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1.
Nature ; 606(7913): 255-256, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35650394
2.
Proc Natl Acad Sci U S A ; 119(23): e2112385119, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35648836

RESUMO

SignificanceChemosensory systems play crucial roles across mosquito life cycles, with underlying molecular receptors often forming functional complexes that require cognate coreceptors. To better understand chemosensory pathways in the malaria vector mosquito Anopheles coluzzii, gene editing were used to localize and functionally characterize the ionotropic receptor coreceptor AcIr76b. Expression of AcIr76b was observed in antennal grooved pegs, coeloconic sensilla, and other accessory olfactory appendages. When AcIr76b was inactivated, mutant mosquitoes displayed altered neuronal responses to amines.. Beyond olfactory phenotypes, AcIr76b mutants display significantly impaired mating and blood feeding capabilities. Our data reveal discrete roles of AcIr76b across chemosensory pathways, suggesting ionotropic pathways as targets for the design of vector control strategies.


Assuntos
Anopheles , Comportamento Alimentar , Malária , Mosquitos Vetores , Receptores Ionotrópicos de Glutamato , Animais , Anopheles/genética , Anopheles/fisiologia , Sangue , Feminino , Edição de Genes , Malária/parasitologia , Malária/transmissão , Mosquitos Vetores/genética , Mosquitos Vetores/fisiologia , Receptores Ionotrópicos de Glutamato/genética , Receptores Ionotrópicos de Glutamato/fisiologia , Sensilas/fisiologia , Olfato
3.
Proc Natl Acad Sci U S A ; 119(26): e2117083119, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35737841

RESUMO

There are still significant knowledge gaps in understanding the intrusion and retention of exogeneous particles into the central nervous system (CNS). Here, we uncovered various exogeneous fine particles in human cerebrospinal fluids (CSFs) and identified the ambient environmental or occupational exposure sources of these particles, including commonly found particles (e.g., Fe- and Ca-containing ones) and other compositions that have not been reported previously (such as malayaite and anatase TiO2), by mapping their chemical and structural fingerprints. Furthermore, using mouse and in vitro models, we unveiled a possible translocation pathway of various inhaled fine particles from the lung to the brain through blood circulation (via dedicated biodistribution and mechanistic studies). Importantly, with the aid of isotope labeling, we obtained the retention kinetics of inhaled fine particles in mice, indicating a much slower clearance rate of localized exogenous particles from the brain than from other main metabolic organs. Collectively, our results provide a piece of evidence on the intrusion of exogeneous particles into the CNS and support the association between the inhalation of exogenous particles and their transport into the brain tissues. This work thus provides additional insights for the continued investigation of the adverse effects of air pollution on the brain.


Assuntos
Encéfalo , Pulmão , Material Particulado , Animais , Sangue , Encéfalo/metabolismo , Humanos , Pulmão/química , Pulmão/metabolismo , Camundongos , Tamanho da Partícula , Material Particulado/análise , Material Particulado/sangue , Material Particulado/química , Material Particulado/metabolismo , Distribuição Tecidual
4.
Lima; Perú. Ministerio de Salud; May. 2022. 37 p. tab.
Monografia em Espanhol | MINSAPERÚ, MINSAPERÚ | ID: biblio-1370463

RESUMO

La guía contiene el procedimiento para la determinación de la hemoglobina mediante hemoglobinómetro portátil, que incluye la punción capilar, recojo de la muestra de sangre y materiales que se utilizaran para su correcta aplicación


Assuntos
Sangue , Heme , Métodos
5.
Retrovirology ; 19(1): 7, 2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35585539

RESUMO

BACKGROUND: The potential risk and association of bovine leukemia virus (BLV) with human remains controversial as it has been reported to be both positive and negative in human breast cancer and blood samples. Therefore, establishing the presence of BLV in comprehensive human clinical samples in different geographical locations is essential. RESULT: In this study, we examined the presence of BLV proviral DNA in human blood and breast cancer tissue specimens from Japan. PCR analysis of BLV provirus in 97 Japanese human blood samples and 23 breast cancer tissues showed negative result for all samples tested using long-fragment PCR and highly-sensitive short-fragment PCR amplification. No IgG and IgM antibodies were detected in any of the 97 human serum samples using BLV gp51 and p24 indirect ELISA test. Western blot analysis also showed negative result for IgG and IgM antibodies in all tested human serum samples. CONCLUSION: Our results indicate that Japanese human specimens including 97 human blood, 23 breast cancer tissues, and 97 serum samples were negative for BLV.


Assuntos
Anticorpos Antivirais , DNA Viral , Vírus da Leucemia Bovina , Provírus , Anticorpos Antivirais/isolamento & purificação , Sangue/virologia , Neoplasias da Mama/virologia , DNA Viral/isolamento & purificação , Feminino , Humanos , Imunoglobulina G/isolamento & purificação , Imunoglobulina M/isolamento & purificação , Japão , Vírus da Leucemia Bovina/genética , Vírus da Leucemia Bovina/imunologia , Provírus/genética
6.
Turkiye Parazitol Derg ; 46(2): 108-113, 2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35604187

RESUMO

Objective: To investigate intestinal and blood parasites in people who have a history of traveling abroad during the Coronavirus disease-2019 pandemic and returning to Turkey. Methods: In this study, 104 patients with gastrointestinal system and/or fever complaints who had traveled abroad during the pandemic period and returned to Turkey were included. Parasitic agents were investigated by taking blood and stool samples from the patients. Additionally, urine samples were obtained from patients with hematuria or dysuria with the suspicion of schistosomiasis. A direct microscopic examination, the Crypto-Giardia immunochromatographic test, and ELISA methods were used in the examination of the stool samples. In order to detect Plasmodium species, blood samples were examined by preparing both the rapid diagnostic test and thick drop and thin smear preparations. Results: One or more parasite species were detected in 38 (38.5%) of 104 patients included in the study. While intestinal parasites were detected in 16 (32%) of 50 patients who traveled to Iran and 16 (33.3%) of 48 patients who traveled to Northern Iraq, blood parasites were not found. Schistosoma mansoni was detected in all 5 of the patients with a history of traveling to Sudan. Plasmodium falciparum was detected in 1 patient who traveled to the African continent. Conclusion: It is vital to take precautions to prevent parasitic diseases, such as malaria and schistosomiasis, during travels to African countries. During travels to neighboring countries of Turkey, such as Northern Iraq and Iran, hygiene should be paid attention to, so as to prevent contracting intestinal parasitic diseases. In addition, it was concluded that people who plan to travel abroad should have information about the endemic parasitic diseases of the country that they are going to.


Assuntos
COVID-19 , Enteropatias Parasitárias , Parasitemia , Parasitos , Doença Relacionada a Viagens , Animais , Sangue/parasitologia , COVID-19/epidemiologia , Fezes/parasitologia , Humanos , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/parasitologia , Pandemias , Parasitemia/epidemiologia , Parasitemia/parasitologia , Parasitos/isolamento & purificação , Plasmodium/isolamento & purificação , Turquia/epidemiologia , Urina/parasitologia
7.
J Virol ; 96(11): e0010922, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35575554

RESUMO

Anelloviruses (AVs) are commensal members of the human blood virome. Even though it was estimated that over 90% of the human population carries AVs, the dynamics of the AV virome ("anellome") are unknown. We investigated the dynamics of blood anellomes in two healthy people followed up for more than 30 years. Both subjects were positive for AVs in the majority of samples. Alphatorquevirus (torque teno virus [TTV]) was the most common genus in both subjects, followed by Betatorquevirus (torque teno minivirus [TTMV]) and Gammatorquevirus (torque teno midivirus [TTMDV]). Almost five times more lineages were found in subject 1 than in subject 2, and the anellomes differed phylogenetically. Both anellomes remained compositionally stable, and 9 out of 64 AV lineages were detected in over half of the time points. We confirmed the long-term and short-term persistence of 13 lineages by specific quantitative PCR (qPCR). AV lineages were detected in blood for over 30 years. Noticeable differences in anellome richness were found between the tested subjects, but both anellomes remained compositionally stable over time. These findings demonstrate that the human blood anellome is personal and that AV infection is chronic and potentially commensal. IMPORTANCE Knowledge of the persistence of AVs in humans is crucial to our understanding of the nature of AV infection (chronic or acute) and the role of AV in the host. We therefore investigated the dynamics of anellovirus infection in two healthy people followed up for 30 years. Our findings suggest that the human blood anellovirus virome (anellome) remains stable and personal for decades.


Assuntos
Anelloviridae , Sangue , Infecções por Vírus de DNA , Torque teno virus , Anelloviridae/classificação , Anelloviridae/genética , Sangue/virologia , DNA Viral , Humanos , Filogenia , Torque teno virus/genética , Viroma
8.
Acta Parasitol ; 67(2): 932-942, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35384598

RESUMO

INTRODUCTION: Phlebotomine sand flies (Diptera: Psychodidae) are known as the vector of diseases such as leishmaniasis, bartonellosis and viral diseases. The aim of this study is to detect the host feeding pattern of sand flies in the endemic areas for leishmaniasis in Turkey (Antalya, Kayseri) and Northern Cyprus (TRNC) as well as the presence of Leishmania DNA in the specimens. METHODS: One-hundred seventy-six blood-fed sand fly specimens were examined for blood meal analysis. A SYBR Green-PCR assay was performed with specific forward primers for each host and a universal reverse primer. Primers of human and goat were used together in multiplex PCR while goat and cow were studied separately. ITS-1 qPCR assay was also performed on both blood-fed and non-blood-fed females to detect Leishmania parasites. RESULTS: Blood sources could be detected in 69 out of 176 blood-fed sand fly specimens. The results of blood meal analysis showed that specimens were fed mostly on cows (22.2%) followed by humans (5.7%), goats (2.8%) and dogs (0.6%). Multiple feeding patterns were also detected as human + cow (3.4%), cow + goat (2.8%) and human + goat (1.7%). Five of the blood-fed specimens were Leishmania spp. positive: P. major s.l. (n = 1), P. tobbi (n = 2) were L. tropica positive from Antalya, P. simici was positive for L. infantum from Kayseri and P. papatasi (n = 1) was positive for L. major from Cyprus. Leishmania infection rates were determined as 3.79%, 1.69% and 2.63% among the blood-fed sand fly specimens in Antalya, Kayseri and TRNC, respectively. CONCLUSION: The SYBR-Green-based multiplex PCR assay is a cost-effective and promising tool for blood meal identification of wild-caught sand flies as well as other blood-sucking arthropods. Feeding patterns of important vector species detected in the present study show the high risk in these endemic areas. As a next step, to identify the blood source in a shorter time and to make the test more sensitive, development of this assay to probe-based and multiplex PCR will be also planned.


Assuntos
Sangue , DNA de Protozoário , Insetos Vetores , Leishmania , Leishmaniose , Psychodidae , Animais , Sangue/parasitologia , Bovinos , Chipre/epidemiologia , DNA/genética , DNA/isolamento & purificação , DNA de Protozoário/genética , DNA de Protozoário/isolamento & purificação , Cães , Doenças Endêmicas , Comportamento Alimentar , Feminino , Análise de Alimentos , Insetos Vetores/parasitologia , Insetos Vetores/fisiologia , Leishmania/genética , Leishmaniose/diagnóstico , Leishmaniose/epidemiologia , Leishmaniose/veterinária , Refeições , Phlebotomus/parasitologia , Phlebotomus/fisiologia , Psychodidae/parasitologia , Psychodidae/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Turquia/epidemiologia
9.
ScientificWorldJournal ; 2022: 1426837, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281746

RESUMO

In this work, we deal with unsteady magnetohydrodynamic allowed convection inflow of blood with a carbon nanotubes model; the single and multiwalled carbon nanotubes of human blood are used as a based fluid. Two numerical methods used to study this model are the weighted average finite difference method and the nonstandard compact finite difference method. The proportional Caputo hybrid operator has been used to fractionalize the proposed model. Stability analysis has been construed by a kind of John von Neumann stability analysis. Numerical results are presented in diverse graphs, which manifest that the method is successful in solving the proposed model.


Assuntos
Nanotubos de Carbono , Sangue , Humanos , Hidrodinâmica , Magnetismo , Modelos Estatísticos , Nanotubos de Carbono/estatística & dados numéricos , Reologia
10.
Arch. endocrinol. metab. (Online) ; 66(1): 68-76, Jan.-Feb. 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1364297

RESUMO

ABSTRACT The lowest dosage of empagliflozin (10 mg) showed similar benefits on glycated hemoglobin (HbA1c) level, body weight, blood pressure, and total and cardiovascular mortality in comparison with the highest available dose (25 mg) in the EMPAREG trial. These findings have not been clearly demonstrated for canagliflozin and dapagliflozin. The objective was to compare the effect of different doses of SGLT2 inhibitors commercially available in Brazil on HbA1c and body weight of patients with type 2 diabetes. MEDLINE, Cochrane and Embase databases were searched from inception until 11th October 2021 for randomized controlled trials of SGLT2 inhibitors in type 2 diabetes patients, lasting at least 12 weeks. HbA1c and body weight variations were described using standard mean difference. We performed direct and indirect meta-analysis, as well as a meta-regression with medication doses as covariates. Eighteen studies were included, comprising 16,095 patients. In the direct meta-analysis, SGLT2 inhibitors reduced HbA1c by 0.62% (95% CI −0.66 to −0.59) and body weight by 0.60 kg (95% CI −0.64 to −0.55). In the indirect meta-analysis, canagliflozin 300 mg ranked the highest regarding reductions in HbA1c and body weight. The remaining medications and dosages were clinically similar, despite some statistically significant differences among them. Canagliflozin 300 mg seems to be more potent in reducing HbA1c and body weight in patients with type 2 diabetes. The remaining SGLT2 inhibitors at different doses lead to similar effects for both outcomes. Whether these glycemic and weight effects are reflected in lower mortality and cardiovascular events is still uncertain and may be a topic for further studies.


Assuntos
Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Hipoglicemiantes/uso terapêutico , Sangue , Peso Corporal , Brasil , Hemoglobina A Glicada/análise , Ensaios Clínicos Controlados Aleatórios como Assunto , Canagliflozina/uso terapêutico
11.
Washington, D.C.; OPS; 2022-02-04.
em Espanhol | PAHO-IRIS | ID: phr-55713

RESUMO

La Región de las Américas cuenta con cerca de 2000 bancos de sangre, los cuales realizan diferentes procesos para certificar más de 10 millones de unidades de sangre al año. Se requiere que estos bancos de sangre implementen proceso de calidad como se manifiesta en el plan regional, las adopcion de las directrices sobre buenas prácticas de fabricacion para centros de sangre permite unificar en la region los criterios de calidad y ademas foartelecer la calidad de los centros de sangre y de sus productos. En los últimos años, la seguridad y calidad en la cadena de transfusión se ha convertido en un tema importante en muchos países y regiones. Los centros de sangre deben establecer y mantener sistemas de calidad basados en los principios de buenas prácticas de fabricación que abarquen todas las actividades que determinan los objetivos y responsabilidades de la política de calidad, y deben implantarlos por medios como la planificación, el control, la garantía y la mejora de la calidad. Un enfoque de buenas prácticas para la fabricación de hemoderivados seguros que satisfagan sistemáticamente las especificaciones predefinidas y las expectativas de los clientes proporciona un modelo que permita un sistema documentado de incorporar la calidad a todo el proceso. Se espera que este documento facilite la armonizacion de los sistemas de calidad en los centros de sangre de la Región.


Assuntos
Sangue , Plasma , Medicamentos Hemoderivados , Manufaturas , Boas Práticas de Fabricação
12.
Molecules ; 27(3)2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35164250

RESUMO

It is not easy to find data in the scientific literature on the quantitative content of individual phytochemicals. It is possible to find groups of compounds and even individual compounds rather easily, but it is not known what their concentration is in cultivated or wild plants. Therefore, the subject of this study was to determine the content of individual compounds in the new Paulownia species, Oxytree, developed in a biotechnology laboratory in 2008 at La Mancha University in Spain. Six secondary metabolites were isolated, and their chemical structure was confirmed by spectral methods. An analytical method was developed, which was then used to determine the content of individual compounds in leaves, twigs, flowers and fruits of Paulownia Clon in Vitro 112®. No flavonoids were found in twigs and fruits of Oxytree, while the highest phenylethanoid glycosides were found in twigs. In this study, we also focused on biological properties (anticoagulant or procoagulant) of extract and four fractions (A-D) of different chemical composition from Paulownia Clon in Vitro 112 leaves using whole human blood. These properties were determined based on the thrombus-formation analysis system (T-TAS), which imitates in vivo conditions to assess whole blood thrombogenecity. We observed that three fractions (A, C and D) from leaves decrease AUC10 measured by T-TAS. In addition, fraction D rich in triterpenoids showed the strongest anticoagulant activity. However, in order to clarify the exact mechanism of action of the active substances present in this plant, studies closer to physiological conditions, i.e., in vivo studies, should be performed, which will also allow to determine the effects of their long-term effects.


Assuntos
Anticoagulantes/farmacologia , Sangue , Lamiales/química , Extratos Vegetais/farmacologia , Anticoagulantes/farmacocinética , Área Sob a Curva , Plaquetas/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Lamiales/metabolismo , Espectrometria de Massas/métodos , Extratos Vegetais/farmacocinética , Folhas de Planta/química
13.
Molecules ; 27(3)2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35164262

RESUMO

Accurate and precise measurement of the relative protein content of blood-based samples using mass spectrometry is challenging due to the large number of circulating proteins and the dynamic range of their abundances. Traditional spectral processing methods often struggle with accurately detecting overlapping peaks that are observed in these samples. In this work, we develop a novel spectral processing algorithm that effectively detects over 1650 peaks with over 3.5 orders of magnitude in intensity in the 3 to 30 kD m/z range. The algorithm utilizes a convolution of the peak shape to enhance peak detection, and accurate peak fitting to provide highly reproducible relative abundance estimates for both isolated peaks and overlapping peaks. We demonstrate a substantial increase in the reproducibility of the measurements of relative protein abundance when comparing this processing method to a traditional processing method for sample sets run on multiple matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) instruments. By utilizing protein set enrichment analysis, we find a sizable increase in the number of features associated with biological processes compared to previously reported results. The new processing method could be very beneficial when developing high-performance molecular diagnostic tests in disease indications.


Assuntos
Sangue , Técnicas de Diagnóstico Molecular/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Algoritmos , Humanos , Reprodutibilidade dos Testes
14.
Proc Natl Acad Sci U S A ; 119(11)2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35217532

RESUMO

The impacts of interferon (IFN) signaling on COVID-19 pathology are multiple, with both protective and harmful effects being documented. We report here a multiomics investigation of systemic IFN signaling in hospitalized COVID-19 patients, defining the multiomics biosignatures associated with varying levels of 12 different type I, II, and III IFNs. The antiviral transcriptional response in circulating immune cells is strongly associated with a specific subset of IFNs, most prominently IFNA2 and IFNG. In contrast, proteomics signatures indicative of endothelial damage and platelet activation associate with high levels of IFNB1 and IFNA6. Seroconversion and time since hospitalization associate with a significant decrease in a specific subset of IFNs. Additionally, differential IFN subtype production is linked to distinct constellations of circulating myeloid and lymphoid immune cell types. Each IFN has a unique metabolic signature, with IFNG being the most associated with activation of the kynurenine pathway. IFNs also show differential relationships with clinical markers of poor prognosis and disease severity. For example, whereas IFNG has the strongest association with C-reactive protein and other immune markers of poor prognosis, IFNB1 associates with increased neutrophil to lymphocyte ratio, a marker of late severe disease. Altogether, these results reveal specialized IFN action in COVID-19, with potential diagnostic and therapeutic implications.


Assuntos
Sangue/metabolismo , COVID-19/imunologia , Interferons/sangue , Proteoma , Transcriptoma , COVID-19/sangue , Estudos de Casos e Controles , Conjuntos de Dados como Assunto , Humanos , Pacientes Internados
15.
PLoS Negl Trop Dis ; 16(2): e0010204, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35130307

RESUMO

BACKGROUND: Culex pipiens quinquefasciatus Say (Cx. quinquefasciatus) and Culex pipiens form molestus Forskal (Cx. molestus) in the Culex pipiens complex group show considerable differences in host seeking, blood feeding, mating behavior and in vector competence. Blood-feeding mosquito behaviors are closely related to their olfactory gene expression and olfactory gene repertoire composition. Comparing olfactory genes between these two subspecies with significantly different blood-feeding behaviors can support further research on the molecular mechanism of the Culex pipiens complex olfactory sensory system, providing a new approach for determining candidate attractant or repellent compounds. METHODS: Non-blood-feeding (NBF) and post-blood-feeding (PBF) olfactory system transcriptomes of the two subspecies were sequenced, and the biological functions of their differentially expressed genes were described by bioinformatics analysis. A quantitative polymerase chain reaction (qPCR) was applied to validate the RNA-seq data. The roles of particular olfactory receptors in Cx. quinquefasciatus blood-feeding behaviors were evaluated by RNAi. RESULTS: Five, 7, 24, and 3 Cx. quinquefasciatus-specific OBPs, Cx. molestus-specific OBPs, Cx. quinquefasciatus-specific ORs and Cx. molestus-specific ORs were identified, respectively. The majority of selected ORs were consistent with the predicted transcriptome sequencing results after qRT-PCR validation. OR5 was expressed only in Cx. quinquefasciatus, and OR65 was the only gene upregulated after blood feeding in Cx. molestus. The blood-feeding rates of the OR5 and OR78 dsRNA groups were significantly lower (4.3%±3.1% and 13.3%±11.5%) than those of the enhanced green fluorescence protein (EGFP) group (64.5%±8.7%). CONCLUSION: Most OBPs and ORs were expressed in both subspecies but showed divergence in expression level. OR5 and OR65 might be species-specific expressed genes that regulate the olfactory behaviors of Cx. quinquefasciatus and Cx. molestus, respectively. The RNA interference of OR5 and OR78 could inhibit the blood-feeding behavior of Cx. quinquefasciatus, providing new targets for screening effective repellent compounds to control mosquito-borne diseases effectively and efficiently.


Assuntos
Culex/genética , Comportamento Alimentar/fisiologia , Receptores Odorantes/genética , Animais , Sangue , Culex/classificação , Culex/metabolismo , Culex/fisiologia , Feminino , Perfilação da Expressão Gênica , Proteínas de Fluorescência Verde/genética , Camundongos , Mosquitos Vetores/genética
16.
Proc Natl Acad Sci U S A ; 119(8)2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35165177

RESUMO

Hydrogen peroxide (H2O2) plays a key role in environmental chemistry, biology, and medicine. H2O2 concentrations typically are 6 to 10 orders of magnitude lower than that of water, making its quantitative detection challenging. We demonstrate that optimized NMR spectroscopy allows direct, interference-free, quantitative measurements of H2O2 down to submicromolar levels in a wide range of fluids, ranging from exhaled breath and air condensate to rain, blood, urine, and saliva. NMR measurements confirm the previously reported spontaneous generation of H2O2 in microdroplets that form when condensing water vapor on a hydrophobic surface, which can interfere with atmospheric H2O2 measurements. Its antimicrobial activity and strong seasonal variation speculatively could be linked to the seasonality of respiratory viral diseases.


Assuntos
Peróxido de Hidrogênio/análise , Espectroscopia de Ressonância Magnética/métodos , Ar/análise , Sangue , Análise Química do Sangue , Líquidos Corporais/química , Expiração/fisiologia , Fezes/química , Humanos , Chuva/química , Saliva/química , Urina/química
17.
Biochem Biophys Res Commun ; 599: 134-141, 2022 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-35182939

RESUMO

Metabolic abnormalities are tightly connected to the perturbation of normal brain functions, thereby causing multiple neurodegenerative diseases. The hypothalamus is the master unit that controls the whole-body energy homeostasis. Thus, altered metabolic activity in the hypothalamus could be a crucial clue to better understand the development of metabolic disorders during aging. The current study aimed to investigate the changes in hypothalamic metabolites according to the aging process using gas chromatography-mass spectrometry. We identified that multiple metabolites and neurotransmitters were effectively reduced in the hypothalamus of aged mice. In addition, we observed increased levels of genes linked to the production and utilization of monocarboxylates in the aged hypothalamus, indicating the initiation of metabolic activity to produce alternative nutrient sources. Lastly, we found a reduced number of astrocytes in the hypothalamus of aged mice, suggesting that reduced nutrient availability in the hypothalamus might be associated with the decreased activity of astrocytes during aging. Collectively, the present study suggests that the deterioration of metabolic activities in the hypothalamus might be a primary cause and/or outcome of metabolic diseases associated with the aging process.


Assuntos
Envelhecimento/metabolismo , Hipotálamo/metabolismo , Metaboloma/fisiologia , Animais , Astrócitos/metabolismo , Sangue/metabolismo , Regulação da Expressão Gênica , Proteína Glial Fibrilar Ácida/imunologia , Hipotálamo/citologia , Hipotálamo/fisiologia , Imuno-Histoquímica/métodos , Masculino , Camundongos Endogâmicos C57BL
18.
Gene ; 822: 146355, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35189248

RESUMO

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) have been thoroughly studied as the pathogens associated with hospital acquired infections. However, data on Serratia marcescens are not enough. S. marcescens is now becoming a propensity for its highly antimicrobial-resistant clinical infections. METHODS: Four carbapenem-resistant S. marcescens (CR-SM) isolates were obtained from hospitalized patients through routine microbiological experiments. We assembled the isolates genomes using whole genome sequencing (WGS) and compared their resistome and virulome patterns. RESULTS: The average length and CG content of chromosomes was 5.33 Mbp and 59.8%, respectively. The number of coding sequences (CDSs) ranged from 4,959 to 4,989. All strains had one single putative conjugative plasmid with IncL incompatibility (Inc) group. The strains harbored blaCTX-M-15, blaTEM-1 and blaSHV-134. All plamsids were positive for blaOXA-48. No blaNDM-1, blaKPC, blaVIM and blaIMP were identified. The blaSRT-2 and aac(6')-Ic genes were chromosomally-encoded. Class 1 integron was detected in strains P8, P11 and P14. The Escher_RCS47 and Salmon_SJ46 prophages played major role in plasmid-mediated carraige of extended spectrum ß-lactamases (ESBLs). The CR-SM strains were equipt with typical virulence factors of oppotunistic pathogens including biofilm formation, adhesins, secretory systems and siderophores. The strains did not have ability to produce prodigiosin but were positive for chitinase and EstA. CONCLUSION: The presence of conjugative plasmids harboring major ß-lactamases within prophage and class 1 integron structures highlights the role of different mobile genetic elements (MGEs) in distribution of AMR factors and more specifically carbapenemases. More molecular studies are required to determine the status of carbapenem resistance in clinical starins. However, appropriate strategies to control the global dissemination of CR-SM are urgent.


Assuntos
Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla , Prófagos/genética , Serratia marcescens/classificação , Sequenciamento Completo do Genoma/métodos , Adulto , Composição de Bases , Sangue/microbiologia , Líquido da Lavagem Broncoalveolar/microbiologia , Tamanho do Genoma , Genoma Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala , Hospitalização , Humanos , Masculino , Filogenia , Plasmídeos/genética , Serratia marcescens/genética , Serratia marcescens/isolamento & purificação , Serratia marcescens/virologia , Fatores de Virulência/genética , Adulto Jovem , beta-Lactamases/genética
19.
Sci Rep ; 12(1): 2099, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35136102

RESUMO

The discovery and utility of clinically relevant circulating biomarkers depend on standardized methods that minimize preanalytical errors. Despite growing interest in studying extracellular vesicles (EVs) and cell-free messenger RNA (cf-mRNA) as potential biomarkers, how blood processing and freeze/thaw impacts the profiles of these analytes in plasma was not thoroughly understood. We utilized flow cytometric analysis to examine the effect of differential centrifugation and a freeze/thaw cycle on EV profiles. Utilizing flow cytometry postacquisition analysis software (FCMpass) to calibrate light scattering and fluorescence, we revealed how differential centrifugation and post-freeze/thaw processing removes and retains EV subpopulations. Additionally, cf-mRNA levels measured by RT-qPCR profiles from a panel of housekeeping, platelet, and tissue-specific genes were preferentially affected by differential centrifugation and post-freeze/thaw processing. Critically, freezing plasma containing residual platelets yielded irreversible ex vivo generation of EV subpopulations and cf-mRNA transcripts, which were not removable by additional processing after freeze/thaw. Our findings suggest the importance of minimizing confounding variation attributed to plasma processing and platelet contamination.


Assuntos
Sangue , Ácidos Nucleicos Livres , Criopreservação , Vesículas Extracelulares , RNA Mensageiro , Citometria de Fluxo , Humanos
20.
Nat Commun ; 13(1): 761, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-35140201

RESUMO

DNA methylation microarrays can be employed to interrogate cell-type composition in complex tissues. Here, we expand reference-based deconvolution of blood DNA methylation to include 12 leukocyte subtypes (neutrophils, eosinophils, basophils, monocytes, naïve and memory B cells, naïve and memory CD4 + and CD8 + T cells, natural killer, and T regulatory cells). Including derived variables, our method provides 56 immune profile variables. The IDOL (IDentifying Optimal Libraries) algorithm was used to identify libraries for deconvolution of DNA methylation data for current and previous platforms. The accuracy of deconvolution estimates obtained using our enhanced libraries was validated using artificial mixtures and whole-blood DNA methylation with known cellular composition from flow cytometry. We applied our libraries to deconvolve cancer, aging, and autoimmune disease datasets. In conclusion, these libraries enable a detailed representation of immune-cell profiles in blood using only DNA and facilitate a standardized, thorough investigation of immune profiles in human health and disease.


Assuntos
Sangue/imunologia , Metilação de DNA/imunologia , Algoritmos , Basófilos , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Ilhas de CpG , Epigênese Genética , Citometria de Fluxo , Humanos , Contagem de Leucócitos , Monócitos , Neutrófilos , Análise de Sequência com Séries de Oligonucleotídeos
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