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1.
Clin Chem Lab Med ; 58(7): 1100-1105, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32573995

RESUMO

Background Comprehensive information has been published on laboratory tests which may predict worse outcome in Asian populations with coronavirus disease 2019 (COVID-19). The aim of this study is to describe laboratory findings in a group of Italian COVID-19 patients in the area of Valcamonica, and correlate abnormalities with disease severity. Methods The final study population consisted of 144 patients diagnosed with COVID-19 (70 who died during hospital stay and 74 who survived and could be discharged) between March 1 and 30, 2020, in Valcamonica Hospital. Demographical, clinical and laboratory data were collected upon hospital admission and were then correlated with outcome (i.e. in-hospital death vs. discharge). Results Compared to patients who could be finally discharged, those who died during hospital stay displayed significantly higher values of serum glucose, aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), urea, creatinine, high-sensitivity cardiac troponin I (hscTnI), prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (APTT), D-dimer, C reactive protein (CRP), ferritin and leukocytes (especially neutrophils), whilst values of albumin, hemoglobin and lymphocytes were significantly decreased. In multiple regression analysis, LDH, CRP, neutrophils, lymphocytes, albumin, APTT and age remained significant predictors of in-hospital death. A regression model incorporating these variables explained 80% of overall variance of in-hospital death. Conclusions The most important laboratory abnormalities described here in a subset of European COVID-19 patients residing in Valcamonica are highly predictive of in-hospital death and may be useful for guiding risk assessment and clinical decision-making.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Arginina/sangue , Aspartato Aminotransferases/sangue , Betacoronavirus , Glicemia/análise , Proteína C-Reativa/análise , Carnosina/sangue , Técnicas de Laboratório Clínico , Comorbidade , Infecções por Coronavirus/fisiopatologia , Creatina Quinase/sangue , Creatinina/sangue , Combinação de Medicamentos , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio , Mortalidade Hospitalar , Humanos , Itália , L-Lactato Desidrogenase/sangue , Leucócitos , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/fisiopatologia , Tempo de Protrombina , Albumina Sérica Humana/análise , Troponina I/sangue , Ureia/sangue
3.
Zhonghua Nei Ke Za Zhi ; 59(5): 372-374, 2020 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-32370466

RESUMO

To investigate the early changes of peripheral blood leukocyte differential counts in patients with COVID-19. Ten patients with COVID-19 and 30 patients with other viral pneumonia (non-COVID-19) admitted to The Sixth People's Hospital of Shanghai and Jinshan Branch Hospital from January 22 to February 17, 2020 were enrolled in this study. The differential counts of white blood cells (WBC) were analyzed. Patients in COVID-19 group showed relatively lower absolute WBC count 4.95(3.90,6.03)×10(9)/L, lymphocyte absolute count 1.20(0.98,1.50)×10(9)/L and eosinophil absolute count 0.01(0.01,0.01)×10(9)/L. Leukopenia developed in two patients(2/10), lymphocytopenia also in two patients(2/10). Seven over ten patients presented with eosinophil cytopenia. In non-COVID-19 group, absolute WBC count was 8.20(6.78,9.03)×10(9)/L (P<0.001), lymphocyte absolute count 1.75(1.20,2.53)×10(9)/L(P=0.036), eosinophil absolute count 0.02(0.01,0.03)×10(9)/L(P=0.005). Lymphocytopenia occurred in 16.7% patients, eosinophil cytopenia in 16.7% patients too. In conclusion, leukopenia, lymphocytopenia and eosinophil cytopenia are more common in COVID-19 patients than those in non-COVID-19 patients.


Assuntos
Infecções por Coronavirus/sangue , Leucócitos/citologia , Pneumonia Viral/sangue , Betacoronavirus , Estudos de Casos e Controles , China , Eosinófilos/citologia , Humanos , Contagem de Leucócitos , Leucopenia , Linfopenia , Pandemias
4.
Medicine (Baltimore) ; 99(14): e19627, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243389

RESUMO

Effects of mutations on AML (acute myeloid leukemia) patients have been an area of clinical interest. The aim of this study was to analyze pre-chemotherapy WBC (white blood cell), platelet, monocyte, hemoglobin, and mean platelet volume (MPV) levels in acute myeloid leukemia patients with Wilms tumor 1 (WT1), FMS-like tyrosine kinase 3 (FLT3), or nucleophosmin (NPM) gene mutations, attempting to detect and compare possible differences in these values.The study included 71 patients with acute myeloid leukemia known to have WT1, FLT3, or NPM gene mutations. The patients were divided into 3 groups: FLT3-mutated AML patients without any accompanying known mutations other than WT1 at the time of diagnosis (Group 1), NPM-mutated AML patients without any accompanying known mutations other than WT1 at the time of diagnosis (Group 2), WT1-mutated AML patients with no other accompanying known mutations at the time of diagnosis (Group 3). We carried out intergroup comparisons of WBC, platelet (PLT), monocyte, hemoglobin, and MPV levels before chemotherapy.There was a statistically significant difference between the groups in terms of WBC parameters (P = .001). There were no statistically significant differences between the groups with respect to hemoglobin, platelet, and monocyte levels.Higher white blood cell counts could be observed in patients with FLT3-mutated AML.


Assuntos
Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/genética , Proteínas Nucleares/sangue , Proteínas WT1/sangue , Tirosina Quinase 3 Semelhante a fms/sangue , Adulto , Feminino , Hemoglobinas/análise , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucócitos , Masculino , Volume Plaquetário Médio , Monócitos/metabolismo , Mutação , Proteínas Nucleares/genética , Contagem de Plaquetas , Proteínas WT1/genética , Tirosina Quinase 3 Semelhante a fms/genética
5.
Cancer Sci ; 111(5): 1856-1861, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32249523

RESUMO

The telomere G-tail (G-tail) plays an essential role in maintaining chromosome stability. In this study, we assessed the leukocyte G-tail length of breast cancer (BC) patients and cancer-free individuals and evaluated the association between the G-tail length and the presence of BC. A significant shortening of the median G-tail length was observed in BC patients compared with cancer-free individuals and was found in the early phase of BC. Our study indicated that the leukocyte G-tail length might be a potential biomarker for BC detection.


Assuntos
Neoplasias da Mama/diagnóstico , Leucócitos/ultraestrutura , Telômero/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/sangue , Neoplasias da Mama/ultraestrutura , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Encurtamento do Telômero
6.
PLoS One ; 15(4): e0230053, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298279

RESUMO

Although anxiety disorders are among the most prevalent of psychiatric disorders, childhood trauma-related studies seldom consider anxiety proneness as distinct aetiological contributor. We aimed to distinguish between trauma- and anxiety-associated physiological profiles. South African adolescent volunteers were categorised for trauma exposure (CTQ, mean score 39±11) and anxiety proneness (AP)(CASI, mean score 37±7, STAI-T, mean score 41±8). Circulating hormone and leukocyte glucocorticoid receptor levels, as well as leukocyte functional capacity, were assessed. AP was associated with lower DHEAs (P<0.05) and higher leukocyte GR expression (P<0.05). DHEAs was also negatively correlated with anxiety sensitivity (CASI, P<0.05). In conclusion, AP may have more predictive power than trauma in terms of health profile. Increased glucocorticoid sensitivity previously reported after trauma, may be a unique function of anxiety and not trauma exposure per se. DHEAs concentration was identified as potentially useful marker for monitoring progressive changes in HPA-axis sensitivity and correlated with psychological measures of anxiety.


Assuntos
Transtornos de Ansiedade/sangue , Desidroepiandrosterona/sangue , Regulação da Expressão Gênica , Leucócitos/metabolismo , Receptores de Glucocorticoides/sangue , Estresse Psicológico/sangue , Adolescente , Transtornos de Ansiedade/psicologia , Feminino , Humanos , Masculino , África do Sul , Estresse Psicológico/psicologia
8.
Clin Chem Lab Med ; 58(7): 1095-1099, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32301746

RESUMO

Objectives The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to date, the epidemic has gradually spread to 209 countries worldwide with more than 1.5 million infected people and 100,000 deaths. Amplification of viral RNA by rRT-PCR serves as the gold standard for confirmation of infection, yet it needs a long turnaround time (3-4 h to generate results) and shows false-negative rates as large as 15%-20%. In addition, the need of certified laboratories, expensive equipment and trained personnel led many countries to limit the rRT-PCR tests only to individuals with pronounced respiratory syndrome symptoms. Thus, there is a need for alternative, less expensive and more accessible tests. Methods We analyzed the plasma levels of white blood cells (WBCs), platelets, C-reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), alkaline phosphatase and lactate dehydrogenase (LDH) of 207 patients who, after being admitted to the emergency room of the San Raffaele Hospital (Milan, Italy) with COVID-19 symptoms, were rRT-PCR tested. Of them, 105 tested positive, whereas 102 tested negative. Results Statistically significant differences were observed for WBC, CRP, AST, ALT and LDH. Empirical thresholds for AST and LDH allowed the identification of 70% of either COVID-19-positive or -negative patients on the basis of routine blood test results. Conclusions Combining appropriate cutoffs for certain hematological parameters could help in identifying false-positive/negative rRT-PCR tests. Blood test analysis might be used as an alternative to rRT-PCR for identifying COVID-19-positive patients in those countries which suffer from a large shortage of rRT-PCR reagents and/or specialized laboratory.


Assuntos
Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Testes Hematológicos/métodos , Pneumonia Viral/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/análise , Alanina Transaminase/sangue , Fosfatase Alcalina/análise , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/análise , Aspartato Aminotransferases/sangue , Betacoronavirus/patogenicidade , Plaquetas , Proteína C-Reativa/análise , Infecções por Coronavirus/sangue , Feminino , Humanos , Itália , L-Lactato Desidrogenase/análise , L-Lactato Desidrogenase/sangue , Laboratórios , Leucócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , RNA Viral , Reação em Cadeia da Polimerase em Tempo Real/métodos , Estudos Retrospectivos , gama-Glutamiltransferase/análise , gama-Glutamiltransferase/sangue
9.
Adv Exp Med Biol ; 1204: 197-214, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32152948

RESUMO

Siglecs are sialic acid (Sia) recognizing immunoglobulin-like receptors expressed on the surface of all the major leukocyte lineages in mammals. Siglecs recognize ubiquitous Sia epitopes on various glycoconjugates in the cell glycocalyx and transduce signals to regulate immunological and inflammatory activities of these cells. The subset known as CD33-related Siglecs is principally inhibitory receptors that suppress leukocyte activation, and recent research has shown that a number of bacterial pathogens use Sia mimicry to engage these Siglecs as an immune evasion strategy. Conversely, Siglec-1 is a macrophage phagocytic receptor that engages GBS and other sialylated bacteria to promote effective phagocytosis and antigen presentation for the adaptive immune response, whereas certain viruses and parasites use Siglec-1 to gain entry to immune cells as a proximal step in the infectious process. Siglecs are positioned in crosstalk with other host innate immune sensing pathways to modulate the immune response to infection in complex ways. This chapter summarizes the current understanding of Siglecs at the host-pathogen interface, a field of study expanding in breadth and medical importance, and which provides potential targets for immune-based anti-infective strategies.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/imunologia , Animais , Glicocálix/imunologia , Humanos , Leucócitos/citologia , Leucócitos/imunologia , Macrófagos/imunologia , Fagocitose , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia
10.
J Cancer Res Clin Oncol ; 146(5): 1115-1124, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32144534

RESUMO

PURPOSE: Aberrant DNA methylation could regulate the expression of tumor suppressor gene DLEC1 and oncogene PBX3 and was related to the occurrence and prognosis of gastric cancer (GC). In this study, the associations between DLEC1 and PBX3 promoter methylation in peripheral blood leukocytes (PBLs) and the risk and prognosis of GC were investigated. METHODS: The methylation status of DLEC1 and PBX3 promoter in PBLs of 368 GC cases and 382 controls was detected by the methylation-sensitive high-resolution melting (MS-HRM) method. Logistic and Cox regression were adopted to analyze the associations of DLEC1 and PBX3 methylation with GC risk and prognosis, respectively. Confounding biases were controlled by propensity score (PS). RESULTS: Compared with negative methylation (Nm), DLEC1-positive methylation (Pm) was associated with increased GC risk in PS (OR 2.083, 95% CI 1.220-3.558, P = 0.007), but PBX3 Pm was not associated with GC risk. In the elderly group (≥ 60 years), DLEC1 Pm was associated with increased GC risk (OR 2.951, 95% CI 1.426-6.104, P = 0.004). The combined effects between DLEC1 methylation and consumption of dairy products, fried food intake and Helicobacter pylori (H. pylori) infection on GC risk were discovered (ORc 3.461, 95% CI 1.847-6.486, P < 0.001, ORc 3.246, 95% CI 1.708-6.170, P < 0.001 and ORc 2.964, 95% CI 1.690-5.197, P < 0.001, respectively). Furthermore, DLEC1 and PBX3 methylation were not associated with GC prognosis. CONCLUSION: DLEC1 methylation in PBLs and the combined effects of gene-environment can influence GC risk.


Assuntos
Proteínas de Homeodomínio/genética , Leucócitos/metabolismo , Proteínas Proto-Oncogênicas/genética , Neoplasias Gástricas/genética , Proteínas Supressoras de Tumor/genética , Estudos de Casos e Controles , Metilação de DNA , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Infecções por Helicobacter/genética , Helicobacter pylori/isolamento & purificação , Humanos , Leucócitos/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia
11.
DNA Cell Biol ; 39(4): 548-554, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32155344

RESUMO

The Qing-Tibet Plateau is characterized by low oxygen pressure, which is an important biomedical and ecological stressor. However, the variation in gene expression during periods of stay on the plateau has not been well studied. We recruited eight volunteers to stay on the plateau for 3, 7, and 30 days. Human Clariom D arrays were used to measure transcriptome changes in the mRNA expression profiles in these volunteers' blood. Analysis of variance (ANOVA) indicated that 699 genes were significantly differentially expressed in response to entering the plateau during hypoxic exposure. The genes with changes in transcript abundance were involved in the terms phosphoprotein, acetylation, protein binding, and protein transport. Furthermore, numerous genes involved in hematopoietic functions, including erythropoiesis and immunoregulation, were differentially expressed in response to hypoxia. This phenomenon may be one of reasons why the majority of people entering the plateau do not have excessive erythrocyte proliferation and are susceptible to infection.


Assuntos
Aclimatação/genética , Doença da Altitude/genética , Doença da Altitude/fisiopatologia , Hipóxia/fisiopatologia , Leucócitos/fisiologia , Altitude , Eritrócitos/citologia , Eritropoese/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Humanos , Leucopoese/genética , Masculino , Oxigênio , Tibet
12.
BMC Infect Dis ; 20(1): 205, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143599

RESUMO

BACKGROUND: The occurrence of segmental/lobar pattern pneumonia (S/L-PP) in children has recently increased. The pathogens of the disease may change for the misuse of antibiotics and the application of vaccines. Therefore, pathogens positive in hospitalized children with S/L-PP and their association with clinical characteristics may have changed. The aim of this study was to analyze the pathogens positive in hospitalized children with S/L-PP and their association with clinical characteristics. METHOD: The current study analyzed the epidemiological and clinical characteristics of pathogens positive in children with S/L-PP under 14 years old at a single hospital between 1st Jan 2014 and 31st Dec 2018 retrospectively. The pathogens were detected by microbial cultivation, indirect immunofluorescence of the kit (PNEUMOSLIDE IgM), Elisa, and/or real-time PCR in the samples of the patients. RESULTS: A total of 593 children with S/L-PP received treatment at a single hospital during the study period by inclusion criteria. Four hundred fifty-one patients were single positive for one pathogen and 83 patients were positive for at least 2 pathogens. Mycoplasma pneumoniae (M.pneumoniae) (72.34%) was the most commonly detected pathogen, followed by Streptococcus pneumoniae (S.pneumoniae) (8.77%). The prevalence of M.pneumoniae in children with S/L-PP increased with time (p < 0.05). The positive rate of M.pneumoniae increased with ages of patients (p < 0.05). M.pneumoniae was statistically associated with the extrapulmonary manifestations while S.pneumoniae was statistically associated with abnormal white blood cells (WBCs) and C reactive proteins (CRPs) (p < 0.05). CONCLUSION: M.pneumoniae was the most positive pathogen in children with S/L-PP. The positive rate of M.pneumoniae in children with S/L-PP increased with time and the ages of children. M.pneumoniae was associated with extrapulmonary manifestations while S.pneumoniae was associated with abnormal WBCs and CRPs.


Assuntos
Mycoplasma pneumoniae/isolamento & purificação , Pneumonia por Mycoplasma/diagnóstico , Pneumonia Pneumocócica/diagnóstico , Streptococcus pneumoniae/isolamento & purificação , Adolescente , Proteína C-Reativa/análise , Criança , Criança Hospitalizada , Pré-Escolar , Feminino , Humanos , Lactente , Leucócitos/citologia , Masculino , Pneumonia por Mycoplasma/epidemiologia , Pneumonia Pneumocócica/epidemiologia , Prevalência , Estudos Retrospectivos , Estações do Ano
13.
J Sports Sci ; 38(9): 1026-1035, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32175820

RESUMO

The length of telomeres is an objective measure of biologic ageing. This study evaluated the extent minutes of walking per week are associated with leukocyte telomere length (LTL) in a random sample of 5,823 U.S. adults. The investigation was cross-sectional and data were obtained from the National Health and Nutrition Examination Survey (NHANES). LTL was measured by the quantitative polymerase chain reaction method. Walking minutes was calculated from walking frequency and duration measures. Results showed that for each year of chronological age, telomeres were 15.6 base pairs shorter (P < 0.0001). With walking minutes and LTL treated as continuous variables, the relationship was quadratic, not linear (F = 11.2, P = 0.0023). With walking time divided into three categories, adults who performed ≥ 150 minutes of walking per week had longer telomeres than those who did no regular walking, and those who did some, but less than the recommendation (F = 5.0, P = 0.0137). Regular walkers were estimated to have a biologic ageing advantage associated with 6.5-7.6 years less biologic ageing compared to non-walkers, after adjusting for covariates. Additional investigations designed to study causality and the mechanisms associated with the walking and LTL relationship are needed.


Assuntos
Envelhecimento/fisiologia , Encurtamento do Telômero/fisiologia , Caminhada/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Leucócitos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Adulto Jovem
14.
Arthroscopy ; 36(3): 658-659, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32139046

RESUMO

As failure rates after arthroscopic rotator cuff remain high, platelet-rich plasma (PRP) has gained interest as a potential biological augmentation to enhance bone-tendon healing. Recent research shows that delayed PRP application fails to significantly improve clinical results or decrease retear rates but may result in less fatty-infiltration of the repaired rotator cuff muscles. In combination with a lower trend toward retear, this may hint that we should not bid farewell to PRP in rotator cuff repair just yet, and whether our current enthusiasm for emerging biological strategies in rotator cuff repair is justified remains subject to additional investigation.


Assuntos
Plasma Rico em Plaquetas , Lesões do Manguito Rotador , Artroscopia , Método Duplo-Cego , Humanos , Leucócitos , Manguito Rotador , Cicatrização
15.
Gene ; 741: 144579, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32171822

RESUMO

Interleukin (IL)-10 is a critical anti-inflammatory and late cytokine being produced after the proinflammatory mediators while IL-6 is a promptly synthesized cytokine in response to inflammation in mammals. This chronological expression of interleukin (Il)-6 and Il-10 was also found in grass carp head kidney leucocytes (HKLs) treated by heat-killed Aeromonas hydrophila, supporting the possible interplay between grass carp (gc)Il-6 and gcIl-10 in HKLs. Our further findings were in agreement with this hypothesis that recombinant gcIl-6 (rgcIl-6) promptly and transiently increased gcil10 mRNA levels in grass carp HKLs. Moreover, rgcIl-6 enhanced its own mRNA level and this self-enhancement of gcil6 mRNA level could be partially blocked by rgcIl-10. These results collectively suggest that gcIl-10 production stimulated by gcIl-6 may provide a negative feedback to gcIl-6 production. Interestingly, rgcIl-6 significantly decreased gcil10 mRNA levels in grass carp HKLs after the treatment for 12 and 24 h in contrast to its enhancement of gcil10 levels after the treatment for 3 h. Involvement of Stat3 but not MEK, p38 MAPK or JNK pathway in the increase of gcil10 mRNA levels by rgcIl-6 was revealed by using the signaling pathway inhibitors. This was supported by the fact that rgcIl-6 stimulated Stat3 phosphorylation in grass carp HKLs. Furthermore, rgcIl-6 had no effect on the stability of gcil10 mRNA after the treatment for 3 to 36 h while it increased gcil10 promoter activity after the treatment for 24 h. Taken these data together, gcIl-6 can stimulate Il-10 production at early stage but subsequently inhibit il10 mRNA expression in grass carp HKLs, shedding light on the dynamic regulation of il10 mRNA expression by Il-6 in fish immune cells.


Assuntos
Carpas/genética , Interleucina-10/genética , Interleucina-6/genética , Fator de Transcrição STAT3/genética , Sequência de Aminoácidos , Animais , Regulação da Expressão Gênica/genética , Rim Cefálico/metabolismo , Leucócitos/metabolismo
16.
PLoS One ; 15(3): e0229949, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32182245

RESUMO

We present a two-tiered microchip system to capture and retrieve rare cells from blood samples with high purity. The first module of the system is a high throughput microfluidic interface that is used to immunomagnetically isolate targeted rare cells from whole blood, and discard > 99.999% of the unwanted leukocytes. The second module is a microwell array that furthers the purification by magnetically guiding each cell into a separate well concurrently, and allows individual retrieval of each cell. We demonstrate the design of the system as well as its characterization by experiments using model cell lines that represent circulating fetal trophoblasts. Our results show that single cells can be retrieved with efficiencies and purities as high as 100% within 145 mins.


Assuntos
Separação Celular , Procedimentos Analíticos em Microchip , Neoplasias/sangue , Análise de Célula Única , Linhagem Celular Tumoral , Humanos , Leucócitos/citologia , Análise em Microsséries , Microfluídica/métodos , Neoplasias/patologia , Trofoblastos/citologia
17.
Sci Total Environ ; 722: 137933, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32213432

RESUMO

Exposure to air pollution is associated with adverse health effects; however, the available evidence of its association with telomere length (TL), an early marker of ageing, in children is still scarce with no study available for preschool children. This study aimed to investigate the association of exposure to air pollution and traffic indicators at home and kindergarten with relative leukocyte TL (LTL) in preschool children. This cross-sectional study included 200 preschool children (5-7 years old) recruited from 27 kindergartens in Sabzevar, Iran (2017). Outdoor annual average levels PM1, PM2.5, and PM10 at residential address and kindergartens were estimated applying land use regression (LUR) models. Moreover, indoor levels of PMs at kindergartens were measured for four days in each season resulting in a total of 16 days of measurements for each kindergarten. Total streets length in different buffers and distance to major road were calculated as traffic indicators at residential address and kindergartens. We applied quantitative real-time polymerase chain reaction (qRT-PCR) to measure relative LTL in blood samples obtained from children. Mixed linear regression models were developed with qPCR plate and kindergarten as random effects, to estimate association of each pollutant and traffic indicator with LTL, controlled for relevant covariates. Higher concentrations of outdoor PM1, PM2.5, and PM10, at home and kindergartens were associated with shorter relative LTL. Similarly, increase in indoor PM2.5 concentrations at kindergartens was associated with shorter relative LTL (ß = -0.18, 95% CI: -0.36, -0.01, P-value < 0.01). Moreover, higher total street length in 100 m buffer around residence and lower residential distance to major roads were associated with shorter relative LTL (ß = -0.25, 95% CI: -0.37, -0.13, P-value < 0.01, and 0.32, 95% CI: 0.20, 0.44, P-value < 0.01, respectively). Overall, our study suggested that higher exposure to air pollution and traffic at kindergarten and residential home were associated with shorter relative LTL in preschool children.


Assuntos
Poluição do Ar , Poluentes Atmosféricos , Criança , Pré-Escolar , Estudos Transversais , Exposição Ambiental , Humanos , Irã (Geográfico) , Leucócitos , Material Particulado , Telômero
18.
Life Sci ; 248: 117467, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32105706

RESUMO

BACKGROUND: NQO1 protein acts as a cellular protective system, on account of its role as a quinone reductase and redox regulator. Nonetheless, new NQO1 roles are emerging-including its regulation of the cellular proliferation of many tumor cells-and this enzyme has been found to relate to the incidence of various diseases, including chronic myeloid leukemia. However, the mechanisms through which NQO1 influences leukemia progression remain unclear. MARTIAL AND METHODS: The current study looks to name NQO1 as a novel molecular target that modulates DNA synthesis and chronic myeloid leukemia growth. RESULTS AND CONCLUSION: Our results indicate that the frequency of the T allele of NQO1 polymorphism in chronic myeloid leukemia patients is higher than that among healthy East Asian individuals (0.492 vs. 0.419) and much higher than the average level of the general population (0.492 vs. 0.289) (1000 Genomes). Functionally, NQO1 knockdown increases the protein expression of the TOP2A and MCM complex, and consequently promotes DNA synthesis and K562 cell growth. NQO1 knockdown also promotes tumorigenesis in a xenograft model. NQO1 overexpression, on the other hand, was found to have the opposite effects. SIGNIFICANCE: Our results show that NQO1 downregulation promotes K562 cellular proliferation via the elevation of DNA synthesis.


Assuntos
DNA de Neoplasias/genética , Regulação Leucêmica da Expressão Gênica , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucócitos/metabolismo , NAD(P)H Desidrogenase (Quinona)/genética , Adulto , Alelos , Animais , Grupo com Ancestrais do Continente Asiático , Linhagem Celular Tumoral , Proliferação de Células , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , DNA de Neoplasias/biossíntese , Feminino , Xenoenxertos , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/etnologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucócitos/patologia , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , NAD(P)H Desidrogenase (Quinona)/antagonistas & inibidores , NAD(P)H Desidrogenase (Quinona)/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Polimorfismo Genético , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais
19.
Biochemistry (Mosc) ; 85(1): 54-67, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32079517

RESUMO

KLF2 is a member of the Krüppel-like transcription factor family of proteins containing highly conserved DNA-binding zinc finger domains. KLF2 participates in the differentiation and regulation of the functional activity of monocytes, T lymphocytes, adipocytes, and vascular endothelial cells. The activity of KLF2 is controlled by several regulatory systems, including the MEKK2,3/MEK5/ERK5/MEF2 MAP kinase cascade, Rho family G-proteins, histone acetyltransferases CBP and p300, and histone deacetylases HDAC4 and HDAC5. Activation of KLF2 in endothelial cells induces eNOS expression and provides vasodilatory effect. Many KLF2-dependent genes participate in the suppression of blood coagulation and aggregation of T cells and macrophages with the vascular endothelium, thereby preventing atherosclerosis progression. KLF2 can have a dual effect on the gene transcription. Thus, it induces expression of multiple genes, but suppresses transcription of NF-κB-dependent genes. Transcription factors KLF2 and NF-κB are reciprocal antagonists. KLF2 inhibits induction of NF-κB-dependent genes, whereas NF-κB downregulates KLF2 expression. KLF2-mediated inhibition of NF-κB signaling leads to the suppression of cell response to the pro-inflammatory cytokines IL-1ß and TNFα and results in the attenuation of inflammatory processes.


Assuntos
Células Endoteliais da Veia Umbilical Humana/imunologia , Fatores de Transcrição Kruppel-Like/imunologia , Fatores de Transcrição Kruppel-Like/fisiologia , Leucócitos/imunologia , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Leucócitos/citologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo
20.
Biochemistry (Mosc) ; 85(Suppl 1): S34-S55, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32087053

RESUMO

This review discusses formation of reactive halogen species (RHS) catalyzed by myeloperoxidase (MPO), an enzyme mostly present in leukocytes. An imbalance between the RHS production and body's ability to remove or neutralize them leads to the development of halogenative stress. RHS reactions with proteins, lipids, carbohydrates, and antioxidants in the content of low-density lipoproteins (LDLs) of the human blood are described. MPO binds site-specifically to the LDL surface and modifies LDL properties and structural organization, which leads to the LDL conversion into proatherogenic forms captured by monocytes/macrophages, which causes accumulation of cholesterol and its esters in these cells and their transformation into foam cells, the basis of atherosclerotic plaques. The review describes the biomarkers of MPO enzymatic activity and halogenative stress, as well as the involvement of the latter in the development of atherosclerosis.


Assuntos
Aterosclerose/metabolismo , Halogenação , Halogênios/metabolismo , Lipoproteínas LDL/metabolismo , Placa Aterosclerótica/metabolismo , Sítios de Ligação , Biomarcadores/metabolismo , Colesterol/metabolismo , Ácidos Graxos Insaturados/metabolismo , Células Espumosas/metabolismo , Radicais Livres/metabolismo , Humanos , Ácido Hipocloroso/metabolismo , Leucócitos/metabolismo , Peroxidase/metabolismo
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