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1.
Medicine (Baltimore) ; 100(36): e26750, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516487

RESUMO

ABSTRACT: To investigate the correlation between preoperative inflammatory markers, Ki-67 expression and the pathological grade of glioma, and to provide a reference for clinical prediction of glioma prognosis.A total of 45 glioma patients who underwent surgery with complete clinical and pathological data were in our hospital from January 2012 to December 2018 were enrolled. Glioma was divided into WHO grade I to IV. Forty-five healthy health examiners with matched clinical characteristics were included to the control group. Blood routine tests were recorded at admission in both the glioma and control group. The ratio of neutrophil to lymphocyte cytometry (NLR), derived neutrophil to lymphocyte ratio (dNLR) (white blood cell count - neutrophil count to neutrophil count), platelet to lymphocyte ratio (PLR) and prognostic nutritional index (PNI, serum albumin content + 5 × lymphocyte count) were calculated. The expression of Ki-67 in glioma was detected by immunohistochemistry. The relationship between the above markers, Ki-67 expression and pathological grade of glioma was evaluated with receiver operating characteristics curve analysis and Spearman correlation test. The correlation between the markers and Ki-67 were also determined.NLR, dNLR, PLR were increased in the glioma group (P < .001, <.001, .002), whereas red blood cell distribution width (RDW) was decreased (P = .009). All the glioma samples expressed Ki-67 with varying degree. Receiver operating characteristics curve analysis reveals NLR, dNLR, PLR, and RDW have significant discriminating ability in differentiating the glioma and control sample. NLR, PLR, PNI, and Ki-67 were significantly correlated with glioma pathology grade (P = .023, .006, .019, <.05), while dNLR and RDW were not associated with glioma grade. Finally, NLR and PLR were related to Ki-67 expression in glioma patients (P = .002, .022), while dNLR and RDW were not related to Ki-67 expression.Preoperative inflammatory markers NLR, PLR, PNI, and postoperative Ki-67 expression are associated with pathological grade of glioma. Detection of these markers may aid in better prediction of glioma prognosis.


Assuntos
Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Antígeno Ki-67/sangue , Linfócitos/citologia , Neutrófilos/citologia , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Feminino , Glioma/metabolismo , Glioma/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
2.
BMC Infect Dis ; 21(1): 760, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34353293

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread around the world. This retrospective study aims to analyze the clinical features of COVID-19 patients with cancer and identify death outcome related risk factors. METHODS: From February 10th to April 15th, 2020, 103 COVID-19 patients with cancer were enrolled. Difference analyses were performed between severe and non-severe patients. A propensity score matching (PSM) analysis was performed, including 103 COVID-19 patients with cancer and 206 matched non-cancer COVID-19 patients. Next, we identified death related risk factors and developed a nomogram for predicting the probability. RESULTS: In 103 COVID-19 patients with cancer, the main cancer categories were breast cancer, lung cancer and bladder cancer. Compared to non-severe patients, severe patients had a higher median age, and a higher proportion of smokers, diabetes, heart disease and dyspnea. In addition, most of the laboratory results between two groups were significantly different. PSM analysis found that the proportion of dyspnea was much higher in COVID-19 patients with cancer. The severity incidence in two groups were similar, while a much higher mortality was found in COVID-19 patients with cancer compared to that in COVID-19 patients without cancer (11.7% vs. 4.4%, P = 0.028). Furthermore, we found that neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were related to death outcome. And a nomogram based on the factors was developed. CONCLUSION: In COVID-19 patients with cancer, the clinical features and laboratory results between severe group and non-severe group were significantly different. NLR and CRP were the risk factors that could predict death outcome.


Assuntos
COVID-19 , Neoplasias , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , COVID-19/complicações , COVID-19/mortalidade , Feminino , Humanos , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/mortalidade , Neutrófilos/citologia , Nomogramas , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
3.
PLoS One ; 16(8): e0256784, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34460840

RESUMO

Viral sepsis has been proposed as an accurate term to describe all multisystemic dysregulations and clinical findings in severe and critically ill COVID-19 patients. The adoption of this term may help the implementation of more accurate strategies of early diagnosis, prognosis, and in-hospital treatment. We accurately quantified 110 metabolites using targeted metabolomics, and 13 cytokines/chemokines in plasma samples of 121 COVID-19 patients with different levels of severity, and 37 non-COVID-19 individuals. Analyses revealed an integrated host-dependent dysregulation of inflammatory cytokines, neutrophil activation chemokines, glycolysis, mitochondrial metabolism, amino acid metabolism, polyamine synthesis, and lipid metabolism typical of sepsis processes distinctive of a mild disease. Dysregulated metabolites and cytokines/chemokines showed differential correlation patterns in mild and critically ill patients, indicating a crosstalk between metabolism and hyperinflammation. Using multivariate analysis, powerful models for diagnosis and prognosis of COVID-19 induced sepsis were generated, as well as for mortality prediction among septic patients. A metabolite panel made of kynurenine/tryptophan ratio, IL-6, LysoPC a C18:2, and phenylalanine discriminated non-COVID-19 from sepsis patients with an area under the curve (AUC (95%CI)) of 0.991 (0.986-0.995), with sensitivity of 0.978 (0.963-0.992) and specificity of 0.920 (0.890-0.949). The panel that included C10:2, IL-6, NLR, and C5 discriminated mild patients from sepsis patients with an AUC (95%CI) of 0.965 (0.952-0.977), with sensitivity of 0.993(0.984-1.000) and specificity of 0.851 (0.815-0.887). The panel with citric acid, LysoPC a C28:1, neutrophil-lymphocyte ratio (NLR) and kynurenine/tryptophan ratio discriminated severe patients from sepsis patients with an AUC (95%CI) of 0.829 (0.800-0.858), with sensitivity of 0.738 (0.695-0.781) and specificity of 0.781 (0.735-0.827). Septic patients who survived were different from those that did not survive with a model consisting of hippuric acid, along with the presence of Type II diabetes, with an AUC (95%CI) of 0.831 (0.788-0.874), with sensitivity of 0.765 (0.697-0.832) and specificity of 0.817 (0.770-0.865).


Assuntos
COVID-19/patologia , Metabolômica , Sepse/diagnóstico , Adulto , Área Sob a Curva , COVID-19/complicações , COVID-19/virologia , Quimiocinas/sangue , Citocinas/sangue , Feminino , Humanos , Cinurenina/sangue , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Sepse/etiologia , Índice de Gravidade de Doença , Triptofano/sangue
4.
Int J Mol Sci ; 22(15)2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34361116

RESUMO

Along with cytokines, extracellular vesicles (EVs) released by immune cells in the joint contribute to osteoarthritis (OA) pathogenesis. By high-resolution flow cytometry, we characterized 18 surface markers and 4 proinflammatory cytokines carried by EVs of various sizes in plasma and synovial fluid (SF) from individuals with knee OA, with a primary focus on immune cells that play a major role in OA pathogenesis. By multiplex immunoassay, we also measured concentrations of cytokines within (endo) and outside (exo) EVs. EVs carrying HLA-DR, -DP and -DQ were the most enriched subpopulations in SF relative to plasma (25-50-fold higher depending on size), suggesting a major contribution to the SF EV pool from infiltrating immune cells in OA joints. In contrast, the CD34+ medium and small EVs, reflecting hematopoietic stem cells, progenitor cells, and endothelial cells, were the most significantly enriched subpopulations in plasma relative to SF (7.3- and 7.7-fold higher). Ratios of EVs derived from neutrophils and lymphocytes were highly correlated between SF and plasma, indicating that plasma EVs could reflect OA severity and serve as systemic biomarkers of OA joint pathogenesis. Select subsets of plasma EVs might also provide next generation autologous biological products for intra-articular therapy of OA joints.


Assuntos
Biomarcadores/metabolismo , Citocinas/metabolismo , Vesículas Extracelulares/metabolismo , Linfócitos/citologia , Neutrófilos/citologia , Osteoartrite/terapia , Líquido Sinovial/metabolismo , Idoso , Feminino , Antígenos HLA-DR/metabolismo , Humanos , Masculino , Osteoartrite/metabolismo , Osteoartrite/patologia
5.
J Med Microbiol ; 70(7)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34259621

RESUMO

Introduction. Contamination of specimens and overuse of broad spectrum antibiotics contribute to false positives and false negatives, respectively. Therefore, useful and applicable biomarkers of bacteremia are still required.Hypothesis/Gap Statement. IL-6 can be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection.Aim. We aimed to evaluate the diagnostic efficiency of neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT) and interleukin-6 (IL-6) in discriminating Gram-negative (G-) bacteria from Gram-positive (G+) bacteria and fungi in febrile patients.Methodology. A total of 567 patients with fever were evaluated. Serum levels of IL-6, PCT, NLR and CRP were compared among a G- group (n=188), a G+ group (n=168), a fungal group (n=38) and a culture negative group (n=173). Sensitivity, specificity, Yuden's index and area under the Receiver operating characteristic (ROC) curve (AUC) were obtained to analyse the diagnostic abilities of these biomarkers in discriminating bloodstream infection caused by different pathogens.Results. Serum IL-6 and PCT in the G- group increased significantly when compared with both the G+ group and fungal group (P <0.05). AUC of IL-6 (0.767, 95 % CI:0.725-0.805) is higher than AUC of PCT (0.751, 95 % CI:0.708-0.796) in discriminating the G- group from G+ group. When discriminating the G- group from fungal group, the AUC of IL-6 (0.695, 95 % CI:0.651-0.747) with a cut-off value of 464.3 pg ml-1 was also higher than the AUC of PCT (0.630, 95 % CI:0.585-0.688) with a cut-off value of 0.68 ng ml-1. Additionally, AUC of NLR (0.685, 95 % CI:0.646-0.727) in discriminating the fungal group from G+ group at the cut-off value of 9.03, was higher than AUC of IL-6, PCT and CRP.Conclusion. This study suggests that IL-6 could be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. In addition, NLR is valuable to discriminate fungal infections from Gram-positive infections in febrile patients with a bloodstream infection.


Assuntos
Biomarcadores/sangue , Febre/sangue , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Positivas/sangue , Micoses/sangue , Adolescente , Adulto , Idoso , Contagem de Células Sanguíneas , Proteína C-Reativa/análise , Calcitonina/sangue , Análise Discriminante , Febre/diagnóstico , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Humanos , Interleucina-6/sangue , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Micoses/diagnóstico , Neutrófilos/citologia , Curva ROC , Estudos Retrospectivos , Adulto Jovem
6.
Clin Interv Aging ; 16: 1231-1239, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234423

RESUMO

Objective: Inflammation plays an important role in stroke. Many inflammatory markers in peripheral blood are proved to be associated with stroke severity or prognosis. But few comprehensive models or scales to evaluate the post-stroke depression (PSD) have been reported. In this study, we aimed to compare the level of systemic inflammation markers between PSD and non-PSD patients and explore the association of these inflammatory markers with PSD. Methods: Totally, 432 ischemic stroke patients were consecutively enrolled in the study and received 1 month follow-up. We used the 17-Hamilton Rating Scale to measure depressive symptoms at 1 month after stroke. With the Hamilton Depression Scale score of >7, patients were diagnosed with PSD. Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and derived neutrophil-to-lymphocyte ratio (dNLR) were calculated from the admission blood work. Results: Finally, 129 patients (30.5%) were diagnosed with PSD at 1 month. PSD patients showed significantly higher levels of SII (501.27 (345.43-782.58) vs 429.60 (315.64-570.98), P=0.001), NLR (2.36 (1.77-3.82) vs 2.17 (1.56-2.80), P=0.010), dNLR (1.67 (1.30-2.51) vs 1.54 (1.16-1.99), P=0.009), PLR (124.65 (95.25-155.15) vs 109.22 (92.38-142.03), P=0.015), especially SII at admission as compared to non-PSD patients. In the logistic analysis, SII value (>547.30) was independently associated with the occurrence of PSD (OR=2.181, 95% CI=1.274-3.732, p =0.004), better than dNLR (OR=1.833, 95% CI=1.071-3.137, p =0.027), PLR (OR= 1.822, 95% CI=1.063-3.122, p =0.029) and NLR (OR =1.728, 95% CI=1.009-2.958, p =0.046). Conclusion: Increased SII, PLR, dNLR, NLR, particularly SII at admission, are significantly correlated with PSD and may add some prognostic clues to find early discovery of PSD.


Assuntos
Depressão/etiologia , Depressão/fisiopatologia , Mediadores da Inflamação/metabolismo , Acidente Vascular Cerebral/complicações , Idoso , Biomarcadores , Plaquetas/citologia , Estudos de Coortes , Depressão/diagnóstico , Feminino , Humanos , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença
7.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34206020

RESUMO

Three dimensional (3D) ultra-structural imaging is an important tool for unraveling the organizational structure of individual chromosomes at various stages of the cell cycle. Performing hitherto uninvestigated ultra-structural analysis of the human genome at prophase, we used serial block-face scanning electron microscopy (SBFSEM) to understand chromosomal architectural organization within 3D nuclear space. Acquired images allowed us to segment, reconstruct, and extract quantitative 3D structural information about the prophase nucleus and the preserved, intact individual chromosomes within it. Our data demonstrate that each chromosome can be identified with its homolog and classified into respective cytogenetic groups. Thereby, we present the first 3D karyotype built from the compact axial structure seen on the core of all prophase chromosomes. The chromosomes display parallel-aligned sister chromatids with familiar chromosome morphologies with no crossovers. Furthermore, the spatial positions of all 46 chromosomes revealed a pattern showing a gene density-based correlation and a neighborhood map of individual chromosomes based on their relative spatial positioning. A comprehensive picture of 3D chromosomal organization at the nanometer level in a single human lymphocyte cell is presented.


Assuntos
Cromossomos/genética , Linfócitos/citologia , Mitose/genética , Troca de Cromátide Irmã/genética , Núcleo Celular/genética , Cromossomos/ultraestrutura , Humanos , Cariotipagem , Linfócitos/ultraestrutura , Microscopia Eletrônica de Varredura
8.
Sci Rep ; 11(1): 13026, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34158545

RESUMO

The objective of the study was to develop and validate a prediction model that identifies COVID-19 patients at risk of requiring oxygen support based on five parameters: C-reactive protein (CRP), hypertension, age, and neutrophil and lymphocyte counts (CHANeL). This retrospective cohort study included 221 consecutive COVID-19 patients and the patients were randomly assigned randomly to a training set and a test set in a ratio of 1:1. Logistic regression, logistic LASSO regression, Random Forest, Support Vector Machine, and XGBoost analyses were performed based on age, hypertension status, serial CRP, and neutrophil and lymphocyte counts during the first 3 days of hospitalization. The ability of the model to predict oxygen requirement during hospitalization was tested. During hospitalization, 45 (41.8%) patients in the training set (n = 110) and 41 (36.9%) in the test set (n = 111) required supplementary oxygen support. The logistic LASSO regression model exhibited the highest AUC for the test set, with a sensitivity of 0.927 and a specificity of 0.814. An online risk calculator for oxygen requirement using CHANeL predictors was developed. "CHANeL" prediction models based on serial CRP, neutrophil, and lymphocyte counts during the first 3 days of hospitalization, along with age and hypertension status, provide a reliable estimate of the risk of supplement oxygen requirement among patients hospitalized with COVID-19.


Assuntos
Proteína C-Reativa/análise , COVID-19/patologia , Hipertensão/complicações , Linfócitos/citologia , Neutrófilos/citologia , Oxigenoterapia , Fatores Etários , Idoso , Área Sob a Curva , Biomarcadores/análise , Biomarcadores/metabolismo , COVID-19/complicações , COVID-19/virologia , Feminino , Humanos , Modelos Logísticos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Curva ROC , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Máquina de Vetores de Suporte
9.
Am J Clin Pathol ; 156(2): 185-197, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34151348

RESUMO

OBJECTIVES: We compared complete blood count (CBC) with differential and markers of inflammation and coagulation in patients with and without coronavirus disease 2019 (COVID-19) presenting to emergency departments in Seattle, WA. METHODS: We reviewed laboratory values for 1 week following each COVID-19 test for adult patients who received a standard severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) test before April 13, 2020. Results were compared by COVID-19 status and clinical course. RESULTS: In total 1,027 patients met inclusion criteria. Patients with COVID-19 (n = 155) had lower leukocytes (P < .0001), lymphocytes (P < .0001), platelets (P < .0001), and higher hemoglobin (P = .0140) than those without, but absolute differences were small. Serum albumin was lower in patients with COVID-19 (P < .0001) and serum albumin, neutrophil to lymphocyte ratio (NLR), and red cell distribution width (RDW) were each associated with disease severity. NLR did not differ between patients with COVID-19 and those without (P = .8012). CONCLUSIONS: Patients with COVID-19 had modestly lower leukocyte, lymphocyte, and platelet counts and higher hemoglobin values than patients without COVID-19. The NLR, serum albumin, and RDW varied with disease severity, regardless of COVID-19 status.


Assuntos
Contagem de Células Sanguíneas , Coagulação Sanguínea , COVID-19/sangue , Inflamação/sangue , Linfócitos/citologia , Adulto , Biomarcadores/sangue , Contagem de Células Sanguíneas/métodos , COVID-19/diagnóstico , Serviço Hospitalar de Emergência , Humanos , Contagem de Leucócitos/métodos , Contagem de Linfócitos/métodos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Contagem de Plaquetas/métodos , SARS-CoV-2/patogenicidade
10.
Sci Rep ; 11(1): 13350, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172816

RESUMO

Coronavirus disease 2019 (COVID-19) is a pandemic viral disease affecting also obstetric patients and uncertainties exist about the prognostic role of inflammatory biomarkers and hemocytometry values in patients with this infection. To clarify that, we have assessed the values of several inflammatory biomarkers and hemocytometry variables in a cohort of obstetric patients hospitalized with COVID-19 and we have correlated the values at admission with the need of oxygen supplementation during the hospitalization. Overall, among 62 (27.3%) pregnant women and 165 (72.7%) postpartum women, 21 (9.2%) patients received oxygen supplementation and 2 (0.9%) required admission to intensive care unit but none died. During hospitalization leukocytes (p < 0.001), neutrophils (p < 0.001), neutrophils to lymphocytes ratio (p < 0.001) and C reactive protein (p < 0.001) decreased significantly, whereas lymphocytes (p < 0.001), platelets (p < 0.001) and ferritin (p = 0.001) increased. Lymphocyte values at admission were correlated with oxygen need, with a 26% higher risk of oxygen supplementation for each 1000 cells decreases. Overall, in obstetric patients hospitalized with COVID-19, C reactive protein is the inflammatory biomarker that better mirrors the course of the disease whereas D-dimer or ferritin are not reliable predictors of poor outcome. Care to the need of oxygen supplementation should be reserved to patients with reduced lymphocyte values at admission.


Assuntos
Proteína C-Reativa/imunologia , COVID-19 , Produtos de Degradação da Fibrina e do Fibrinogênio/imunologia , Linfócitos , Adulto , Biomarcadores/sangue , COVID-19/epidemiologia , COVID-19/imunologia , Feminino , Humanos , Linfócitos/citologia , Linfócitos/imunologia , Gravidez , Estudos Retrospectivos
11.
Cell Transplant ; 30: 9636897211024942, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34180719

RESUMO

The aim of this clinical trial was to control the cytokine storm by administering mesenchymal stem cells (MSCs) to critically-ill COVID-19 patients, to evaluate the healing effect, and to systematically investigate how the treatment works. Patients with moderate and critical COVID-19 clinical manifestations were separated as Group 1 (moderate cases, n = 10, treated conventionally), Group 2 (critical cases, n = 10, treated conventionally), and Group 3 (critical cases, n = 10, treated conventionally plus MSCs transplantation therapy of three consecutive doses on treatment days 0, 3, and 6, (as 3 × 106 cells/kg, intravenously). The treatment mechanism of action was investigated with evaluation markers of the cytokine storm, via biochemical parameters, levels of proinflammatory and anti-inflammatory cytokines, analyses of tissue regeneration via the levels of growth factors, apoptosis markers, chemokines, matrix metalloproteinases, and granzyme-B, and by the assessment of the immunomodulatory effects via total oxidant/antioxidant status markers and the levels of lymphocyte subsets. In the assessment of the overall mortality rates of all the cases, six patients in Group-2 and three patients in Group-3 died, and there was no loss in Group-1. Proinflammatory cytokines IFNγ, IL-6, IL-17A, IL-2, IL-12, anti-inflammatory cytokines IL-10, IL-13, IL-1ra, and growth factors TGF-ß, VEGF, KGF, and NGF levels were found to be significant in Group-3. When Group-2 and Group-3 were compared, serum ferritin, fibrinogen and CRP levels in Group-3 had significantly decreased. CD45 +, CD3 +, CD4 +, CD8 +, CD19 +, HLA-DR +, and CD16 + / CD56 + levels were evaluated. In the statistical comparison of the groups, significance was only determined in respect of neutrophils. The results demonstrated the positive systematic and cellular effects of MSCs application on critically ill COVID-19 patients in a versatile way. This effect plays an important role in curing and reducing mortality in critically ill patients.


Assuntos
COVID-19/terapia , Transplante de Células-Tronco Mesenquimais , Adulto , Proteína C-Reativa/análise , COVID-19/patologia , COVID-19/virologia , Estado Terminal , Citocinas/sangue , Feminino , Humanos , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-8/sangue , Antígenos Comuns de Leucócito/metabolismo , Linfócitos/citologia , Linfócitos/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Resultado do Tratamento
12.
Int J Biol Macromol ; 184: 57-67, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34116091

RESUMO

ß-Galactosidase was immobilized on modified nanosilver reduced graphene oxide (Ag@rGO) nanocomposite prepared by in vitro synthesis using same enzyme. The effectiveness factor, η value of the immobilized enzyme was calculated to be 0.968, suggesting enhancement in enzyme activity after immobilization. The morphological structure of the crosslinked biopolymer was analyzed using electron microscopy and other characterization techniques. The kinetics displayed a decrease in Km value from 0.50 to 0.44 mmol L-1 while there was an increase in Vmax values from 0.031 to 0.039 µmol min-1 mL-1. The immobilized enzyme retained 85% activity after its 10th repeated use. Inhibition constant (Ki) value suggests galactose to be a more potent inhibitor of the enzyme. Despite the inhibitory potential of these hydrolysis products, the immobilized enzyme preparation retained 44.2% activity in the presence of both inhibitory sugars. The as-synthesized nanobiocatalyst was found quite effective in hydrolyzing 89% of lactose from whey. Hence, this nanobiocatalyst can be used in removing lactose from dairy waste, whey before releasing it into the water bodies. Also, the cytotoxicity and genotoxicity of Ag@rGO NC was assessed on human blood lymphocytes using flow cytometry and comet assay, respectively.


Assuntos
Grafite/química , Lactose/química , Prata/química , beta-Galactosidase/metabolismo , Biocatálise , Enzimas Imobilizadas/metabolismo , Humanos , Hidrólise , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Nanopartículas Metálicas , Nanocompostos , Prata/farmacologia
13.
Virol J ; 18(1): 115, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088324

RESUMO

BACKGROUND: It is important to recognize the coronavirus disease 2019 (COVID-19) patients in severe conditions from moderate ones, thus more effective predictors should be developed. METHODS: Clinical indicators of COVID-19 patients from two independent cohorts (Training data: Hefei Cohort, 82 patients; Validation data: Nanchang Cohort, 169 patients) were retrospected. Sparse principal component analysis (SPCA) using Hefei Cohort was performed and prediction models were deduced. Prediction results were evaluated by receiver operator characteristic curve and decision curve analysis (DCA) in above two cohorts. RESULTS: SPCA using Hefei Cohort revealed that the first 13 principal components (PCs) account for 80.8% of the total variance of original data. The PC1 and PC12 were significantly associated with disease severity with odds ratio of 4.049 and 3.318, respectively. They were used to construct prediction model, named Model-A. In disease severity prediction, Model-A gave the best prediction efficiency with area under curve (AUC) of 0.867 and 0.835 in Hefei and Nanchang Cohort, respectively. Model-A's simplified version, named as LMN index, gave comparable prediction efficiency as classical clinical markers with AUC of 0.837 and 0.800 in training and validation cohort, respectively. According to DCA, Model-A gave slightly better performance than others and LMN index showed similar performance as albumin or neutrophil-to-lymphocyte ratio. CONCLUSIONS: Prediction models produced by SPCA showed robust disease severity prediction efficiency for COVID-19 patients and have the potential for clinical application.


Assuntos
COVID-19/diagnóstico , COVID-19/patologia , Análise de Componente Principal/métodos , Índice de Gravidade de Doença , Adulto , Idoso , Biomarcadores/análise , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Monócitos/citologia , Neutrófilos/citologia , Estudos Retrospectivos , SARS-CoV-2
14.
Eur Rev Med Pharmacol Sci ; 25(10): 3868-3878, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34109595

RESUMO

OBJECTIVE: This study aimed to compare the mortality rate between advanced-stage non-small cell lung cancer patients (NSCLC) with and without COVID-19. This study also explores the possible laboratory characteristics used for prognostication in patients with NSCLC and COVID-19. Additionally, this study evaluated potential differences in laboratory values between the case and control groups. PATIENTS AND METHODS: This is a single-center retrospective cohort study conducted in Dharmais National Cancer Hospital, Indonesia, enrolling patients with NSCLC undergoing chemotherapy or targeted therapy between May 2020 and January 2021. All patients with NSCLC and COVID-19 in these periods were enrolled into the case group. The control group was age-matched NSCLC patients without COVID-19 that was derived from the NSCLC cohort through randomization. RESULTS: There were 342 patients with NSCLC between May 2020 and January 2021. Twenty-seven (7.9%) of the patients were infected by COVID-19. To facilitate comparison, thirty-five age-matched controls with NSCLC were selected from the cohort. The mortality rate in patients with COVID-19 was 46.2%. Eleven patients (40.7%) had severe COVID-19, of which none survived. NLR >8.35 has a sensitivity of 83.3%, specificity of 92.9%, LR+ of 12, and LR- of 0.18. The AUC was 0.946 (95% CI 0.867-1.000), p<0.001. PLR >29.14 has a sensitivity of 75.0%, specificity of 71.4%, LR+ 2.62, LR- 0.35, and AUC 0.851 (95% CI 0.706-0.996), p=0.002. Both NLR and PLR were associated with shorter time-to-mortality in the unadjusted and adjusted model CONCLUSIONS: NLR and PLR are independent predictors of mortality in COVID-19 patients with NSCLC.


Assuntos
Plaquetas/citologia , COVID-19/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Linfócitos/citologia , Neutrófilos/citologia , Idoso , Área Sob a Curva , COVID-19/complicações , COVID-19/virologia , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Indonésia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Curva ROC , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade , Taxa de Sobrevida
15.
Radiol Oncol ; 55(3): 347-353, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34051707

RESUMO

BACKGROUND: The aim of the study was to evaluate pretreatment inflammatory markers as prognostic factors in patients with unresectable uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion. PATIENTS AND METHODS: 54 patients (44% male, median age: 61 years) were retrospectively assessed. A median of 3 (range: 1-11) treatment sessions were performed with melphalan (92%) or fotemustin (8%). Inflammatory indices were calculated as follows: neutrophils/nl to lymphocytes/nl ratio (NLR), systemic immune-inflammation index ([platelets/nl × neutrophils/nl]/[lymphocytes/nl]; SII), and platelets/nl to lymphocytes/nl ratio (PLR). The cut-off for dichotomization purposes was set at the median (inflammatory indices, hepatic tumor burden) or the upper level of normal. Kaplan Meier analysis was performed for median overall survival (OS) in months, and Cox proportional hazard model for uni(UVA) and multivariate (MVA) hazard ratio (HR, 95%CI) analyses were performed. RESULTS: Median OS of the study cohort was 7.7 (6.3-10.9) months. In UVA OS was prolonged for low C reactive protein (CRP) (13.5 vs. 5.2; p = 0.0005), low SII (10.8 vs. 5.6; p = 0.0005), low NLR (11.1 vs. 6.3; p = 0.0045), low aspartate aminotransferase (AST) (11.5 vs. 5.6; p = 0.015), alanine aminotransferases (ALT) (11.5 vs. 5.6; p = 0.01), and tumor burden ≦ 50% (8.2 vs. 4.8; p = 0.007). MVA confirmed low CRP (HR: 0.29, 0.11-0.7; p = 0.005), low SII (HR: 0.19, 0.11-0.7; p = 0.008), and low ALT (HR: 0.13, 0.02-0.63; p = 0.011) as independent predictors for prolonged OS. Patients with ≦ 1, 2, 3 elevated significant MVA-factors survived a median of 14.9, 7.7, and 3.9 months, respectively (p = 0.0001). CONCLUSIONS: Pretreatment inflammatory markers (CRP, SII) and AST were independent prognostic survival markers in patients with uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion. A combination of factors may help to identify patients potentially benefitting from treatment.


Assuntos
Neoplasias Hepáticas/sangue , Melanoma/sangue , Neoplasias Uveais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Antineoplásicos/uso terapêutico , Aspartato Aminotransferases/sangue , Biomarcadores Tumorais/sangue , Plaquetas/citologia , Proteína C-Reativa/análise , Quimioterapia do Câncer por Perfusão Regional/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Linfócitos/citologia , Masculino , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Melanoma/secundário , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Neutrófilos/citologia , Compostos de Nitrosoureia/uso terapêutico , Compostos Organofosforados/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Carga Tumoral , Neoplasias Uveais/sangue
17.
Biochem Biophys Res Commun ; 559: 135-140, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33940384

RESUMO

Dedicator of cytokinesis 8 (DOCK8) is a guanine nucleotide exchange factor (GEF) for Cdc42. In humans, homozygous or compound heterozygous deletions in DOCK8 cause a combined immunodeficiency characterized by various allergic diseases including food allergies. Although group 2 innate lymphoid cells (ILC2s) contribute to the development of allergic inflammation by producing interleukin (IL)-5 and IL-13, the role of ILC2s in DOCK8 deficiency has not been fully explored. With the use of cytometry by time-of-flight (CyTOF), we performed high-dimensional phenotyping of intestinal immune cells and found that DOCK8-deficient (Dock8-/-) mice exhibited expansion of ILC2s and other leukocytes associated with type 2 immunity in the small intestine. Moreover, IL-5- and IL-13-producing cells markedly increased in Dock8-/- mice, and the majority of them were lineage-negative cells, most likely ILC2s. Intestinal ILC2s expanded when DOCK8 expression was selectively deleted in hematopoietic cells. Importantly, intestinal ILC2 expansion was also observed in Dock8VAGR mice having mutations in the catalytic center of DOCK8, thereby failing to activate Cdc42. Our findings indicate that DOCK8 is a negative regulator of intestinal ILC2s to inhibit their expansion via Cdc42 activation, and that deletion of DOCK8 causes a skewing to type 2 immunity in the gut.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/imunologia , Imunidade Inata , Intestino Delgado/imunologia , Linfócitos/imunologia , Animais , Deleção de Genes , Fatores de Troca do Nucleotídeo Guanina/genética , Intestino Delgado/citologia , Intestino Delgado/metabolismo , Linfócitos/citologia , Camundongos Endogâmicos C57BL
18.
PLoS One ; 16(5): e0249964, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34003821

RESUMO

Coronavirus disease 2019 (COVID-19) is highly contagious and has affected the whole world. We seek to investigate the clinical and laboratory characteristics of COVID-19 patients in the high altitude areas of Sichuan, China. In this retrospective cohort study, a total of 67 patients with laboratory-confirmed SARS-CoV-2 infections in Sichuan's Ngawa Tibetan and Qiang Autonomous Prefecture were included from February 1, 2020, to March 2, 2020. Their clinical characteristics, as well as radiological and laboratory features, were extracted. Four (6.0%) patients were categorized as severe cases; 39 (58.2%) were non-severe cases, and 24 (35.8%) were asymptomatic cases. A total of 46 (68.7%) patients were associated with cluster infection events in this study. The most common symptoms were cough, sputum production, dyspnea, fatigue or myalgia, and headache. Seven (10.4%) patients showed leucopenia, and 20 (29.9%) patients showed lymphopenia. Lymphocyte counts and neutrophil-to-lymphocyte ratios (NPR) were different between the three groups. In total, 14 (20.9%) patients had thrombocytopenia, and prothrombin times (PT) and fibrinogen levels differed between groups. We also found significant differences in sodium, chloride and calcium levels between the three groups. Antiviral therapy did not lead to obvious adverse events or shortened durations from initial positive to subsequent negative nuclei acid tests. Advanced age, hypertension, high neutrophil count, the neutrophil-to-lymphocyte ratio, fibrinogen and lactate dehydrogenase levels were identified as independent risk factors for symptomatic cases of COVID-19. In conclusion, the symptoms of patients in high altitude areas were mild, and about one third were asymptomatic. We also identified several independent risk factors for symptomatic cases of COVID-19.


Assuntos
COVID-19/patologia , Adolescente , Adulto , Idoso , Altitude , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/virologia , China/epidemiologia , Tosse/etiologia , Feminino , Fibrinogênio/análise , Humanos , L-Lactato Desidrogenase/metabolismo , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Adulto Jovem
19.
Biomed Res Int ; 2021: 9678363, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33997045

RESUMO

Background: The preoperative platelet-to-lymphocyte ratio (PLR) evaluates the prognosis of gastric cancer patients. However, whether preoperative PLR may be used to evaluate the prognosis of mucinous gastric carcinoma (MGC) patients is poorly investigated. The present study evaluated the effect of preoperative PLR on overall survival in gastric cancer patients with a mucinous component. Methods: A total of 336 MGC were enrolled in this study, and the characteristics of the tumor, including pathological features and clinical data, were retrospectively analyzed. Results: A high PLR was associated with larger tumor size, advanced tumor invasion, lymph node metastasis, advanced TNM stage, tumor location, total gastrectomy, low hemoglobin level, low albumin level, high fibrinogen level, high platelet level, and high neutrophil-to-lymphocyte ratio (NLR, all P's < 0.05). Multivariate analysis identified age (HR = 1.876; 95% CI 1.361-2.585, P < 0.001), TNM stage (HR = 2.350; 95% CI 1.216-4.542, P = 0.011), globulin (HR = 1.520; 95% CI 1.067-2.165, P = 0.020), total gastrectomy (HR = 0.537; 95% CI 0.373-0.772, P = 0.001), and PLR (HR = 1.582; 95% CI 1.066-2.348, P = 0.023) as independent prognostic factors for OS. Conclusion: Preoperative PLR is related to pathological features and may independently evaluate the survival of MGC. Therefore, preoperative PLR may help physicians develop treatment plans and evaluate survival in these patients.


Assuntos
Plaquetas/citologia , Linfócitos/citologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Análise de Sobrevida
20.
Nat Commun ; 12(1): 3116, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035253

RESUMO

Changes in the epigenetic regulation of gene expression have a central role in evolution. Here, we extensively profiled a panel of human, chimpanzee, gorilla, orangutan, and macaque lymphoblastoid cell lines (LCLs), using ChIP-seq for five histone marks, ATAC-seq and RNA-seq, further complemented with whole genome sequencing (WGS) and whole genome bisulfite sequencing (WGBS). We annotated regulatory elements (RE) and integrated chromatin contact maps to define gene regulatory architectures, creating the largest catalog of RE in primates to date. We report that epigenetic conservation and its correlation with sequence conservation in primates depends on the activity state of the regulatory element. Our gene regulatory architectures reveal the coordination of different types of components and highlight the role of promoters and intragenic enhancers (gE) in the regulation of gene expression. We observe that most regulatory changes occur in weakly active gE. Remarkably, novel human-specific gE with weak activities are enriched in human-specific nucleotide changes. These elements appear in genes with signals of positive selection and human acceleration, tissue-specific expression, and particular functional enrichments, suggesting that the regulatory evolution of these genes may have contributed to human adaptation.


Assuntos
Elementos Facilitadores Genéticos/genética , Epigênese Genética/genética , Epigenômica/métodos , Linfócitos/metabolismo , Sequências Reguladoras de Ácido Nucleico/genética , Animais , Linhagem Celular , Sequenciamento de Cromatina por Imunoprecipitação/métodos , Evolução Molecular , Regulação da Expressão Gênica , Humanos , Linfócitos/citologia , Primatas , RNA-Seq/métodos
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