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1.
Foods ; 13(4)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38397572

RESUMO

Ochratoxin A (OTA) is a mycotoxin widely found in foodstuffs such as cereal grains. It greatly threatens human health owing to its strong toxicity and high stability. Aptasensors have emerged as promising tools for the analysis of small molecule contaminants. Nucleic-acid-based signal amplification enables detectable signals to be obtained from aptasensors. However, this strategy often requires the use of complex primers or multiple enzymes, entailing problems such as complex system instability. Herein, we propose a fluorescent aptasensor for the ultrasensitive detection of OTA in cereal products, with signal amplification through RecJf exonuclease-assisted target recycling. The aptamer/fluorescein-labeled complementary DNA (cDNA-FAM) duplex was effectively used as the target-recognition unit as well as the potential substrate for RecJf exonuclease cleavage. When the target invaded the aptamer-cDNA-FAM duplex to release cDNA-FAM, RecJf exonuclease could cleave the aptamer bonded with the target and release the target. Thus, the target-triggered cleavage cycling would continuously generate cDNA-FAM as a signaling group, specifically amplifying the response signal. The proposed exonuclease-assisted fluorescent aptasensor exhibited a good linear relationship with OTA concentration in the range from 1 pg/mL to 10 ng/mL with an ultralow limit of detection (6.2 ng/kg of cereal). The analytical method showed that recoveries of the cereal samples ranged from 83.7 to 109.3% with a repeatability relative standard deviation below 8%. Importantly, the proposed strategy is expected to become a common detection model because it can be adapted for other targets by replacing the aptamer. Thus, this model can guide the development of facile approaches for point-of-care testing applications.

2.
Arch Microbiol ; 205(10): 345, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37768397

RESUMO

Four Gram-staining-negative, aerobic, yellow-pigmented and rod-shaped bacteria, named strains BD1B2-1T, NT2B1T, YF14B1 and DM2B3-1, were isolated from four rhizosphere soil samples of banana in China. Comparison of the 16S rRNA gene sequences showed that all these strains were most closely related to an invalidly published species, 'Rhodocytophaga rosea' 172606-1, with similarities ranging from 87.7 to 88.0%. According to the phylogenomic analysis, the four strains were clustered in an independent lineage and closely related to the genus Rhodocytophaga. The genomic sizes of these strains were approximately 9.49-9.77 Mbp with the DNA G + C contents of 38.8-39.0 mol%. They all contained C16:1 ω5c, iso-C15:0 and iso-C17:0 3-OH as the major fatty acids and menaquinone 7 as the only respiratory quinone. They all had phosphatidylethanolamine as the major polar lipids. Based on phenotypic and phylogenomic characteristics, the four strains should represent two novel species within a novel genus, for which the names Xanthocytophaga agilis gen. nov., sp. nov. (BD1B2-1T = GDMCC 1.2890T = JCM 35374T) and Xanthocytophaga flavus sp. nov. (NT2B1T = GDMCC 1.2889T = JCM 35375T) are proposed; the former is assigned as the type species of the novel genus Xanthocytophaga gen. nov. In addition, based on the phenotypic and phylogenomic data, we proposed to reclassify the existing genus Rhodocytophaga in the family Cytophagaceae into a novel family Rhodocytophagaceae fam. nov. The novel family consists of the type genus Rhodocytophaga and the novel genus Xanthocytophaga.

3.
Front Oncol ; 12: 1033044, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36324584

RESUMO

Background: Colon cancer is common worldwide, with high morbidity and poor prognosis. Ferroptosis is a novel form of cell death driven by the accumulation of iron-dependent lipid peroxides, which differs from other programmed cell death mechanisms. Programmed cell death is a cancer hallmark, and ferroptosis is known to participate in various cancers, including colon cancer. Novel ferroptosis markers and targeted colon cancer therapies are urgently needed. To this end, we performed a preliminary exploration of ferroptosis-related genes in colon cancer to enable new treatment strategies. Methods: Ferroptosis-related genes in colon cancer were obtained by data mining and screening for differentially expressed genes (DEGs) using bioinformatics analysis tools. We normalized the data across four independent datasets and a ferroptosis-specific database. Identified genes were validated by immunohistochemical analysis of pathological and healthy clinical samples. Results: We identified DEGs in colon cancer that are involved in ferroptosis. Among these, five core genes were found: ELAVL1, GPX2, EPAS1, SLC7A5, and HMGB1. Bioinformatics analyses revealed that the expression of all five genes, except for EPAS1, was higher in tumor tissues than in healthy tissues. Conclusions: The preliminary exploration of the five core genes revealed that they are differentially expressed in colon cancer, playing an essential role in ferroptosis. This study provides a foundation for subsequent research on ferroptosis in colon cancer.

4.
Brain Imaging Behav ; 16(4): 1803-1812, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35338430

RESUMO

Previous studies have reported changes in white matter microstructures in patients with insomnia. However, few neuroimaging studies have focused specifically on white matter tracts in insomnia patients after having received treatment. In this prospective study, diffusion-tensor imaging was used in two samples of heart-kidney imbalance insomnia patients who were treated with placebo or Jiao-Tai-Wan, a traditional Chinese medicine commonly used to treat heart-kidney imbalance insomnia, to assess the changes in white matter tracts. Tract-based spatial statistical analyses were first applied to compare the changes in mean diffusivity and fractional anisotropy of white matter between 75 heart-kidney imbalance insomnia patients and 41 healthy control participants. In subsequent randomized, double-blind, placebo-controlled trials, comparisons of mean diffusivity and fractional anisotropy were also performed in 24 heart-kidney imbalance insomnia patients (8 males; 16 females; 42.5 ± 10.4 years) with Jiao-Tai-Wan and 26 heart-kidney imbalance insomnia patients (11 males; 15 females; 39.7 ± 9.4 years) with a placebo, with age and sex as covariates. Fractional anisotropy values in left corticospinal tract were increased in heart-kidney imbalance insomnia patients. Heart-kidney imbalance insomnia patients showed lower mean diffusivity and fractional anisotropy values of several white matter tracts than healthy control participants, such as the bilateral anterior limb of internal capsule, bilateral superior longitudinal fasciculus and bilateral posterior corona radiata. After being treated with Jiao-Tai-Wan, heart-kidney imbalance insomnia patients showed a trend towards reduced fractional anisotropy values in the left corticospinal tract. Jiao-Tai-Wan may improve the sleep quality by reversing the structural changes of the left corticospinal tract caused by heart-kidney imbalance insomnia.


Assuntos
Leucoaraiose , Distúrbios do Início e da Manutenção do Sono , Substância Branca , Anisotropia , Medicamentos de Ervas Chinesas , Feminino , Humanos , Rim , Imageamento por Ressonância Magnética/métodos , Masculino , Estudos Prospectivos , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Substância Branca/diagnóstico por imagem
5.
Scand J Gastroenterol ; 57(7): 862-871, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35170370

RESUMO

BACKGROUND: Several studies have revealed that serum vitamin D is an important factor for metabolic associated fatty liver disease (MAFLD), but there had been no consistent conclusion. METHODS: Of 427,507 subjects who underwent health examination, 83,625 who met the inclusion criteria were included in a cross-sectional analysis. Clinical and laboratory data were collected for analysis. MAFLD was diagnosed by abdominal imaging. RESULTS: Multivariate linear regression models discovered a negative association between serum vitamin D and MAFLD (OR: 0.92, 95% CI: 0.90 to 0.94, p = .001), after adjusting for other well-identified risk factors. The same result was found when serum vitamin D was handled as a categorical variable (quartile, Q1-Q4) (Q4 vs. Q1, OR: 0.82, 95% CI: 0.77 to 0.87, p < .001), and a significant linear trend was observed (p for trend <.001). After analysis, a nonlinear relationship was detected between serum vitamin D and MAFLD, with an inflection point of 2.23 (44.6 nmol/L or 17.84 ng/mL). The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.16 (1.06 to 1.28) and 0.89 (0.86 to 0.91), respectively. All interactions with MAFLD were not significant for age, sex, diabetes, hypertension, smoking and body mass index (p for interaction = .110, .558, .335, .195, .616 and .401, respectively). CONCLUSIONS: There was a nonlinear relationship between serum vitamin D and MAFLD. When the serum vitamin D level was ≥44.6 nmol/L (17.84 ng/mL), a negative correlation between serum vitamin D and MAFLD was detected. Below this level, serum vitamin D might promote the progression of MAFLD.


Assuntos
Hepatopatias , Hepatopatia Gordurosa não Alcoólica , Deficiência de Vitamina D , Estudos Transversais , Humanos , Vitamina D , Deficiência de Vitamina D/complicações , Vitaminas
6.
Brain Imaging Behav ; 16(2): 617-626, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34480258

RESUMO

OBJECTIVES: Alzheimer's disease (AD) is the most common type of dementia, and characterizing brain changes in AD is important for clinical diagnosis and prognosis. This study was designed to evaluate the classification performance of intravoxel incoherent motion (IVIM) diffusion-weighted imaging in differentiating between AD patients and normal control (NC) subjects and to explore its potential effectiveness as a neuroimaging biomarker. METHODS: Thirty-one patients with probable AD and twenty NC subjects were included in the prospective study. IVIM data were subjected to postprocessing, and parameters including the apparent diffusion coefficient (ADC), slow diffusion coefficient (Ds), fast diffusion coefficient (Df), perfusion fraction (fp) and Df*fp were calculated. The classification model was developed and confirmed with cross-validation (group A/B) using Support Vector Machine (SVM). Correlations between IVIM parameters and Mini-Mental State Examination (MMSE) scores in AD patients were investigated using partial correlation analysis. RESULTS: Diffusion MRI revealed significant region-specific differences that aided in differentiating AD patients from controls. Among the analyzed regions and parameters, the Df of the right precuneus (PreR) (ρ = 0.515; P = 0.006) and the left cerebellum (CL) (ρ = 0.429; P = 0.026) demonstrated significant associations with the cognitive function of AD patients. An area under the receiver operating characteristics curve (AUC) of 0.84 (95% CI: 0.66, 0.99) was calculated for the validation in dataset B after the prediction model was trained on dataset A. When the datasets were reversed, an AUC of 0.90 (95% CI: 0.75, 1.00) was calculated for the validation in dataset A, after the prediction model trained in dataset B. CONCLUSION: IVIM imaging is a promising method for the classification of AD and NC subjects, and IVIM parameters of precuneus and cerebellum might be effective biomarker for the diagnosis of AD.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico por imagem , Biomarcadores , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Imageamento por Ressonância Magnética , Movimento (Física) , Estudos Prospectivos , Reprodutibilidade dos Testes
7.
Front Cell Dev Biol ; 9: 731698, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35096806

RESUMO

Background: Maternal high-fat diet (MHFD) has been shown to increase susceptibility to neurological disease in later offspring, but the underlying mechanism is not clear. Fibroblast growth factor 21 (FGF21) has been reported to have a neuroprotective effect in stroke, but its mechanism of action remains unknown. In this study, we investigated the mechanism of the effect of MHFD on stroke in offspring in adulthood and the mechanism by which FGF21 acts on stroke and restores neurological function. Methods: We performed transcriptome sequencing analysis on D21 neonatal rats. Bodyweight and blood indicators were recorded in the adult rats after MHFD. FGF21 was administered 7 h after photochemical modeling twice a day for three consecutive days. Results: We found numerous mRNA changes between the MHFD group and a normal maternal normal diet (MND) group at D21, including genes related to astrocyte and PI3K/Akt pathways. The body weight, blood glucose, and triglycerides of the MHFD offspring were higher, ischemic lesions were larger, the number of activated astrocytes was lower, and the neurological function score was worse than that of the MND group. After FGF21 administration, WB and qPCR analyses showed that astrocytes and the PI3K/Akt pathway were upregulated, while NF-κB and inflammatory cytokines expression were inhibited in stroke and peri-stroke regions. Conclusion: Taken together, we conclude that MHFD alters the characteristics of astrocytes and other transcriptome changes in their offspring, leading to a worse prognosis of stroke, while FGF21 plays a neuroprotective role by inhibiting NF-κB and inflammatory factors and activating the PI3K/Akt pathway and activating more astrocytes in the MND group than the MHFD group.

8.
Neuroimage Clin ; 27: 102355, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32736325

RESUMO

Disruption of brain circuits is one of the core mechanisms of Parkinson's disease (PD). Understanding structural connection alterations in PD is important for effective treatment. However, due to methodological limitations, most studies were unable to account for confounding factors such as crossing fibers and were unable to identify damages to specific fiber tracts. In the present study, we aimed to demonstrate tract-specific white matter structural changes in PD patients and their relationship with clinical symptoms. Ninety-eight PD patients, divided into early (ES) and middle stage (MS) groups, and 76 healthy controls (HCs) underwent brain magnetic resonance imaging scans and clinical assessments. Fixel-based analysis was used to investigate fiber tract alterations in PD patients. Compared to HCs, the PD patients showed decreased fiber density (FD) in the corpus callosum (CC), increased FD in the cortical spinal tract (CST), and increased fiber-bundle cross-section (FC, log-transformed: log-FC) in the superior cerebellar peduncle (SCP). Analysis of variance (ANOVA) revealed significant differences in FD in the CST and log-FC in the SCP among the three groups. Post-hoc analysis revealed that the mean FD values of the CST were higher in ES and MS patient groups compared to HCs, and the mean log-FC values of the SCP were higher in ES and MS patient groups compared to HCs. Additionally, the FD values of the CC in PD patients were negatively correlated with the Unified Parkinson's Disease Rating Scale part-III (UPDRS-III) scores (r = -0.257, p = 0.032), Hamilton Depression Rating Scale 17 Items (HAMD-17) scores (r = -0.230, p = 0.033), and Hamilton Anxiety Scale (HAMA) scores (r = -0.248, p = 0.032). Moreover, log-FC values of the SCP (r = 0.274, p = 0.028) and FD values of the CST (r = 0.384, p < 0.001) were positively correlated with the UPDRS-III scores. We concluded that PD patients had both decreased and increased white matter integrity within specific fiber bundles. Additionally, these white matter alterations were different across disease stages, suggesting the occurrence of complex pathological and compensatory changes during the development of PD.


Assuntos
Doença de Parkinson , Substância Branca , Encéfalo , Imagem de Difusão por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética , Doença de Parkinson/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
9.
Front Aging Neurosci ; 12: 161, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581771

RESUMO

Background: The imbalance between the production and clearance of alpha-synuclein and its consequent accumulation plays a pivotal role in the pathogenesis of Parkinson's disease (PD). The diminished clearance of alpha-synuclein may be partly attributable to impaired interstitial fluid, which can be reflected by the extent of dilated perivascular space (dPVS). We studied the association between dPVS and dopamine neuronal degeneration. Method: We screened 71 healthy controls (HCs) and 88 patients from the Parkinson Progression Markers Initiative (PPMI) database. The dPVS was evaluated in different brain regions on axial T2-weighted images, and dopamine transporter (DAT) imaging data was used to elucidate the extent of dopaminergic neuronal degeneration. Patients with PD were further divided into two groups (SN + PD and SN - PD groups) according to whether dPVS was observed in the substantia nigra (SN). DAT uptake values and clinical scales were compared between the patients with PD and HCs and against dPVS scores. We also investigated the correlation between baseline dPVS scores and longitudinal DAT changes. Results: Relative to the HCs, patients with PD had more dPVS in the SN and basal ganglia (BG). PD patients with dPVS in the SN region exhibited greater expression of tau protein in cerebrospinal fluid (P = 0.038) and a trend towards decreased DAT binding (P = 0.086) relative to those without SN dPVS. No correlations were found between dPVS scores and DAT uptake values or between dPVS scores and longitudinal DAT changes. Conclusion: The dPVS in the SN of patients with PD may reflect the degeneration of dopaminergic neurons.

10.
J Agric Food Chem ; 68(6): 1563-1570, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31927998

RESUMO

Ethanamizuril(N-{4-[4-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-2-methyl-phenoxy]-phenyl}-acetamide, EZL) is a new anticoccidiosis compound and belongs to the class of triazines. In this study, the metabolism, distribution, and excretion of EZL were evaluated in chickens after administration of EZL at a single dosage. According to the relevant drug biotransformation rules, the exact molecular mass detection, the fragmentation characteristics, and the retention times, a total of five metabolites were identified in vivo in chickens, including two phase I metabolites and three phase II conjugated metabolites. The major metabolic pathways of EZL in chickens were deacetylation, hydroxylation, and glucuronidation. Regarding 14C-tissue residues after administration, kidney was considered to be the target tissue, as 14C-tissue residues could be detected at 240 h postdose. DeacetylEZL (M3) was the main metabolite, accounting for 68.65% and 25.62% of 14C in kidney at 6 and 24 h, respectively. In heart, muscle, skin+fat, and lung tissues, EZL was the main radioactive substance accounting for 94.88%, 97.32%, 96.23%, and 91.3% of 14C, respectively. In the liver, EZL and M3 were 20.76% and 54.65% of 14C, respectively. In chicken tissues the ratio of M5 was too low to be quantitated and it was mainly detected in chicken fecal and bile samples. In chicken excreta, EZL, M3, and glucuronidation of EZL (M5) accounted for 7.02%, 12.33%, and 10.32% of the dose, respectively and were eliminated primarily. This study presents the first detection of EZL metabolites, which is helpful for further understanding of the metabolic mechanism and in vivo intermediate processes of EZL. The results of this study will be good bases for better understanding EZL's anticoccidiosis mechanism and will serve as a helpful reference for assessing the risks to animals and humans.


Assuntos
Coccidiostáticos/farmacocinética , Triazinas/farmacocinética , Animais , Biotransformação , Galinhas , Coccidiostáticos/administração & dosagem , Coccidiostáticos/metabolismo , Hidroxilação , Rim/química , Rim/metabolismo , Fígado/química , Fígado/metabolismo , Pulmão/química , Pulmão/metabolismo , Músculos/química , Músculos/metabolismo , Triazinas/administração & dosagem , Triazinas/metabolismo
11.
Psychiatry Res Neuroimaging ; 296: 111029, 2020 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-31918166

RESUMO

Parkinson's disease (PD) pathology may damage emotion circuit and cause depression. We investigated whether the neural basis of depressive symptoms varies at different PD stages. Seventy-six healthy controls (HC) and 98 PD patients (divided into early and middle stage groups) underwent brain magnetic resonance imaging (MRI) and general neuropsychological tests. Voxel-based morphometry and tract-based analysis were used to study the association between brain structural alterations and the Hamilton Depression Scale 17 Item (HAMD-17) scores in different groups. Comparing with HC group, PD patients showed widespread brain alterations in both gray and white matter. The HAMD-17 scores were positively correlated with GM volume in the right pre-central gyrus of early PD patients. In the middle stage group, HAMD-17 scores were positively correlated with GM volume in midbrain and right superior temporal gyrus, and negatively associated with GM volume in left anterior cingulate and superior frontal gyrus. In white matter analysis, The HAMD-17 scores were positively correlated with fractional anisotropy value of the bilateral inferior fronto-occipital fasciculus in the early stage group, but not the middle stage group. We concluded that the neural basis of depressive symptoms might be distinct in different stages of PD, implying the need for differential treatments.


Assuntos
Encéfalo/patologia , Depressão/patologia , Doença de Parkinson/patologia , Anisotropia , Encéfalo/diagnóstico por imagem , Depressão/diagnóstico por imagem , Emoções , Feminino , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Doença de Parkinson/diagnóstico por imagem , Lobo Temporal/patologia , Substância Branca/patologia
12.
Front Neurosci ; 14: 583557, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33613172

RESUMO

BACKGROUND: Dilated perivascular spaces (dPVS) are considered to be a type of cerebral small vessel disease (CSVD) as well as an important part of the glymphatic system. Although obesity has been shown to play a significant role in the development of CSVD, there are no studies addressing the correlation between obesity and dPVS. We aimed to study the relationship between abdominal fat distribution and dPVS in neurologically healthy cohorts. METHODS: A total of 989 subjects, who were examined during a health examination project, were included in this study. We measured both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas using abdominal computed tomography. The dPVS scores were also evaluated in the basal ganglia (BG) and the centrum semiovale (CSO). RESULTS: In a multivariate ordinal regression analysis, the relationship between VAT area and CSO-dPVS scores remained significant (ß [95% confidence interval {CI} = 0.00003395] [0.00001074-0.00005716], P = 0.004), especially in male cohorts (ß [95% CI] = 0.00004325 [0.00001772-0.00006878], P = 0.001) after adjusting for age; sex; and glucose, creatinine, uric acid, high-density lipoprotein, and low-density lipoprotein levels, while no association was found between SAT area and dPVS scores. The effects of quartile VAT area on CSO-dPVS were also significant in male cohorts (odds ratio [95% CI] = 1.33 [1.139 - 1.557], P < 0.001). CONCLUSION: We demonstrated a positive association between VAT and CSO-dPVS scores in a healthy cohort, which was more prominent in males.

13.
World Neurosurg ; 134: e75-e81, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31648055

RESUMO

OBJECTIVE: Ultra-early hematoma growth (uHG), the black hole sign, and the blend sign are common predictors of hematoma enlargement (HE). This study aimed to develop a new diagnostic criterion for predicting HE using uHG and to compare the accuracy of uHG, the black hole sign, and the blend sign in predicting HE in patients with spontaneous intracerebral hemorrhage (sICH). METHODS: We retrospectively analyzed data of 920 patients with sICH from August 2013 to January 2018. Receiver operating characteristic curves were plotted to determine the optimal threshold values of uHG to predict HE. The effects of the black hole sign, blend sign, and uHG on HE were assessed using univariate and multivariate logistic regression models, and their prediction accuracies were analyzed using receiver operator analyses. RESULTS: The black hole sign was identified in 131 patients, the blend sign in 163 patients, and uHG >6.46 mL/h in 441 patients. Logistic analysis showed that the black hole sign, blend sign, and uHG >6.46 mL/h were independent predictors of HE. The sensitivity values of uHG >6.46 mL/h, the black hole sign, and the blend sign were 70.43%, 24.19%, and 36.56%, respectively, and specificity values were 57.77%, 88.28%, and 87.06%, respectively. uHG had the greatest area under the curve. The black hole and blend signs were more commonly found in patients with uHG >6.46 mL/h (P < 0.001). CONCLUSIONS: uHG >6.46 mL/h was the optimal predictor used for identifying patients at high risk of developing HE. A greater uHG value was associated with an increased prevalence of the black hole and blend signs.


Assuntos
Hemorragia Cerebral/cirurgia , Hematoma/cirurgia , Adulto , Idoso , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Progressão da Doença , Feminino , Hematoma/complicações , Hematoma/diagnóstico por imagem , Humanos , Hipertrofia/complicações , Hipertrofia/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
14.
Biotechnol Bioeng ; 117(2): 330-341, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31631324

RESUMO

Mesothelin is a protein expressed at high levels on the cell surface in a variety of cancers, with limited expression in healthy tissues. The presence of mesothelin on tumor tissue correlates with increased invasion and metastasis, and resistance to traditional chemotherapies, through mechanisms that remain poorly understood. Molecules that specifically recognize mesothelin and interrupt its contribution to tumor progression have significant potential for targeted therapy and targeted drug delivery applications. A number of mesothelin-targeting therapies are in preclinical and clinical development, although none are currently approved for routine clinical use. In this work, we report the development of a mesothelin-targeting protein based on the fibronectin type-III non-antibody protein scaffold, which offers opportunities for applications where antibodies have limitations. We engineered protein variants that bind mesothelin with high affinity and selectively initiate apoptosis in tumor cells expressing mesothelin. Interestingly, apoptosis does not occur through a caspase-mediated pathway and does not require downregulation of cell-surface mesothelin, suggesting a currently unknown pathway through which mesothelin contributes to cancer progression. Importantly, simultaneous treatment with mesothelin-binding protein and chemotherapeutic mitomycin C had a greater cytotoxic effect on mesothelin-positive cells compared to either molecule alone, underscoring the potential for combination therapy including biologics targeting mesothelin.


Assuntos
Antineoplásicos , Sistemas de Liberação de Medicamentos/métodos , Fibronectinas , Proteínas Ligadas por GPI , Engenharia de Proteínas/métodos , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fibronectinas/química , Fibronectinas/genética , Fibronectinas/metabolismo , Fibronectinas/farmacologia , Proteínas Ligadas por GPI/química , Proteínas Ligadas por GPI/metabolismo , Humanos , Células MCF-7 , Mesotelina , Mitomicina/química , Mitomicina/metabolismo , Mitomicina/farmacologia , Ligação Proteica
15.
Front Neurol ; 10: 1164, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31736868

RESUMO

Background/Objective: Hematoma expansion (HE) predicts poor outcome and is an appealing treatment target in spontaneous intracerebral hemorrhage (ICH). Clinical evidence has shown an association of HE with peripheral white blood cells (WBC) count, but the individual contributions of leukocyte subtypes between literatures are described inconsistently. Our aim was to determine the relationship between admission absolute and differential leukocyte counts and HE by using different growth definitions. Methods: We analyzed spontaneous ICH patients who underwent baseline cranial computed tomography and blood sampling within 6 h of stroke onset in our institution between September 2013 and August 2018. Hematoma volume was calculated using a semiautomated 3-dimensional reconstruction algorithm. According to commonly used absolute or relative growth definitions (>6 mL, >12.5 mL, or >33%), we defined 5 types of HE. A propensity score-matching analysis was performed to evaluate the influence of complete blood count components on HE across the various growth definitions. The receiver operating characteristic analysis assessed the predictive ability of leukocyte counts for HE. Results: A total of 1,066 patients were included, of whom 11-21% met the 5 HE definitions. After propensity score-matching, except using the definition of >12.5 mL growth or its combination with >33% growth, both WBC and neutrophil count were independently associated with reduced risk of HE (odds ratio [OR] for 103 cells increase; OR, 0.86-0.99; all p < 0.05) after adjusting confounders in multivariate analyses. However, monocyte count was correlated with increased risk of HE under the usage of >12.5 mL expansion definition only (OR, 1.43; p = 0.024). There was no association between lymphocyte count and HE (all p > 0.05). Regardless of the growth definition, admission eosinophil count was directly associated with the risk of HE (OR, 6.92-31.60; all p < 0.05), and was the best predictive subtype with area under the curve 0.64, sensitivity 69.5%, and specificity 58.9% at the optimal cut-off value of 45 cells/µL. Conclusions: Growth definition affects the relationship of HE with leukocyte subtypes counting. Eosinophil count robustly predicts HE, and may be a surrogate when using an inflammatory marker to help select acute ICH patients with high expansion risk for hemostasis treatment in clinical trial and practice.

16.
EBioMedicine ; 43: 454-459, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31060901

RESUMO

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is a devastating disease with high mortality rate. This study aimed to predict hematoma expansion in spontaneous ICH from routinely available variables by using support vector machine (SVM) method. METHODS: We retrospectively reviewed 1157 patients with spontaneous ICH who underwent initial computed tomography (CT) scan within 6 h and follow-up CT scan within 72 h from symptom onset in our hospital between September 2013 and August 2018. Hematoma region was manually segmented at each slice to guarantee the measurement accuracy of hematoma volume. Hematoma expansion was defined as a proportional increase of hematoma volume > 33% or an absolute growth of hematoma volume > 6 mL from initial CT scan to follow-up CT scan. Univariate and multivariate analyses were performed to assess the association between clinical variables and hematoma expansion. SVM machine learning model was developed to predict hematoma expansion. FINDINGS: 246 of 1157 (21.3%) patients experienced hematoma expansion. Multivariate analyses revealed the following 6 independent factors associated with hematoma expansion: male patient (odds ratio [OR] = 1.82), time to initial CT scan (OR = 0.73), Glasgow Coma Scale (OR = 0.86), fibrinogen level (OR = 0.72), black hole sign (OR = 2.52), and blend sign (OR = 4.03). The SVM model achieved a mean sensitivity of 81.3%, specificity of 84.8%, overall accuracy of 83.3%, and area under receiver operating characteristic curve (AUC) of 0.89 in prediction of hematoma expansion. INTERPRETATION: The designed SVM model presented good performance in predicting hematoma expansion from routinely available variables. FUND: This work was supported by Health Foundation for Creative Talents in Zhejiang Province, China, Natural Science Foundation of Zhejiang Province, China (LQ15H180002), the Science and Technology Planning Projects of Wenzhou, China (Y20180112), Scientific Research Staring Foundation for the Returned Overseas Chinese Scholars of Ministry of Education of China, and Project Foundation for the College Young and Middle-aged Academic Leader of Zhejiang Province, China. The funders had no role in study design, data collection, data analysis, interpretation, writing of the report.


Assuntos
Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Hematoma/complicações , Hematoma/patologia , Máquina de Vetores de Suporte , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Hemorragia Cerebral/metabolismo , Feminino , Escala de Coma de Glasgow , Hematoma/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Razão de Chances , Prognóstico , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Adulto Jovem
17.
Environ Technol ; 38(3): 305-315, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27241886

RESUMO

Though activated sludge systems have contributed significantly to the control of hygiene of our society, the wastewater treatment generates large amount of excess sludge. The oxic-settling-anaerobic (OSA)-based biological processes have been shown to be promising approaches for sludge reduction during wastewater treatment. However, the sludge reduction mechanism is still unclear. Four conditions were examined to clarify the sludge reduction mechanism in the OSA-based process. Sludge retention time (SRT) was the main 'contributor' to sludge reduction. The sludge reduction percentage of the process with side hydrolysis and acidification was 42%, with the contribution by long SRT of 33%, energy uncoupling of 7.7%, and hydrolysis/acidification of 1.1%. In addition, the sludge reduction in the OSA-based process had no obvious impact on the efficiency of nutrient removal. The clarified mechanism for sludge reduction in the OSA-based process could provide valuable clue for future system optimization.


Assuntos
Reatores Biológicos , Esgotos , Eliminação de Resíduos Líquidos/métodos , Compostos de Amônio/análise , Análise da Demanda Biológica de Oxigênio , Nitratos/análise , Nitritos/análise , Nitrogênio/análise , Fosfatos/análise , Fatores de Tempo , Poluentes Químicos da Água
18.
Int J Syst Evol Microbiol ; 66(8): 3201-3206, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27216930

RESUMO

A novel Gram-reaction-positive, non-motile and facultatively anaerobic bacterium, designated strain S01T, was isolated from a nutrient agar plate kept on a laboratory clean bench at Guangdong Institute of Microbiology, PR China, which was contaminated from an unknown source. Strain S01T was found to be catalase-positive and oxidase-negative. Similarity searches revealed that the strain shared the highest 16S rRNA gene similarity with Corynebacterium humireducens MFC-5T (95.9 %). However, phylogenetic analysis based on the 16S rRNA gene sequences showed that strain S01T was closely related to Corynebacteriumdoosanense JCM 17317T (94.8 %) and Corynebacterium maris JCM 17018T (94.8 %). The major fatty acids were C18:1ω9c, C16:0, 10-methyl C18:0 and C18:0. The respiratory quinones predominantly consisted of MK-8(H2), with small amounts of MK-8 and MK-9(H2). Polar lipids contained phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, an unidentified aminolipid, two unidentified glycolipids and two unidentified lipids. Mycolic acids were present. The cell-wall peptidoglycan contained meso-diaminopimelic acid and the major cell-wall sugars were galactose, arabinose and glucose. The genomic DNA G+C content of strain S01T was 70.7±0.1 mol%. The results of phenotypic, phylogenetic and chemotaxonomic analyses indicated that strain S01T represents a novel species of the genus Corynebacterium, for which the name Corynebacterium guangdongense sp. nov. is proposed. The type strain is S01T (=GDMCC 1.1022T=CCTCC AB 2015423T=KCTC 39608T).


Assuntos
Corynebacterium/classificação , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , China , Corynebacterium/genética , Corynebacterium/isolamento & purificação , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Glicolipídeos/química , Laboratórios , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
19.
Int J Syst Evol Microbiol ; 65(10): 3457-3461, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26297659

RESUMO

An aerobic, non-motile and Gram-staining-positive bacterial strain (1PNM-19T) was isolated from a lead-zinc ore in an abandoned mine and was investigated in a taxonomic study using a polyphasic approach. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain 1PNM-19T was affiliated to the genus Deinococcus and most closely related to Deinococcus aquatilis DSM 23025T and Deinococcus ficus DSM 19119T. The major respiratory quinone was determined to be menaquinone 8 (MK-8) and the major fatty acids contained summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. A complex polar lipid profile consisted of different unidentified glycolipids and polar lipids, two unidentified aminolipids, an unidentified phosphoglycolipid, phospholipid and aminophospholipid. The genomic DNA G+C content of strain 1PNM-19T was 71.7 ± 0.1 mol%. Based on data from this taxonomic study, strain 1PNM-19T represents a novel species of the genus Deinococcus, for which the name Deinococcus metalli sp. nov. is proposed. The type strain is 1PNM-19T ( = GIMCC 1.654T = CCTCC AB 2014198T = DSM 27521T).


Assuntos
Deinococcus/classificação , Mineração , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Deinococcus/genética , Deinococcus/isolamento & purificação , Ácidos Graxos/química , Chumbo , Dados de Sequência Molecular , Fosfolipídeos/química , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química , Zinco
20.
J Biotechnol ; 200: 6-7, 2015 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-25687102

RESUMO

We report the complete genome sequence of Streptomyces vietnamensis GIMV4.0001(T), a new and genetically manipulable producer of the benzoisochromanequinone antibiotic granaticin, whose unique sugar attachment pattern in structure has drawn much attention among chemical and biochemical researchers. The genome of S. vietnamensis GIMV4.0001(T) consists of one linear chromosome (8,867,142 bp, 72.09% G+C content) and one linear megaplasmid named pSVL1 (286,635 bp, 69.04% G+C content), encoding a total of 7356 protein coding genes. Twenty-nine gene clusters for secondary metabolites were predicted on the chromosome.


Assuntos
Antibacterianos/biossíntese , Cromossomos Bacterianos , Genoma Bacteriano , Streptomyces/genética , Streptomyces/metabolismo , Sequência de Bases , Dados de Sequência Molecular , Naftoquinonas/metabolismo
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