RESUMO
Aspergillus fumigatus represents a public health problem due to the high mortality rate in immunosuppressed patients and the emergence of antifungal-resistant isolates. Protein acetylation is a crucial post-translational modification that controls gene expression and biological processes. The strategic manipulation of enzymes involved in protein acetylation has emerged as a promising therapeutic approach for addressing fungal infections. Sirtuins, NAD+-dependent lysine deacetylases, regulate protein acetylation and gene expression in eukaryotes. However, their role in the human pathogenic fungus A. fumigatus remains unclear. This study constructs six single knockout strains of A. fumigatus and a strain lacking all predicted sirtuins (SIRTKO). The mutant strains are viable under laboratory conditions, indicating that sirtuins are not essential genes. Phenotypic assays suggest sirtuins' involvement in cell wall integrity, secondary metabolite production, thermotolerance, and virulence. Deletion of sirE attenuates virulence in murine and Galleria mellonella infection models. The absence of SirE alters the acetylation status of proteins, including histones and non-histones, and triggers significant changes in the expression of genes associated with secondary metabolism, cell wall biosynthesis, and virulence factors. These findings encourage testing sirtuin inhibitors as potential therapeutic strategies to combat A. fumigatus infections or in combination therapy with available antifungals.
Assuntos
Aspergilose , Aspergillus fumigatus , Sirtuínas , Aspergillus fumigatus/patogenicidade , Aspergillus fumigatus/genética , Aspergillus fumigatus/enzimologia , Sirtuínas/genética , Sirtuínas/metabolismo , Virulência , Animais , Camundongos , Aspergilose/microbiologia , Aspergilose/tratamento farmacológico , Acetilação , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Mariposas/microbiologiaRESUMO
OBJECTIVE: To evaluate the association between headache, myofascial temporomandibular disorder (TMD), and awake bruxism (AB). BACKGROUND: Bruxism seems to act as a risk factor for TMD and its associated comorbidities, such as headaches. METHODS: In total, 406 medical records of individuals who sought care at a university dental clinic were screened. The Research Diagnostic Criteria for Temporomandibular Disorders was used to assess and diagnose TMD, as well as to obtain self-reports of AB and headache. RESULTS: The sample consisted of 307 medical records. About 72.5% (221/305) of the sample reported having headaches, and 67.4% (180/267) and 68.4% (210/307) were diagnosed with AB and TMD, respectively. Individuals who reported having AB (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.09-4.7) and who were diagnosed with myofascial TMD (OR, 2.53; 95% CI, 1.15-5.5) were more likely to have had headaches in the past 6 months when compared with patients without myofascial TMD and bruxism. Also, individuals who self-reported headache were 2.27 times (95% CI, 1.09-4.7) more likely to have AB and 2.45 times (95% CI, 1.13-5.34) more likely to have myofascial pain than individuals without headaches. CONCLUSIONS: Individuals with myofascial TMD, headaches, or AB were more likely to have at least one of the other conditions.
Assuntos
Bruxismo , Transtornos da Articulação Temporomandibular , Bruxismo/complicações , Bruxismo/epidemiologia , Estudos Transversais , Cefaleia/complicações , Cefaleia/epidemiologia , Humanos , Transtornos da Articulação Temporomandibular/complicações , Transtornos da Articulação Temporomandibular/epidemiologia , VigíliaRESUMO
BACKGROUND: Neurocysticercosis (NCC) is a neglected tropical disease and its diagnosis is still a challenge due to non-specific manifestations. Neuroimaging techniques are used in the diagnosis of NCC, however, due to the high cost of these methods and the advantages presented in the use of immunological tests, such as ease of performance and satisfactory results, immunoassays are commonly used to detect antibodies against Taenia sp. antigens. The aim of the present study was to produce, characterize and apply specific polyclonal immunoglobulin Y (IgY) anti-Taenia crassiceps extracted from egg yolk of hens immunized with T. crassiceps metacestodes. METHODS: Indirect enzyme-linked immunosorbent assay (ELISA), avidity ELISA, immunoblotting and indirect immunofluorescence tests were performed for characterization of IgY antibodies. Diagnostic performance was verified by ELISA for immune complex detection testing 90 serum samples. RESULTS: Values of sensitivity, specificity, positive and negative likelihood ratios (LR+/LR-) and area under the curve (AUC) were calculated and presented the following results: sensitivity 83.3%, specificity 96.7%, AUC 0.966, LR+ 25.0 and LR- 0.17. CONCLUSIONS: Results of this pioneering and innovative study demonstrate that anti-T. crassiceps IgY antibodies present potential applicability and can be used as an efficient tool in human NCC serodiagnosis.
Assuntos
Neurocisticercose , Animais , Anticorpos Anti-Helmínticos , Complexo Antígeno-Anticorpo , Antígenos de Helmintos , Galinhas , Gema de Ovo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulinas , Neurocisticercose/diagnóstico , Sensibilidade e EspecificidadeRESUMO
Human neurocysticercosis (NCC) is a worldwide neglected disease caused by Taenia solium metacestode and responsible for various complications and neurological disorders. This study aimed to evaluate the use of specific immunoglobulin Y (IgY) produced by laying hens immunized with a hydrophobic fraction of Taenia crassiceps metacestodes (hFTc) in NCC diagnosis. Egg yolk IgY antibodies were fractionated, purified and characterized. Enzyme-linked immunosorbent assay (ELISA) was carried out to evaluate the production kinetics and avidity maturation of anti-hFTc IgY antibodies throughout the IgY obtention process. Antigen recognition tests were carried out by Western blotting and immunofluorescence antibody test using purified and specific anti-hFTc IgY antibodies for detection of parasitic antigens of T. crassiceps and T. solium metacestodes. Sandwich ELISA was performed to detect circulating immune complexes formed by IgG and parasitic antigens in human sera. The results showed high diagnostic values (93.2% sensitivity and 94.3% specificity) for immune complexes detection in human sera with confirmed NCC. In conclusion, specific IgY antibodies produced from immunized hens with hFTc antigens were efficient to detect T. solium immune complexes in human sera, being an innovative and potential tool for NCC immunodiagnosis.
Assuntos
Antígenos de Helmintos/imunologia , Imunoglobulinas/sangue , Testes Imunológicos/métodos , Neurocisticercose/parasitologia , Taenia/isolamento & purificação , Animais , Afinidade de Anticorpos , Galinhas , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Neurocisticercose/imunologia , Óvulo , Taenia/imunologiaRESUMO
This study aimed to evaluate the total extract of Taenia crassiceps metacestodes (TC) and its antigenic fractions obtained by Triton X-114 fractionation techniques, such as detergent (DC) and aqueous (AC), in the immunodiagnosis of human neurocysticercosis (NCC). Cerebrospinal fluid samples were divided into two groups: Group 1 (n=40), which was further divided into active (n=20) and inactive (n=20) NCC, and Group 2 (control group), which comprised 39 CSF samples from patients who had another neurological disorder, were suffering from other infectious diseases of the brain or had other parasitic infections. The total extracts and antigenic fractions were tested by enzyme-linked immunosorbent assay (ELISA) to detect human IgG anti-Taenia solium. T. crassiceps fractions (DC and AC) showed the same value of sensitivity (Se), 100%, for active and inactive NCC and a specificity (Sp) of 97.4%. The DS fraction obtained from T. solium showed 100% Se for active NCC, 95% Se for inactive NCC and a 92.3% Sp. The AS fraction obtained from T. solium showed 100% Se for both active and inactive NCC and a 94.9% Sp. There was a positive correlation between the total saline extract of T. crassiceps (TC) and T. solium (TS) and their fractions (DC, AC, DS and AS). Positive predictive value, negative predictive value, diagnostic efficiency and Youden index were calculated. In conclusion, these results demonstrated that detergent and aqueous fractions obtained from T. crassiceps metacestodes are important sources of specific antigens and are efficient for immunodiagnosis of active and inactive NCC.
Assuntos
Anticorpos Anti-Helmínticos/líquido cefalorraquidiano , Antígenos de Helmintos/imunologia , Antígenos de Helmintos/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Neurocisticercose/diagnóstico , Neurocisticercose/imunologia , Taenia/imunologia , Animais , Antígenos de Helmintos/química , Fracionamento Químico/métodos , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Imunoglobulina G/líquido cefalorraquidiano , Larva/química , Larva/imunologia , Masculino , Camundongos , Neurocisticercose/líquido cefalorraquidiano , Octoxinol , Polietilenoglicóis , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Cloreto de Sódio , Taenia/fisiologiaRESUMO
We investigate the composition of anuran communities of land-bridge islands off the southeastern coast of Brazil. These islands provide natural long-term experiments on the effects of fragmentation in the Brazilian Atlantic Forest (BAF). We hypothesize that Pleistocene sea-level changes, in combination with other abiotic variables such as area and habitat diversity, has affected anuran species richness and community composition on these islands. Data from the literature and collections databases were used to produce species lists for eight land-bridge islands and for the mainland adjacent to the islands. We assess the effects of area, number of breeding habitats and distance to the mainland upon anuran species richness on land-bridge islands. Additionally we use nestedness analysis to quantify the extent to which the species on smaller and less habitat-diverse islands correspond to subsets of those on larger and more diverse ones. We found that area has both direct and indirect effects on anuran species richness on land-bridge islands, irrespective of distance to the mainland. However, on islands with comparable sizes, differences in species richness can be attributed to the number and quality of breeding habitats. Anuran communities on these islands display a nested pattern, possibly caused by selective extinction related to habitat loss. Common lowland pond-breeders were conspicuous by their absence. In the BAF, the conservation of fragments with a high diversity of breeding habitats could compensate for the generally negative effect of small area upon species richness. We suggest that sea-level changes have an important role in shaping composition of anuran species on coastal communities.