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It has been well documented that mutations in coding DNA or cis-regulatory elements underlie natural phenotypic variation in many organisms. However, the development of sophisticated functional tools in recent years in a wide range of traditionally non-model systems have revealed many 'unusual suspects' in the molecular bases of phenotypic evolution, including upstream open reading frames (uORFs), cryptic splice sites, and small RNAs. Furthermore, large-scale genome sequencing, especially long-read sequencing, has identified a cornucopia of structural variation underlying phenotypic divergence and elucidated the composition of supergenes that control complex multi-trait polymorphisms. In this review article we highlight recent studies that demonstrate this great diversity of molecular mechanisms producing adaptive genetic variation and the panoply of evolutionary paths leading to the 'grandeur of life'.
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Evolução Molecular , Fases de Leitura Aberta , Fenótipo , Fases de Leitura Aberta/genética , Humanos , Animais , Variação Genética/genética , MutaçãoRESUMO
Anethole is a terpenoid with antioxidant, anti-inflammatory, and neuronal blockade effects, and the present work was undertaken to study the neuroprotective activity of anethole against diabetes mellitus (DM)-induced neuropathy. Streptozotocin-induced DM rats were used to investigate the effects of anethole treatment on morphological, electrophysiological, and biochemical alterations of the sciatic nerve (SN). Anethole partially prevented the mechanical hyposensitivity caused by DM and fully prevented the DM-induced decrease in the cross-sectional area of the SN. In relation to electrophysiological properties of SN fibers, DM reduced the frequency of occurrence of the 3rd component of the compound action potential (CAP) by 15%. It also significantly reduced the conduction velocity of the 1st and 2nd CAP components from 104.6 ± 3.47 and 39.8 ± 1.02 to 89.9 ± 3.03 and 35.4 ± 1.56 m/s, respectively, and increased the duration of the 2nd CAP component from 0.66 ± 0.04 to 0.82 ± 0.09 ms. DM also increases oxidative stress in the SN, altering values related to thiol, TBARS, SOD, and CAT activities. Anethole was capable of fully preventing all these DM electrophysiological and biochemical alterations in the nerve. Thus, the magnitude of the DM-induced neural effects seen in this work, and the prevention afforded by anethole treatment, place this compound in a very favorable position as a potential therapeutic agent for treating diabetic peripheral neuropathy.
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Derivados de Alilbenzenos , Anisóis , Diabetes Mellitus Experimental , Estresse Oxidativo , Nervo Isquiático , Animais , Derivados de Alilbenzenos/farmacologia , Nervo Isquiático/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Ratos , Anisóis/farmacologia , Anisóis/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/prevenção & controle , Neuropatias Diabéticas/metabolismo , Potenciais de Ação/efeitos dos fármacos , Antioxidantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
Tegumentary leishmaniasis encompasses a spectrum of clinical manifestations caused by the parasitic protozoa of the genus Leishmania. In Brazil, there are at least seven Leishmania species that are endemic and responsible for this set of clinical manifestations of the disease. Current treatment is limited to a restricted number of drugs that in general have several drawbacks including parenteral use, toxicity, and severe side effects. Amphotericin B is considered a second-line drug for tegumentary leishmaniasis in Brazil, while miltefosine was recently approved for clinical use in the treatment of this disease. In this study, we investigated the in vitro susceptibility of Leishmania strains representative of the species endemic to Brazil, as well as a panel of thirteen clinical isolates of tegumentary leishmaniasis, to both amphotericin B and miltefosine. A moderate variation in the susceptibility to both drugs was found, where the EC50 values varied from 11.43 to 52.67 µM for miltefosine and from 12.89 to 62.36 nM for amphotericin B in promastigotes, while for the intracellular amastigotes, values ranged from 1.08 to 9.60 µM and from 1.69 to 22.71 nM for miltefosine and amphotericin B respectively. Furthermore, the clinical isolates and strains of the subgenus Viannia were evaluated for the presence of Leishmania RNA virus 1 (LRV1), as this is an important factor associated with disease severity and treatment outcome. These findings provide a preclinical dataset of the activity of these drugs against the causative species of tegumentary leishmaniasis in Brazil.
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Antiprotozoários , Leishmania , Leishmaniose Cutânea , Leishmaniose , Humanos , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Brasil/epidemiologia , Leishmaniose/tratamento farmacológico , Fosforilcolina/farmacologia , Fosforilcolina/uso terapêutico , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/parasitologiaRESUMO
Pseudomonas aeruginosa is a common respiratory pathogen that causes injurious airway inflammation during acute pneumonia. Peroxisome proliferator-activated receptor (PPAR)-γ is involved in the regulation of metabolic and inflammatory responses in different cell types and synthetic agonists of PPAR-γ exert anti-inflammatory effects on myeloid cells in vitro and in models of inflammation in vivo. We sought to determine the effect of the PPAR-γ agonist pioglitazone on airway inflammation induced by acute P. aeruginosa pneumonia, focusing on bronchial epithelial cells. Mice pretreated with pioglitazone or vehicle (24 and 1 h) were infected with P. aeruginosa via the airways. Pioglitazone treatment was associated with increased expression of chemokine (Cxcl1, Cxcl2, and Ccl20) and cytokine genes (Tnfa, Il6, and Cfs3) in bronchial brushes obtained 6 h after infection. This pro-inflammatory effect was accompanied by increased expression of Hk2 and Pfkfb3 genes encoding rate-limiting enzymes of glycolysis; concurrently, the expression of Sdha, important for maintaining metabolite flux in the tricarboxylic acid cycle, was reduced in bronchial epithelial cells of pioglitazone treated-mice. Pioglitazone inhibited bronchoalveolar inflammatory responses measured in lavage fluid. These results suggest that pioglitazone exerts a selective proinflammatory effect on bronchial epithelial cells during acute P. aeruginosa pneumonia, possibly by enhancing intracellular glycolysis.
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Pneumonia , Tiazolidinedionas , Animais , Células Epiteliais/metabolismo , Hipoglicemiantes , Inflamação , Camundongos , PPAR gama/agonistas , PPAR gama/genética , Pioglitazona/farmacologia , Pseudomonas aeruginosa , Tiazolidinedionas/farmacologiaRESUMO
The parasitic protozoa Leishmania (Leishmania) infantum is the etiological agent of human visceral leishmaniasis and canine leishmaniasis in South America, where Brazil is the most affected country. This zoonotic disease is transmitted by the bite of an infected phlebotomine sand fly and dogs constitute the main domestic reservoir of the parasite. In this study, we screened 2348 dogs of the municipality of Embu das Artes, Brazil, for antibodies against the parasite. Prevalence for canine leishmaniasis seropositivity was 2.81%, as assessed using a Dual-Path Platform rapid test for canine leishmaniasis. Twenty-five seropositive dogs were euthanized for parasite isolation and 14 isolates were successful obtained. Nucleotide sequencing of the internal transcribed spacer confirmed the isolates to be L. (L.) infantum, and very low sequence variability was observed among them. The in vitro susceptibility to miltefosine and paromomycin was assessed and moderate variation in paromomycin susceptibility was found among the isolates in the promastigote and intracellular amastigote stages. On the other hand, in vitro susceptibility to miltefosine of these isolates was homogenous, particularly in the amastigote stage (EC50 values from 0.69 to 2.07 µM). In addition, the miltefosine sensitivity locus was deleted in all the isolates, which does not corroborate the hypothesis that the absence of this locus is correlated with a low in vitro susceptibility. Our findings confirm that the municipality of Embu das Artes is endemic for canine leishmaniasis and that isolates from this region are susceptible to paromomycin and miltefosine, indicating the potential of these drugs to be clinically evaluated in the treatment of human visceral leishmaniasis in Brazil.
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Doenças do Cão , Leishmania infantum , Leishmaniose Visceral , Animais , Brasil/epidemiologia , Doenças do Cão/parasitologia , Cães , Humanos , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/veterinária , Paromomicina/uso terapêuticoRESUMO
Agonists of peroxisome proliferator-activated receptor (PPAR)-γ have been suggested as potential adjuvant therapy in bacterial pneumonia because of their capacity to inhibit inflammation and enhance bacterial clearance. Previous studies only assessed the effects of pretreatment with these compounds, thereby bearing less relevance for the clinical scenario. Moreover, PPAR-γ agonists have not been studied in pneumonia caused by Klebsiella pneumoniae, a common human respiratory pathogen of which antibiotic treatment is hampered by increasing antimicrobial resistance. Here we show that administration of the PPAR-γ agonist pioglitazone 6 or 8 h after infection of mice with a highly virulent strain of Klebsiella pneumoniae via the airways results in reduced cytokine and myeloperoxidase levels in the lungs at 24 h after infection, as well as reduced bacterial growth in the lungs and decreased dissemination to distant organs at 42 h post-infection. These results suggest that pioglitazone may be an interesting agent in the treatment of Klebsiella pneumonia.
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Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/crescimento & desenvolvimento , PPAR gama/agonistas , Pioglitazona/administração & dosagem , Animais , Feminino , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Injeções Intraperitoneais , Infecções por Klebsiella/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Sepsis is a dysregulated host response to infection and a major cause of death worldwide. Respiratory tract infections account for most sepsis cases and depending on the place of acquisition, i.e., community or hospital acquired infection, differ in etiology, antimicrobial resistance and outcomes. Accordingly, the host response may be different in septic patients secondary to community-acquired pneumonia and hospital acquired pneumonia (HAP). Proteomic analysis is a useful approach to evaluate broad alterations in biological pathways that take place during sepsis. Here we evaluated plasma proteome changes in sepsis secondary to HAP. METHODS: Plasma samples were obtained from patients (n = 27) at admission and after 7 days of follow-up, and were analyzed according to the patients' outcomes. The patients' proteome profiles were compared with healthy volunteers (n = 23). Pooled plasma samples were labeled with isobaric tag for relative and absolute quantitationand analyzed by LC-MS/MS. We used bioinformatics tools to find altered functions and pathways. Results were validated using biochemical estimations and ELISA tests. RESULTS: We identified 159 altered proteins in septic patients; most of them were common when comparing patients' outcomes, both at admission and after 7 days. The top altered biological processes were acute inflammatory response, response to wounding, blood coagulation and homeostasis. Lipid metabolism emerged as the main altered function in patients, with HDL as a central node in the network analysis, interacting with downregulated proteins, such as APOA4, APOB, APOC1, APOL1, SAA4 and PON1. Validation tests showed reduced plasma levels of total cholesterol, HDL-C, LDL-C, non-HDL cholesterol, apolipoproteins ApoA1 and ApoB100, and Paraoxonase 1 in HAP patients. CONCLUSION: Proteomic analysis pointed to impairment of lipid metabolism as a major change in septic patients secondary to HAP, which was further validated by the reduced levels of cholesterol moieties and apolipoproteins in plasma. Our results stress the involvement of lipids in the pathogenesis of sepsis, which is in accordance with previous reports supporting the role of lipid moieties in pathogen toxin clearance and in modulating inflammatory responses.
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Although imaging the live Trypanosoma cruzi parasite is a routine technique in most laboratories, identification of the parasite in infected tissues and organs has been hindered by their intrinsic opaque nature. We describe a simple method for in vivo observation of live single-cell Trypanosoma cruzi parasites inside mammalian host tissues. BALB/c or C57BL/6 mice infected with DsRed-CL or GFP-G trypomastigotes had their organs removed and sectioned with surgical blades. Ex vivo organ sections were observed under confocal microscopy. For the first time, this procedure enabled imaging of individual amastigotes, intermediate forms and motile trypomastigotes within infected tissues of mammalian hosts.
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Análise de Célula Única/métodos , Trypanosoma cruzi/citologia , Trypanosoma cruzi/patogenicidade , Animais , Doença de Chagas/parasitologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microscopia ConfocalRESUMO
In continuation of our efforts to find new antimicrobial compounds, series of fatty N-acyldiamines were prepared from fatty methyl esters and 1,2-ethylenediamine, 1,3-propanediamine or 1,4-butanediamine. The synthesized compounds were screened for their antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis), Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and for their antifungal activity against four species of Candida (C. albicans, C. tropicalis, C. glabrata and C. parapsilosis). Compounds 5a (N-(2-aminoethyl)dodecanamide), 5b (N-(2-aminoethyl)tetracanamide) and 6d (N-(3-aminopropyl)oleamide) were the most active against Gram-positive bacteria, with MIC values ranging from 1 to 16µg/mL and were evaluated for their activity against 21 clinical isolates of methicillin-resistant S. aureus. All the compounds exhibited good to moderate antifungal activity. Compared to chloramphenicol, compound 6b displayed a similar activity (MIC50=16µg/mL). A positive correlation could be established between lipophilicity and biological activity.
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Antibacterianos/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Diaminas/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Diaminas/síntese química , Diaminas/química , Relação Dose-Resposta a Droga , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
In Brazil, Leishmania amazonensis is the etiological agent of cutaneous and diffuse cutaneous leishmaniasis. The state of Maranhão in the Northeast of Brazil is prevalent for these clinical forms of the disease and also has high rates of HIV infection. Here, we characterized the drug susceptibility of a L. amazonensis clinical isolate from a 46-year-old man with diffuse cutaneous leishmaniasis coinfected with HIV from this endemic area. This patient underwent several therapeutic regimens with meglumine antimoniate, liposomal amphotericin B, and pentamidine, without success. In vitro susceptibility assays against promastigotes and intracellular amastigotes demonstrated that this isolate had low susceptibility to amphotericin B, when compared with the reference strain of this species that is considered susceptible to antileishmanial drugs. Additionally, we investigated whether the low in vitro susceptibility would affect the in vivo response to amphotericin B treatment. The drug was effective in reducing the lesion size and parasite burden in mice infected with the reference strain, whereas those infected with the clinical isolate and a resistant line (generated experimentally by stepwise selection) were refractory to amphotericin B treatment. To evaluate whether the isolate was intrinsically resistant to amphotericin B in animals, infected mice were treated with other drugs that had not been used in the treatment of the patient (miltefosine, paromomycin, and a combination of both). Our findings demonstrated that all drug schemes were able to reduce lesion size and parasite burden in animals infected with the clinical isolate, confirming the amphotericin B-resistance phenotype. These findings indicate that the treatment failure observed in the patient may be associated with amphotericin B resistance, and demonstrate the potential emergence of amphotericin B-resistant L. amazonensis isolates in an area of Brazil endemic for cutaneous leishmaniasis.
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Anfotericina B , Antiprotozoários , Resistência a Medicamentos , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Animais , Brasil , Pessoa de Meia-Idade , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Humanos , Masculino , Camundongos , Leishmania/efeitos dos fármacos , Leishmania/isolamento & purificação , Leishmania/classificação , Leishmania mexicana/efeitos dos fármacos , Leishmania mexicana/isolamento & purificação , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Testes de Sensibilidade Parasitária , Camundongos Endogâmicos BALB C , Leishmaniose Tegumentar Difusa/parasitologia , Leishmaniose Tegumentar Difusa/tratamento farmacológicoRESUMO
We report in this work the preparation and in vitro antimicrobial evaluation of novel amphiphilic aromatic amino alcohols synthesized by reductive amination of 4-alkyloxybenzaldehyde with 2-amino-2-hydroxymethyl-propane-1,3-diol. The antibacterial activity was determined against four standard strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa) and 21 clinical isolates of methicillin-resistant Staphylococcus aureus. The antifungal activity was evaluated against four yeast (Candida albicans, Candida tropicalis, Candida glabrata and Candida parapsilosis). The results obtained showed a strong positive correlation between the lipophilicity and the antibiotic activity of the tested compounds. The best activities were obtained against the Gram-positive bacteria (MIC=2-16µgml(-1)) for the five compounds bearing longer alkyl chains (4c-g; 8-14 carbons), which were also the most active against Candida (MIC=2-64µgml(-1)). Compound 4e exhibited the highest levels of inhibitory activity (MIC=2-16µgml(-1)) against clinical isolates of MRSA. A concentration of twice the MIC resulted in bactericidal activity of 4d against 19 of the 21 clinical isolates.
Assuntos
Amino Álcoois/farmacologia , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Tensoativos/farmacologia , Amino Álcoois/síntese química , Amino Álcoois/química , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Relação Estrutura-Atividade , Tensoativos/síntese química , Tensoativos/químicaRESUMO
Immune exhaustion and senescence are scarcely studied in HIV-pediatric patients. We studied the circulatory CD8 T cells activation/exhaustion and senescent phenotype of children and adolescents vertically infected with HIV or uninfected controls based on the expression of human leukocyte antigen (HLA-DR), CD38, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), programmed death 1 (PD-1) and CD57 by flow cytometry, during approximately one year. Eleven HIV-infected (HI) and nine HIV-uninfected (HU) children/adolescents who received two doses or one dose of meningococcal C conjugate vaccine (MenC), respectively, were involved in this study. Blood samples were collected before the immunization (T0), 1-2 months after the first dose (T1), and 1-2 months after the second dose (T2), which was administered approximately one year after the first one. HI patients not receiving combined antiretroviral therapy (cART) showed a higher frequency of CD8 T cells TIGIT+, PD-1+ or CD57+, as well as a higher frequency of CD8 T cells co-expressing CD38/HLA-DR/TIGIT or CD38/HLA-DR/PD-1 when compared to HI treated or HU individuals, at all times that they were assessed. CD8 T cells co-expressing CD38/DR/TIGIT were inversely correlated with the CD4/CD8 ratio but positively associated with viral load. The co-expression of CD38/DR/TIGIT or CD38/DR/PD-1 on CD8 T cells was also inversely associated with the CD4 T cells expressing co-stimulatory molecules CD127/CD28. The results showed a higher expression of exhaustion/senescence markers on CD8 T cells of untreated HI children/adolescents and its correlations with viral load.
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Infecções por HIV , Receptor de Morte Celular Programada 1 , Humanos , Criança , Adolescente , Receptor de Morte Celular Programada 1/uso terapêutico , Antígenos HLA-DR/uso terapêutico , Linfócitos T CD8-Positivos , Linfócitos T CD4-Positivos , Infecções por HIV/tratamento farmacológico , Receptores Imunológicos/uso terapêuticoRESUMO
The clinical presentation of COVID-19 is highly variable, and understanding the underlying biological processes is crucial. This study utilized a proteomic analysis to investigate dysregulated processes in the peripheral blood mononuclear cells of patients with COVID-19 compared to healthy volunteers. Samples were collected at different stages of the disease, including hospital admission, after 7 days of hospitalization, and 30 days after discharge. Metabolic pathway alterations and increased abundance of neutrophil-related proteins were observed in patients. Patients progressing to critical illness had significantly low-abundance proteins in the pentose phosphate and glycolysis pathways compared with those presenting clinical recovery. Important biological processes, such as fatty acid concentration and glucose metabolism disorder, remained altered even after 30 days of hospital discharge. Temporal proteomic changes revealed distinct pathways in critically ill and non-critically ill patients. Our study emphasizes the significance of longitudinal cellular proteomic studies in identifying disease progression-related pathways and persistent protein changes post-hospitalization.
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The parasitic protozoan Leishmania (Leishmania) infantum is the etiological agent of human visceral leishmaniasis in South America, an infectious disease associated with malnutrition, anemia, and hepatosplenomegaly. In Brazil alone, around 2700 cases are reported each year. Treatment failure can occur as a result of drug, host, and/or parasite-related factors. Here, we isolated a Leishmania species from a pediatric patient with visceral leishmaniasis that did not respond to chemotherapy, experiencing a total of nine therapeutic relapses and undergoing a splenectomy. The parasite was confirmed as L. (L.) infantum after sequencing of the ribosomal DNA internal transcribed spacer, and the clinical isolate, in both promastigote and amastigote forms, was submitted to in vitro susceptibility assays with all the drugs currently used in the chemotherapy of leishmaniasis. The isolate was susceptible to meglumine antimoniate, amphotericin B, pentamidine, miltefosine, and paromomycin, similarly to another strain of this species that had previously been characterized. These findings indicate that the multiples relapses observed in this pediatric patient were not due to a decrease in the drug susceptibility of this isolate; therefore, immunophysiological aspects of the patient should be further investigated to understand the basis of treatment failure in this case.
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The physicochemical properties and fatty acid composition of Attalea dubia (Mart.) Burret (indaiá) seed oil were investigated. The oil was extracted in a soxhlet apparatus using petroleum ether and evaluated for iodine, acid, peroxide, ester, and saponification values. The oil was also analyzed using infrared and nuclear magnetic resonance spectroscopy. The fatty acid profile of the oil was determined by GC-MS. For each analysis indaiá oil was compared to Orbignya phalerata (babassu) oil. The two oils appeared to be very similar in their fatty acid composition, in which lauric acid (the most abundant), myristic acid, caprylic acid, and capric acid were the four main fatty acids detected. The unsaturated fatty acids content was lower for indaiá oil (5.8%) than for babassu oil (9.4%). The results suggest that indaiá palm tree could be cultivated as a new source of vegetable oil with potential for food and cosmetic industries.
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Arecaceae/química , Ácidos Graxos/análise , Óleos de Plantas/análise , Sementes/química , Arecaceae/classificação , Caprilatos/análise , Ácidos Decanoicos/análise , Ácidos Graxos Insaturados/análise , Cromatografia Gasosa-Espectrometria de Massas , Concentração de Íons de Hidrogênio , Ácidos Láuricos/análise , Espectroscopia de Ressonância Magnética , Ácido Mirístico/análise , Óleos de Plantas/química , Especificidade da Espécie , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Introduction: Although facial involvement in discoid lupus erythematosus (DLE) is common, eyelid involvement is atypical. Identifying this condition is challenging due to misdiagnosis, and it is essential to avoid potential deformities of the eyelid margin. Case Presentation: We, herein, report the dermoscopic findings in 2 female patients with a confirmed diagnosis of DLE who presented eyelids involvement. Discussion/Conclusion: This study highlights the importance of performing a dermoscopy examination to help physicians obtain an early diagnosis of DLE.
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Recognizing the other's emotions is an important skill for the social context that can be modulated by variables such as gender, age, and race. A number of studies seek to elaborate specific face databases to assess the recognition of basic emotions in different contexts. Objectives: This systematic review sought to gather these studies, describing and comparing the methodologies used in their elaboration. Methods: The databases used to select the articles were the following: PubMed, Web of Science, PsycInfo, and Scopus. The following word crossing was used: "Facial expression database OR Stimulus set AND development OR Validation." Results: A total of 36 articles showed that most of the studies used actors to express the emotions that were elicited from specific situations to generate the most spontaneous emotion possible. The databases were mainly composed of colorful and static stimuli. In addition, most of the studies sought to establish and describe patterns to record the stimuli, such as color of the garments used and background. The psychometric properties of the databases are also described. Conclusions: The data presented in this review point to the methodological heterogeneity among the studies. Nevertheless, we describe their patterns, contributing to the planning of new research studies that seek to create databases for new contexts.
Reconhecer as emoções do outro é uma habilidade importante para o contexto social, que pode ser modulada por variáveis como sexo, idade e raça. Vários estudos buscam elaborar bancos de faces específicos para avaliar o reconhecimento de emoções básicas em diferentes contextos. Objetivos: Esta revisão sistemática buscou reunir esses estudos, descrevendo e comparando as metodologias utilizadas em sua elaboração. Métodos: As bases de dados utilizadas para a seleção dos artigos foram: PubMed, Web of Science, PsycInfo e Scopus. Foi utilizado o seguinte cruzamento de palavras: "facial expression database OR stimulus set AND development OR validation". Resultados: O total de 36 artigos mostrou que a maioria dos estudos utilizou atores para expressar as emoções, que foram suscitadas de situações específicas para serem o mais espontâneas possível. Os bancos de faces foram compostos principalmente de estímulos coloridos e estáticos. Além disso, a maioria dos estudos buscou estabelecer e descrever padrões para registrar os estímulos, como a cor das roupas utilizadas e o fundo. As propriedades psicométricas dos bancos de faces também são descritas. Conclusões: Os dados apresentados nesta revisão apontam para a heterogeneidade metodológica entre os estudos. Apesar disso, descrevemos seus padrões, contribuindo para o planejamento de novas pesquisas que buscam criar bancos de faces específicos para novos contextos.
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The respiratory epithelium provides a first line of defense against pathogens. Hypoxia-inducible factor (HIF)1α is a transcription factor which is stabilized in hypoxic conditions through the inhibition of prolyl-hydroxylase (PHD)2, the enzyme that marks HIF1α for degradation. Here, we studied the impact of HIF1α stabilization on the response of primary human bronchial epithelial (HBE) cells to the bacterial component, flagellin. The treatment of flagellin-stimulated HBE cells with the PHD2 inhibitor IOX2 resulted in strongly increased HIF1α expression. IOX2 enhanced the flagellin-induced expression of the genes encoding the enzymes involved in glycolysis, which was associated with the intracellular accumulation of pyruvate. An untargeted pathway analysis of RNA sequencing data demonstrated the strong inhibitory effects of IOX2 toward key innate immune pathways related to cytokine and mitogen-activated kinase signaling cascades in flagellin-stimulated HBE cells. Likewise, the cell-cell junction organization pathway was amongst the top pathways downregulated by IOX2 in flagellin-stimulated HBE cells, which included the genes encoding claudins and cadherins. This IOX2 effect was corroborated by an impaired barrier function, as measured by dextran permeability. These results provide a first insight into the effects associated with HIF1α stabilization in the respiratory epithelium, suggesting that HIF1α impacts properties that are key to maintaining homeostasis upon stimulation with a relevant bacterial agonist.
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Brônquios , Flagelina , Subunidade alfa do Fator 1 Induzível por Hipóxia , Prolina Dioxigenases do Fator Induzível por Hipóxia , Brônquios/citologia , Flagelina/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Transdução de SinaisRESUMO
Metabolic adaptations shape immune cell function. In the acute response, a metabolic switch towards glycolysis is necessary for mounting a proinflammatory response. During the clinical course of sepsis, both suppression and activation of immune responses take place simultaneously. Leukocytes from septic patients present inhibition of cytokine production while other functions such as phagocytosis and production of reactive oxygen species (ROS) are preserved, similarly to the in vitro endotoxin tolerance model, where a first stimulation with lipopolysaccharide (LPS) affects the response to a second stimulus. Here, we sought to investigate how cellular metabolism is related to the modulation of immune responses in sepsis and endotoxin tolerance. Proteomic analysis in peripheral blood mononuclear cells (PBMCs) from septic patients obtained at intensive care unit admission showed an upregulation of proteins related to glycolysis, the pentose phosphate pathway (PPP), production of ROS and nitric oxide, and downregulation of proteins in the tricarboxylic acid cycle and oxidative phosphorylation compared to healthy volunteers. Using the endotoxin-tolerance model in PBMCs from healthy subjects, we observed increased lactate production in control cells upon LPS stimulation, while endotoxin-tolerant cells presented inhibited tumor necrosis factor-α and lactate production along with preserved phagocytic capacity. Inhibition of glycolysis and PPP led to impairment of phagocytosis and cytokine production both in control and in endotoxin-tolerant cells. These data indicate that glucose metabolism supports leukocyte functions even in a condition of endotoxin tolerance.
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Endotoxinas , Sepse , Humanos , Proteoma , Leucócitos Mononucleares , Lipopolissacarídeos/farmacologia , Proteômica , Espécies Reativas de Oxigênio , Leucócitos , Via de Pentose Fosfato , Lactatos , Glucose , CitocinasRESUMO
Pequi (Caryocar brasiliense Camb.), babaçu (Orbignya phalerata Mart.), buriti (Mauritia flexuosa), and passion fruit (Passiflora edulis) oils were studied to determine their antibacterial, antioxidant and cytotoxic activities, as well as their total phenol and carotenoid contents. The fatty acid contents were determined by GC-MS. The three types of passion fruit oils studied were refined, cold pressed or extracted from seeds in a Soxhlet apparatus. The oils thus obtained showed differences in antioxidant activity and carotenoid content, but were similar in regard to total phenols. Buriti and pequi had the highest carotenoid contents, while refined and cold pressed passion fruit oil displayed the highest antioxidant activity. Pequi oil was the only oil to display antibacterial and cytotoxic activity.