Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 146
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Bioresour Technol ; 295: 122244, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31627064

RESUMO

Under the situation of increasingly severe challenge of energy consumption, it is of great importance to make full use of bioresources such as forestry and agricultural residues. Herein, the corncob residues generated after processing corncob were enzymatically hydrolyzed to yield fermentable sugars. To overcome the recalcitrance of corncob residues, three kinds of pretreatment methods, i.e., sulfonation, PFI refining, and wet grinding, were applied; their effects on enzymatic hydrolysis and main characteristics of corncob residues substrate were investigated. The results showed that the enzymatic digestibility of the substrate was greatly enhanced by employing each method. The wet grinding exhibited obvious advantages, e.g., the conversion yield of cellulose to glucose and glucose concentration reached 96.7% and 32.2 g/L after 59 h of enzymatic hydrolysis, respectively. The improvement in enzymatic hydrolysis was mainly attributed to the altered characteristics of the substrate such as swelling ability, specific surface area, and particle size and distribution.

2.
Clin Biochem ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31476287

RESUMO

BACKGROUND: Thyroglobulin antibody (TG-Ab) and thyroid peroxidase antibody (TPO-Ab) are cornerstone biomarkers for autoimmune thyroid diseases, and establishment of appropriate thresholds is crucial for physicians to appropriately interpret test results. Therefore, we established the thresholds of TG-Ab and TPO-Ab in the Chinese population through analysis of real-world big data, and explored the influence of age, gender, and seasonal factors on their levels. METHODS: The data of 35,869 subjects downloaded from electronic health records were analyzed after filtering based on exclusion criteria and outliers. The influence of each factor on antibody levels was analyzed by stratification. Thresholds of TG-Ab and TPO-Ab were established through Clinical Laboratory Standards Institute document C28-A3 and National Academy of Clinical Biochemistry (NACB) guidelines, respectively. RESULTS: There were significant differences according to gender after age stratification; the level of TG-Ab gradually increased with age in females. There were significant differences in TG-Ab and TPO-Ab distributions with respect to age after gender stratification. Moreover, differences were observed between seasons for TG-Ab and TPO-Ab. The thresholds of TG-Ab and TPO-Ab were 107 [90% confidence interval (CI):101-115] IU/mL and 29 (90% CI: 28-30) IU/mL, respectively, using C28-A3 guidelines, but were 84 (90% l CI: 50-126) IU/mL and 29 (90% CI: 27-34) IU/mL, respectively, using NACB guidelines. CONCLUSION: The levels of TG-Ab and TPO-Ab were significantly affected by gender, age, and season. The thresholds for TG-Ab and TPO-Ab for the Chinese population were established by big data analysis.

3.
Resuscitation ; 143: 1-9, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31377393

RESUMO

OBJECTIVE: To explore a new algorithm and strategy for rhythm analysis during chest compressions (CCs), and to improve the efficiency of cardiopulmonary resuscitation (CPR) by minimizing interruptions. METHODS: The clinical data and ECG of patients with sudden cardiac arrest (CA) from three hospitals in China were collected with Philips MRx monitor/defibrillators. The length of each analyzed ECG segment was 23 s, the first 11.5 s was selected to contain CPR compressions, the next 5 s had no compressions, and the last 6.5 s had no requirement. Three experienced emergency doctors annotated the ECG segments without compression artifacts. A two-step analysis through CPR (ATC) algorithm was applied to the selected data. The first step was analysis during chest compressions. If a shockable rhythm was not detected, compression-free analysis followed. The results of the ATC algorithm were compared with the annotations by the physicians, to determine the sensitivity and specificity of the algorithm. RESULTS: In total 166 CA patients were included with 100 out-of-hospital cardiac arrest (OHCA) patients and 66 in-hospital cardiac arrest (IHCA) patients. A total of 1578 ECG segments were analyzed, including 115 (7.3%) shockable rhythms, 1278 (81.0%) non-shockable rhythms, and 185 (11.7%) intermediate/unknown rhythms. The specificity of all non-shockable rhythms was 99.8% at the end of chest compressions, and 99.5% after analysis without compression artifact. 70.5% of ventricular fibrillation (VF) rhythms were detected by the end of chest compressions. After the CC-free analysis, 93.6% of VF was identified. CONCLUSION: The ATC algorithm achieved sensitivity of 93.6% and specificity of 99.5% after the two-step analysis, and 70.5% of the patients with shockable rhythms did not require CC-free analysis. Such an approach has the potential to substantially reduce CC interruptions when identifying shockable rhythms.

4.
Shock ; 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31390337

RESUMO

PURPOSE: A retrospective study was first performed to assess the multidrug resistant (MDR) pathogen in severe acute pancreatitis (SAP) patients who were treated using the step-up approach. We aim to assess the risk factors between MDR pathogen and potential covariates in SAP patients. METHODS: The clinical data of 51 SAP patients who were treated from June, 2013 to December, 2016 were retrospectively collected. A total of 23 patients in the MDR group and 28 patients in the non-MDR group were reviewed. The risk factors for MDR pathogen-induced infections in SAP patients were analyzed. RESULTS: Hyperlipidemia was the leading cause of SAP in our study. The mean duration of hospital stay was significantly longer in the patients with MDR pathogen infections (P=0.0135). The hospitalization expenses of MDR group were much higher than those in non-MDR group. The mortality of MDR group (56.5%) was higher than that in non-MDR group (28.6%) (P=0.0436). Gram-negative isolates (63.8%) were commonly detected in SAP patients. Acinetobacter baumannii was the most common MDR pathogens. Systemic disease (P = 0.0136), initial use of carbapenem (P = 0.0438), and open necrosectomy (P = 0.0002) were the potential risk factors for MDR pathogen-induced infections in SAP. Furthermore, the logistic regression analysis revealed that open necrosectomy was the independent variable for MDR infections (OR: 15.6, 95% CI: 2.951-82.469, P = 0.0012). CONCLUSIONS: MDR pathogen-induced infections were common in SAP patients and Acinetobacter baumannii was the main pathogen. Meanwhile, open necrosectomy was the independent risk factor for the infection of MDR pathogen.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

5.
Mikrochim Acta ; 186(9): 640, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31440852

RESUMO

A fluorometric method is described for "turn-on" sensing of pH values via black phosphorus quantum dots (BPQD). Water-stable BPQD were synthesized by a liquid exfoliation method and characterized by TEM, FT-IR, XPS, and absorption and fluorescence spectra. The nanoparticles of BPQD have a uniform distribution with an average size of 5.2 nm. They exhibit bright green fluorescence, with excitation/emission maxima at 420/515 nm. The fluorescence of the BPQD is likely to arise from the quasi-molecular fluorophores of polycyclic aromatic compounds carrying P-P, P-O-P, and PxOy functions on its surface. The protonation and deprotonation of hydroxyl groups of BPQD causes a different degree of quenching of the BPQD. At pH values below 4.0, protons bind to BPQD to form non-fluorescent ground state complexes. At pH values above 4.0, the hydroxyl groups become deprotonated, and this induces the recovery of fluorescence. The sensor has a linear response in the pH range of 1.0-9.0. It was successfully applied to the determination of the pH values in human urine and serum samples. Graphical abstract Schematic representation of the preparation of black phosphorus quantum dots (BPQDs) from powdered BP crystals using liquid-phase exfoliation in N-methyl-2-pyrrolidone solution. The BPQDs display green fluorescence at high pH values but no fluorescence at very low pH values.

6.
Meat Sci ; 156: 156-165, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31170569

RESUMO

This study investigated the purification and biochemical characteristics of the protease produced by Pediococcus pentosaceus isolated from Harbin dry sausages. The optimized fermented conditions were as follows: fermentation time 36 h, initial pH 5 and fermentation temperature 30 °C. A 29.6 kDa extracellular protease was purified using ammonium sulphate deposition, ion exchange layer system and gel filtration. The protease produced by P. pentosaceus had a certain pH and thermal stability at pH 6 and 30 °C. The microbial protease activity could be inhibited by ethylene diamine tetraacetic acid disodium salt (EDTA). Vmax and Km of the protease were 43.9 mg/min and 8.3 mg/mL, respectively. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) reflected the ability of the protease to hydrolyse sarcoplasmic and myofibrillar proteins, particularly those of myosin heavy chain, paramyosin, actin, phosphorylase and creatine kinase-M types. 3D structure modelling of the P. pentosaceus protease found two domains in the protease protein and the correlation of the active sites with protease properties and substrate specificity. In conclusion, P. pentosaceus can be used as a starter culture or enzyme producing strain for inoculation in Harbin dry sausages.

7.
Meat Sci ; 156: 205-213, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31202095

RESUMO

The effect of partial replacement of NaCl by using sodium substitutes (SS) on the physical, microbial and sensory characteristics of Harbin dry sausage was investigated. There were three salt formulations, including control (100% NaCl), NaCl partly substituted by KCl (SS1) (70% NaCl and 30% KCl), and NaCl partly substituted by KCl combined with other components (SS2) (70% NaCl, 20% KCl, 3.5% maltodextrin, 4% L-Lys, 1% L-Ala, 0.5% citric acid and 1% Ca-lactate). After a 12-day fermentation, the higher moisture content and Aw and lower pH were found in the SS2 treatment, compared to the control and SS1 treatments (P < .05). A decreased microbial diversity during fermentation was found in all sausages, and Staphylococcus spp. and Lactobacillus spp. became the dominant genera. Additionally, the SS2 treatment showed a higher L*-value and lower hardness and chewiness values (P < .05). Therefore, the formulation of SS2 could achieve a NaCl reduction of 30% in Harbin dry sausages with a better sensory acceptability.

8.
Int J Chron Obstruct Pulmon Dis ; 14: 1229-1237, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239658

RESUMO

Background: High-flow nasal cannula (HFNC) oxygen therapy in acute hypoxic respiratory failure is becoming increasingly popular. However, evidence to support the use of HFNC in acute respiratory failure (ARF) with hypercapnia is limited. Methods: Chronic obstructive pulmonary disease (COPD) patients with moderate hypercapnic ARF (arterial blood gas pH 7.25-7.35, PaCO2>50 mmHg) who received HFNC or non-invasive ventilation (NIV) in the intensive care uint from April 2016 to March 2018 were analyzed retrospectively. The endpoint was treatment failure, defined as either invasive ventilation, or a switch to the other study treatment (NIV for patients in the NFNC group, and vice-versa), and 28-day mortality. Results: Eighty-two COPD patients (39 in the HFNC group and 43 in the NIV group) were enrolled in this study. The mean age was 71.8±8.2 and 54 patients (65.9%) were male. The treatment failed in 11 out of 39 patients with HFNC (28.2%) and in 17 of 43 patients with NIV (39.5%) (P=0.268). No significant differences were found for 28-day mortality (15.4% in the HFNC group and 14% in the NIV group, P=0.824). During the first 24 hrs of treatment, the number of nursing airway care interventions in the HFNC group was significantly less than in the NIV group, while the duration of device application was significantly longer in the HFNC group (all P<0.05). Skin breakdown was significantly more common in the NIV group (20.9% vs 5.1%, P<0.05). Conclusion: Among COPD patients with moderate hypercarbic ARF, the use of HFNC compared with NIV did not result in increased rates of treatment failure, while there were fewer nursing interventions and skin breakdown episodes reported in the HFNC group.

9.
Meat Sci ; 156: 33-43, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31125945

RESUMO

The effects of partially replacing NaCl with sodium substitutes (SS) on the lipid and protein oxidation and flavor development of Harbin dry sausage was investigated. There were three salt formulations, including a control (100% NaCl), NaCl partially substituted with KCl (SS1) (70% NaCl and 30% KCl), and NaCl partially substituted with KCl combined with other components (SS2) (70% NaCl, 20% KCl, 4% lysine, 1% alanine, 0.5% citric acid, 1% Ca-lactate and 3.5% maltodextrin). The levels of lipid and protein oxidation increased in all sausages during fermentation (P < 0.05). In addition, lower oxidation of lipids and proteins were found in the SS2 treatment (P < 0.05) due to the lower NaCl concentration. The SS, especially the SS2, promoted the formation of volatile compounds originated from carbohydrate and amino acid metabolism, ß-lipid oxidation and esterification; however, this substitute inhibited the formation of volatile compounds originated from lipid autooxidation (P < 0.05). Overall, SS2 could improve the flavor development of Harbin dry sausage and reduce NaCl by 30%.

10.
Radiother Oncol ; 134: 37-43, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31005222

RESUMO

PURPOSE: To investigate the prognostic value of skull-base invasion (SBI) for nasopharyngeal carcinoma (NPC), propose a subclassification of SBI. METHODS: 792 and 433 patients with pathologically proven NPC and complete clinical and magnetic resonance imaging records at Sun Yat-sen University Cancer Center and Foshan Hospital were enrolled, and investigated using heat map/cluster, network and survival analyses. RESULTS: The results of heat map/cluster analyses and network analysis showed that T3 patients with pterygoid process and/or base of the sphenoid bone invasion (T3 slight) had better treatment outcomes than those with other SBIs (T3 severe). Significant differences were observed between T3-slight and T3-severe groups with regard to 5-year overall survival (OS) (93.0% vs. 83.5%, p = 0.014) and progression-free survival (PFS) (82.5% vs. 74.1%, p = 0.044) rates. No significant difference was observed between T3-slight group and T2 patients with regard to 5-year OS (93.0% vs. 84.7%, p = 0.062) and PFS (82.5% vs. 78.9%, p = 0.459) rates. Therefore, we downgraded patients with T3 slight to T2, yielding a new T classification sample. The survival curves of the 5-year OS and PFS rates of T2 and T3 were more reasonable after sample redistribution than those before sample redistribution. The differences in the 5-year OS and PFS rates between T2 and T3 patients after sample redistribution approached significance (p = 0.075 and 0.051, respectively). CONCLUSIONS: Different types of SBIs had different effects on the prognosis for NPC. We recommend patients with T3 slight not be defined as T3 but, rather, as T2.

11.
Phytomedicine ; 59: 152758, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31004884

RESUMO

BACKGROUND: Emerging evidence has indicated the therapeutic potential of emodin with its multiple pharmacological effects. PURPOSE: To evaluate role of emodin in regulating insulin resistance (IR) and to elucidate the underlying molecular mechanisms. STUDY DESIGN/METHODS: Fasting blood glucose (FBG) and lipid levels were measured before and after intragastric administration of emodin in type 2 diabetes mellitus (T2DM) rats. Glucose consumption was determined in L6 cells to investigate the effect of emodin on glucose metabolism. Expression of miR-20b and SMAD7 was quantified by real-time PCR for mRNAs or western blot analysis for proteins. RESULTS: Emodin ameliorated hyperglycemia and dyslipidemia in T2DM rats, and glucose metabolism in a concentration- and time-dependent manner. MiR-20b was markedly upregulated in the setting of IR and overexpression of miR-20b disrupted glucose metabolism by repressing SMAD7 in L6 cells. Knockdown of this miRNA produced the opposite effects. Emodin abolished the abnormal upregulation of miR-20b and indirectly upregulated SMAD7. CONCLUSION: Emodin improves glucose metabolism to produce anti-IR effects, and downregulation of miR-20b thereby upregulation of SMAD7 is an underlying mechanism for the beneficial effects of emodin.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Emodina/farmacologia , Glucose/metabolismo , Resistência à Insulina , Insulina/metabolismo , Músculo Esquelético/efeitos dos fármacos , RNA Mensageiro , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Regulação para Baixo/efeitos dos fármacos , Emodina/uso terapêutico , Transportador de Glucose Tipo 4/metabolismo , Hiperglicemia/metabolismo , Hiperglicemia/prevenção & controle , Masculino , Músculo Esquelético/metabolismo , RNA Mensageiro/metabolismo , Ratos , Proteína Smad7/metabolismo , Regulação para Cima/efeitos dos fármacos
12.
BMC Pediatr ; 19(1): 79, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30885166

RESUMO

BACKGROUND: Maternofetal carnitine transport through the placenta is the main route of fetal carnitine uptake. Decreased free carnitine levels discovered by newborn screening has identified many asymptomatic adult women with systemic primary carnitine deficiency (PCD). Here, we presented amplitude integrated electroencephalogram (aEEG) and magnetic resonance imaging (MRI) findings from a neonate with epilepsy whose mother was carnitine deficient. CASE PRESENTATION: A one-day-old female newborn was admitted after experiencing seizures for half a day; status epilepticus was found on the continuous normal voltage background pattern with immature sleep-wake cycling during aEEG monitoring. On T1-weighted, T2-weighted, FLAIR, and DWI head MRI, there were various degrees of hyperintense signals and diffusion restrictions in the deep white matter of the right hemisphere. Tandem mass spectrometry discovered carnitine deficiency on the second day, which elevated to normal by the 9th day before L-carnitine supplementation was started. The patient was treated with phenobarbital after admission. No further seizures were noted by day 5. It was confirmed that the patient's mother had a low level of serum-free carnitine. Gene analyses revealed that the newborn had heterozygote mutations on c.1400C > G of the SLC22A5 gene, and her mother had homozygous mutations on c.1400C > G. The patient had a good outcome at the 8-month follow up. CONCLUSIONS: Maternal carnitine deficiency that occurs during the perinatal period may manifest as secondary epilepsy with cerebral injury in neonates. The short-term neurodevelopmental outcomes were good. Early diagnosis of asymptomatic PCD in female patients can provide guidance for future pregnancies.

13.
Oxid Med Cell Longev ; 2019: 4248529, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30881590

RESUMO

Hypoxic-ischemic encephalopathy (HIE) is detrimental to newborns and is associated with high mortality and poor prognosis. Thus, the primary aim of the present study was to determine whether glycine could (1) attenuate HIE injury in rats and hypoxic stress in PC12 cells and (2) downregulate mitochondria-mediated autophagy dependent on the adenosine monophosphate- (AMP-) activated protein kinase (AMPK) pathway. Experiments conducted using an in vivo HIE animal model and in vitro hypoxic stress to PC12 cells revealed that intense autophagy associated with mitochondrial function occurred during in vivo HIE injury and in vitro hypoxic stress. However, glycine treatment effectively attenuated mitochondria-mediated autophagy. Additionally, after identifying alterations in proteins within the AMPK pathway in rats and PC12 cells following glycine treatment, cyclosporin A (CsA) and 5-aminoimidazole-4-carboxamide-1-b-4-ribofuranoside (AICAR) were administered in these models and indicated that glycine protected against HIE and CoCl2 injury by downregulating mitochondria-mediated autophagy that was dependent on the AMPK pathway. Overall, glycine attenuated hypoxic-ischemic injury in neurons via reductions in mitochondria-mediated autophagy through the AMPK pathway both in vitro and in vivo.


Assuntos
Glicina/uso terapêutico , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Degradação Mitocondrial/efeitos dos fármacos , Proteínas Quinases/metabolismo , Animais , Autofagia , Glicina/farmacologia , Prognóstico , Ratos
14.
J Enzyme Inhib Med Chem ; 34(1): 203-217, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30835140

RESUMO

A series of quinazoline derivatives with benzylidene hydrazine carboxamide were designed and synthesised as EGFR inhibitors. Most compounds exhibited exceptional anti-proliferative activity against A549, HepG2, MCF-7 and H1975 cells. Furthermore, six compounds demonstrated excellent inhibition activity against EGFRWT with the IC50 value both less than 2 nM. Among the six compounds, 44 exhibited the strongest activity (0.4 nM) and potently inhibited EGFRL858R/T790M (0.1 µM). Excitingly, the most potent compound 14 showed excellent enzyme inhibitory activity with 6.3 nM and 8.4 nM for both EGFRWT and EGFRT790M/L858R. The result of AO single staining and Annexin V/PI staining showed that the compound 14 and 44 could induce remarkable apoptosis of A549 cells. The compound 14 arrested the cell cycle at the S phase and compound 44 arrested the cell cycle at the G0 phase in A549 cells. These preliminary results demonstrate that compound 14 and 44 may be promising lead compound-targeting EGFR.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desenho de Drogas , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Gefitinibe/química , Gefitinibe/farmacologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinazolinas/síntese química , Quinazolinas/química , Relação Estrutura-Atividade
15.
Mol Med Rep ; 19(4): 3190-3200, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30816482

RESUMO

Hepatic fibrosis is characterized by the aberrant production and deposition of extracellular matrix (ECM) proteins. Growing evidence indicates that the epithelial­mesenchymal transition serves a crucial role in the progression of liver fibrogenesis. Although a subset of microRNAs (miRNAs or miRs) has recently been identified as essential regulators of the EMT gene expression, studies of the EMT in hyperglycemic­induced liver fibrosis are limited. In the current study, it was observed that high glucose­treated AML12 cells occurred EMT process, and miR­32 expression was markedly increased in the liver tissue of streptozotocin­induced diabetic rats and in high glucose­treated AML12 cells. Additionally, the contribution of the EMT to liver fibrosis by targeting metastasis­associated gene 3 (MTA3) under hyperglycemic conditions was suppressed by AMO­32. The results indicated that miR­32 and MTA3 may be considered as novel drug targets in the prevention and treatment of liver fibrosis under hyperglycemic conditions. These finding improves the understanding of the progression of liver fibrogenesis.


Assuntos
Transição Epitelial-Mesenquimal/genética , Glucose/metabolismo , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , MicroRNAs/genética , Proteínas de Neoplasias/genética , Animais , Biomarcadores , Células Cultivadas , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Progressão da Doença , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Glucose/efeitos adversos , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Cirrose Hepática/patologia , Masculino , Interferência de RNA , Ratos
16.
Mol Med Rep ; 19(5): 3527-3536, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896796

RESUMO

Myocardial infarction (MI) is the most common event in cardiovascular disease. Carvedilol, a ß­blocker with multiple pleiotropic actions, is widely used for the treatment cardiovascular diseases. However, the underlying mechanisms of carvedilol on alleviating MI are not fully understood. The aim of the present study was to investigate whether the beneficial effects of carvedilol were associated with regulation of microRNA­1 (miR­1). It was demonstrated that carvedilol ameliorated impaired cardiac function and decreased infarct size in a rat model of MI induced by coronary artery occlusion. Similarly, carvedilol reversed the H2O2­induced decrease in cardiomyocyte viability in a dose­dependent manner. The in vivo and in vitro models demonstrated the downregulation of miR­1 following treatment with carvedilol. Overexpression of miR­1, a known pro­apoptotic miRNA, decreased cell viability and induced cell apoptosis. Transfection of miR­1 abolished the beneficial effects of carvedilol. The expression of heat shock protein 60 (HSP60), a direct target of miR­1, was identified to be decreased in MI and H2O2­induced apoptosis, which was associated with a decrease in Bcl­2 and an increase in Bax; expression was restored following treatment with carvedilol. It was concluded that carvedilol partially exhibited its beneficial effects by downregulating miR­1 and increasing HSP60 expression. miR­1 has become a member of the group of carvedilol­responsive miRNAs. Future studies are required to fully elucidate the potential overlapping or compensatory effects of known carvedilol­responsive miRNAs and their underlying mechanisms of action in the pathophysiology of cardiovascular diseases.


Assuntos
Apoptose/efeitos dos fármacos , Apoptose/genética , Carvedilol/farmacologia , Chaperonina 60/genética , MicroRNAs/genética , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Interferência de RNA , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citoproteção/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Proteína X Associada a bcl-2/metabolismo
17.
Exp Neurol ; 317: 34-50, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30802446

RESUMO

Perinatal asphyxia often results in neonatal cerebral hypoxia-ischemia (HI), which is associated with high mortality and severe long-term neurological deficits in newborns. Currently, there are no effective drugs to mitigate the functional impairments post-HI. Previous studies have shown that fibroblast growth factor 21 (FGF21) has a potential neuroprotective effect against brain injury. However, the effect of FGF21 on neonatal HI brain injury is unclear. In the present study, both in vivo and in vitro models were used to assess whether recombinant human FGF21 (rhFGF21) could exert a neuroprotective effect after HI and explore the associated mechanism. The results showed that the rhFGF21 treatment remarkably reduced the infarct volume, ameliorated the body weight and improved the tissue structure after HI in neonatal rats. In addition, the rhFGF21 treatment lengthened the running endurance times in the rotarod test and decreased the mean escape latencies and increased the number of platform crossings in the Morris water maze test at 21 d post-HI insult. In contrast, the FGFR1 inhibitor PD173074 and PI3K inhibitor LY294002 partially reversed these therapeutic effects. In isolated primary cortical neurons, the rhFGF21 treatment protected primary neurons from oxygen-glucose deprivation (OGD) insult by inhibiting neuronal apoptosis and promoting neuronal survival. Both our in vivo and in vitro results reveal that rhFGF21 could inhibit neuronal apoptosis by activating the PI3K/Akt signaling pathway via FGF21/FGFR1/ß-klotho complex formation. Therefore, rhFGF21 may be a promising therapeutic agent for promoting functional recovery after HI-induced neonatal brain injury.

18.
Drug Des Devel Ther ; 13: 581-588, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30804664

RESUMO

Background: IL-36γ is considered to be a valuable biomarker in psoriatic patients, which is expressed as an inactive precursor that needs to be proteolytically processed and activated, and neutrophil-derived proteases seemed to be potent activating enzymes of IL-36γ. Objectives: This study aims to investigate the activation of IL-36γ by cathepsin G (CG) and neutrophil elastase (NE). Materials and methods: We used inactive recombinant full-length (FL)-IL-36γ with different doses of NE or CG to stimulate HaCaT cells; neutrophil extracellular traps (NETs) were prepared to act on FL-IL-36γ and then stimulate HaCaT cells. Real-time quantitative PCR and ELISA were performed to detect CXCL-1 and CXCL-8 expression. We developed imiquimod-induced psoriasis-like mouse model to evaluate the effect of hypodermic injection of neutrophil-derived protease or its inhibitor. Histopathology and Western blotting were conducted for effect assessment. Results: Purified CG cleaved and activated recombinant human FL-IL-36γ to promote CXCL-1 and CXCL-8 expression by human keratinocytes, and NETs activated FL-IL-36γ and the activation was inhibited by serpin A3. CG induced expression of a more truncated IL-36γ in psoriasiform lesion of mice and aggravated the psoriasis-like lesion induced by imiquimod, whereas recombinant serpin A3 alleviated the severity of the psoriasis-like mouse mode. Conclusion: CG has the ability to cleave and activate IL-36γ and aggravate imiquimod-induced mouse psoriasiform lesion. Thus, CG-specific inhibitors might be promising therapeutic drugs for psoriasis.


Assuntos
Catepsina G/metabolismo , Inflamação/metabolismo , Interleucina-1/metabolismo , Elastase de Leucócito/metabolismo , Psoríase/metabolismo , Animais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Células Tumorais Cultivadas
19.
Ecotoxicol Environ Saf ; 170: 399-406, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30550970

RESUMO

In past decades, China has experienced substantial economic growth and industrialization. However, the effects of vast development of China on Hg input to the nearby oceans are still unclear. In this study, four representative 210Pb-dated sediment cores were collected in the central and southern part of Bohai sea to investigate vertical changes of Hg contents and explore the relationship between the Hg deposition and pollution history in this region utilizing a large amount of information available. The results indicated that Hg median concentrations of sediment core B62, B66, JQ17 and HZ24 were 0.043 mg/kg, 0.054 mg/kg, 0.033 mg/kg and 0.018 mg/kg respectively, among which, B66 in Yellow river estuary and B62 in central part of Bohai Sea had higher concentrations and HZ24 in Bohai Strait had a lower concentration. 210Pb profile appeared as a three segments model in the core B62, but as many steps of decay with depth in B66. For HZ24, 210Pb activity only fluctuated with depth without any discernible trend. Sedimentary rates of these cores decreased as follows: B66>B62>JQ17>HZ24. Vertical distributions of Hg concentrations in sediment cores were totally different from each other. Hg concentrations in sediment core B62 experienced an initial fluctuation followed by a decreasing trend, while sediment core HZ24 almost showed the uniform decreasing trends from the surface to the bottom. There were three segments of variation in sediment cores JQ17: initial fluctuation followed by an obviously decreasing tendency and then a converted variation from surface to bottom. Hg contents changes in core B62 might reflect the additive effects from atmospheric deposition at a larger scale and the river-delivered sediment accumulation, while Hg vertical changes in B66 mainly had a close relationship with the input of Yellow river. The converted variation at the bottom section in sediment cores JQ17 was inferred to have some relationship with the Chengbei platform construction in the corresponding periods.


Assuntos
Sedimentos Geológicos/química , Mercúrio/análise , Poluentes Químicos da Água/análise , China , Monitoramento Ambiental , Estuários , Rios/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA