e pesquisas mostram o impacto da endometriose em diversas áreas da vida, justificando como tais pacientes têm maior probabilidade de desenvolver depressão, ansiedade e estresse. OBJETIVO: O objetivo da presente revisão sistemática foi explorar o campo da psicologia na endometriose, identificando estudos que usaram a técnica da terapia cognitiva comportamental como tratamento da endometriose e da dor pélvica crônica. MéTODOS: As palavras chaves utilizadas foram Endometriose AND Terapia comportamental; Disciplinas e atividades comportamentais; Terapia cognitiva comportamental; Saúde mental; Técnicas psicológicas; Psicologia; Psicoterapia; Serviços de saúde mental, e a busca foi realizada nos bancos de dados PubMed / Medline, SCIELO, LILACS e CAPES. O estudo seguiu as diretrizes dos Principais Itens para Relatar Revisões Sistemáticas e Metanálises (PRISMA, na sigla em inglês) e foram considerados todos os estudos cuja estratégia de intervenção utilizada estava relacionada à terapia cognitivo-comportamental. RESULTADOS: Dos 129 artigos encontrados, somente 5 foram selecionados, e foi possível identificar que a intervenção psicológica cuja abordagem trouxe técnicas da terapia cognitivo-comportamental promoveu diminuição na sensação de dor, melhora nos escores de depressão e estresse e mudanças significativas em aspectos da qualidade de vida como vitalidade, funcionalidade física e social, bem-estar emocional, controle e autonomia. CONCLUSãO: A terapia cognitivo-comportamental pode ser muito promissora para o tratamento psicológico/emocional de quem tem endometriose. No entanto, a presente revisão sistemática destaca a necessidade de desenvolver estudos mais estruturados com métodos consistentes, claros e replicáveis para se chegar a um protocolo de intervenção psicológica para pacientes que convivem com esse quadro ginecológico-físico-emocional.