Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 163
Filtrar
1.
Poult Sci ; 100(9): 101358, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34358955

RESUMO

This study investigated the effects of dietary supplementation with Bacillus subtilis (B. subtilis) or Bacillus licheniformis (B. licheniformis) on growth performance, immunity, antioxidant capacity, short chain fatty acid (SCFA) production, and the cecal microflora in broiler chickens. In total, 360 male, 1-day-old Cobb 500 birds were randomly divided into 3 groups: the control group was fed a basal diet; the B. subtilis group was fed a basal diet supplemented with 1.5 × 109 CFU/kg B. subtilis; the B. licheniformis group was fed a basal diet supplemented with 1.5 × 109 CFU/kg B. licheniformis. Results showed that chickens supplemented with either B. subtilis or B. licheniformis had comparatively higher (P < 0.05) body weight and average daily gain, whereas no difference (P > 0.05) was observed in feed efficiency. Concentrations of serum IgA, IgY, and IgM, as well as anti-inflammatory IL-10 were significantly increased (P < 0.05), and proinflammatory IL-1ß and IL-6 were significantly decreased (P < 0.05) by B. subtilis or B. licheniformis supplementation. Moreover, chickens fed with diets supplemented by either B. subtilis or B. licheniformis had greater antioxidant capacity, indicated by the notable increases (P < 0.05) in glutathione peroxidase, superoxide dismutase, and catalase, along with decrease (P < 0.05) in malondialdehyde. Compared to the control group, levels of SCFA, excluding acetic and propionic acid, in cecal content had improved (P < 0.05) by adding B. licheniformis, and significant increase (P < 0.05) in acetic and butyric acid was observed with B. subtilis supplementation. Microbial analysis showed that both B. subtilis or B. licheniformis supplementation could increase butyrate-producing bacteria such as Alistipes and Butyricicoccus, and decrease pathogenic bacteria such as the Synergistetes and Gammaproteobacteria. In summary, dietary supplemented with B. subtilis or B. licheniformis improved growth performance, immune status, and antioxidant capacity, increased SCFA production, and modulated cecal microbiota in chickens. Moreover, B. licheniformis was more effective than B. subtilis with the same supplemental amount.


Assuntos
Bacillus licheniformis , Microbioma Gastrointestinal , Probióticos , Ração Animal/análise , Animais , Antioxidantes , Bacillus subtilis , Galinhas , Dieta/veterinária , Suplementos Nutricionais , Ácidos Graxos Voláteis , Masculino
2.
Int J Pharm ; 606: 120869, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34245845

RESUMO

Excessive growth of tumor within biliary wall and formation of biofilm on inner surface of stent can cause restenosis or even obstruction after stent implantation. Therefore, it is important and valuable to develop a new biliary stent for anti-cholangiocarcinoma and anti-biofilm formation. Herein, we designed, prepared and primarily evaluated a new trilayered film for biliary stents consisting of one poly (lactic acid) (PLA) layer loaded with anti-tumor paclitaxel (PTX layer), one middle PLA isolation layer (isolation layer) and one PLA layer loaded with antimicrobial ofloxacin (OFLX layer). It is postulated that the PTX layer releases drug towards biliary wall with tumor, the OFLX layer releases drug towards lumen of bile duct and the isolation layer is used to separate from the PTX layer and the OFLX layer and facilitate drug release in unidirectional way. The prepared trilayered films were characterized in terms of morphology, microstructure, crystallinity and biodegradability. It was found that the films could effectively tune drug release by addition of different amounts of drug or PEG, release PTX and OFLX in opposite directions, effectively inhibit the proliferation of human cholangiocarcinoma RBE cells, the adherence of E. coli and S. aureus and the formation of biofilm in vitro. It is potential that the trilayered films can be used to fabricate a new biliary stent with a dual function of anti-cholangiocarcinoma and anti-biofilm formation.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Stents Farmacológicos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/tratamento farmacológico , Escherichia coli , Humanos , Paclitaxel , Staphylococcus aureus , Stents
3.
J Mol Recognit ; 34(11): e2919, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34137098

RESUMO

Pathogens are one of the important factors affecting national economic construction. An ideal detection system for pathogen control with excellent sensitivity, high specificity, and time-saving is needed. Here, we reported a method for bacterial detection using gold nanoparticles-mediated fluorescent "chemical nose" sensors (GFCEs). The technique consists of gold nanoparticles-coated magnetic particle using benzaldehyde, octyl aldehyde, and pyrimidine-4-formaldehyde modified, respectively. And these positively charged nanocompound interacting with three different fluorescent proteins (FPs) to form three kinds of GFCEs, respectively, named GFCE1, GFCE2, and GFCE3. Upon binding with pathogenic cells, functionalized gold nanoparticles could identify patches on hydrophobic/functional surfaces of microorganisms, and self-assemble with living bacteria by complementary electrostatic interactions. The binding ability between GFCEs and bacteria determines the change of fluorescence response of three FPs from GFCEs. These feature fluorescent level are pathogen-specific, highly repeatable, and can be analyzed by Linear Discriminant Analysis (LDA). The combination of GFCE1 and GFCE2 has the best performance when detecting pathogens with concentrations of 106 cfu mL-1 . The first discriminant within 15 minutes is 93.8%, which could be used for subsequent identification of unknown samples. The commonly applicable system provides a simple way for the rapid bacterial detection without preprocessing procedures.

4.
Theranostics ; 11(15): 7294-7307, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34158851

RESUMO

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by death of motor neurons in the brain and spinal cord. However, so far, there is no effective treatment for ALS. Methods: In this study, R13, a prodrug of 7,8-dihydroxyflavone, selectively activating tyrosine kinase receptor B (TrkB) signaling pathway, was administered prophylactically to 40-day old SOD1G93A mice for 90 days. The motor performance was investigated by rotarod test, climbing-pole test, grip strength test and hanging endurance test. Afterwards, the spinal cord and medulla oblongata of 130-day old mice were harvested, and the proteomics revealed the effect of R13 on mouse protein expression profile. Astrocytes and microglial proliferation were assessed by immunohistochemical analysis. The number of motor neurons in the spinal cord is determined by Nissl staining. The effect of R13 on gastrocnemius morphology was assessed by HE staining. The effect of R13 on the survival rate was accomplished with worms stably expressing G93A SOD1. Results: Behavioral tests showed that R13 significantly attenuated abnormal motor performance of SOD1G93A mice. R13 reduced the advance of spinal motor neuron pathology and gastrocnemius muscle atrophy. The proliferation of microglia and astrocytes was reduced by R13 treatment. Mitochondriomics analysis revealed that R13 modified the mitochondrial protein expression profiles in the medulla oblongata and spinal cord of SOD1G93A mice, particularly promoting the expression of proteins related to oxidative phosphorylation (OXPHOS). Further study found that R13 activated AMPK/PGC-1α/Nrf1/Tfam, promoted mitochondrial biogenesis and ameliorated mitochondrial dysfunction. Lastly, R13 prolonged the survival rate of worms stably expressing G93A SOD1. Conclusions: These findings suggest oral R13 treatment slowed the advance of motor system disease in a reliable animal model of ALS, supporting that R13 might be useful for treating ALS.


Assuntos
Esclerose Amiotrófica Lateral , Sistema Nervoso Central/enzimologia , Flavonas/farmacologia , Mitocôndrias , Atividade Motora , Superóxido Dismutase-1 , Superóxido Dismutase , Esclerose Amiotrófica Lateral/tratamento farmacológico , Esclerose Amiotrófica Lateral/enzimologia , Esclerose Amiotrófica Lateral/genética , Esclerose Amiotrófica Lateral/fisiopatologia , Animais , Humanos , Camundongos , Camundongos Transgênicos , Mitocôndrias/enzimologia , Mitocôndrias/genética , Atividade Motora/efeitos dos fármacos , Atividade Motora/genética , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo
5.
J Mol Recognit ; 34(9): e2896, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33822415

RESUMO

Portable and quantitative detection of Escherichia coli (E. coli) has the potential to reform clinical diagnostics, food safety, and environmental monitoring. At present, most commercial devices used for pathogen detection have disadvantages such as expensive, highly complex operations, or limited detection specificity. Using the common luminometer and the properties of pyruvate kinase utilizing phosphoenolpyruvate to generate adenosine triphosphate (ATP), we have developed a method that could specifically quantify E. coli. The system is based on a sandwich hybridization procedure wherein both oligonucleotide probes recognize each end of the target of pathogenic 16S rRNAs segment. The detection probe DNA-conjugated pyruvate kinase can link ATP production to the detection of pathogenic nucleic acid in the samples. The luminometer-based system is capable of detecting E. coli with single bacteria resolution. The platform should be easily used to the detection of many other toxic analytes through the application of suitable functional-DNA recognition elements.

6.
Sci Total Environ ; 773: 145056, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33582341

RESUMO

Water is essential for the industrial production of hydrogen. This study investigates the production of hydrogen from biomass and coal. To date, there are few studies focusing on the water footprint of biomass-to-hydrogen and coal-to-hydrogen processes. This research conducted a life cycle water use analysis on wheat straw biomass and coal to hydrogen via pyrolysis gasification processes. The results show that the water consumption of the entire biomass-to-hydrogen process was 76.77 L/MJ, of which biomass cultivation was the dominant contributor (99%). Conversely, the water consumption of the coal-to-hydrogen process was only 1.06 L/MJ, wherein the coal production stage accounted for only 4.15% for the total water consumption, which is far lower than that of the biomass-to-hydrogen process. The hydrogen production stage of biomass hydrogen production accounted for 76% of the total water consumption when excluding the water consumption of straw growth, whereas that of the coal hydrogen production stage was 96%. This research provides the associated water consumption, within a specified boundary, of both hydrogen production processes, and the influence of major factors on total water consumption was demonstrated using sensitivity analysis.

7.
Clin Lab ; 67(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33616329

RESUMO

BACKGROUND: Isolated central nervous system (CNS) blast crisis was uncommon in chronic myeloid leukemia (CML). METHODS: The present study reported an interesting case of a CML patient administered with dasatinib presenting with headache and seizure unconsciousness. Imaging investigation, immunophenotyping, bone marrow cytology inspection, chromosomal analysis, and polymerase chain reaction (PCR) were performed on a 41-year-old CML patient. RESULTS: Bone marrow examination revealed complete cytogenetic remission and there were no obvious abnormalities in head CT and MR. Cytomorphological examination of cerebrospinal fluid (CSF) showed 50% blasts. Flow cytometry analysis was showed 78.3% CSF cells expressing the specific myeloid antigens. PCR analysis on CSF cells was positive for BCR/ABL P210 fusion gene. All the above CSF findings were suggestive of CNS infiltrating isolated from bone marrow cytogenetic remission. CONCLUSIONS: Isolated CNS blast crisis of CML with dasatinib were rare. The mechanism still remains unclear and the treatment regimen requires further exploration. Flow cytometry showed great value to detect the blast cells in this patient.


Assuntos
Crise Blástica , Leucemia Mielogênica Crônica BCR-ABL Positiva , Adulto , Crise Blástica/tratamento farmacológico , Crise Blástica/genética , Medula Óssea , Sistema Nervoso Central , Dasatinibe/uso terapêutico , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética
8.
Biosens Bioelectron ; 176: 112953, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33418182

RESUMO

The rapid identification of pathogenic microorganisms plays a crucial role in the timely diagnosis and treatment strategies during a global pandemic, especially in resource-limited area. Herein, we present a sensitive biosensor strategy depended on botulinum neurotoxin type A light chain (BoNT/A LC) activated complex assay (BACA). BoNT/A LC, the surrogate of BoNT/A which embodying the most potent biological poisons, could serve as an ultrasensitive signal reporter with high signal-to-noise ratio to avoid common strong background response, poor stability and low intensity of current biosensor methods. A nanoparticle hybridization system, involving specific binding probes that recognize pathogenic 16S rRNAs or SARS-CoV-2 gene site, was developed to measure double-stranded biotinylated target DNA containing a single-stranded overhang using Fluorescence Resonance Energy Transfer (FRET)-based assay and colorimetric method. The method is validated widely by six different bacteria strains and severe acute respiratory related coronavirus 2 (SARS-CoV-2) nucleic acid, demonstrating a single cell or 1 aM nucleic acid detecting sensitivity. This detection strategy offers a solution for general applications and has a great prospect to be a simple instrument-free colorimetric tool, especially when facing public health emergency.


Assuntos
Técnicas Biossensoriais/métodos , Toxinas Botulínicas Tipo A , Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico , COVID-19/virologia , Pandemias , SARS-CoV-2/isolamento & purificação , Bactérias/genética , Bactérias/isolamento & purificação , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Humanos , SARS-CoV-2/genética , Especificidade da Espécie
9.
Ultrasonics ; 110: 106272, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33065465

RESUMO

Sonodynamic therapy (SDT) is a promising modality for cancer treatment. Sinoporphyrin sodium (DVDMS), purified from Photofrin II, shows great potential in SDT evidenced by growing studies. The purpose of the current study was to investigate the antitumor effect of SDT combined with DVDMS on human glioblastoma (U87 MG) cell line in vitro. The cellular uptake of DVDMS was investigated by confocal microscopy and IVIS spectrum imaging system. In addition, DVDMS toxicity and anti-tumor effect of SDT were assessed by flow cytometry. The generation of intracellular reactive oxygen species (ROS) was determined using DCFH-DA staining. Simultaneously, fluorescence microscopy was performed to access the destabilization of mitochondrial membrane potential (MMP). The results showed that DVDMS could easily enter the cells and accumulated in the cytoplasm, especially the mitochondria. And the intracellular DVDMS increased with incubation time or concentrations. The results also showed remarkable cytotoxicity of DVDMS-mediated SDT (center frequency: 0.970 MHz; peak-rarefactional pressure: 0.52-MPa; acoustic power: 0.32 W; pulse repetition frequency: 1 Hz; duty cycle: 1-30%; duration: 3 min) on U87 MG cells, while DVDMS alone was non-toxic to the cells. In comparison with the control group, the SDT-treated group showed significant generation of intracellular ROS and loss of MMP at 1 h post-treatment. These results indicated that DVDMS-mediated SDT could induce great cytotoxicity in U87 MG cells via the production of ROS and showed potentials in the treatment for glioblastoma.


Assuntos
Antineoplásicos/farmacologia , Glioblastoma/terapia , Porfirinas/farmacologia , Terapia por Ultrassom/métodos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Desenho de Equipamento , Humanos , Técnicas In Vitro , Potencial da Membrana Mitocondrial , Necrose , Espécies Reativas de Oxigênio/metabolismo
10.
Nat Commun ; 11(1): 5928, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230103

RESUMO

CD19-specific chimeric antigen receptor T cell (CD19 CAR T) therapy has shown high remission rates in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL). However, the long-term outcome and the factors that influence the efficacy need further exploration. Here we report the outcome of 51 r/r B-ALL patients from a non-randomized, Phase II clinical trial (ClinicalTrials.gov number: NCT02735291). The primary outcome shows that the overall remission rate (complete remission with or without incomplete hematologic recovery) is 80.9%. The secondary outcome reveals that the overall survival (OS) and relapse-free survival (RFS) rates at 1 year are 53.0 and 45.0%, respectively. The incidence of grade 4 adverse reactions is 6.4%. The trial meets pre-specified endpoints. Further analysis shows that patients with extramedullary diseases (EMDs) other than central nervous system (CNS) involvement have the lowest remission rate (28.6%). The OS and RFS in patients with any subtype of EMDs, higher Tregs, or high-risk genetic factors are all significantly lower than that in their corresponding control cohorts. EMDs and higher Tregs are independent high-risk factors respectively for poor OS and RFS. Thus, these patient characteristics may hinder the efficacy of CAR T therapy.


Assuntos
Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Linfócitos T/transplante , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Receptores de Antígenos de Linfócitos T/imunologia , Recidiva , Indução de Remissão , Fatores de Risco , Segurança , Taxa de Sobrevida , Linfócitos T/imunologia , Adulto Jovem
11.
Theranostics ; 10(25): 11794-11819, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052247

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease manifested by cognitive impairment. As a unique approach to open the blood-brain barrier (BBB) noninvasively and temporarily, a growing number of studies showed that low-intensity focused ultrasound in combination with microbubbles (FUS/MB), in the absence of therapeutic agents, is capable of ameliorating amyloid or tau pathology, concurrent with improving memory deficits of AD animal models. However, the effects of FUS/MB on both the two pathologies simultaneously, as well as the memory behaviors, have not been reported so far. Methods: In this study, female triple transgenic AD (3×Tg-AD) mice at eight months of age with both amyloid-ß (Aß) deposits and tau phosphorylation were treated by repeated FUS/MB in the unilateral hippocampus twice per week for six weeks. The memory behaviors were investigated by the Y maze, the Morris water maze and the step-down passive avoidance test following repeated FUS/MB treatments. Afterwards, the involvement of Aß and tau pathology were assessed by immunohistochemical analysis. Neuronal health and phagocytosis of Aß deposits by microglia in the hippocampus were examined by confocal microscopy. Further, hippocampal proteomic alterations were analyzed by employing two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) combined with mass spectrometry. Results: The three independent memory tasks were indicative of evident learning and memory impairments in eight-month-old 3×Tg-AD mice, which developed intraneuronal Aß, extracellular diffuse Aß deposits and phosphorylated tau in the hippocampus and amygdala. Following repeated FUS/MB treatments, significant improvement in learning and memory ability of the 3×Tg-AD mice was achieved. Amelioration in both Aß deposits and phosphorylated tau in the sonicated hemisphere was induced in FUS/MB-treated 3×Tg-AD mice. Albeit without increase in neuron density, enhancement in axonal neurofilaments emerged from the FUS/MB treatment. Confocal microscopy revealed activated microglia engulfing Aß deposits in the FUS/MB-treated hippocampus. Further, proteomic analysis revealed 20 differentially expressed proteins, associated with glycolysis, neuron projection, mitochondrial pathways, metabolic process and ubiquitin binding etc., in the hippocampus between FUS/MB-treated and sham-treated 3×Tg-AD mice. Conclusions: Our findings reinforce the positive therapeutic effects on AD models with both Aß and tau pathology induced by FUS/MB-mediated BBB opening, further supporting the potential of this treatment regime for clinical applications.


Assuntos
Doença de Alzheimer/terapia , Hipocampo/patologia , Transtornos da Memória/terapia , Microbolhas/uso terapêutico , Terapia por Ultrassom/métodos , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos da radiação , Modelos Animais de Doenças , Feminino , Hipocampo/efeitos da radiação , Humanos , Transtornos da Memória/diagnóstico , Transtornos da Memória/genética , Transtornos da Memória/patologia , Camundongos , Camundongos Transgênicos , Presenilina-1/genética , Presenilina-1/metabolismo , Proteômica , Ondas Ultrassônicas , Proteínas tau/genética , Proteínas tau/metabolismo
12.
ACS Omega ; 5(24): 14814-14821, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32596619

RESUMO

Field-deployable detectors of disease biomarkers provide a simple and fast analysis of clinical specimens. However, most of the existing field-deployable diagnostics have poor sensitivity and are not suitable for the detection of biomarkers with low abundance. Herein, we report a highly sensitive and rapid colorimetric readout paper-based assay for pathogen detection by integrating the unique collateral activity of a Cas12a-activated universal field-deployable detector (CUFD). The collateral effect of Cas12a results in a nonspecific destruction of a fluorophore biotin-labeled ssDNA reporter for the CUFD. This technique can quantify seven different kinds of pathogens in blood samples without any purification procedure, with sensitivity as low as 10 aM for the Shigella dysenteriae DNA. This CUFD technique has significant potential for the detection of pathogenic DNA as well as other types of DNA or RNA targets at the point-of-care application.

13.
Biomed Eng Online ; 19(1): 52, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32552718

RESUMO

BACKGROUND: Colorectal cancer is the third leading cause of cancer-related deaths worldwide. Sonodynamic therapy (SDT) is an emerging cancer therapy, and in contrast to photodynamic therapy, could non-invasively reach deep-seated tissues and locally activates a sonosensitizer preferentially accumulated in the tumor area to produce cytotoxicity effects. In comparison with traditional treatments, SDT may serve as an alternative strategy for human colon cancer treatment. Here, we investigated the sonodynamic effect using sinoporphyrin sodium (DVDMS) as a novel sonosensitizer on human colon cancer cells in vitro. RESULTS: The absorption spectra of DVDMS revealed maximum absorption at 363 nm wavelength and emission peak at 635 nm. Confocal microscopy images revealed the DVDMS was primarily localized in the cytoplasm, while no evident signal was detected within the nuclei. Flow cytometry analysis showed rapid intracellular uptake of DVDMS by two types of human colon cancer cells (HCT116 and RKO). Cell viability of HCT116 was tolerant with the concentration of DVDMS up to 20 µg/mL, while the case of RKO was 5 µg/mL. In comparison with the control group, the SDT-treated groups of these two types of human colon cancer cells showed significant increase in cellular apoptosis and necrosis ratio. Increased intracellular reactive oxygen species (ROS) production was detected, indicating the involvement of ROS in mediating SDT effects. CONCLUSION: DVDMS results an effective sonosensitizer for the ultrasound-mediated cancer cell killing, and its anticancer effect seems to rely on its ability to produce ROS under ultrasound exposure.


Assuntos
Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Porfirinas/farmacologia , Terapia por Ultrassom/métodos , Apoptose/efeitos dos fármacos , Transporte Biológico , Células HCT116 , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Necrose/induzido quimicamente , Porfirinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
BMC Gastroenterol ; 20(1): 171, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503434

RESUMO

BACKGROUND: Alternative splicing (AS) is an important mechanism of regulating eukaryotic gene expression. Understanding the most common AS events in colorectal cancer (CRC) will help developing diagnostic, prognostic or therapeutic tools in CRC. METHODS: Publicly available RNA-seq data of 28 pairs of CRC and normal tissues and 18 pairs of metastatic and normal tissues were used to identify AS events using PSI and DEXSeq methods. RESULT: The highly significant splicing events were used to search a database of The Cancer Genome Atlas (TCGA). We identified AS events in 9 genes in CRC (more inclusion of CLK1-E4, COL6A3-E6, CD44v8-10, alternative first exon regulation of ARHGEF9, CHEK1, HKDC1 and HNF4A) or metastasis (decrease of SERPINA1-E1a, CALD-E5b, E6). Except for CHEK1, all other 8 splicing events were confirmed by TCGA data with 382 CRC tumors and 51 normal controls. The combination of three splicing events was used to build a logistic regression model that can predict sample type (CRC or normal) with near perfect performance (AUC = 1). Two splicing events (COL6A3 and HKDC1) were found to be significantly associated with patient overall survival. The AS features of the 9 genes are highly consistent with previous reports and/or relevant to cancer biology. CONCLUSIONS: The significant association of higher expression of the COL6A3 E5-E6 junction and HKDC1 E1-E2 with better overall survival was firstly reported. This study might be of significant value in the future biomarker, prognosis marker and therapeutics development of CRC.


Assuntos
Processamento Alternativo/genética , Colágeno Tipo VI/genética , Neoplasias Colorretais/genética , Hexoquinase/genética , Isoformas de Proteínas/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/mortalidade , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Modelos Logísticos , Prognóstico , Análise de Sequência de RNA
15.
BMJ Open ; 10(6): e036404, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32503872

RESUMO

INTRODUCTION: We developed a zero-dimensional (0D) model to assess the patient-specific haemodynamics in the circle of Willis (CoW). Similar numerical models for simulating the cerebral blood flow (CBF) had only been validated qualitatively in healthy volunteers by magnetic resonance (MR) angiography and transcranial Doppler (TCD). This study aims to validate whether a numerical model can simulate patient-specific blood flow in the CoW under pathological conditions. METHODS AND ANALYSIS: This study is a diagnostic accuracy study. We aim to collect data from a previously performed prospective study that involved patients with aneurysmal subarachnoid haemorrhage (aSAH) receiving both TCD and brain Computerd Tomography angiography (CTA) at the same day. The cerebral flow velocities are calculated by the 0D model, based on the vessel diameters measured on the CTA of each patient. In this study, TCD is considered the gold standard for measuring flow velocity in the CoW. The agreement will be analysed using Pearson correlation coefficients. ETHICS AND DISSEMINATION: This study protocol has been approved by the Medical Ethics Review Board of the University Medical Center Groningen: METc2019/103. The results will be submitted to an international scientific journal for peer-reviewed publication. TRIAL REGISTRATION NUMBER: NL8114.


Assuntos
Círculo Arterial do Cérebro/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiologia , Círculo Arterial do Cérebro/diagnóstico por imagem , Protocolos Clínicos , Angiografia por Tomografia Computadorizada , Humanos , Modelos Estatísticos , Reprodutibilidade dos Testes , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/fisiopatologia , Ultrassonografia Doppler Transcraniana
16.
Int J Biol Macromol ; 159: 659-666, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32439451

RESUMO

The moisture sorption and desorption properties of hard capsules have a great influence on the quality of capsule products. However, studies on them have rarely been reported. Herein, we studied the moisture sorption and desorption properties of three kinds of hard capsules (gelatin, hydroxypropyl methyl cellulose (HPMC) and pullulan capsules) in terms of hygroscopicity, crystallinity, thermal behaviors and so on. It is found that HPMC capsules have weaker moisture sorption ability and moisture keeping ability than pullulan or gelatin capsules with lower moisture sorption rates, equilibrium moisture contents, moisture keeping rates and higher critical relative humidity. In comparison with gelatin capsules, pullulan capsules have weaker moisture sorption ability and comparable moisture keeping ability. HPMC or pullulan capsules can more effectively protect high, moderate and low hygroscopic capsule contents (chitosan, potato starch or ethyl cellulose) from outside moisture absorption. The diffraction peaks of the moisture equilibrated gelatin, HPMC and pullulan capsules are much smaller than those of their dried ones. The dried and the moisture equilibrated gelatin, HPMC or pullulan capsules all have smooth surface morphology. HPMC or pullulan capsules can be an attractive alternative to animal gelatin capsules due to their appropriate moisture sorption and desorption properties.


Assuntos
Cápsulas/química , Gelatina/química , Glucanos/química , Derivados da Hipromelose/química , Água/análise , Varredura Diferencial de Calorimetria , Cápsulas/análise , Quitosana/química , Gelatina/análise , Glucanos/análise , Derivados da Hipromelose/análise , Amido/química , Propriedades de Superfície , Difração de Raios X
17.
Carbohydr Polym ; 238: 116190, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32299551

RESUMO

κ-Carrageenan (κ-Ca) is often used to facilitate gelling of aqueous solutions of polysaccharides. However, studies on its effects on pullulan's rheological and texture properties and pullulan (PUL) hard capsule performances have rarely been reported. Herein, effects of κ-Ca on PUL solutions, hydrogels, films and hard capsules were investigated. It was found that the gelling temperature of 15 % (w/w) PUL solutions with 0.07 % KCl increased from 34 ℃ to 42 ℃ as the concentration of κ-Ca increased from 0.6 % to 1.2 %, and the gelling temperature rose from 25 ℃ to 37 ℃ by adding a small amount of KCl (0.07 %) for 15 % PUL solutions with 0.9 % κ-Ca. As the κ-Ca concentration increased, hardness, fracturability and adhesiveness rose for PUL gels and tensile stress increased for PUL films. PUL capsules could be easily prepared by the aid of κ-Ca, and performances of capsules could be adjusted by changing the amount of κ-Ca.

18.
J Mol Neurosci ; 70(6): 878-886, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32124252

RESUMO

The purpose of this study is to investigate the correlation between single-nucleotide polymorphism (SNP) at the 3' end of the untranslated region (UTR) of Sirtuin 2 (SIRT2) gene and the risk of developing Alzheimer's disease (AD), and to explore its underlying mechanisms. In total, 260 patients with AD and 260 healthy controls were recruited in this study. The genotype of rs2015 and rs2241703 loci of the SIRT2 gene was analyzed by Sanger sequencing for all participants. Quantitative real-time Polymerase chain reaction (qRT-PCR) was used to analyze microRNAs (miRNAs) and SIRT2 mRNA levels. Western blotting was used to analyze the expression level of SIRT2 protein. The dual luciferase reporter gene assay and cell transfection were performed to examine the role of miRNAs in regulating SIRT2 expression. Carriers of the SIRT2 gene rs2015 locus A allele were 0.69 times less likely to develop AD than the carriers of the C allele (95% confidence interval (CI): 0.59-0.80, p < 0.01). The carriers of the SIRT2 gene rs2241703 locus A allele were 1.43 times more likely to develop AD than the carriers of the G allele (95% CI: 1.23-1.61, p < 0.01). The rs2015 locus single-nucleotide polymorphism (SNP) affected the binding efficiency between miR-376a-5p and miR-8061 and the 3'UTR of the SIRT2 gene, and miR-376a-5p and miR-8061 bound to SIRT2 rs2015 A allele to down-regulate the expression of the SIRT2 protein. The rs2241703 SNP affected the binding efficiency between miR-486-3p and the 3'UTR of SIRT2 gene, and miR-486-3p bound to SIRT2 rs2241703 A allele to down-regulate SIRT2 protein expression. The SIRT2 gene rs2015 and rs2241703 loci SNPs are associated with the risk of AD. The rs2015 locus SNP affects regulation of miR-376a-5p and miR-8061 in SIRT2 expression and the rs2241703 locus SNP affects regulation of miR-486-3p in SIRT2, but further studies are needed to verify this mechanism.


Assuntos
Doença de Alzheimer/genética , Polimorfismo de Nucleotídeo Único , Sirtuína 2/genética , Regiões 3' não Traduzidas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sirtuína 2/metabolismo
19.
BMC Cancer ; 20(1): 124, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059711

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the second leading cancer killer in the US today and patients with metastatic disease have only a 14% 5-year survival. One of the most impactful recent advances in cancer therapy, immune checkpoint inhibition, has not been shown to be effective for the majority of these patients. In this study, we use The Cancer Genome Atlas (TCGA) and recently developed informatic-based tools to identify targets for immune based therapy in colorectal cancer patients. METHODS: Open access, pre-processed (level 3) mRNA data and clinical data from colorectal patients from the TCGA was downloaded from FireCloud. Using the Microenvironment Cell Populations-Counter method (MCP-Counter), cytotoxic lymphocyte scores were calculated for all patients. Patients were then grouped by cytotoxic lymphocyte score (High vs Low), pathologic stage, and location to identify differentially expressed genes. Pathway enrichment analysis was performed using Reactome to determine differentially expressed genes associated with immune pathways. Survival analysis was performed with identified differentially expressed genes. RESULTS: In the TCGA dataset, there are 461 colon and 172 rectal cancer patients. After stratifying patients by cytotoxic lymphocyte score, anatomical location, and stage, we found a significant number of differentially expressed genes. We identified one pathway, "immunoregulatory interactions between a lymphoid and non-lymphoid cell", that was highly enriched and included in all tumor locations and stages. Survival analysis performed with differentially expressed genes in this pathway identified 21 different genes associated with survival and cytotoxic lymphocyte infiltration, with ~ 70% of these genes occurring in the metastatic right-sided CRC group. Specifically, all genes associated with survival in the metastatic right-sided colorectal cancer group with low cytotoxic lymphocyte scores positively impacted survival. CONCLUSIONS: Utilizing the TCGA, a publicly available dataset, and informatics-based analyses, we identified potential targets to improve immune based therapy in colorectal cancer. Additionally, we note the most targets in metastatic right-sided CRC patients, the patient group with the worst predicted survival. The results from this study demonstrate the ability of informatics-based analytic techniques to identify new therapeutic targets as well as improve patient selection for intervention, helping us to achieve the goals of precision-based oncology.


Assuntos
Neoplasias Colorretais/etiologia , Neoplasias Colorretais/patologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias Colorretais/mortalidade , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Transdução de Sinais , Linfócitos T Citotóxicos/patologia
20.
IEEE Trans Cybern ; 50(7): 3281-3293, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30932860

RESUMO

Electroencephalogram (EEG) has been widely used in emotion recognition due to its high temporal resolution and reliability. Since the individual differences of EEG are large, the emotion recognition models could not be shared across persons, and we need to collect new labeled data to train personal models for new users. In some applications, we hope to acquire models for new persons as fast as possible, and reduce the demand for the labeled data amount. To achieve this goal, we propose a multisource transfer learning method, where existing persons are sources, and the new person is the target. The target data are divided into calibration sessions for training and subsequent sessions for test. The first stage of the method is source selection aimed at locating appropriate sources. The second is style transfer mapping, which reduces the EEG differences between the target and each source. We use few labeled data in the calibration sessions to conduct source selection and style transfer. Finally, we integrate the source models to recognize emotions in the subsequent sessions. The experimental results show that the three-category classification accuracy on benchmark SEED improves by 12.72% comparing with the nontransfer method. Our method facilitates the fast deployment of emotion recognition models by reducing the reliance on the labeled data amount, which has practical significance especially in fast-deployment scenarios.


Assuntos
Eletroencefalografia/classificação , Eletroencefalografia/métodos , Emoções/classificação , Aprendizado de Máquina , Adulto , Encéfalo/fisiologia , Interfaces Cérebro-Computador , Humanos , Reconhecimento Automatizado de Padrão/métodos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...