RESUMEN
With rising society stress, depression-induced osteoporosis is increasing. However, the mechanism involved is unclear. In this study, we explored the effect of plasma exosomal miRNAs on bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation in a chronic unpredictable mild stress (CUMS)-induced depression rat model. After 12 weeks of CUMS-induced depression, the pathological changes in the bone tissue and markers of osteogenic differentiation were tested by micro-computed tomography, hematoxylin-eosin staining, and quantitative real-time reverse transcription PCR (qRT-PCR). Plasma exosomes from rats were isolated and co-incubated with BMSCs for 14 d to detect the effect on osteogenic markers. Next-generation sequencing identified the miRNAs in the plasma exosomes, and the differential miRNAs were analyzed and verified by qRT-PCR. BMSCs were infected with lentivirus to upregulate miRNA-30a-5p and incubated in a medium that induced osteogenic differentiation for 14 d. The effect of miR-30a-5p on osteogenic differentiation was determined by qPCR and alizarin red staining. CUMS-induced depression rat model was established successfully, and exhibited reduced bone mass and damaged bone microstructure compared to that of the controls. The observed pathological changes suggested the occurrence of osteoporosis in the CUMS group, and the mRNA expression of osteogenic markers was also significantly reduced. Incubation of BMSCs with plasma exosomes from the CUMS group for 14 d resulted in a significant decrease in the expression of osteogenic markers. Twenty-five differentially expressed miRNAs in plasma exosomes were identified and upregulation of miR-30a-5p was observed to significantly inhibit the expression of osteogenic markers in BMSCs. Our findings contributed to a comprehensive understanding of the mechanism of osteoporosis caused by depression, and demonstrated the potential of miR-30a-5p as a novel biomarker or therapeutic target for the treatment of osteoporosis.
Asunto(s)
Diferenciación Celular , Depresión , Modelos Animales de Enfermedad , Exosomas , Células Madre Mesenquimatosas , MicroARNs , Osteogénesis , Ratas Sprague-Dawley , Animales , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , MicroARNs/sangre , Osteogénesis/genética , Exosomas/metabolismo , Exosomas/genética , Diferenciación Celular/genética , Depresión/genética , Depresión/sangre , Ratas , Masculino , Estrés Psicológico/complicaciones , Estrés Psicológico/sangre , Osteoporosis/genética , Osteoporosis/sangreRESUMEN
Substantial morbidity and mortality are associated with postcardiac arrest brain injury (PCABI). MicroRNAs(miRNAs) are essential regulators of neuronal metabolism processes and have been shown to contribute to alleviated neurological injury after cardiac arrest. In this study, we identified miRNAs related to the prognosis of patients with neurological dysfunction after cardiopulmonary resuscitation based on data obtained from the Gene Expression Omnibus (GEO) database. Then, we explored the effects of miR-483-5p on mitochondrial biogenesis, mitochondrial-dependent apoptosis, and oxidative stress levels after ischemiaâreperfusion injury in vitro and in vivo. MiR-483-5p was downregulated in PC12 cells and hippocampal samples compared with that in normal group cells and hippocampi. Overexpression of miR-483-5p increased the viability of PC12 cells after ischemiaâreperfusion injury and reduced the proportion of dead cells. A western blot analysis showed that miR-483-5p increased the protein expression of PCG-1, NRF1, and TFAM and reduced the protein expression of Bax and cleaved caspase 3, inhibiting the release of cytochrome c from mitochondria and alleviating oxidative stress injury by inhibiting the production of ROS and reducing MDA activity. We confirmed that miR-483-5p targeted TNFSF8 to regulate the AMPK/JNK pathway, thereby playing a neuroprotective role after cardiopulmonary resuscitation. Hence, this study provides further insights into strategies for inhibiting neurological impairment after cardiopulmonary resuscitation and suggests a potential therapeutic target for PCABI.
Asunto(s)
Paro Cardíaco , MicroARNs , Fármacos Neuroprotectores , Daño por Reperfusión , Ratas , Animales , Humanos , Sistema de Señalización de MAP Quinasas , Fármacos Neuroprotectores/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Apoptosis/genética , Daño por Reperfusión/metabolismo , Mitocondrias/metabolismo , Paro Cardíaco/complicaciones , Paro Cardíaco/genética , Paro Cardíaco/metabolismoRESUMEN
Previous studies have shown that AMPK plays an important role in cerebral ischemia-reperfusion injury by participating in apoptosis, but the exact mechanism and target of action remains unclear. This study aimed to investigate the protective mechanism of AMPK activation on brain injury secondary to cardiac arrest. HE, Nills and TUNEL assays were used to evaluate neuronal damage and apoptosis. The relationships between AMPK, HNF4α and apoptotic genes were verified by ChIP-seq, dual-luciferase and WB assays. The results showed that AMPK improved the 7-day memory function of rats, and reduced neuronal cell injury and apoptosis in the hippocampal CA1 region after ROSC, while the use of HNF4α inhibitor weakened the protective effect of AMPK. Further research found that AMPK positively regulated the expression of HNF4α, and AMPK could promote the expression of Bcl-2 and inhibit the expression of Bax and Cleaved-Caspase 3. In vitro experiments showed that AMPK ameliorated neuronal injury by inhibiting apoptosis through the activation of HNF4α. Combined with ChIP-seq, JASPAR analysis and Dual-luciferase assay, the binding site of HNF4α to the upstream promoter of Bcl-2 was found. Taken together, AMPK attenuates brain injury after CA by activating HNF4α to target Bcl-2 to inhibit apoptosis.
Asunto(s)
Lesiones Encefálicas , Paro Cardíaco , Daño por Reperfusión , Ratas , Animales , Ratas Sprague-Dawley , Proteínas Quinasas Activadas por AMP/metabolismo , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Paro Cardíaco/complicaciones , Paro Cardíaco/tratamiento farmacológicoRESUMEN
BACKGROUND: The underlying mechanisms for infantile bronchopneumonia development remain unknown. METHODS: Peripheral blood mononuclear cell (PBMCs) and serum derived from severe and mild infantile bronchopneumonia were obtained, and the expression of various molecules was detected with enzyme-linked immunosorbent assay and quantitative PCR. Such molecules were also detected in granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced bone marrow-derived NFκB2-/- dendritic cells (DCs) or NIK SMI1 (NF-κB-inducing kinase inhibitor) administrated DCs. RESULTS: The relative mRNA expression levels of type I interferons (IFNs) (IFN-α4, IFN-ß), Th17 cell-associated markers (interleukin-17A, retinoic-acid-receptor-related orphan nuclear receptor gamma, and GM-CSF), and non-canonical NF-κB member (NFκB2) were significantly up-regulated in PBMCs and DCs derived from infantile bronchopneumonia compared with healthy controls. However, compared with Th17 cell-associated markers and non-canonical NF-κB molecules, the expression of IFN-α4 and IFN-ß was significantly inhibited in severe infantile bronchopneumonia compared with mild infantile bronchopneumonia. The relative protein expression of the above molecules also showed a similar expression pattern in the PBMCs or serum. NF-κB2 knockout or NIK SMI1 administration could reverse the diminished expression of IFN-ß in GM-CSF-induced bone marrow-derived DCs. CONCLUSIONS: GM-CSF-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in DCs contributes to the development of severe bronchopneumonia in infant. IMPACT: Granulocyte-macrophage colony-stimulating factor-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in dendritic cells is critical for the development of infantile bronchopneumonia. Our findings reveal a possible mechanism underlying the development of severe infantile bronchopneumonia. The results could provide therapeutic molecular target for the treatment of such disease.
Asunto(s)
Bronconeumonía , Interferón Tipo I , Humanos , Lactante , Factor Estimulante de Colonias de Granulocitos y Macrófagos , FN-kappa B , Leucocitos MononuclearesRESUMEN
An efficient strategy for the identification of potential nephroprotective substances in Zhu-Ling decoction has been established with the integration of absorbed components characterization, pharmacokinetics, and activity evaluation. A qualitative method was developed to characterize the chemical constituents absorbed components in vivo of Zhu-Ling decoction by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. A quantitative method was established and validated for the simultaneous determination of eight compounds in rat plasma by using ultra-performance liquid chromatography-triple quadruple tandem mass spectrometry. Finally, the nephroprotective activities of absorbed components with high exposure were assessed by cell survival rate, superoxide dismutase, and malondialdehyde activities in hydrogen peroxide-induced Vero cells. As a result, 111 compounds in Zhu-Ling decoction and 36 absorbed components were identified in rat plasma and urine, and poricoic acid A, poricoic acid B, alisol A, 16-oxo-alisol A, and dehydro-tumulosic acid had high exposure levels in rat plasma. Finally, poricoic acid B, poricoic acid A, 16-oxo-alisol A, and dehydro-tumulosic acid showed remarkable nephroprotective activity against Vero cells damage induced by hydrogen peroxide. Besides, superoxide dismutase and malondialdehyde activities were obviously regulated in hydrogen peroxide-induced Vero cells by treatment with the four compounds mentioned above. Therefore, these four compounds were considered to be effective substances of Zhu-Ling decoction due to their relatively high exposure in vivo and biological activity. This study provided a chemical basis for the action mechanism of Zhu-Ling decoction in the treatment of chronic kidney diseases.
Asunto(s)
Medicamentos Herbarios Chinos , Triterpenos , Chlorocebus aethiops , Ratas , Animales , Peróxido de Hidrógeno , Células Vero , Espectrometría de Masas/métodos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Cromatografía Líquida de Alta Presión/métodosRESUMEN
PURPOSE: Many studies have shown that cytochrome P450 (CYP) gene polymorphisms are usually associated with an increased risk of cardiovascular and cerebrovascular diseases. To explore the association of CYP2C8 and CYP2J2 gene polymorphisms with hypertensive intracerebral hemorrhage (HICH) in the Han Chinese population. METHODS: Forty HICH patients and 40 control subjects were recruited for this study. Two single nucleotide polymorphisms (SNP) (rs1058932, rs2275622) in the CYP2C8 gene and two SNPs (rs2271800, rs1155002) in the CYP2J2 gene were selected for genotyping by direct sequencing. Statistical analysis was applied to examine the effect of genetic variation on HICH. RESULTS: We found that variant alleles of CYP2C8 rs1058932 (A) and rs2275622 (C) were both significantly associated with HICH, especially in females. We also found significant associations of CYP2C8 rs1058932 (A) and rs2275622 (C) variant alleles with poor outcomes in HICH patients, especially in males. CONCLUSIONS: CYP2C8 gene polymorphisms might increase the risk of HICH in the Han Chinese population and might lead to poor outcomes. This finding adds to the body of literature supporting novel therapeutic strategies for HICH.
Asunto(s)
Citocromo P-450 CYP2J2 , Hemorragia Intracraneal Hipertensiva , Masculino , Femenino , Humanos , Citocromo P-450 CYP2C8/genética , Sistema Enzimático del Citocromo P-450/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Organic pollutants in water bodies pose a serious environmental problem, and photocatalytic technology is an efficient and environmentally friendly water treatment method. Titanium dioxide (TiO2) is a widely used photocatalyst, but it suffers from some drawbacks such as a narrow light response range, fast charge recombination, and low photocatalytic activity. To improve the photocatalytic performance of TiO2, this article reviews the preparation methods, performance evaluation, and applications of modified TiO2 photocatalysts. Firstly, the article introduces the effects of doping modification, semiconductor composite modification, and other modification methods on the structure and properties of TiO2 photocatalysts, as well as the common characterization techniques and activity test methods of photocatalysts. Secondly, the article discusses the effects and mechanisms of modified TiO2 photocatalysts on degrading dye, pesticide, and other organic pollutants in water bodies, as well as the influencing factors. Finally, the article summarizes the main achievements and advantages of modified TiO2 photocatalysts in degrading organic pollutants in water bodies, points out the existing problems and challenges, and prospects for the development direction and future of this field.
Asunto(s)
Contaminantes Ambientales , Plaguicidas , TecnologíaRESUMEN
Antibiotic contamination in water has received significant attention in recent years for the reason that the residuals of antibiotics can promote the progression of antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs). It is difficult to treat antibiotics using conventional biological treatment methods. In order to investigate an efficient new method of treating antibiotics in water, in this study, microwave (MW) was employed in revitalizing peroxymonosulfate (PMS) to treat typical antibiotic tetracycline (TC). The Box-Behnken design (BBD) was applied to organize the experimental schemes. The response surface methodology (RSM) optimization was run to derive the best experimental conditions and validated using actual data. Moreover, the main mechanisms of PMS activation via MW were resolved. The results demonstrated that the relationship between TC removal rate and influencing factors was consistent with a quadratic model, where the P-value was less than 0.05, and the model was considered significant. The optimal condition resulting from the model optimization were power = 800 W, [PMS] = 0.4 mM, and pH = 6.0. Under such conditions, the actual removal of TC was 99.3%, very close to the predicted value of 99%. The quenching experiment confirmed that SO4â¢- and â¢OH were jointly responsible for TC removal.
Asunto(s)
Antagonistas de Receptores de Angiotensina , Microondas , Inhibidores de la Enzima Convertidora de Angiotensina , Antibacterianos/análisis , Tetraciclina , Peróxidos , AguaRESUMEN
OBJECTIVE: Cardiac arrest (CA) is caused by a nonshockable rhythm with a low success rate of return of spontaneous circulation (ROSC) and a poor prognosis. This study intended to establish a nonshockable rhythm CA model caused by asphyxia. MATERIALS AND METHODS: Healthy adult male Wistar rats were injected with vecuronium bromide to induce CA. After the CA duration reached the target time point, cardiopulmonary resuscitation was performed. The survival status and neurological and cardiac function were evaluated after ROSC. Brain histopathology, including hematoxylin staining, Nissl staining and Terminal dUTP nick-end labeling (TUNEL) staining, was performed to evaluate the surviving cells and apoptotic cells. Apoptosis-related proteins after ROSC for 72 h were analyzed by western blot. RESULTS: CA was successfully induced in all animals. The time for the three groups of animals to PEA was 320 ± 22 s in the CA-8 group, 322 ± 28 s in the CA-12 group and 320 ± 18 s in the CA-15 group. The time to asystole was 436 ± 54 s in the CA-8 group, 438 ± 62 s in the CA-12 group and 433 ± 56 s in the CA-15 group. The NDS of rats in the CA group was significantly decreased after ROSC for 24 h. The NDS in the CA-15 group was 5-16 points, while it was 58-67 points and 15-43 points in the CA-8 and CA-12 groups, respectively. The cardiac function of animals in the CA group was impaired after ROSC, and the ejection fraction, fractional shortening, stroke volume and cardiac output, were all significantly decreased. Brain histopathology showed that the number of surviving neurons was decreased, and the number of apoptotic cells was increased in CA group, the longer the CA duration, the more apoptotic cells increased. The expression of the proapoptotic protein Bax and the apoptotic executive protein caspase3 in the hippocampus of CA rats was significantly increased, while the expression of the antiapoptotic protein Bcl-2 was significantly reduced. CONCLUSIONS: The use of vecuronium can successfully induce CA caused by nonshockable rhythm in rats, which will help to further study the pathophysiological changes after CA by nonshockable rhythm.
Asunto(s)
Reanimación Cardiopulmonar , Paro Cardíaco , Ratas , Masculino , Animales , Asfixia/complicaciones , Ratas Wistar , Paro Cardíaco/etiología , EncéfaloRESUMEN
Converting agricultural waste into value-added biopesticides to replace chemical pesticides for plant protection is a good alternative for environmental sustainability and resource recycling. In this study, five tropical wastes (cassava peels, banana pseudostem, coconut shell, sugarcane bagasse, and pineapple peels) were screened as substrates for the rapid production of biopesticide Trichoderma Brev T069. Five single tests and a Box-Behnken design (BBD) with response surface methodology were used to optimize the culture conditions to improve the spore yield. The results showed that cassava peel was the optimal solid fermentation substrate, and the optimization enabled a spore yield of 9.31 × 109 spores/g at 3rd day, which was equal to 93.19% of spore yield obtained at 5th day (9.99 × 109 spores/g). A newly packed-bed bioreactor with agitation and ventilation system was developed and used to expand the production that 250 kg of biopesticide (2.89 × 109 spores/g) could be available on the 3rd day. A pot experiment indicated that the biopesticide T. Brev T069 obtained under this production system, when applied at 1 × 107 spores/g of soil had a 64.65% biocontrol efficiency on banana fusarium wilt. This study provides a practical solution for turning a tropical waste into an effective biopesticide which can prevent banana wilt disease, thereby helping to reduce disease management cost and overcome environmental hazards caused by synthetic pesticides.
Asunto(s)
Manihot , Musa , Plaguicidas , Saccharum , Trichoderma , Agentes de Control Biológico , Reactores Biológicos , Celulosa , Fermentación , Trichoderma/fisiologíaRESUMEN
Four new daphnane-type diterpenes named tianchaterpenes C-F (1-4) and six known ones were isolated from Stelleropsis tianschanica. Their structures were elucidated based on chemical and spectral analyses. The comparisons of calculated and experimental electronic circular dichroism (ECD) methods were used to determine the absolute configurations of new compounds. Additionally, compounds 1-10 were evaluated for their cytotoxic activities against HGC-27 cell lines; the results demonstrate that compound 2 had strong cytotoxic activities with IC50 values of 8.8 µM, for which activity was better than that of cisplatin (13.2 ± 0.67 µM).
Asunto(s)
Antineoplásicos Fitogénicos , Antineoplásicos , Diterpenos , Medicamentos Herbarios Chinos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Diterpenos/química , Diterpenos/farmacología , Medicamentos Herbarios Chinos/química , Estructura MolecularRESUMEN
Nepeta bracteata Benth. is used clinically to treat tracheal inflammation, coughs, asthma, colds, fevers, adverse urination, and other symptoms, along with functions in clearing heat and removing dampness. However, there have been few studies characterizing the material basis of its efficacy. Therefore, the aim of this study was to screen for compounds with anti-inflammatory activities in N. bracteata Benth. Using silica gel, ODS C18, and Sephadex LH-20 column chromatography, as well as semipreparative HPLC, 10 compounds were separated from N. bracteata Benth. extract, including four new diterpenoids (1-4), one amide alkaloid (5), and five known diterpenoids (6-10). The structures of all the isolates were elucidated by HR-ESI-MS, NMR, and CD analyses. Using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, we investigated the anti-inflammatory activities of compounds 1-10. It is worth noting that all were able to inhibit nitric oxide (NO) production with IC50 values < 50 µM and little effect on RAW 264.7 macrophage viability. Compounds 2 and 4 displayed remarkable inhibition with IC50 values of 19.2 and 18.8 µM, respectively. Meanwhile, screening on HCT-8 cells demonstrated that compounds 2 and 4 also had moderate cytotoxic activities with IC50 values of 36.3 and 41.4 µM, respectively, which is related to their anti-inflammatory effects.
Asunto(s)
Abietanos/farmacología , Antiinflamatorios/farmacología , Nepeta/química , Extractos Vegetales/farmacología , Abietanos/química , Abietanos/toxicidad , Animales , Antiinflamatorios/química , Antiinflamatorios/toxicidad , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Lipopolisacáridos/toxicidad , Ratones , Óxido Nítrico/metabolismo , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Células RAW 264.7RESUMEN
Protein kinase RNA-like Endoplasmic Reticulum Kinase (PERK) is an endoplasmic reticulum stress sensor that possesses pro-survival capability and contributes to cell homeostasis and survival. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) has been recognized as a stem cell marker in intestinal epithelial cells. To determine whether PERK modulates the proliferation of intestinal stem cells, we investigated the effects of PERK knock-down on intestinal Lgr5-positive stem cells in mice. Lgr5-EGFP knock-in mice were fed with lentivirus-PERK shRNA twice a day for three days. Isolated intestinal Lgr5-positive stem cells were treated with lentivirus-PERK shRNA. The number of Lgr5-positive cells, the proliferation and apoptotic indices, several biomarkers for proliferation and differentiation, and Akt expression in intestinal stem cells were detected in vivo, in vitro and in two intestinal epithelial injury models caused by radiotherapy and sepsis. PERK knock-down could significantly diminish the number and proliferation of Lgr5-positive cells, induce the low expression of several proliferation markers and the high expression of several differentiation markers in Lgr5-positive cells, enhance the apoptotic Lgr5-positive cells, and reduce the Akt expression in intestinal Lgr5-positive stem cells. Similar results were observed in radiotherapy- and sepsis-induced intestinal injuries. Moreover, PERK inhibition markedly decreased the survival of mice in response to radiation and sepsis. These results suggest a critical role for PERK in the proliferation and survival of intestinal stem cells in mice.
Asunto(s)
Proliferación Celular/genética , Receptores Acoplados a Proteínas G/genética , Células Madre/metabolismo , eIF-2 Quinasa/genética , Animales , Apoptosis/genética , Diferenciación Celular/genética , Linaje de la Célula/genética , Retículo Endoplásmico/genética , Células Epiteliales/citología , Células Epiteliales/metabolismo , Mucosa Intestinal/citología , Mucosa Intestinal/crecimiento & desarrollo , Intestinos/citología , Intestinos/crecimiento & desarrollo , Lentivirus/genética , Ratones , Células Madre/citologíaRESUMEN
BACKGROUND: Alpha-fetoprotein (AFP) has received extensive attention in the differential diagnosis of hepatocellular carcinoma (HCC), especially for AFP-negative HCC (AFP-NHCC). The current study aimed to explore the value of targeted regulation of LHPP expression-related microRNAs (miRs) and protein induced by vitamin K deficiency or antagonist-II (PIVKA-II) in the differential diagnosis of AFP-NHCC. METHODS: A retrospective study was conducted on a testing set-including 214 AFP-NHCC patients, 200 cirrhosis, and 210 controls, and a validation set-including 140 AFP-NHCC patients, 134 cirrhosis, and 128 controls recruited from The First Affiliated Hospital of Hunan Normal University. Serum miRs were examined using quantitative real-time PCR method. Serum PIVKA-II was measured by enzyme-linked immunosorbent assay. RESULTS: Compared with adjacent tissues, LHPP protein levels in cancer tissues were significantly decreased (P < .05). Predictive software and dual-luciferase reporter assays showed that miR-363-5p and miR-765 can target LHPP expression. Serum miR-363-5p, miR-765, and PIVKA-II levels were significantly higher in AFP-HCC patients than in cirrhosis and controls. A logistic regression model combining miR-363-5p, miR-765, and PIVKA-II was performed. This model presented a high discriminating value (AUC: 0.930, sensitivity/specificity: 79.4%/95.4%) than any single indicator. In the validation set, this model still showed a high discriminating value (AUC: 0.936, sensitivity/specificity: 83.6%/94.7%). CONCLUSION: Current model combining serum miR-363-5p, miR-765, and PIVKA-II has potential significance for diagnosis of AFP-NHCC.
Asunto(s)
Carcinoma Hepatocelular/genética , Pirofosfatasa Inorgánica/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , Deficiencia de Vitamina K/genética , alfa-Fetoproteínas/metabolismo , Adulto , Anciano , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/patología , Estudios de Casos y Controles , Femenino , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Modelos Logísticos , Masculino , MicroARNs/sangre , Persona de Mediana Edad , Protrombina/análisis , Reproducibilidad de los Resultados , Estudios Retrospectivos , Deficiencia de Vitamina K/sangreRESUMEN
Medical image fusion techniques can fuse medical images from different morphologies to make the medical diagnosis more reliable and accurate, which play an increasingly important role in many clinical applications. To obtain a fused image with high visual quality and clear structure details, this paper proposes a convolutional neural network (CNN) based medical image fusion algorithm. The proposed algorithm uses the trained Siamese convolutional network to fuse the pixel activity information of source images to realize the generation of weight map. Meanwhile, a contrast pyramid is implemented to decompose the source image. According to different spatial frequency bands and a weighted fusion operator, source images are integrated. The results of comparative experiments show that the proposed fusion algorithm can effectively preserve the detailed structure information of source images and achieve good human visual effects.
Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Redes Neurales de la Computación , Algoritmos , Humanos , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Several heart failure (HF) risk models exist, however, most of them perform poorly when applied to real-world situations. This study aimed to develop a convenient and efficient risk model to identify patients with high readmission risk within 90 days of HF. METHODS: A multivariate logistic regression model was used to predict the risk of 90-day readmission. Data were extracted from electronic medical records from January 1, 2017 to December 31, 2017 and follow-up records of patients with HF within 3 months after discharge. Model performance was evaluated using a receiver operating characteristic curve. All statistical analysis was done using R version 3.5.0. RESULTS: A total of 350 patients met the inclusion criterion of being readmitted within in 90 days. All data sets were randomly divided into derivation and validation cohorts at a 7/3 ratio. The baseline data were fairly consistent among the derivation and validation cohorts. The variables most clearly related to readmission were logarithm of serum N-terminal pro b-type natriuretic peptide (NT-proBNP) level, red cell volume distribution width (RDW-CV), and Charlson comorbidity index (CCI). The model had good discriminatory ability (C-statistic = 0.73). CONCLUSIONS: We developed and validated a multivariate logistic regression model to predict the 90-day readmission risk for Chinese patients with HF. The predictors included in the model are derived from electronic medical record (EMR) admission data, making it easier for physicians and pharmacists to identify high-risk patients and tailor more intensive precautionary strategies.
Asunto(s)
Registros Electrónicos de Salud , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/terapia , Readmisión del Paciente , Adulto , Anciano , Femenino , Insuficiencia Cardíaca/diagnóstico , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Alta del Paciente , Fragmentos de Péptidos/sangre , Curva ROC , Medición de RiesgoRESUMEN
Natural daphnane diterpenoids, mainly distributed in plants of the Thymelaeaceae and Euphorbiaceae families, usually include a 5/7/6-tricyclic ring system with poly-hydroxyl groups located at C-3, C-4, C-5, C-9, C-13, C-14, or C-20, while some special types have a characteristic orthoester motif triaxially connectedat C-9, C-13, and C-14. The daphnane-type diterpenoids can be classified into five types: 6-epoxy daphnane diterpenoids, resiniferonoids, genkwanines, 1-alkyldaphnanes and rediocides, based on the oxygen-containing functions at rings B and C, as well as the substitution pattern of ring A. Up to now, nearly 200 daphnane-type diterpenoids have been isolated and elucidated from the Thymelaeaceae and Euphorbiaceae families. In-vitro and in-vivo experiments of these compounds have shown that they possess a wide range of biological activities, including anti-HIV, anti-cancer, anti-leukemic, neurotrophic, pesticidal and cytotoxic effects. A comprehensive account of the structural diversity is given in this review, along with the cytotoxic activities of daphnane-type diterpenoids, up to April 2019.
Asunto(s)
Diterpenos/química , Euphorbiaceae/química , Thymelaeaceae/química , Animales , Fármacos Anti-VIH/química , Antineoplásicos/química , Humanos , Estructura MolecularRESUMEN
Fourteen chemical constituents, including 5-hydroxy-4-methoxy-1-tetralone(1), 4,8-dihydroxy-1-tetralone(2), 4,5-dihydroxy-α-tetralone(3), blumenol B(4), dehydrovomifoliol(5), megastigm-5-ene-3,9-diol(6), juglanin B(7), blumenol C(8), loliolide(9), oleracone B(10), syringarsinol(11), pinoresinol(12), methyl 4-hydroxy-3-methoxybenzoate(13), and isovanillic acid(14), were isolated from the dichloromethane fraction of 95% methanol extract of green walnut husks by silica gel and MCI column chromatography, and Pre-HPLC. Their structures were determined by spectroscopic methods, such as NMR, MS and so on. Among them, compounds 1, 4-6, 8-13 were isolated from the green walnut husks for the first time, and compounds 4-6, 8, 10, 12, 13 were isolated from the Juglans genus for the first time. All of isolates were detected their inhibitory activities against HeLa, HGC-27 and Ht-29 cell lines by the MTT assay. The result showed that compounds 2, 3, 7, 9 and 11 exhibited inhibitory activity against the tested cell line. The IC_(50) of 7 were 26.5, 9.0, 25.4 µmol·L~(-1), respectively.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Juglans/química , Fitoquímicos/farmacología , Extractos Vegetales/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Células HT29 , Células HeLa , Humanos , Estructura Molecular , Fitoquímicos/aislamiento & purificaciónRESUMEN
Four new sesquiterpenoids, known as diarthronchas Aâ»D (1â»4), and one known daphnauranol B (5) were isolated from the methanol extract of the roots of Diarthron tianschanica. The compounds structures were determined on the basis of spectroscopic data. All of the isolated compounds were profiled for their antineoplastic activity.
Asunto(s)
Antineoplásicos/farmacología , Raíces de Plantas/química , Sesquiterpenos/farmacología , Thymelaeaceae/química , Antineoplásicos/química , Línea Celular Tumoral , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Humanos , Concentración 50 Inhibidora , Sesquiterpenos/química , Análisis Espectral/métodos , Relación Estructura-ActividadRESUMEN
Neuroinflammation is a key contributor to neuronal damage in neurodegenerative diseases. In our previous work on natural effective neuroinflammatory inhibitors, Alhagi sparsifolia Shap. (Leguminosae), a folk medicine widely distributed in Xinjiang, attracted our attention because of its significant anti-neuroinflammatory effect. Therefore, further investigation of the bioactive material basis was carried out. As a result, 33 major components were characterized and identified by chromatographic and spectral methods, respectively. Furthermore, the anti-neuroinflammatory effects of the extract and purified constituents were evaluated in LPS-induced N9 cells in vitro. The results displayed that compounds 1, 2, 3, 5, 6, 8, 11, 15, 16, 17, 22, 23, 25, 26, 28, 30, 33 could exhibit significant inhibitory activities without obvious cytotoxicities at their effective concentrations. Especially, isorhamnetin (1) (IC50 17.87µM), quercetin (2) (10.22µM), 3',7-dihydroxyl-4'-methoxylisoflavone (5) (17.43µM), 3',7-dihydroxyl-4',6-dimethoxylisoflavone (6) (11.21µM), syringgaresinol (16) (2.68µM), bombasinol A (17) (7.61µM), aurantiamide (23) (14.91µM) and 1,3,3,4-tetramethyl cyclopentene (33) (2.63µM) showed much stronger inhibiting effect than that of the positive control minocycline (19.89µM). Therefore, the effective compositions might be responsible for the significant neuroinflammation inhibitory activities exhibited by the herb. Moreover, compounds 16 and 33 could be good leading compounds for the development of potential therapeutic agents against neurodegenerative diseases.