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1.
Analyst ; 149(5): 1489-1495, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38314794

RESUMEN

A novel cyclooxygenase-2 (COX-2) targeted H2S-activated cancer-specific fluorescent probe, namely, COX2-H2S, was designed and synthesized, with naphthalimide as the fluorophore and indomethacin as the targeting group. This H2S-sensing probe was developed to differentiate tumor cells from normal cells and was tested in living cells, Caenorhabditis elegans (C. elegans), and zebrafish. The probe could successfully be used for imaging endogenous and exogenous H2S in living cells, demonstrating high sensitivity and specificity and strong anti-interference. COX2-H2S had the ability to not only discern cancer cells from normal cells but also specifically recognize 9L/lacZ cells from other glioblastoma cells (U87-MG and LN229). It could also be successfully applied for the fluorescent live imaging of H2S in both C. elegans and zebrafish.


Asunto(s)
Sulfuro de Hidrógeno , Neoplasias , Animales , Humanos , Caenorhabditis elegans , Ciclooxigenasa 2 , Colorantes Fluorescentes , Sulfuro de Hidrógeno/análisis , Neoplasias/diagnóstico por imagen , Imagen Óptica/métodos , Pez Cebra , Línea Celular Tumoral
2.
Ann Clin Microbiol Antimicrob ; 23(1): 52, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38879505

RESUMEN

BACKGROUND: Emerging evidence has indicated a link between the gut microbiota and acute lymphoblastic leukaemia (ALL). However, the acute changes in gut microbiota during chemotherapy and the predictive value of baseline gut microbiota in infectious complication remain largely unknown. METHODS: Faecal samples (n = 126) from children with ALL (n = 49) undergoing induction chemotherapy were collected at three timepoints, i.e., initiation of chemotherapy (baseline, T0), 7 days (T1) and 33 days (T2) after initiation of chemotherapy. Gut microbiome profile was performed via metagenomic shotgun sequencing. The bioBakery3 pipeline (Kneaddata, Metaphlan 3 and HUMAnN) was performed to assign taxonomy and functional annotations. Gut microbiome at T0 were used to predict infection during chemotherapy. RESULTS: The microbial diversities and composition changed significantly during chemotherapy, with Escherichia coli, Klebsiella pneumoniae and Bifidobacterium longum being the most prominent species. The microbial metabolic pathways were also significantly altered during chemotherapy, including the pathway of pyruvate fermentation to acetate and lactate, and assimilatory sulfate reduction pathway. The receiver operating characteristic (ROC) models based on Bifidobacterium longum at T0 could predict infectious complications during the first month of chemotherapy with the area under the curve (AUC) of 0.720. CONCLUSIONS: Our study provides new insights into the acute changes in microbial and functional characteristics in children with ALL during chemotherapy. The baseline gut microbiota could be potential biomarkers for infections during chemotherapy. TRIAL REGISTRATION: The study was approved by the Ethics Committee of Zhujiang Hospital, Southern Medical University (2021-KY-171-01) and registered on http://www.chictr.org.cn (ChiCTR2200065406, Registration Date: November 4, 2022).


Asunto(s)
Heces , Microbioma Gastrointestinal , Metagenómica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Femenino , Masculino , Heces/microbiología , Niño , Preescolar , Quimioterapia de Inducción , Biomarcadores , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Metagenoma , Escherichia coli/genética , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efectos de los fármacos
3.
Nucleic Acids Res ; 50(12): e72, 2022 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-35349708

RESUMEN

Dimension reduction and (spatial) clustering is usually performed sequentially; however, the low-dimensional embeddings estimated in the dimension-reduction step may not be relevant to the class labels inferred in the clustering step. We therefore developed a computation method, Dimension-Reduction Spatial-Clustering (DR-SC), that can simultaneously perform dimension reduction and (spatial) clustering within a unified framework. Joint analysis by DR-SC produces accurate (spatial) clustering results and ensures the effective extraction of biologically informative low-dimensional features. DR-SC is applicable to spatial clustering in spatial transcriptomics that characterizes the spatial organization of the tissue by segregating it into multiple tissue structures. Here, DR-SC relies on a latent hidden Markov random field model to encourage the spatial smoothness of the detected spatial cluster boundaries. Underlying DR-SC is an efficient expectation-maximization algorithm based on an iterative conditional mode. As such, DR-SC is scalable to large sample sizes and can optimize the spatial smoothness parameter in a data-driven manner. With comprehensive simulations and real data applications, we show that DR-SC outperforms existing clustering and spatial clustering methods: it extracts more biologically relevant features than conventional dimension reduction methods, improves clustering performance, and offers improved trajectory inference and visualization for downstream trajectory inference analyses.


Asunto(s)
Algoritmos , Transcriptoma , Análisis por Conglomerados , RNA-Seq , Análisis de la Célula Individual/métodos , Transcriptoma/genética , Secuenciación del Exoma
4.
Molecules ; 29(11)2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38893378

RESUMEN

Metabolic reprogramming mediates antibiotic efficacy. However, metabolic adaptation of microbes evolving from antibiotic sensitivity to resistance remains undefined. Therefore, untargeted metabolomics was conducted to unveil relevant metabolic reprogramming and potential intervention targets involved in gentamicin resistance. In total, 61 metabolites and 52 metabolic pathways were significantly altered in gentamicin-resistant E. coli. Notably, the metabolic reprogramming was characterized by decreases in most metabolites involved in carbohydrate and amino acid metabolism, and accumulation of building blocks for nucleotide synthesis in gentamicin-resistant E. coli. Meanwhile, fatty acid metabolism and glycerolipid metabolism were also significantly altered in gentamicin-resistant E. coli. Additionally, glycerol, glycerol-3-phosphate, palmitoleate, and oleate were separately defined as the potential biomarkers for identifying gentamicin resistance in E. coli. Moreover, palmitoleate and oleate could attenuate or even abolished killing effects of gentamicin on E. coli, and separately increased the minimum inhibitory concentration of gentamicin against E. coli by 2 and 4 times. Furthermore, palmitoleate and oleate separately decreased intracellular gentamicin contents, and abolished gentamicin-induced accumulation of reactive oxygen species, indicating involvement of gentamicin metabolism and redox homeostasis in palmitoleate/oleate-promoted gentamicin resistance in E. coli. This study identifies the metabolic reprogramming, potential biomarkers and intervention targets related to gentamicin resistance in bacteria.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana , Escherichia coli , Ácidos Grasos Monoinsaturados , Gentamicinas , Ácido Oléico , Gentamicinas/farmacología , Gentamicinas/metabolismo , Escherichia coli/metabolismo , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Ácido Oléico/metabolismo , Ácido Oléico/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Antibacterianos/farmacología , Ácidos Grasos Monoinsaturados/metabolismo , Ácidos Grasos Monoinsaturados/farmacología , Pruebas de Sensibilidad Microbiana , Metabolómica/métodos , Redes y Vías Metabólicas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia Arriba/efectos de los fármacos
5.
Molecules ; 29(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38792188

RESUMEN

The purpose of this study was to resolve the issue of physical instability in amorphous solid drugs, which can result in unwanted crystallization, affecting solubility and dissolution rates. The focus was on precipitating physically stable amorphous forms of the nilotinib free base, an anticancer drug, by monitoring preparation conditions such as precipitation temperature and filter cake thickness. A comprehensive set of characterization techniques, including powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and focused beam reflectance measurement (FBRM), were used. These were supplemented by advanced data analysis methods that incorporated pair distribution function (PDF), reduced crystallization temperature (Rc), and principal component analysis (PCA) to evaluate the physical stability of the amorphous samples. Results emphasized that optimal physical stability was achieved when amorphous solids were prepared at a precipitation temperature of 10 °C and a filter cake thickness of 4 cm. Moreover, the integration of PDF analysis with Rc values was confirmed as an innovative approach for assessing physical stability, thus offering enhanced efficiency and accuracy over conventional accelerated stability testing methods.

6.
Pediatr Blood Cancer ; : e30382, 2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37283279

RESUMEN

OBJECTIVE: To analyze the prognostic factors of sepsis in children with acute leukemia admitted to the pediatric intensive care unit (PICU) and to compare the efficacy of different scoring systems for predicting the outcome of children. METHODS: Patients with an acute leukemia diagnosis admitted to a tertiary care university hospital PICU due to sepsis during chemotherapy between May 2015 and August 2022 were retrospectively analyzed through an electronic medical record system. RESULTS: During this period, 693 children with acute leukemia initially diagnosed were admitted to the center, and 155 (22.3%) of them were transferred to PICU due to deterioration of the disease during treatment. Total 109 (70.3%) patients were transferred to PICU due to sepsis. Here, 17 patients was excluded (prior treatment from another hospital; referring from other hospitals; discontinued treatment; incomplete medical record). Of the 92 patients studied, the mortality rate was 35.9%. Multivariate analysis revealed that remission status, lactate level, invasive mechanical ventilation (IMV), and inotropic support within 48 hours after PICU transfer were independent risk factors for PICU mortality. The pediatric sequential organ failure assessment (PSOFA) score had the greatest predictive validity for hospital mortality (area under the receiver operating characteristic curve [AUROC]: 0.83, 95% confidence intervals [CI]: 0.74-0.92), followed by the pediatric early warning score (PEWS) (0.82, 0.73-0.91) and pediatric critical illness score (PCIS) (0.79, 0.69-0.88). CONCLUSION: The mortality rate among children with acute leukemia complicated with sepsis is high after being transferred to the PICU. Various scoring systems can be used to monitor the clinical status of patients, identify sepsis early, detect critical illness, and determine the optimal time for transfer to the PICU for supportive treatment, thereby improving the prognosis of these patients.

7.
Environ Sci Technol ; 57(7): 2918-2927, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36691294

RESUMEN

To improve the reactivity and lifetime of catalysts in the catalytic ozonation of toluene, a simple strategy was provided to regulate the morphology and microstructure of δ-MnO2 via the hydrothermal reaction temperature. The effects of the reaction temperature and the ozone to toluene concentration ratio on the catalyst performance were investigated. The optimized MnO2-260 catalyst prepared at the limiting hydrothermal temperature (260 °C) showed high catalytic activity (XTol = 95%) and excellent stability (1200 min) at the approximately ambient temperature of 40 °C, which was superior to the results in previous studies. The structure and morphology of δ-MnO2 were characterized by extended X-ray absorption fine structure, X-ray diffraction, scanning electron microscopy, positron annihilation lifetime spectroscopy, electron spin resonance, and other techniques. Experimental results and density functional theory calculations were in agreement that surface oxygen vacancy clusters, especially surface oxygen dimer vacancies, are critical in ozone activation. Oxygen vacancies can facilitate the adsorption and activation of O3 to generate reactive oxygen species (ROS, including 1O2, O2-, and •OH), leading to superior ozonation activity to degrade toluene and intermediates. Meanwhile, free radical detection and scavenger tests indicated that •OH is the primary ROS during toluene ozonation rather than 1O2 or O2-.


Asunto(s)
Óxidos , Ozono , Óxidos/química , Especies Reactivas de Oxígeno , Compuestos de Manganeso/química , Tolueno , Oxígeno , Catálisis , Espectroscopía de Resonancia por Spin del Electrón
8.
BMC Public Health ; 23(1): 2507, 2023 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-38097968

RESUMEN

BACKGROUND: Inflammatory bowel disease (IBD) is a global health concern with varying levels and trends across countries and regions. Understanding these differences is crucial for effective prevention and treatment strategies. METHODS: Using data from the 2019 Global Burden of Disease study, we examine IBD incidence, mortality, and disability-adjusted life years (DALYs) rates in 198 countries from 1990 to 2019. To assess changes in the burden of IBD, estimated annual percentage changes (EAPC) were calculated, and a Bayesian age-period-cohort model was used to predict the future 30-year trends of IBD. RESULTS: In 2019, there were 405,000 new IBD cases globally (95% uncertainty interval (UI) 361,000 to 457,000), with 41,000 deaths (95% UI 35,000 to 45,000) and 1.62million DALYs (95% UI 1.36-1.92million). The global age-standardized incidence rate in 2019 was 4.97 per 100,000 person-years (95% UI 4.43 to 5.59), with a mortality rate of 0.54 (95% UI 0.46 to 0.59) and DALYs rate of 20.15 (95% UI 16.86 to 23.71). From 1990 to 2019, EAPC values for incidence, mortality, and DALYs rates were - 0.60 (95% UI - 0.73 to - 0.48), - 0.69 (95% UI - 0.81 to - 0.57), and - 1.04 (95% UI - 1.06 to - 1.01), respectively. Overall, the burden of IBD has shown a slow decline in recent years. In SDI stratification, regions with higher initial SDI (high-income North America and Central Europe) witnessed decreasing incidence and mortality rates with increasing SDI, while regions with lower initial SDI (South Asia, Oceania, and Latin America) experienced a rapid rise in incidence but a decrease in mortality with increasing SDI. Predictions using a Bayesian model showed lower new cases and deaths from 2020 to 2050 than reference values, while the slope of the predicted incidence-time curve closely paralleled that of the 2019 data. CONCLUSION: Increasing cases, deaths, and DALYs highlight the sustained burden of IBD on public health. Developed countries have stabilized or declining incidence rates but face high prevalence and societal burden. Emerging and developing countries experience rising incidence. Understanding these changes aids policymakers in effectively addressing IBD challenges in different regions and economic contexts.


Asunto(s)
Carga Global de Enfermedades , Enfermedades Inflamatorias del Intestino , Humanos , Teorema de Bayes , Años de Vida Ajustados por Calidad de Vida , Prevalencia , Incidencia , Salud Global , Enfermedades Inflamatorias del Intestino/epidemiología
9.
Ophthalmic Physiol Opt ; 42(6): 1326-1337, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36102169

RESUMEN

INTRODUCTION: To compare intrasession agreement and repeatability of wavefront aberration measurements from three different aberrometers obtained using Hartmann-Shack, ray tracing and automated retinoscopy methods, as well as their interdevice agreement. METHODS: Three consecutive measurements were obtained using the Pentacam AXL Wave, the iTrace and the OPD-Scan III in 47 eyes of 47 patients. Wavefront refractions, root mean square of total aberrations (RMS total), RMS of higher-order aberrations (HOA) and second-, third- and fourth-order HOAs were exported for 4-mm pupils. Wavefront refractions were converted into vector components: M, J0 and J45 . Intrasession agreement and repeatability were evaluated using intraclass correlation coefficients (ICCs) and repeatability coefficients (RCs); interdevice agreement was assessed using the Bland-Altman method. RESULTS: The intrasession agreement and repeatability of RMS HOA were comparable between the three devices; both the Pentacam AXL Wave and the OPD-Scan III had better intrasession agreement and repeatability for the RMS total than the iTrace (p ≤ 0.02). Intrasession repeatability for the majority of second- and third-order aberrations was better on the Pentacam AXL Wave than on the iTrace (p ≤ 0.01) and OPD-Scan III (p ≤ 0.04), although their agreement and repeatability in spherical aberration were comparable (p ≥ 0.24). Significant systematic differences and proportional bias were detected for almost all refraction power vectors and Zernike coefficients among the three devices. CONCLUSIONS: In this study, all three devices provided good-to-excellent agreement for aberration measurements. Most of the individual Zernike's components were not exchangeable between different aberrometers. Their relative intrasession performance in agreement and repeatability varied significantly across different ocular aberration parameters.


Asunto(s)
Aberración de Frente de Onda Corneal , Humanos , Aberrometría/métodos , Refracción Ocular , Reproducibilidad de los Resultados , Retinoscopía
10.
BMC Surg ; 22(1): 166, 2022 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-35538567

RESUMEN

BACKGROUND: Gynecologic patients undergoing day surgery are discharged in an intermediate stage of recovery. The quality of discharge teaching and discharge readiness are important to patients' postsurgical outcomes, but little research has focused on them. METHODS: Quality of discharge teaching and discharge readiness were measured, and Spearman correlations were conducted. Postsurgical outcomes were recorded on postoperative Day 1, postoperative Day 7, and postoperative Day 28. Generalized estimating equations were used to explore factors that influence postsurgical outcomes. RESULTS: Discharge teaching was verified to be positively correlated with the discharge readiness of participants. The generalized estimating equations indicated that discharge teaching skills, effects of doctors and nurses, patient-reported physical conditions and social support following discharge were protective factors for postsurgical outcomes. CONCLUSIONS: Doctors and nurses should improve discharge teaching skills and effects to improve the postsurgical outcomes of gynecological patients undergoing day surgery. At discharge, doctors and nurses should assess patients' physical condition and facilitate a social support system.


Asunto(s)
Procedimientos Quirúrgicos Ambulatorios , Alta del Paciente , Femenino , Humanos , Medición de Resultados Informados por el Paciente
11.
Angew Chem Int Ed Engl ; 60(15): 8121-8129, 2021 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-33410570

RESUMEN

It is challenging to construct high-performing excimer-based luminescent analytic tools at low molecular concentrations. We report that enzyme-instructed self-assembly (EISA) enables the monomer-excimer transition of a coumarin dye (Cou) at low molecular concentrations, and the resulting higher ordered luminescent supramolecular assemblies (i.e., nanofibers) efficiently record the spatiotemporal details of alkaline phosphatase (ALP) activity in vitro and in vivo. Cou was conjugated to short self-assembly peptides with a hydrophilic ALP-responsive group. By ALP triggering, EISA actuated a nanoparticles-nanofibers transition at low peptide concentrations followed by monomer-excimer transition of Cou. Analysis of structure-property relationships revealed that the self-assembly motif was a prerequisite for peptides to induce the monomer-excimer transition of Cou. Luminescent supramolecular nanofibers of pYD (LSN-pYD) illuminated the intercellular bridge of cancer cells and distinguished cancer cells (tissues) from normal cells (tissues) efficiently and rapidly, promising potential use for the early diagnosis of cancer. This work extends the functions of EISA and provides a new application of supramolecular chemistry.


Asunto(s)
Fosfatasa Alcalina/metabolismo , Cumarinas/análisis , Ensayo de Inmunoadsorción Enzimática , Colorantes Fluorescentes/análisis , Luminiscencia , Imagen Óptica , Fosfatasa Alcalina/química , Cumarinas/metabolismo , Colorantes Fluorescentes/metabolismo , Células HeLa , Humanos , Sustancias Macromoleculares/análisis , Sustancias Macromoleculares/metabolismo , Estructura Molecular , Nanofibras/análisis
12.
Fish Shellfish Immunol ; 104: 8-17, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32473357

RESUMEN

The banana shrimp (Fenneropenaeus merguiensis) is a common cultural species worldwide. With the development of the shrimp farming industry, increasing number of diseases have emerged and cause huge impacts. Decapod iridescent virus 1 (DIV1) is a new virus of the family Iridoviridae isolated in China that causes very high mortality in shrimp. In this study, DIV1 and PBS were injected into two groups of shrimp, and hemocytes were collected for comparative transcriptomic analysis. We confirmed that F. merguiensis was the new host of DIV1 by nested PCR. A total of 100,759 unigenes were assembled from the control group and the DIV1 infected group, with an average length of 733.06 bp and N50 of 1136 bp. Significant hits were found in 21,465 unigenes compared to known sequences in major databases including COG (33.30%), GO (42.17%), KEGG (46.76%), KOG (61.37%), Pfam (66.90%), Swissprot (54.21%) and Nr (93.86%). A total of 1003 differentially expressed genes (DEGs) were identified, including 929 up-regulated genes and 74 down-regulated genes. Several known immune-related genes, including caspase, C-type lectin, Wnt5 and integrin, were among the differentially expressed transcripts. A total of 14,459 simple sequence repeats, including 8128 monomers, 3276 dimers, 1693 trimers, 150 quadmers, 4 pentamers and 16 hexamers, were found in the transcriptomic dataset. Our study is the first comprehensive investigation of the transcriptomic response to DIV1 infection in F. merguiensis. Collectively, these results not only provide valuable information for characterizing the immune mechanisms of the shrimp responses to DIV1 infection, they open new ways for the study of the molecular mechanisms of DIV1 infection in F. merguiensis.


Asunto(s)
Hemocitos/inmunología , Inmunidad Innata/genética , Iridoviridae/fisiología , Penaeidae/inmunología , Transcriptoma , Animales , Perfilación de la Expresión Génica , Penaeidae/genética
13.
J Cell Mol Med ; 23(6): 4313-4325, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30957417

RESUMEN

Disordered intestinal metabolism is highly correlated with atherosclerotic diseases. Resveratrol protects against atherosclerotic diseases. Accordingly, this study aims to discover novel intestinal proatherosclerotic metabolites and potential therapeutic targets related to the anti-atherosclerotic effects of resveratrol. An untargeted metabolomics approach was employed to discover novel intestinal metabolic disturbances during atherosclerosis and resveratrol intervention. We found that multiple intestinal metabolic pathways were significantly disturbed during atherosclerosis and responsive to resveratrol intervention. Notably, resveratrol abolished intestinal fatty acid and monoglyceride accumulation in atherosclerotic mice. Meanwhile, oleate accumulation was one of the most prominent alterations in intestinal metabolism. Moreover, resveratrol attenuated oleate-triggered accumulation of total cholesterol, esterified cholesterol and neutral lipids in mouse RAW 264.7 macrophages by activating ABC transporter A1/G1-mediated cholesterol efflux through PPAR (peroxisome proliferator-activated receptor) α/γ activation. Furthermore, we confirmed that PPARα and PPARγ activation by WY14643 and pioglitazone, respectively, alleviated oleate-induced accumulation of total cholesterol, esterified cholesterol and neutral lipids by accelerating ABC transporter A1/G1-mediated cholesterol efflux. This study provides the first evidence that resveratrol abolishes intestinal fatty acid and monoglyceride accumulation in atherosclerotic mice, and that resveratrol suppresses oleate-induced accumulation of total cholesterol, esterified cholesterol and neutral lipids in macrophages by activating PPARα/γ signalling.


Asunto(s)
Antioxidantes/farmacología , Aterosclerosis/metabolismo , Intestinos/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Macrófagos/metabolismo , Metaboloma/efectos de los fármacos , Resveratrol/farmacología , Animales , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/patología , Colesterol/metabolismo , Intestinos/patología , Macrófagos/efectos de los fármacos , Macrófagos/patología , Masculino , Ratones , Ratones Noqueados para ApoE , PPAR alfa/metabolismo , PPAR gamma/metabolismo
14.
Appl Environ Microbiol ; 85(24)2019 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-31604764

RESUMEN

Transcriptional regulation of cellulolytic and xylolytic genes in ascomycete fungi is controlled by specific carbon sources in different external environments. Here, comparative transcriptomic analyses of Penicillium oxalicum grown on wheat bran (WB), WB plus rice straw (WR), or WB plus Avicel (WA) as the sole carbon source under solid-state fermentation (SSF) revealed that most of the differentially expressed genes (DEGs) were involved in metabolism, specifically, carbohydrate metabolism. Of the DEGs, the basic core carbohydrate-active enzyme-encoding genes which responded to the plant biomass resources were identified in P. oxalicum, and their transcriptional levels changed to various extents depending on the different carbon sources. Moreover, this study found that three deletion mutants of genes encoding putative transcription factors showed significant alterations in filter paper cellulase production compared with that of a parental P. oxalicum strain with a deletion of Ku70 (ΔPoxKu70 strain) when grown on WR under SSF. Importantly, the ΔPoxAtf1 mutant (with a deletion of P. oxalicumAtf1, also called POX03016) displayed 46.1 to 183.2% more cellulase and xylanase production than a ΔPoxKu70 mutant after 2 days of growth on WR. RNA sequencing and quantitative reverse transcription-PCR revealed that PoxAtf1 dynamically regulated the expression of major cellulase and xylanase genes under SSF. PoxAtf1 bound to the promoter regions of the key cellulase and xylanase genes in vitro This study provides novel insights into the regulatory mechanism of fungal cellulase and xylanase gene expression under SSF.IMPORTANCE The transition to a more environmentally friendly economy encourages studies involving the high-value-added utilization of lignocellulosic biomass. Solid-state fermentation (SSF), that simulates the natural habitat of soil microorganisms, is used for a variety of applications such as biomass biorefinery. Prior to the current study, our understanding of genome-wide gene expression and of the regulation of gene expression of lignocellulose-degrading enzymes in ascomycete fungi during SSF was limited. Here, we employed RNA sequencing and genetic analyses to investigate transcriptomes of Penicillium oxalicum strain EU2101 cultured on medium containing different carbon sources and to identify and characterize transcription factors for regulating the expression of cellulase and xylanase genes during SSF. The results generated will provide novel insights into genetic engineering of filamentous fungi to further increase enzyme production.


Asunto(s)
Factor de Transcripción Activador 1/metabolismo , Ascomicetos/enzimología , Ascomicetos/genética , Celulasa/genética , Fermentación , Regulación Fúngica de la Expresión Génica , Xilosidasas/genética , Ascomicetos/crecimiento & desarrollo , Biomasa , Celulasa/metabolismo , Medios de Cultivo/química , ADN de Hongos/genética , Eliminación de Gen , Genes Fúngicos/genética , Lignina/metabolismo , Penicillium/enzimología , Penicillium/genética , Penicillium/crecimiento & desarrollo , Regiones Promotoras Genéticas , ARN de Hongos/genética , Microbiología del Suelo , Xilosidasas/metabolismo
15.
Metabolomics ; 15(3): 36, 2019 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-30830452

RESUMEN

INTRODUCTION: Macrophage metabolism contributes to the progression of metabolic diseases, and peroxisome proliferator-activated receptors (PPARs) play vital roles in macrophage metabolism and the treatment of metabolic diseases. However, the role of PPARs in metabolic reprogramming related to lipid accumulation in macrophages, a key pathological event in metabolic diseases, remains unclear. OBJECTIVES: We aimed to identify PPAR-mediated metabolic reprogramming and potential therapeutic targets associated with lipid accumulation in macrophages. METHODS: Following treatment with oleate, oleate + WY-14643 and oleate + pioglitazone to induce alterations in PPAR signaling, lipids and relevant metabolism, macrophage samples were analyzed employing an untargeted metabolomics based on gas chromatography-mass spectrometry. RESULTS: The metabolomics approach revealed that multiple metabolic pathways were altered during lipid accumulation in oleate-treated macrophages and responsive to WY-14643 and pioglitazone treatment. Notably, levels of most metabolites involved in amino acid metabolism and nucleotide metabolism were accumulated in oleate-treated macrophages, and these effects were alleviated or abolished by PPARA/G activation. Additionally, during oleate-induced lipid accumulation and lipid lowering with WY-14643 and pioglitazone in macrophages, levels of most amino acids were positively associated with neutral lipid, total cholesterol, cholesterol ester, total free fatty acid and triglyceride levels but negatively associated with expression of genes related to PPARA/G signaling. Furthermore, glycine was found to be a potential biomarker for assessing lipid accumulation and the lipid-lowering effects of PPARA/G in oleate-treated macrophages. CONCLUSION: The results of this study revealed a high correlation of amino acid metabolism with lipid accumulation and the lipid-lowering effects of PPARA/G in macrophages.


Asunto(s)
Lípidos/fisiología , Macrófagos/metabolismo , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Aminoácidos/metabolismo , Animales , Ésteres del Colesterol/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Cromatografía de Gases y Espectrometría de Masas/métodos , Metabolismo de los Lípidos/fisiología , Ratones , Ácido Oléico/metabolismo , Ácido Oléico/farmacología , PPAR alfa/metabolismo , Pioglitazona/farmacología , Pirimidinas/farmacología , Células RAW 264.7 , Factores de Transcripción/metabolismo
16.
Fish Shellfish Immunol ; 92: 480-488, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31207301

RESUMEN

Antibacterial peptides (AMPs) are expected to replace some or all of the antibiotics and become a new feed additive. However, the high production cost and unclear mechanism limited the application of AMPs. In this research, the effects of a commercial polypeptide (Polypeptide S100) whose main components are AMPs on the growth, antibacterial immune and intestinal microbial of Litopenaeus vannamei were study. L. vannamei (initial weight of 0.16 ±â€¯0.03 g) were fed for 123 days with basal diet added Polypeptide S100 at two levels each (0.5% and 1%) as experimental groups, and a basal diet as control. Dietary inclusion of Polypeptide S100 at 1% level significantly increased the weight gain (WG) and specific growth rate (SGR) of L. vannamei. The survival rates of L. vannamei in 0.5% and 1% Polypeptide S100 groups were significantly higher than the control when infected by Vibrio harveyi but not Vibrio parahaemolyticus. The activities of total superoxide dismutase (T-SOD) and lysozyme (LZM) in the two experimental groups were all significantly higher than the control. Differently, the activities of amylase (AMS) and lipase (LPS) were significantly higher in 0.5% Polypeptide S100 group but lower in 1.0% Polypeptide S100 group. Illumina MiSeq high-throughput sequencing showed that the dominant phyla in the intestine of L. vannamei were Proteobacteria, followed by Actinobacteria, Bacteroidetes, Chloroflexi, Cyanobacteria, Fusobacteria and Tenericutes, and the abundance of predominant phyla Cyanobacteria were upregulated significantly in the experimental groups. At the family level, significant increase was observed in Pseudomonadaceae and Xanthomonadaceae but decrease in Vibrionaceae in the 1.0% Polypeptide S100 group. The abundance of predominant genus Photobacterium were obviously downregulated in the two experimental groups. Unlikely, the abundance of Pseudomonas and Stenotrophomonas were distinctly increased in the 1.0% Polypeptide S100 group but not significantly different from the control in 0.5% Polypeptide S100 group. All these results suggested that Polypeptide S100 could improve the growth performance, antibacterial immune and intestinal microbiota structure of L. vannamei.


Asunto(s)
Microbioma Gastrointestinal/efectos de los fármacos , Penaeidae/efectos de los fármacos , Penaeidae/inmunología , Péptidos/metabolismo , Proteínas S100/metabolismo , Alimentación Animal/análisis , Animales , Péptidos Catiónicos Antimicrobianos/farmacología , Dieta , Suplementos Dietéticos/análisis , Penaeidae/crecimiento & desarrollo , Penaeidae/microbiología , Péptidos/administración & dosificación , Proteínas S100/administración & dosificación
17.
Endocr Pract ; 25(4): 320-327, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30995427

RESUMEN

Objective: Previous neuroimaging studies have shown that diabetic retinopathy (DR) is accompanied by abnormal spontaneous brain activity. The purpose of the current study was to investigate changes in brain neural homogeneity in patients with DR using regional homogeneity (ReHo). Methods: A total of 56 subjects were recruited, including 28 patients with DR (16 female and 12 male patients) and 28 healthy controls (HCs) (16 female and 12 male patients) approximately matched for age and sex. All subjects underwent resting-state functional magnetic resonance imaging scans. The ReHo method was applied to explore neural homogeneity in the brain. The patients with DR were distinguished from HCs following the construction of receiver operating characteristic curves. The ReHo method was applied to assess changes in synchronous neural activity. Results: Compared to HCs, the ReHo values in the left and right posterior lobes of the cerebellum in patients with DR were significantly increased, whereas ReHo values in the right anterior cingulate gyrus, right cuneus, bilateral precuneus, and left-middle frontal gyrus were significantly decreased. In addition, the ReHo value in the right cuneus showed a positive correlation with the best corrected visual acuity in patients with DR. Conclusion: Dysfunctional brain homology may reveal the pathological mechanisms underlying the visual pathways of patients with DR. Abbreviations: AUC = area under the curve; BA = Brodmann area; DR = diabetic retinopathy; fMRI = functional magnetic resonance imaging; HC = healthy control; MRI = magnetic resonance imaging; rs-fMRI = resting-state fMRI; ReHo = regional homogeneity; ROC = receiver operating characteristic.


Asunto(s)
Retinopatía Diabética , Imagen por Resonancia Magnética , Encéfalo , Mapeo Encefálico , Femenino , Lóbulo Frontal , Humanos , Masculino
20.
Zhongguo Zhong Yao Za Zhi ; 44(23): 5174-5183, 2019 Dec.
Artículo en Zh | MEDLINE | ID: mdl-32237355

RESUMEN

The study aimed to explore the in vivo immunoregulatory function of Grifola frondosa polysaccharide( GFP) on animal disease models. Databases of PubMed,Embase,Web of Scinece,CNKI,CBM and Wan Fang Data were searched from the date of their establishment to February 2018. Two reviewers independently screened included studies and evaluated their quality by using SYRCLE's risk of bias tool. R software was used to analyze the data. Finally,20 animal experiment studies were included. According to Metaanalysis. For cellular immunity,GFP could effectively enhance the proliferation of effect or T cells,natural killer cells and macrophages in mice. The percentage of CD4+T cells( MD = 1. 89,95% CI [0. 94,2. 83],P < 0. 000 1),CD8+T cells( MD = 8. 46,95% CI[5. 93,11. 00],P<0. 000 1),NK cells( MD= 2. 67,95% CI [0. 23,5. 11],P= 0. 03),and macrophages( MD= 14. 09,95% CI[0. 84,27. 34],P= 0. 04) were all higher than those in control group. For humoral immunity,GFP could increase the secretion of TNF-α and INF-γ. The secretion of TNF-α( SMD = 15. 92,95% CI [9. 07,22. 76],P<0. 000 1) and INF-γ( SMD = 5. 34,95% CI[3. 42,7. 26],P<0. 000 1) were all higher than those in control group. In conclusion,GFP could regulate immunologic function by enhancing the proliferation activity of immune cells( CD4+T cells,CD8+T cells,NK cells and macrophages) and the secretion of immune factors( TNF-α and INF-γ) . However,it is necessary to further standardize the selection of specific surface markers of immune cells and the administration of GFP,in order to reduce the heterogeneity among the studies. At the same time,more attention shall be paid to experimental design,implementation and full report,especially to the establishment and implementation of animal experimental registration system,so as to improve the transparency and quality of the whole process of animal experimental research,enhance the value of basic research ultimately,and provide a reliable theoretical basis for the transformation of basic research into clinical research.


Asunto(s)
Grifola/química , Sistema Inmunológico , Polisacáridos/farmacología , Animales , Citocinas/inmunología , Modelos Animales de Enfermedad , Células Asesinas Naturales/inmunología , Macrófagos/inmunología , Ratones , Linfocitos T/inmunología
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