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The efflux systems are considered important mechanisms of bacterial resistance due to their ability to extrude various antibiotics. Several naturally occurring compounds, such as sesquiterpenes, have demonstrated antibacterial activity and the ability to inhibit efflux pumps in resistant strains. Therefore, the objective of this research was to analyze the antibacterial and inhibitory activity of the efflux systems NorA, Tet(K), MsrA, and MepA by sesquiterpenes nerolidol, farnesol, and α-bisabolol, used either individually or in liposomal nanoformulation, against multi-resistant Staphylococcus aureus strains. The methodology consisted of in vitro testing of the ability of sesquiterpenes to reduce the Minimum Inhibitory Concentration (MIC) and enhance the action of antibiotics and ethidium bromide (EtBr) in broth microdilution assays. The following strains were used: S. aureus 1199B carrying the NorA efflux pump, resistant to norfloxacin; IS-58 strain carrying Tet(K), resistant to tetracyclines; RN4220 carrying MsrA, conferring resistance to erythromycin. For the EtBr fluorescence measurement test, K2068 carrying MepA was used. It was observed the individual sesquiterpenes exhibited better antibacterial activity as well as efflux pump inhibition. Farnesol showed the lowest MIC of 16.5 µg/mL against the S. aureus RN4220 strain. Isolated nerolidol stood out for reducing the MIC of EtBr to 5 µg/mL in the 1199B strain, yielding better results than the positive control CCCP, indicating strong evidence of NorA inhibition. The liposome formulations did not show promising results, except for liposome/farnesol, which reduced the MIC of EtBr against 1199B and RN4220. Further research is needed to evaluate the mechanisms of action involved in the inhibition of resistance mechanisms by the tested compounds.
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Staphylococcus aureus Resistente à Meticilina , Sesquiterpenos , Farneseno Álcool/farmacologia , Staphylococcus aureus/metabolismo , Staphylococcus aureus Resistente à Meticilina/metabolismo , Lipossomos , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Antibacterianos/farmacologia , Sesquiterpenos/farmacologia , Etídio/farmacologia , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/metabolismoRESUMO
Carotenoids are isoprenoids widely distributed in foods that have been always part of the diet of humans. Unlike the other so-called food bioactives, some carotenoids can be converted into retinoids exhibiting vitamin A activity, which is essential for humans. Furthermore, they are much more versatile as they are relevant in foods not only as sources of vitamin A, but also as natural pigments, antioxidants, and health-promoting compounds. Lately, they are also attracting interest in the context of nutricosmetics, as they have been shown to provide cosmetic benefits when ingested in appropriate amounts. In this work, resulting from the collaborative work of participants of the COST Action European network to advance carotenoid research and applications in agro-food and health (EUROCAROTEN, www.eurocaroten.eu, https://www.cost.eu/actions/CA15136/#tabs|Name:overview) research on carotenoids in foods and feeds is thoroughly reviewed covering aspects such as analysis, carotenoid food sources, carotenoid databases, effect of processing and storage conditions, new trends in carotenoid extraction, daily intakes, use as human, and feed additives are addressed. Furthermore, classical and recent patents regarding the obtaining and formulation of carotenoids for several purposes are pinpointed and briefly discussed. Lastly, emerging research lines as well as research needs are highlighted.
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Carotenoides , Alimentos , Antioxidantes , Carotenoides/análise , Dieta , Humanos , Vitamina ARESUMO
OBJECTIVE: To evaluate the circulating cell-free mitochondrial DNA (ccf-mtDNA) levels, a marker of cellular stress and damage, in older adults with late-life depression (LLD) and frailty. We hypothesize that individuals with both frailty and LLD will have higher ccf-mtDNA levels than individuals with either condition in isolation. METHODS: Fifty-three older adults (Never Depressed+Robust (reference group, n = 16), LLD+Robust (n = 9), Never Depressed+Prefrail/Frail (n = 5), and LLD+Prefrail/Frail (n = 23)) were included in the study. DNA was extracted from EDTA plasma samples, and ccf-mtDNA was quantified by RT-PCR. RESULTS: We found a statistically significant difference in the levels of ccf-mtDNA across groups (F(3,49) = 3.07, p = 0.036), with individuals in the LLD+Prefrail/Frail group showing the highest levels of ccf-mtDNA. CONCLUSION: The coexistence of LLD and frailty is associated with increased markers of cellular damage and stress (i.e., ccf-mtDNA). Our results suggest that these conditions may share cellular stress and mitochondrial dysfunction phenomena as a common biological mechanism, offering potential future opportunities for geroscience-guided interventions for these conditions.
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Ácidos Nucleicos Livres , Fragilidade , Idoso , Ácidos Nucleicos Livres/genética , DNA Mitocondrial/genética , Depressão , Humanos , MitocôndriasRESUMO
We report on the atomistic molecular dynamics, applying the constant potential method to determine the structural and electrostatic interactions at the electrode-electrolyte interface of electrochemical supercapacitors as a function of the cation radius (Cs+, Rb+, K+, Na+, Li+). We find that the electrical double layer is susceptible to the size, hydration layer volume, and cations' mobility and analyzed them. Besides, the transient potential shows an increase in magnitude and length as a function of the monocation size, i.e., Cs+ > Rb+ > K+ > Na+ > Li+. On the other hand, the charge distribution along the electrode surface is less uniform for large monocations. Nonetheless, the difference is not observed as a function of the radius of the cation for the integral capacitance. Our results are comparable to studies that employed the fixed charge method for treating such systems.
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The global prevalence of attention-deficit/hyperactivity disorder (ADHD) is estimated to be between 6% and 7% in children worldwide. The pathophysiology of this heterogeneous neurodevelopmental disorder remains unknown. Mitochondrial dysfunction has been proposed as a possible contributing factor to the etiology of ADHD. There is limited literature available to help our understanding of this hypothesis, and thus we conducted a systematic review of the number and quality of studies pertaining to mitochondrial genetic alterations in ADHD. A systematic search was conducted in the relevant databases Medline (PubMed) and Embase up to March 2021. Inclusion criteria included randomized control trials, cross-sectional studies, and case-control studies. This search resulted in a total of 507 articles that emerged from the search criteria. Of these results, 10 primary research articles were selected for in depth review based on the inclusion and exclusion criteria. These studies all reported on mitochondrial genetic variation in ADHD cases such as increased copy number, single-nucleotide polymorphisms, and haplogroup associations. This initial review of the experimental literature suggests mitochondrial genetic variation, in both the mitochondrial DNA and nuclear-encoded mitochondrial genes, may indeed contribute to ADHD pathophysiology. The studies reviewed here provide promising evidence for future research to further examine the mitochondrial genetics contributing to ADHD pathophysiology. We suggest that expansion of investigations into mitochondrial mechanisms may have potential to inform new treatment options for ADHD.
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PURPOSES/BACKGROUND: Antidepressants (ADs) play a valuable role in treating the depressive episodes of bipolar disorder. However, 14% of these individuals taking ADs experience AD-associated mania (AAM) within a few weeks of starting treatment. Numerous studies have suggested potential clinical and genetic risk factors. We aimed to conduct a comprehensive systematic review and meta-analysis that integrates the past literature with the recent studies and identifies important predictors for AAM. METHODS/PROCEDURES: The review was limited to experimentally designed studies that contain the relevant search terms in PubMed and PsychInfo. After removing studies that were in discordance with our criteria, the review included 24 reports examining clinical risk factors and 10 investigating genetic risk factors. Our meta-analysis was conducted on 5 clinical risk factors, each of which had at least 4 articles with extractable data. FINDINGS/RESULTS: The only clinical factors in the literature that have been shown to be more indicative of AAM risk are AD monotherapy and tricyclic ADs. Among genetic factors, the serotonin transporter gene polymorphism may play a minor role in AAM. Our meta-analysis provided support for the number of prior depressive episodes. IMPLICATIONS/CONCLUSION: Prevention of AAM may be served by early detection of recurrent depression episodes. Further large-scale longitudinal studies are required to determine the underpinnings of AAM.
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Antidepressivos/efeitos adversos , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/genética , Transtorno Bipolar/tratamento farmacológico , Depressão/tratamento farmacológico , Humanos , Polimorfismo GenéticoRESUMO
The maternally inherited mitochondrial DNA (mtDNA) is located inside every mitochondrion, in variable number of copies, and it contains 37 crucial genes for cellular bioenergetics. This chapter will discuss the unique features of this circular genome including heteroplasmy, haplogroups, among others, along with the corresponding clinical relevance for each. The discussion also covers the nuclear-encoded mitochondrial genes (N > 1000) and the epistatic interactions between mtDNA and the nuclear genome. Examples of mitochondrial diseases related to specific mtDNA mutation sites of relevance for humans are provided. This chapter aims to provide an overview of mitochondrial genetics as an emerging hot topic for the future of medicine.
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Metabolismo Energético , Mitocôndrias , DNA Mitocondrial/genética , Metabolismo Energético/genética , Epistasia Genética , Genes Mitocondriais/genética , Genoma/genética , Humanos , Mitocôndrias/genética , Doenças Mitocondriais/genética , MutaçãoRESUMO
OBJECTIVES: A recent genome-wide association study (GWAS) in obsessive-compulsive disorder (OCD) reported a significant marker in the dispatched homolog 1 (Drosophila) gene (DISP1 gene) associated with serotonin reuptake inhibitor (SRI) antidepressant response (Qin et al., ). DISP1 has never been examined before in terms of association with SRI response until this GWAS. We attempt to replicate the GWAS finding by investigating the association of the DISP1 rs17162912 polymorphism with SRI response in our sample of 112 European Caucasian OCD patients. METHODS: Patients were previously treated naturalistically with up to 6 different SRIs sequentially, including 5 selective SRIs (fluoxetine, fluvoxamine, sertraline, paroxetine, and citalopram) and 1 SRI (clomipramine). Each medication trial was evaluated retrospectively for response and was rated categorically as either responder or nonresponder using the Clinical Global Impression-Improvement scale. Fisher's exact test was used to investigate the relationship between the DISP1 rs17162912 genotype distribution and SRI response. RESULTS: We did not observe a significant association between rs17162912 and SRI response (p = .32). CONCLUSION: This replication study did not support the role of DISP1 in predicting SRI response in OCD; however, methodological differences between the original GWAS and our study, as well as limited power and low minor allele frequency, may have hindered replication.
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Antidepressivos/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/genética , Polimorfismo de Nucleotídeo Único , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , População Branca/genética , Adulto JovemRESUMO
While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.
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Genética Populacional , Mutação , População Negra/genética , Brasil , Humanos , População Branca/genéticaRESUMO
There is a consensus that modern humans arrived in the Americas 15,000-20,000 y ago during the Late Pleistocene, most probably from northeast Asia through Beringia. However, there is still debate about the time of entry and number of migratory waves, including apparent inconsistencies between genetic and morphological data on Paleoamericans. Here we report the identification of mitochondrial sequences belonging to haplogroups characteristic of Polynesians in DNA extracted from ancient skulls of the now extinct Botocudo Indians from Brazil. The identification of these two Polynesian haplogroups was confirmed in independent replications in Brazil and Denmark, ensuring reliability of the data. Parallel analysis of 12 other Botocudo individuals yielded only the well-known Amerindian mtDNA haplogroup C1. Potential scenarios to try to help understand these results are presented and discussed. The findings of this study may be relevant for the understanding of the pre-Columbian and/or post-Columbian peopling of the Americas.
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DNA Mitocondrial/genética , Haplótipos/genética , Migração Humana/história , Indígenas Sul-Americanos/genética , Havaiano Nativo ou Outro Ilhéu do Pacífico/genética , Filogenia , Sequência de Bases , Brasil , História Antiga , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
Schizophrenia (SCZ) is a severe psychiatric illness with a lifetime prevalence of 0.4 %. A disturbance of energy metabolism has been suggested as part of the etiopathogenesis of the disorder. Several lines of evidence have proposed a connection between etiopathogenesis of SCZ and human brain evolution, which was characterized by an increase in the energy requirement, demanding a co-evolution of the mitochondrial system. Mitochondria are key players in brain energy homeostasis and multiple lines of evidence suggest that the system is disrupted in SCZ. In this review, we will describe the current knowledge on pathways/system involved in the human brain evolution as well as the main theories regarding the evolutionary origin of SCZ. We will furthermore discuss the role of mitochondria in the context of brain energy metabolism and its role in the etiopathogenesis of SCZ. Understanding SCZ in the context of human brain evolution opens a new perspective to elucidate pathophysiological mechanisms involved in the origin and/or portions of the complex symptomatology of this severe mental disorder.
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Mitocôndrias/patologia , Doenças Mitocondriais/complicações , Esquizofrenia/etiologia , Esquizofrenia/patologia , Animais , HumanosRESUMO
A highly diastereo- and enantioselective Mannich-type reaction of azlactones with aldimines catalyzed by a chiral phosphoric acid is described. Only 3 mol % catalyst was required to prepare the Mannich adducts in good yields with high stereochemical control (up to >19:1 dr, >99:1 er). Moreover, the final product contains two consecutive stereogenic centers, one of which is quaternary.
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Iminas/química , Lactonas/química , Ácidos Fosfóricos/química , Catálise , Cristalografia por Raios X , Modelos Moleculares , Estrutura Molecular , EstereoisomerismoRESUMO
The aim of this study was to carry out a systematic literature review to investigate the main immune cells responsible for implantation failures. We selected papers from PubMed, Embase and Virtual Health Library databases. Eligible articles included publications between January 1, 2010 and April 24, 2022. Inclusion criteria were: observational and case-control studies; and the exclusion criteria were: review papers, letters to the editor, abstracts, animal studies and case reports. We extracted the following information: day of collection, number of patients, control group, age of patients, type of sample used, immune cells and cytokines. As main findings in our mapping, we found that in peripheral blood, CD3+, CD4+, CD8+, CD16+, CD56+, CD57+, CD69+, CD154+, CD158a+, NKp46 cells were increased and the CD4+, CD45+, Foxp3 and NKp46 markers were reduced. From the endometrial biopsies, there was an increase in CD3+, CD4+, CD5+, CD8+, CD16+, CD25+, CD45+, CD56+, CD57+, CD68+, CD127+ and a reduction in CD45+, CD56+, NKp46 and FoxP3 cells. Cytokines found increased in peripheral blood included IL-6, IL-10, IL-17, INF-γ, TGF-ß, TNF-α; while IL-4, IL-6, IL-10, IL-35, FoxP3, TGF-ß, SOCS3 were reduced. As for the biopsies, there was an increase in IL-2, IL-6, IL-17, IL-22, IL-23, INF-A1, INF-B1, INF-γ, TNF-R and a reduction in IL-6, IL-10, INF-γ, TGFß, TNF-α. We concluded that immune cells can be modulated during pregnancy failure, but further studies are needed to elucidate the modulating effect of the immune system on the endometrium of these patients.
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Interleucina-10 , Interleucina-17 , Gravidez , Feminino , Humanos , Interleucina-6 , Fator de Necrose Tumoral alfa , Citometria de Fluxo , Citocinas , Sistema Imunitário , Fatores de Transcrição ForkheadRESUMO
Schizophrenia is a severe mental illness and a major risk factor for suicide, with approximately 50% of schizophrenia patients attempting and 10% dying from suicide. Although genetic components play a significant role in schizophrenia risk, the underlying genetic risk factors for suicide are poorly understood. The complement component C4 gene, an immune gene involved in the innate immune system and located in the major histocompatibility complex (MHC) region, has been identified to be strongly associated with schizophrenia risk. In addition, recent findings have also suggested that the MHC region has been associated with suicide risk across disorders, making C4 a potential candidate of interest for studying suicidality in schizophrenia patients. Despite growing interest in investigating the association between the C4 gene and schizophrenia, to our knowledge, no work has been done to examine the potential of C4 variants as suicide risk factors in patients with schizophrenia. In this study, we investigated the association between different C4 copy number variants and predicted C4 brain expression with suicidal outcomes (suicide attempts/suicidal ideation). We directly genotyped 434 schizophrenia patients to determine their C4A and C4B copy number variants. We found the C4AS copy number to be marginally and negatively associated with suicide risk, potentially being protective against suicide attempts (OR = 0.49; p = 0.05) and suicidal ideation (OR = 0.65; p = 0.07). Furthermore, sex-stratified analyses revealed that there are no significant differences between males and females. Our preliminary findings encourage additional studies of C4 and potential immune dysregulation in suicide.
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BACKGROUND: Mitochondrial dysfunction is implicated in the neuropathology of bipolar disorder (BD). Higher circulating cell-free mitochondrial DNA (ccf-mtDNA), generally reflecting poorer mitochondrial health, has been associated with greater symptoms severity in BD. The current study examines the association of serum ccf-mtDNA and brain structure in relation to youth BD. We hypothesized that higher ccf-mtDNA will be associated with measures of lower brain structure, particularly in the BD group. METHODS: Participants included 40 youth (BD, n = 19; Control group [CG], n = 21; aged 13-20 years). Serum ccf-mtDNA levels were assayed. T1-weighted brain images were acquired using 3T-MRI. Region of interest (ROI) analyses examined prefrontal cortex (PFC) and whole brain gray matter, alongside exploratory vertex-wise analyses. Analyses examined ccf-mtDNA main-effects and ccf-mtDNA-by-diagnosis interaction effects controlling for age, sex, and intracranial volume. RESULTS: There was no significant difference in ccf-mtDNA levels between BD and CG. In ROI analyses, higher ccf-mtDNA was associated with higher PFC surface area (SA) (ß = 0.32 p < 0.001) and PFC volume (ß = 0.32 p = 0.002) in the overall sample. In stratified analyses, higher ccf-mtDNA was associated with higher PFC SA within both subgroups (BD: ß = 0.39 p = 0.02; CG: ß = 0.24 p = 0.045). Higher ccf-mtDNA was associated with higher PFC volume within the BD group (ß = 0.39 p = 0.046). In vertex-wise analyses, higher ccf-mtDNA was associated with higher SA and volume in frontal clusters within the overall sample and within the BD group. There were significant ccf-mtDNA-by-diagnosis interactions in three frontal and parietal clusters, whereby higher ccf-mtDNA was associated with higher neurostructural metrics in the BD group but lower neurostructural metrics in CG. CONCLUSIONS: Contrasting our hypothesis, higher ccf-mtDNA was consistently associated with higher, rather than lower, regional neuralstructural metrics among youth with BD. While this finding may reflect a compensatory mechanism, future repeated-measures prospective studies evaluating the inter-relationship among ccf-mtDNA, mood, and brain structure across developmental epochs and illness stages are warranted.
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BACKGROUND: Type 1 diabetes increases the prevalence of urinary incontinence and may be responsible for additional changes to those existing in a regular gestational period. This study aimed to describe the presence and symptoms of urinary incontinence in pregnant women with type 1 diabetes. METHODS: In this Cross-sectional case control study, forty pregnant women in third gestational trimester were allocated in two equal groups - control group (CG) and type 1 diabetic group (1DMG). The patients answered the International Consultation on Incontinence Questionnaire Short Form and, to characterize the sample, they answered the Pregnancy Physical Activity Questionnaire, gynecological history and, after delivery, the newborn weight was registered. The groups were compared using the Student's T Test for parametric variables and the U-Mann Whitney Test for non-parametric variables, both at 5% probability. RESULTS: The International Consultation on Incontinence Questionnaire Short Form score (p = 0.026) is higher in 1DMG (3.95 ± 4.70) compared to CG (1.05 ± 2.23). No correlations were found between time of diagnosis, HbA1c and newborn weight in relation to ICIQ-SF and other variables in CG and 1DMG with ICIQ-SF (p < 0.05). CONCLUSION: Type 1 diabetes mellitus, in the third trimester of gestation, seem to be associated with increase in the ICIQ-SF score.
HIGHLIGHTS: No correlation between gestational characteristics and urinary incontinence symptoms.The diabetic women group had more episiotomies and abortions.The diabetic women had higher scores in the total score of the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF).
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Diabetes Mellitus Tipo 1 , Terceiro Trimestre da Gravidez , Gravidez em Diabéticas , Incontinência Urinária , Humanos , Feminino , Gravidez , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Adulto , Estudos Transversais , Estudos de Casos e Controles , Incontinência Urinária/epidemiologia , Incontinência Urinária/diagnóstico , Incontinência Urinária/etiologia , Incontinência Urinária/fisiopatologia , Gravidez em Diabéticas/epidemiologia , Inquéritos e Questionários , PrevalênciaRESUMO
BACKGROUND: Disrupted cellular communication, inflammatory responses and mitochondrial dysfunction are consistently observed in late-life depression (LLD). Exosomes (EXs) mediate cellular communication by transporting molecules, including mitochondrial DNA (EX-mtDNA), playing critical role in immunoregulation alongside tumor necrosis factor (TNF). Changes in EX-mtDNA are indicators of impaired mitochondrial function and might increase vulnerability to adverse health outcomes. Our study examined EX-mtDNA levels and integrity, exploring their associations with levels of TNF receptors I and II (TNFRI and TNFRII), and clinical outcomes in LLD. METHODS: Ninety older adults (50 LLD and 40 controls (HC)) participated in the study. Blood was collected and exosomes were isolated using size-exclusion chromatography. DNA was extracted and EX-mtDNA levels and deletion were assessed using qPCR. Plasma TNFRI and TNFRII levels were quantified by multiplex immunoassay. Correlation analysis explored relationships between EX-mtDNA, clinical outcomes, and inflammatory markers. RESULTS: Although no differences were observed in EX-mtDNA levels between groups, elevated levels correlated with poorer cognitive performance (r = -0.328, p = 0.002) and increased TNFRII levels (r = 0.367, p = 0.004). LLD exhibited higher deletion rates (F(83,1) = 4.402, p = 0.039), with a trend remaining after adjusting for covariates (p = 0.084). Deletion correlated with poorer cognitive performance (r = -0.335, p = 0.002). No other associations were found. LIMITATION: Cross-sectional study with a small number of participants from a specialized geriatric psychiatry treatment center. CONCLUSION: Our findings suggest that EX-mtDNA holds promise as an indicator of cognitive outcomes in LLD. Additional research is needed to further comprehend the role of EX-mtDNA levels/integrity in LLD, paving the way for its clinical application in the future.
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Disfunção Cognitiva , DNA Mitocondrial , Exossomos , Receptores Tipo II do Fator de Necrose Tumoral , Receptores Tipo I de Fatores de Necrose Tumoral , Humanos , DNA Mitocondrial/genética , DNA Mitocondrial/sangue , Masculino , Feminino , Idoso , Disfunção Cognitiva/sangue , Disfunção Cognitiva/genética , Exossomos/genética , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Receptores Tipo II do Fator de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Idoso de 80 Anos ou mais , Depressão/sangue , Depressão/genética , Estudos de Casos e Controles , Biomarcadores/sangueRESUMO
This study aimed to evaluate the antibacterial and inhibitory action of NorA, Tet(K), MsrA and MepA efflux pumps in S. aureus strains using the sesquiterpenes named trans-caryophyllene and caryophyllene oxide, both isolated and encapsulated in liposomes. The antibacterial and inhibitory action of these efflux pumps was evaluated through the serial microdilution test in 96-well microplates. Each sesquiterpene and liposome/sesquiterpene was combined with antibiotics and ethidium bromide (EtBr). The antibiotics named norfloxacin, tetracycline and erythromycin were used. The 1199 B, IS-58, RN4220 and K2068 S. aureus strains carrying NorA, Tet(K), MsrA and MepA, respectively, were tested. In the fluorescence measurement test, K2068 S. aureus was incubated with the sesquiterpenes and EtBr, and the fluorescence emission by EtBr was measured. The tested substances did not show direct antibacterial activity, with MIC >1024 µg/mL. Nonetheless, the isolated trans-caryophyllene and caryophyllene oxide reduced the MIC of antibiotics and EtBr, indicating inhibition of NorA, Tet(K) and MsrA. In the fluorescence test, these same sesquiterpenes increased fluorescence emission, indicating inhibition of MepA. Therefore, the sesquiterpenes named trans-caryophyllene and caryophyllene oxide did not show direct antibacterial action; however, in their isolated form, they showed possible inhibitory action on NorA, Tet(K), MsrA and MepA efflux pumps. They may also act in antibiotic potentiation. Further studies are needed to identify the mechanisms involved in antibiotic potentiation and efflux pump inhibitory action.
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Lipossomos , Staphylococcus aureus , Staphylococcus aureus/metabolismo , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Sesquiterpenos Policíclicos , Etídio , Proteínas de Bactérias/metabolismo , Proteínas Associadas à Resistência a Múltiplos MedicamentosRESUMO
BACKGROUND: The Toronto Adolescent and Youth (TAY) Cohort Study will characterize the neurobiological trajectories of psychosis spectrum symptoms, functioning, and suicidality (i.e., suicidal thoughts and behaviors) in youth seeking mental health care. Here, we present the neuroimaging and biosample component of the protocol. We also present feasibility and quality control metrics for the baseline sample collected thus far. METHODS: The current study includes youths (ages 11-24 years) who were referred to child and youth mental health services within a large tertiary care center in Toronto, Ontario, Canada, with target recruitment of 1500 participants. Participants were offered the opportunity to provide any or all of the following: 1) 1-hour magnetic resonance imaging (MRI) scan (electroencephalography if ineligible for or declined MRI), 2) blood sample for genomic and proteomic data (or saliva if blood collection was declined or not feasible) and urine sample, and 3) heart rate recording to assess respiratory sinus arrhythmia. RESULTS: Of the first 417 participants who consented to participate between May 4, 2021, and February 2, 2023, 412 agreed to participate in the imaging and biosample protocol. Of these, 334 completed imaging, 341 provided a biosample, 338 completed respiratory sinus arrhythmia, and 316 completed all 3. Following quality control, data usability was high (MRI: T1-weighted 99%, diffusion-weighted imaging 99%, arterial spin labeling 90%, resting-state functional MRI 95%, task functional MRI 90%; electroencephalography: 83%; respiratory sinus arrhythmia: 99%). CONCLUSIONS: The high consent rates, good completion rates, and high data usability reported here demonstrate the feasibility of collecting and using brain imaging and biosamples in a large clinical cohort of youths seeking mental health care.
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Proteômica , Transtornos Psicóticos , Criança , Humanos , Adolescente , Estudos de Coortes , Neuroimagem , EncéfaloRESUMO
OBJECTIVE: To investigate the oral soft-tissue injuries in people aged 60 or older. METHODS: Cross-sectional research conducted with 262 elders aged 60-93 years (mean 69.84, SD ± 6.212) from the Dende community in Northeast, Brazil. Data were collected through an identification questionnaire and the Community Indicator in Oral Health. Data were computed by the Software SPSS, version 15. RESULTS: There was a predominance of female gender (64.1%), retired, low schooling and income of up to one minimum wage. It was detected a prevalence of soft-tissue injuries in 38.4% (n = 101) of the elders, distributed as follows: red spots 60(57.7%), blisters 20(19.2%), lesions and/or wound 16(15.4%), and white spot 8(7.7%). Among the elders, 40(15.3%) smoked and 20(7.6%) used alcohol. It was verified a statistical association between injuries and using prosthesis (p = 0.039), medicine (p = 0.023) and calculus (p = 0.016). CONCLUSION: The oral health of this population is precarious, and there is a high prevalence of oral lesions.