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Background: Coronary artery bypass graft (CABG) is intended to restore myocardial perfusion and alleviate morbidity among patients suffering from coronary artery disease. Due to procedural complexity, and anesthetic medications, post-operative complications are more prevalent, requiring the integration of rehabilitation strategies. This review aimed to determine the effect of single and multiple exercise therapy on rehabilitation after CABG surgery. Methods: We conducted a systematic search of databases (EBSCOhost, Scopus, PubMed, and Web of Science) from 01 January 2000 to 15 September 2022. The protocol of this systematic review is registered to PROSPERO. Results: We found nine randomized control trials composed of 599 CABG patients. In-patient cardiac rehabilitation (CR), a combination of inspiratory muscle training, mobilization, active upper and lower limb exercise, and aerobic exercise as multiple exercise therapy, found significant improvement in 6-minute walking distance (6MWD) than single exercise therapy (breathing exercise) at discharge and follow-up (moderate quality evidence). Contrary, multiple exercises group compared to single exercise groups did not improve the peak volume of oxygen ( VO 2 ) at discharge. Still, significant improvement was found at follow-up (moderate quality of evidence). On the other hand, the out-patient CR made up of high-intensity inspiratory muscle training, upper and lower limbs resistance training, and aerobic exercise as multiple exercise therapy significantly improved 6MWD and peak VO 2 at discharge (High-quality evidence). Conclusions: Our review revealed that multiple exercise therapy significantly improves functional and exercise capacity in in-patient and out-patient cardiac rehabilitation settings than single exercise therapy, but more than double exercise therapy protocol may be inefficient for improvement of quality of life. Inspiratory muscle training and resistance training in exercise therapy protocols significantly supplant the outcome, which requires further investigation.
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Four polyoxometalate (POM)-based organic-inorganic hybrid compounds, namely, (H2bimb)6H8[((Mn(H2O)3(µ-bimb))0.5(Mn(H2O)4)(Mn(H2O)5)0.5(AgP5W30O110))2]·29H2O (1), [(Cu(Hbimb)(H2O)2(µ-bimb)Cu(Hbimb)(H2O))(Cu(H2O)2(µ-bimb)Cu(H2O)3)((Cu(H2O)2)0.5(µ-bimb)(Cu(H2O)3)0.5)H2(AgP5W30O110)]·12.5H2O (2), (H2bimb)2H[(Zn(Hbimb)(H2O)4(Zn(Hbimb)(H2O)2)0.5)2(AgP5W30O110)]·12H2O (3), and (H2bimb)3H2[(Ag(H2O)2)0.5(Ag(Hbimb)Ag(Hbimb)(µ-bimb)Ag)(Ag(H2O)2)0.5(AgP5W30O110)]·7H2O (4) (bimb = 1,4-bis(1H-imidazol-1-yl)benzene), were hydrothermally synthesized using a silver-centered Preyssler-type POM K14[AgP5W30O110]·18H2O (abbreviated as K-{AgP5W30}) as a precursor. In 1-4, {AgP5W30} clusters integrating the merits of Ag+ and {P5W30} units are modified by different transition metal (TM)-organic fragments to extend the structures into three-dimensional frameworks. As nonenzymatic electrochemical sensor materials, 1-4 show good electrocatalytic activity, high sensitivity, and a low detection limit for detecting hydrogen peroxide (H2O2); 4 possesses the highest sensitivity of 195.47 µA·mM-1·cm-2 for H2O2 detection. Most importantly, the average level of H2O2 detection of these {AgP5W30}-based materials outperforms that of Na-centered Preyssler-type {NaP5W30} and most Keggin-type POM-based materials. The performances of such {AgP5W30} materials mainly stem from the unique advantage of high-negatively charged {AgP5W30} clusters together with the good synergistic effect between {AgP5W30} and TMs. This work expands on the research of high-efficiency POM-based nonenzymatic electrochemical H2O2 sensors using Ag-containing POMs with high negative charges, which is also of great theoretical and practical significance to carry out health monitoring and environmental analysis.
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Peróxido de Hidrógeno , Plata , Aniones , Peróxido de Hidrógeno/química , Polielectrolitos , Plata/químicaRESUMEN
OBJECTIVE: To investigate the effect of maternal zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns. METHODS: Pregnant rats were divided into zinc adequate (ZA), zinc deficient (ZD), and paired fed (PF) groups. Serum zinc contents and AKP activity in mother rats and offspring at P21 (end of lactation) and P60 (weaned, adult) were detected. Cognitive ability of offspring at P21 and P60 were determined by Morris water maze. The expression of proteins including DNMT3a, DNMT1, GADD45ß, MeCP2 and BDNF in the offspring hippocampus were detected by Western-blot. The methylation status of BDNF promoter region in hippocampus of offspring rats was detected by MS-qPCR. RESULTS: Compared with the ZA and PF groups, pups in the ZD group had lower zinc levels and AKP activity in the serum, spent more time finding the platform and spent less time going through the platform area. Protein expression of DNMT1 and GADD45b were downregulated in the ZD group during P0 and P21 but not P60 compared with the ZA and PF group, these results were consistent with a reduction in BDNF protein at P0 (neonate), P21. However, when pups of rats in the ZD group were supplemented with zinc ion from P21 to P60, MeCP2 and GADD45b expression were significantly downregulated compared with the ZA and PF group. CONCLUSION: Post-weaning zinc supplementation may improve cognitive impairment induced by early life zinc deficiency, whereas it may not completely reverse the abnormal expression of particular genes that are involved in DNA methylation, binding to methylated DNA and neurogenesis.
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Metilación de ADN , Desnutrición , Animales , Antígenos de Diferenciación/genética , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Femenino , Hipocampo/metabolismo , Aprendizaje , Desnutrición/metabolismo , Embarazo , Ratas , ZincRESUMEN
The efficient capture of multi-pollutant residues in food is vital for food safety monitoring. In this study, in-situ-fabricated magnetic MIL-53(Al) metal organic frameworks (MOFs), with good magnetic responsiveness, were synthesized and applied for the magnetic solid-phase extraction (MSPE) of chloramphenicol, bisphenol A, estradiol, and diethylstilbestrol. Terephthalic acid (H2BDC) organic ligands were pre-coupled on the surface of amino-Fe3O4 composites (H2BDC@Fe3O4). Fe3O4@MIL-53(Al) MOF was fabricated by in-situ hydrothermal polymerization of H2BDC, Al (NO3)3, and H2BDC@Fe3O4. This approach highly increased the stability of the material. The magnetic Fe3O4@MIL-53(Al) MOF-based MSPE was combined with high-performance liquid chromatography-photo diode array detection, to establish a novel sensitive method for analyzing multi-pollutant residues in milk. This method showed good linear correlations, in the range of 0.05-5.00 µg/mL, with good reproducibility. The limit of detection was 0.004-0.108 µg/mL. The presented method was verified using a milk sample, spiked with four pollutants, which enabled high-throughput detection and the accuracies of 88.17-107.58% confirmed its applicability, in real sample analysis.
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Contaminantes Ambientales , Estructuras Metalorgánicas , Animales , Cromatografía Líquida de Alta Presión/métodos , Contaminantes Ambientales/análisis , Límite de Detección , Fenómenos Magnéticos , Estructuras Metalorgánicas/química , Leche/química , Reproducibilidad de los Resultados , Extracción en Fase Sólida/métodosRESUMEN
BACKGROUND: Virescent mutation broadly exists in plants and is an ideal experimental material to investigate regulatory mechanisms underlying chlorophyll synthesis, photosynthesis and plant growth. Up to date, the molecular mechanisms in two virescent mutations have been clarified in cottons (Gossypiuma hirsutum). A virescent mutation has been found in the cotton strain Sumian 22, and the underlying molecular mechanisms have been studied. METHODS: The virescent mutant and wild type (WT) of Sumian 22 were cross-bred, and the F1 population were self-pollinated to calculate the segregation ratio. Green and yellow leaves from F2 populations were subjected to genome sequencing and bulked-segregant analysis was performed to screen mutations. Real-time quantitative PCR (RT-qPCR) were performed to identify genes in relations to chlorophyll synthesis. Intermediate products for chlorophyll synthesis were determined to validate the RT-qPCR results. RESULTS: The segregation ratio of green and virescent plants in F2 population complied with 3:1. Compared with WT, a 0.34 Mb highly mutated interval was identified on the chromosome D10 in mutant, which contained 31 genes. Among them, only ABCI1 displayed significantly lower levels in mutant than in WT. Meanwhile, the contents of Mg-protoporphyrin IX, protochlorophyllide, chlorophyll a and b were all significantly lower in mutant than in WT, which were consistent with the inhibited levels of ABCI1. In addition, a mutation from A to T at the -317 bp position from the start codon of ABCI1 was observed in the genome sequence of mutant. CONCLUSIONS: Inhibited transcription of ABCI1 might be the mechanism causing virescent mutation in Sumian 22 cotton, which reduced the transportation of protoporphyrin IX to plastid, and then inhibited Mg-protoporphyrin IX, Protochlorophyllide and finally chlorophyll synthesis. These results provided novel insights into the molecular mechanisms underlying virescent mutation in cotton.
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Fitomejoramiento , Hojas de la Planta , Clorofila , Clorofila A , Mapeo Cromosómico , Mutación , FenotipoRESUMEN
To date, the overall response rate to checkpoint blockade remains unsatisfactory, partially due to the limited understanding of the tumor immune microenvironment. The retinoic acid-related orphan receptor γt (RORγt) is the key transcription factor of T helper cell 17 (Th17) cells and plays an essential role in tumor immunity. In this study, we used JG-1, a potent and selective small-molecule RORγt agonist to evaluate the therapeutic potential and mechanism of action of targeting RORγt in tumor immunity. JG-1 promotes Th17 cells differentiation and inhibition of regulatory T (Treg) cells differentiation. JG-1 demonstrates robust tumor growth inhibition in multiple syngeneic models and shows a synergic effect with the Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) antibody. In tumors, JG-1 not only promotes Th17 cells differentiation and increases C-C Motif Chemokine Receptor 6 (CCR6)- Chemokine (C-C motif) ligand 20 (CCL20) expression, but also inhibits both the expression of transforming growth factor-ß1 (TGF-ß1) and the differentiation and infiltration of Treg cells. In summary, JG-1 is a lead compound showing a potent activity in vitro and robust tumor growth inhibition in vivo with synergetic effects with anti-CTLA-4.
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Anticuerpos/uso terapéutico , Antineoplásicos/uso terapéutico , Antígeno CTLA-4/antagonistas & inhibidores , Neoplasias/tratamiento farmacológico , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/agonistas , Animales , Antineoplásicos/farmacología , Linfocitos B/efectos de los fármacos , Antígeno CTLA-4/inmunología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Femenino , Humanos , Ganglios Linfáticos/citología , Ratones Endogámicos C57BL , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/metabolismo , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Transducción de Señal/efectos de los fármacos , Bazo/citología , Linfocitos T/efectos de los fármacos , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
Immune checkpoint blockade therapy has become a first-line treatment in various cancers. But there are only a small percent of colorectal patients responding to PD-1/PD-L1 blockage immunotherapy. How to increase their treatment efficacy is an urgent and clinically unmet need. It is acknowledged that immunogenic cell death (ICD) induced by some specific chemotherapy can enhance antitumor immunity. Chemo-based combination therapy can yield improved outcomes by activating the immune system to eliminate the tumor, compared with monotherapy. Here, we develop a PD-L1-targeting immune liposome (P-Lipo) for co-delivering irinotecan (IRI) and JQ1, and this system can successfully elicit antitumor immunity in colorectal cancer through inducing ICD by IRI and interfering in the immunosuppressive PD-1/PD-L1 pathway by JQ1. P-Lipo increases intratumoral drug accumulation and promotes DC maturation, and thereby facilitates adaptive immune responses against tumor growth. The remodeling tumor immune microenvironment was reflected by the increased amount of CD8+ T cells and the release of IFN-γ, and the reduced CD4+Foxp3+ regulatory T cells (Tregs). Collectively, the P-Lipo codelivery system provides a chemo-immunotherapy strategy that can effectively remodel the tumor immune microenvironment and activate the host immune system and arrest tumor growth.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Azepinas/farmacología , Inhibidores de Puntos de Control Inmunológico/farmacología , Irinotecán/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Triazoles/farmacología , Animales , Antígeno B7-H1/metabolismo , Línea Celular Tumoral , Femenino , Ratones , Ratones Endogámicos BALB C , Receptor de Muerte Celular Programada 1 , Linfocitos T Reguladores/metabolismo , Microambiente Tumoral/efectos de los fármacosRESUMEN
A series of 6-substituted carbazole-based retinoic acid-related orphan receptor gamma-t (RORγt) modulators were discovered through 6-position modification guided by insights from the crystallographic profiles of the "short" inverse agonist 6. With the increase in the size of the 6-position substituents, the "short" inverse agonist 6 first reversed its function to agonists and then to "long" inverse agonists. The cocrystal structures of RORγt complexed with the representative "short" inverse agonist 6 (PDB: 6LOB), the agonist 7d (PDB: 6LOA) and the "long" inverse agonist 7h (PDB: 6LO9) were revealed by X-ray analysis. However, minor differences were found in the binding modes of "short" inverse agonist 6 and "long" inverse agonist 7h. To further reveal the molecular mechanisms of different RORγt inverse agonists, we performed molecular dynamics simulations and found that "short" or "long" inverse agonists led to different behaviors of helixes H11, H11', and H12 of RORγt. The "short" inverse agonist 6 destabilizes H11' and dislocates H12, while the "long" inverse agonist 7h separates H11 and unwinds H12. The results indicate that the two types of inverse agonists may behave differently in downstream signaling, which may help identify novel inverse agonists with different regulatory mechanisms.
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Carbazoles/farmacología , Cristalografía , Agonismo Inverso de Drogas , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/agonistas , Receptores de Ácido Retinoico/agonistas , Carbazoles/síntesis química , Simulación de Dinámica Molecular , Estructura Molecular , Relación Estructura-Actividad , Receptor de Ácido Retinoico gammaRESUMEN
In order to observe the anti-tumor effect of cinobufotalin on H22 liver cancer mice and to explore its regulatory mechanism, 50 Kunming mice were subcutaneously inoculated with H22 intraperitoneal passage cells under the armpit to establish H22 hepatocellular carcinoma model. They were then randomly divided into model group, cinobufotalin low dose group, cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group, which received 0.01% ethanol solution, 1 mg·kg~(-1) cinobufotalin, 5 mg·kg~(-1) cinobufotalin, 5 mg·kg~(-1) cisplatin, 5 mg·kg~(-1)cisplatin + 5 mg·kg~(-1) cinobufotalin respectively for 10 days. The general condition of mice during the intervention was observed, and the inhibition rate, tumor mass, thymus index, histopathological changes of the tumors, apoptotic rate of the tumors, the expressions of phosphatidylinositol 3-kinase(PI3 K), protein kinase B(Akt), apoptosis related gene(Fas), Fas ligand(FasL) mRNA and protein phosphorylated Akt(pAkt) protein in the tumors of each group were compared. The results showed that during the modeling period, the mice showed a decline in food intake, dark fur, poor mental status, and gradually worsened over time. The mental status of mice in each intervention group was improved gradually, especially in the cisplatin+cinobufotalin group. As compared with the model group, the tumor mass of each intervention group was lower(P<0.05). As compared with the cinobufotalin low dose group, the tumor mass was lower and inhibition rate was higher in the cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group(P<0.05). As compared with the cinobufotalin high dose group and the cisplatin group, the tumor mass was lower and the inhibition rate was higher in cisplatin+cinobufotalin group(P<0.05). As compared with the model group, the thymus index was higher in cinobufotalin high dose group and cisplatin + cinobufotalin group, while was lower in cisplatin group(P<0.05). As compared with the cinobufotalin low dose group, the thymus index was higher in the cinobufotalin high dose group and lower in the cisplatin group(P<0.05). As compared with the cinobufotalin high dose group, the thymus index was lower in cisplatin group(P<0.05). As compared with cisplatin group, the thymus index was higher in cisplatin+cinobufotalin group(P<0.05). Pathological staining showed that a large number of heterogeneous cells and mitotic phenomena were observed in the model group. Cell fragments and neutrophils were observed in the tumor tissues of the intervention groups, showing diffuse necrosis, and the diffuse necrosis was more obvious in the cisplatin+cinobufotalin group. As compared with the model group, the apoptotic rate of the tumors and the relative expressions of Fas mRNA and protein were higher in the intervention groups, while the relative expressions of PI3 K, FasL mRNA and protein and the relative expression of pAkt protein were lower in the intervention groups(P<0.05). As compared with the cinobufotalin low dose group, the apoptotic rate of the tumors and relative expression of Fas and protein were higher in the cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group, while the relative expressions of PI3 K, FasL mRNA and protein and pAkt protein were lower(P<0.05). As compared with the cinobufotalin high dose group and the cisplatin group, apoptotic rate of the tumors and the relative expression of Fas mRNA and protein were higher in the cisplatin+cinobufotalin group, while the relative expressions of PI3 K, FasL mRNA and protein and pAkt protein were lower in the cisplatin+cinobufotalin group(P<0.05). In summary, cinobufotalin has significant anti-tumor effect on H22 liver cancer mice, and can enhance the immune function of mice and synergistically enhance the effect of chemotherapy. Its mechanism may be associated with regulating PI3 K/Akt/Fas/FasL signaling pathway related genes and protein expression.
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Bufanólidos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Apoptosis , Cisplatino , Proteína Ligando Fas , RatonesRESUMEN
A novel HPLC-UV method was developed for the determination of four tetracyclines based on magnetic solid phase extraction in tandem with liquid-liquid extraction. The water-soluble amino functionalized magnetite nanoparticle (MNP-NH2) was used as an adsorbent for extraction/preconcentration of tetracycline, oxytetracycline, chlortetracycline, and doxycycline from bovine milk samples. Fourier transform infrared spectrometer, transmission electron microscope, X-ray diffraction, and elemental analyze techniques were used to characterize the material. Some key parameters which influence liquid-liquid extraction and magnetic dispersive solid-phase extraction procedure, including volume of extraction solvent, the amount of adsorbent, the pH, extraction and desorption time, the composition of the eluent, and elution frequency were investigated. The proposed method exhibited a linear range of 50.0-2500.0 µg L-1 (r2 = 0.9941) with and good reproducibility (RSD < 2.2%, n = 3). The limit of detection and quantification were 40.0 and 50.0 µg L-1. This method was verified using milk sample spiked with four tetracyclines (100.0-200.0 µg L-1), and accuracies of 87.8-107.5%, which confirmed its applicability in real-sample analysis. The proposed method also shows potential application prospects for other water-soluble adsorbents.
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Antibiotic compounds in natural waters are normally present at low concentrations. In this paper, an easy and highly sensitive screening method using graphene oxide-functionalized magnetic composites (GO@NH2@Fe3O4) combined with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) was established for twelve quinolone antibiotics. GO@NH2@Fe3O4 composites were utilized as adsorbents for magnetic solid-phase extraction. This method combines the advantages of magnetic solid-phase extraction and MALDI-TOF MS, which allows for fast detection of quinolones at low concentrations. To improve absorption efficiency, the following parameters were individually optimized: sample acidity, extraction time, amount of adsorbent used, eluent used, and desorption time. Under the optimum conditions, the established method gave a low detection limit of 0.010 mg/L and allowed the high-throughput screening of twelve quinolone antibiotics (enoxacin, norfloxacin, ciprofloxacin, pefloxacin, fleroxacin, gatifloxacin, enrofloxacin, levofloxacin, sparfloxacin, danofloxacin, difloxacin, and lomefloxacin). The proposed method, having an easily prepared sorbent with a high affinity for quinolones and a convenient, high-throughput detection step, has been shown to have merit for the detection of antibiotics in water samples. Graphical abstract Schematic illustration of the (A) preparation of GO@NH2@Fe3O4 and (B) operating procedure for the MSPE and MALDI-TOF MS detection of QNs.
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Antibacterianos/análisis , Grafito/química , Quinolonas/análisis , Extracción en Fase Sólida/métodos , Contaminantes Químicos del Agua/análisis , Antibacterianos/aislamiento & purificación , Límite de Detección , Imanes/química , Modelos Moleculares , Quinolonas/aislamiento & purificación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Agua/análisis , Contaminantes Químicos del Agua/aislamiento & purificaciónRESUMEN
Triptolide is a major active ingredient isolated from the traditional Chinese herb Tripterygium wilfordii Hook F. However, its use in clinical practice is limited due to its severe hepatotoxicity. Autophagy, a highly conserved intracellular process, is essential for maintaining cytoplasmic homeostasis. Considering that abnormalities in autophagy are closely associated with drug-mediated hepatotoxicity, we applied human normal liver HL7702 cells to elucidate the roles of autophagy in triptolide-induced hepatotoxicity. Our study revealed that triptolide was cytotoxic to HL7702 cells. It markedly increased autophagosome formation and expression of autophagy-related proteins, namely Beclin1 and microtubule-associated protein 1 light chain 3II, and induced oxidative stress. These proautophagic effects were counteracted by pretreatment with N-acetylcysteine, a reactive oxygen species scavenger. Moreover, the pharmacological suppression of autophagy further exacerbated triptolide-elicited decrease in cell viability, increase in lactate dehydrogenase leakage, and activation of apoptosis proteases (caspase 3 and caspase 9). Our findings suggest that triptolide-induced oxidative stress consequently enhances autophagic activity, and autophagy is a cytoprotective mechanism against triptolide-induced cytotoxicity in HL7702 cells.
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Autofagia/efectos de los fármacos , Diterpenos/toxicidad , Hepatocitos/efectos de los fármacos , Fenantrenos/toxicidad , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Línea Celular , Compuestos Epoxi/toxicidad , Glutatión/metabolismo , Hepatocitos/metabolismo , Hepatocitos/ultraestructura , Humanos , Malondialdehído/metabolismo , Microscopía Electrónica de Transmisión , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: During the last decade buckwheat was reported to have positive health effects. The present study investigated a high-polyphenol buckwheat protein (Fagopyrum esculentum Moench) prepared by enzyme-assisted processing, together with its physicochemical properties, in vitro digestibility, and antioxidant activity. RESULTS: Buckwheat protein prepared from the synergistic enzymatic action of α-amylase and amyloglucosidase (E-BWP) had much higher polyphenol content than buckwheat protein prepared by isoelectric precipitation (I-BWP) or salt extraction (S-BWP). Rutin degraded during the process, giving quercetin. The protein constituents and amino acid composition of E-BWP were very similar to those of native buckwheat and were able to meet the WHO/FAO requirements for both children and adults. During in vitro digestion, E-BWP showed anti-digestive behavior with a nitrogen release that was lower than that of I-BWP or S-BWP. The positive effect of the polyphenol content of E-BWP resulted in a higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) content and greater reducing activity. CONCLUSION: Buckwheat protein with high polyphenol content was successfully developed by enzyme-assisted processing. It had a well-balanced amino acid profile, antidigestive behavior, and high antioxidant activities. The results suggest that enzyme-assisted processing is promising in the production of polyphenol-enriched cereal protein, contributing higher functionality with good nutritional and antioxidant properties. © 2018 Society of Chemical Industry.
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Antioxidantes/química , Fagopyrum/química , Fagopyrum/metabolismo , Glucano 1,4-alfa-Glucosidasa/química , Proteínas de Plantas/química , Polifenoles/análisis , alfa-Amilasas/química , Antioxidantes/metabolismo , Biocatálisis , Digestión , Manipulación de Alimentos , Humanos , Proteínas de Plantas/metabolismo , Polifenoles/metabolismo , Semillas/química , Semillas/metabolismoRESUMEN
The human visual system efficiently extracts local elements from cluttered backgrounds and integrates these elements into meaningful contour perception. This process is a critical step before object recognition, in which contours often play an important role in defining the shapes and borders of the to-be-recognized objects. However, the neural mechanism of the contour integration is still under debate. The investigation of the neural mechanism underlying contour integration could deepen our understanding of perceptual grouping in the human visual system and advance the development of the algorithms for image grouping and segmentation in computer vision. Here, we review two theoretical frameworks that were proposed over the past decades. The first framework is based on hardwired horizontal connection in primary visual cortex, while the second one emphasizes the role of recurrent connections within intra- and inter-areas. At the end of review, we also raise the unsolved issues that need to be addressed in future studies.
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Percepción de Forma , Corteza Visual/fisiología , Percepción Visual , Humanos , Modelos Neurológicos , Reconocimiento Visual de ModelosRESUMEN
The complexation of corn protein hydrolyzate (CPH) with tannic acid (TA) was utilized to improve the foaming properties of CPH itself, and the air-water interfacial behavior of CPH-TA complex was also investigated. The results showed that the surface hydrophobicity of pure CPH was significantly decreased in bulk solution after the complexation with TA. Compared with pure CPH, the foams stabilized by CPH-TA complex showed higher interfacial thickness between the bubbles, which well explained the better long term stability of the corresponding foams. Therefore, the complexation maintained the good foaming capacity of CPH itself, but considerably increased its foam stability. Moreover, the air-water interfacial behavior study demonstrated that the complexation slightly decreased the interfacial activity of CPH itself, but considerably increased its interfacial viscoelasticity, suggesting more stable of the air-water interface stabilized by CPH-TA complex compared with that stabilized by CPH alone. These findings indicated that foaming properties of the surface active components were closely related with its air-water interfacial behavior. The study suggested that CPH-TA complex could be used as a stabilizer in constructing the peptides-based foams.
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The homomeric α7 nicotinic receptor (α7 nAChR) is widely expressed in the human brain that could be activated to suppress neuroinflammation, oxidative stress and neuropathic pain. Consequently, a number of α7 nAChR agonists have entered clinical trials as anti-Alzheimer's or anti-psychotic therapies. However, high-resolution crystal structure of the full-length α7 receptor is thus far unavailable. Since acetylcholine-binding protein (AChBP) from Lymnaea stagnalis is most closely related to the α-subunit of nAChRs, it has been used as a template for the N-terminal domain of α-subunit of nAChR to study the molecular recognition process of nAChR-ligand interactions, and to identify ligands with potential nAChR-like activities.Here we report the discovery and optimization of novel acetylcholine-binding protein ligands through screening, structure-activity relationships and structure-based design. We manually screened in-house CNS-biased compound library in vitro and identified compound 1, a piperidine derivative, as an initial hit with moderate binding affinity against AChBP (17.2% inhibition at 100 nmol/L). During the 1st round of optimization, with compound 2 (21.5% inhibition at 100 nmol/L) as the starting point, 13 piperidine derivatives with different aryl substitutions were synthesized and assayed in vitro. No apparent correlation was demonstrated between the binding affinities and the steric or electrostatic effects of aryl substitutions for most compounds, but compound 14 showed a higher affinity (Ki=105.6 nmol/L) than nicotine (Ki=777 nmol/L). During the 2nd round of optimization, we performed molecular modeling of the putative complex of compound 14 with AChBP, and compared it with the epibatidine-AChBP complex. The results suggested that a different piperidinyl substitution might confer a better fit for epibatidine as the reference compound. Thus, compound 15 was designed and identified as a highly affinitive acetylcholine-binding protein ligand. In this study, through two rounds of optimization, compound 15 (Ki=2.8 nmol/L) has been identified as a novel, piperidine-based acetylcholine-binding protein ligand with a high affinity.
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Proteínas Portadoras/química , Ligandos , Piperidinas/química , Piperidinas/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Proteínas Portadoras/metabolismo , Diseño de Fármacos , Modelos Moleculares , Simulación del Acoplamiento Molecular , Nicotina/farmacología , Piperidinas/síntesis química , Piridinas/farmacología , Ensayo de Unión Radioligante , Relación Estructura-ActividadRESUMEN
OBJECTIVE: To investigate whether full-movement neuromuscular electrical stimulation, which can generate full range of movement, reduces spasticity and/or improves motor function more effectively than control, sensory threshold-neuromuscular electrical stimulation, and motor threshold-neuromuscular electrical stimulation in sub-acute stroke patients. DESIGN: A randomized, single-blind, controlled study. SETTING: Physical therapy room and functional assessment room. PARTICIPANTS: A total of 72 adult patients with sub-acute post-stroke hemiplegia and plantar flexor spasticity. METHOD: Patients received 30-minute sessions of neuromuscular electrical stimulation on the motor points of the extensor hallucis and digitorum longus twice a day, five days per week for four weeks. MEASURES: Composite Spasticity Scale, Ankle Active Dorsiflexion Score, and walking time in the Timed Up and Go Test were assessed at pretreatment, posttreatment, and at two-week follow-up. RESULTS: After four weeks of treatment, when comparing interclass pretreatment and posttreatment, only the full-movement neuromuscular electrical stimulation group had a significant reduction in the Composite Spasticity Scale (mean % reduction = 19.91(4.96)%, F = 3.878, p < 0.05) and improvement in the Ankle Active Dorsiflexion Score (mean scores = 3.29(0.91), F = 3.140, p < 0.05). Furthermore, these improvements were maintained two weeks after the treatment ended. However, there were no significant differences in the walking time after four weeks of treatment among the four groups (F = 1.861, p > 0.05). CONCLUSIONS: Full-movement neuromuscular electrical stimulation with a stimulus intensity capable of generating full movement can significantly reduce plantar flexor spasticity and improve ankle active dorsiflexion, but cannot decrease walking time in the Timed Up and Go Test in sub-acute stroke patients.
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Articulación del Tobillo/fisiopatología , Terapia por Estimulación Eléctrica/métodos , Pie/fisiopatología , Hemiplejía/rehabilitación , Espasticidad Muscular/rehabilitación , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/complicaciones , Femenino , Hemiplejía/etiología , Humanos , Masculino , Persona de Mediana Edad , Espasticidad Muscular/etiología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
The aims of this work were to construct corn protein hydrolysate (CPH)-based curcumin nanoparticles (Cur NPs) and to compare the colloidal stability, bioaccessibility and antioxidant activity of the Cur NPs stabilized CPH and sodium caseinate (NaCas) respectively. The results indicated that Cur solubility could be considerably improved after the Cur NPs fabrication. The spectroscopy results demonstrated that the solubilization of Cur should be attributed to its complexation with CPH or NaCas. The Cur NPs exhibited good colloidal stability after 1 week's storage but showed smaller (40 nm) size in CPH than in NaCas (100 nm). After lyophilization, the Cur NPs powders showed good rehydration properties and chemical stability, and compared with NaCas, the size of Cur NPs stabilized by CPH was still smaller. Additionally, the Cur NPs exhibited higher chemical stability against the temperature compared with free Cur, and the CPH could protect Cur from degradation more efficiently. Comparing with NaCas, the Cur NPs stabilized by CPH exhibited better bioaccessibility and antioxidant activity. This study demonstrated that CPH may be better than NaCas in Cur NPs fabrication and it opens up the possibility of using hydrophobic protein hydrolysate to construct the NPs delivery system.
RESUMEN
In heterologous expression systems, KCNE2 has been demonstrated to interact with multiple α-subunits of voltage-dependent cation channels and modulate their functions. However, the physiological and pathological roles of KCNE2 in cardiomyocytes are poorly understood. The present study aimed to investigate the effects of bidirectional modulation of KCNE2 expression on action potential (AP) duration (APD) and voltage-dependent K(+) channels in cardiomyocytes. Adenoviral gene delivery and RNA interference were used to either increase or decrease KCNE2 expression in cultured neonatal and adult rat or neonatal mouse ventricular myocytes. Knockdown of KCNE2 prolonged APD in both neonatal and adult myocytes, whereas overexpression of KCNE2 shortened APD in neonatal but not adult myocytes. Consistent with the alterations in APD, KCNE2 knockdown decreased transient outward K(+) current (Ito) densities in neonatal and adult myocytes, whereas KCNE2 overexpression increased Ito densities in neonatal but not adult myocytes. Furthermore, KCNE2 knockdown accelerated the rates of Ito activation and inactivation, whereas KCNE2 overexpression slowed Ito gating kinetics in neonatal but not adult myocytes. Delayed rectifier K(+) current densities were remarkably affected by manipulation of KCNE2 expression in mouse but not rat cardiomyocytes. Simulation of the AP of a rat ventricular myocyte with a mathematical model showed that alterations in Ito densities and gating properties can result in similar APD alterations in KCNE2 overexpression and knockdown cells. In conclusion, endogenous KCNE2 in cardiomyocytes is important in maintaining cardiac electrical stability mainly by regulating Ito and APD. Perturbation of KCNE2 expression may predispose the heart to ventricular arrhythmia by prolonging APD.
Asunto(s)
Potenciales de Acción , Ventrículos Cardíacos/metabolismo , Miocitos Cardíacos/metabolismo , Canales de Potasio con Entrada de Voltaje/metabolismo , Potasio/metabolismo , Adenoviridae/genética , Factores de Edad , Animales , Animales Recién Nacidos , Células Cultivadas , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Vectores Genéticos , Ventrículos Cardíacos/citología , Activación del Canal Iónico , Cinética , Ratones Endogámicos C57BL , Canales de Potasio con Entrada de Voltaje/genética , Interferencia de ARN , Ratas Sprague-Dawley , TransfecciónRESUMEN
A new cationic triazole-based metal-organic framework encapsulating Keggin-type polyoxometalates, with the molecular formula [Co(BBPTZ)3][HPMo12O40]â 24 H2O [compoundâ 1; BBPTZ = 4,4'-bis(1,2,4-triazol-1-ylmethyl)biphenyl] is hydrothermally synthesized and characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, powder X-ray diffraction, and single-crystal X-ray diffraction. The structure of compoundâ 1 contains a non-interpenetrated 3D CdSO4 (cds)-type framework with two types of channels that are interconnected with each other; straight channels that are occupied by the Keggin-type POM anions, and wavelike channels that contain lattice water molecules. The catalytic activity of compoundâ 1 in the oxidative desulfurization reaction indicates that it is not only an effective and size-selective heterogeneous catalyst, but it also exhibits distinct structural stability in the catalytic reaction system.