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Skin wounds are repaired by a complex series of events and overlapping phases in which bacterial infection and insufficient angiogenesis at the wound site delay the healing process. Thus, functional wound dressings with enhanced antibacterial activity and angiogenic capacity have attracted attention. Herein, bacterial cellulose (BC)-based dressings were successfully fabricated by functionalization with a polydopamine (PDA) coating and copper sulfide nanoparticles (CuS NPs). Under 808 nm laser illumination, the BC/PDA/CuS composite membranes exhibited outstanding adjustable photothermal and photodynamic activities as well as controlled Cu2+ release, endowing the composite membranes with synergetic antibacterial activity. Specially, a bactericidal efficiency of 99.7 % and 88.0 % for Staphylococcus aureus and Escherichia coli was achieved after treatment with BC/PDA/CuS5 sample under NIR irradiation (0.8 W/cm2, 10 min), respectively. Moreover, the BC/PDA/CuS5 composite membrane could enhance the angiogenesis due to the released Cu2+. In vivo experiments revealed that the BC/PDA/CuS5 composite membrane dressing could accelerate the wound closure process of the full-thickness skin defects with S. aureus by synergistically reducing inflammation, enhancing collagen deposition, and promoting vascularization under NIR irradiation. Additionally, the BC/PDA/CuS5 composite membrane exhibited high biocompatibility and biosafety. This work offers a new strategy to prepare multifunctional BC-based dressing for clinical wound healing.
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Celulosa , Staphylococcus aureus , Celulosa/farmacología , Cobre/farmacología , Antibacterianos/farmacología , Vendajes , HidrogelesRESUMEN
Aeromonas salmonicida is an ancient fish pathogen. Lysozymes are important molecules in the innate immune system that fight bacterial infections. The expression characteristics of C-type lysozyme in crucian carp infected with A. salmonicida and its antibacterial effect against A. salmonicida had not been investigated. Thus, we used bioinformatics to analyze the gene and protein characteristics of C-type lysozymes in crucian carp. Changes in C-type lysozyme expression before and after crucian carp infection with A. salmonicida were detected, and the in vitro antibacterial effect of recombinant carp C-type lysozyme on A. salmonicida was validated. The results showed that the coding DNA sequence region of the lysozyme gene sequence was 438 bp long, encoding 145 amino acids and containing two conserved catalytic sites: Glu53 and Asp69. Phylogenetic analysis revealed that crucian carp C-type lysozymes clustered with Cyprinus carpio lysozyme C. After crucian carp were infected with A. salmonicida, the gene and protein expression of C-type lysozymes in the liver, spleen, kidney, and hindgut were significantly upregulated, with the liver showing the highest upregulation that was 15 times higher than that in the uninfected group. In addition, recombinant C-type lysozyme exhibited significant antibacterial activity against A. salmonicida, with an average inhibition zone radius of 0.92 cm when using 40 µg recombinant lysozyme. In conclusion, this study reveals the important role of C-type lysozymes in the innate immune response of crucian carp and provides a theoretical basis for preventing crucian carp infection with A. salmonicida.
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An asymmetric wound dressing acts as a skin-like structure serves as a protective barrier between a wound and its surroundings. It allows for the absorption of tissue fluids and the release of active substances at the wound site, thus speeding up the healing process. However, the production of such wound dressings requires the acquisition of specialized tools, expensive polymers, and solvents that contain harmful byproducts. In this study, an asymmetric bacterial cellulose (ABC) wound dressing using starch as a porogen has been developed. By incorporating silver-metal organic frameworks (Ag-MOF) and curcumin into the ABC membrane, the wound dressing gains antioxidant, reactive oxygen species (ROS) scavenging, and anti-bacterial activities. Compared to BC-based wound dressings, this dressing promotes efficient dissolution and controlled release of curcumin and silver ions. In a full-thickness skin defect model, wound dressing not only inhibits the growth of bacteria on infected wounds but also regulates the release of curcumin to reduce inflammation and promote the production of epithelium, blood vessels, and collagen. Consequently, this dressing provides superior wound treatment compared to BC-based dressing.
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Curcumina , Plata , Plata/química , Curcumina/farmacología , Curcumina/química , Antibacterianos/farmacología , Antibacterianos/química , Cicatrización de Heridas , Celulosa/química , Antiinflamatorios/farmacologíaRESUMEN
ß-Glucans affect the immune system and have antitumor activity; therefore, they are being investigated as immunomodulators and chemotherapeutic adjuvants. In this study, we investigated a specific ß-glucan, exopolysaccharide (EPS-1) derived from Aureobasidium pullulans (CGMCC 20363), to investigate its impact on the efficacy of rituximab against diffuse large B cell lymphoma (SU-DHL-8 cells) in vitro and in vivo. The results show that compared to rituximab alone, EPS-1 enhanced the inhibition of SU-DHL-8, had antitumor effects in vivo, and improved the response of the immune system of the host. RNA sequencing results reveal that EPS-1 had a chemotactic effect on T cells through the JAK-STAT signaling pathway and recruited immune cells into tumor tissues. EPS-1 also played an antitumor role through the mitochondrial and death receptor Fas-related apoptotic pathways. In summary, EPS-1 may be an effective adjuvant to treat diffuse large B cell lymphoma in combination with rituximab.
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Linfoma de Células B Grandes Difuso , beta-Glucanos , Adyuvantes Inmunológicos , Aureobasidium , Glucanos/farmacología , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Receptores de Muerte Celular , Rituximab/farmacología , beta-Glucanos/farmacologíaRESUMEN
The nanostructured antimicrobial agents, self-assembled by the antimicrobial peptides (AMPs), represent an intriguing platform for the treatment of pathogens. Although the structural characteristics significantly influence antimicrobial functionality, the role of chirality is usually ignored and still unclear. Herein, two homochiral AMPs (all L- or all D-amino acids), including C16-LV4LR4 (LL) and C16-DV4DR4 (DD), and a heterochiral AMP with alternating D-/L-amino acids, C16-DV4LR4 (DL), were self-assembled into left-handed, right-handed, and right-handed helical nanofibers, respectively. The valine configuration determined the supramolecular chirality of the nanofibers. However, the DL molecules exhibited a highly aggregated propensity to form more stable helical nanofibers with a lower degree of twist and a larger helical pitch. This characteristic resulted in the optimal antimicrobial activity of the DL nanofibers against both Gram-negative and Gram-positive bacteria. Furthermore, the membrane permeability assay confirmed the higher activity for damaging the cell membrane by the DL nanofibers. These results demonstrated the significance of molecular chirality in directing the self-assembly of the amphiphilic peptides, eventually affecting their antimicrobial activity. This study opens up the possibility to fabricate promising nanostructured antimicrobial materials by controlling the chirality and structure of the materials.
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Nanofibras , Nanoestructuras , Aminoácidos/química , Antibacterianos/química , Antibacterianos/farmacología , Nanofibras/química , Péptidos/químicaRESUMEN
In real life, people's life gradually tends to be simple, so the convenience of online shopping makes more and more research begin to explore the convenience optimization of shopping, in which the fitting system is the research product. However, due to the immaturity of the virtual fitting system, there are a lot of problems, such as the expression of clothing color is not clear or deviation. In view of this, this paper proposes a 3D clothing color display model based on deep learning to support human modeling-driven. Firstly, the macro-micro adversarial network (MMAN) based on deep learning is used to analyze the original image, and then, the results are preprocessed. Finally, the 3D model with the original image color is constructed by using UV mapping. The experimental results show that the accuracy of the MMAN algorithm reaches 0.972, the established three-dimensional model is emotional enough, the expression of the clothing color is clear, and the difference between the color difference and the original image is within 0.01, and the subjective evaluation of volunteers is more than 90 points. The above results show that it is effective to use deep learning to build a 3D model with the original picture clothing color, which has great guiding significance for the research of character model modeling and simulation.
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Aprendizaje Profundo , Algoritmos , Vestuario , Cuerpo Humano , Humanos , Interfaz Usuario-ComputadorRESUMEN
Hydrogels with pH sensitivity and stable mechanical and antibacterial properties have many desirable qualities and broad applications. A hydrogel based on bacterial cellulose and chitosan, impregnated with silver sulfadiazine (<1% w/w), was prepared using glutaraldehyde as the crosslinking agent. The presence of SSd was confirmed by Fourier transform infrared spectroscopy. Micropore size, swelling ratio, pH- sensitivity, and gram positive and negative antibacterial properties were studied by disk diffusion and colony forming unit. X-ray diffraction confirmed the presence of amorphous and crystalline regions in the hydrogel matrix following addition of SSd. The elemental composition, morphology, and mechanical properties of the hydrogels were characterized. Incorporation of SSd into bacterial cellulose-chitosan hydrogels significantly improved their mechanical and antibacterial properties. The antibacterial activity against E. coli and S. aureus was evaluated and SSd-BC/Ch hydrogels are more toxic to S. aureus than to E. coli. We use FESEM to observe bacterial morphology before and after exposure to SSd-BC/Ch hydrogels. The BacLight LIVE/DEAD membrane permeability kit is used to evaluate the membrane permeability of bacteria. These antibacterial hydrogels have many promising applications in food packaging, tissue engineering, drug delivery, clinical, biotechnological, and biomedical fields.
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Antibacterianos/farmacología , Celulosa/química , Quitosano/química , Hidrogeles/química , Sulfadiazina de Plata/farmacología , Bacterias/efectos de los fármacos , Bacterias/ultraestructura , Permeabilidad de la Membrana Celular/efectos de los fármacos , Celulosa/ultraestructura , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Reología , Espectrometría por Rayos X , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
BACKGROUND AND AIMS: Coronary in-stent restenosis (ISR) is an important complication of percutaneous coronary intervention (PCI). However, the relationship between lipoprotein associated phospholipase A2 (Lp-PLA2) level and ISR after PCI is rarely reported. This study aims to explore the relationship between Lp-PLA2 and the occurrence of ISR at post-PCI and its predictive value for ISR. METHODS AND RESULTS: Plasma Lp-PLA2 mass were measured in 847 patients planting 1262 stents and evaluated along with known risk indicators. One-year angiographic follow-up showed that baseline elevated Lp-PLA2 mass was strongly associated with early restenosis (95% CI = 1.062-3.050, P < 0.05). Beyond the first year, the occurrence of late restenosis (95% CI = 1.043-3.214, P < 0.05) was significantly larger in the elevated Lp-PLA2 group. Kaplan-Meier analysis after three-year clinical follow up suggested that Lp-PLA2 mass did add the positive effect on the occurrence of major adverse cardiovascular events (MACEs). CONCLUSION: In conclusion, increased baseline plasma Lp-PLA2 predicts increased risks of re-stenosis and MACEs, which may be a novel biomarker for predicting ISR and MACEs.
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Reestenosis Coronaria , Intervención Coronaria Percutánea , 1-Alquil-2-acetilglicerofosfocolina Esterasa , Constricción Patológica , Angiografía Coronaria , Reestenosis Coronaria/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Intervención Coronaria Percutánea/efectos adversos , Factores de Riesgo , Stents/efectos adversosRESUMEN
PURPOSE: Although there are many different methods of treating type 2 diabetes (T2D), it is still difficult to draw coincident conclusions concerning the efficacy and safety of different classes of new drugs, and the recommendation level of them has still kept uncertain as second anti-diabetic agents. Therefore, the aim of this study was to summarize evidence on the efficacy and safety of DPP-4is, GLP-1RAs and SGLT-2is as monotherapy or add-on to metformin (Met) for treatment of T2D. MATERIALS AND METHODS: We searched PubMed, Embase, Cochrane library and ClinicalTrials.gov for relevant articles in keeping with established methods using terms associated with anti-diabetic agents up to February, 2020, with no start date restriction. Weighted mean difference and risk ratios with 95% confidence intervals were calculated within traditional and network meta-analysis. Primary outcomes were the mean change in hemoglobin A1c (HbA1c), fasting plasma glucose (FPG) change and the frequency of hypoglycemic events from baseline after 12 weeks of treatment. RESULTS: In total, 64 eligible studies comprising 37,780 patients and 7 treatment strategies were included. The results of primary outcomes showed that GLP-1RAs were significantly more effective than DPP-4is or SGLT-2is in reducing HbA1c when add-on to Met. For FPG, both GLP-1RAs and SGLT-2is significantly reduced FPG compared with DPP-4is whether add-on to Met or not. For hypoglycemia, monotherapy has a lower risk than combination therapy except for SGLT-2is. Ranking probability analysis indicated that GLP-1RAs and SGLT-2is, respectively, reduced HbA1c and FPG most when add-on to Met. Meanwhile, GLP-1RAs took the lowest risk to induce the hypoglycemia, whereas GLP-1RAs plus Met the highest. CONCLUSIONS: Both GLP-1RAs and SGLT-2is have their own advantages in efficacy and safety. Monotherapy is beneficial for reducing the risk of hypoglycemia. The recommendation should be a patient-centered approach when selecting treatment choices.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Incretinas/uso terapéutico , Metformina/administración & dosificación , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Ensayos Clínicos como Asunto/estadística & datos numéricos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Quimioterapia Combinada , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemiantes/uso terapéutico , Metformina/efectos adversos , Metaanálisis en Red , Inhibidores del Cotransportador de Sodio-Glucosa 2/administración & dosificación , Resultado del TratamientoRESUMEN
Bacterial cellulose (BC) is a substrate material with high purity and robust mechanical strength, but due to its small pore size and relatively expensive price, it is restricted as an oil-/water separation membrane. In this study, cheaper plant cellulose needle-leaf bleached kraft pulp (NBKP) was added to BC to increase the pore size of the composite membrane, and a superhydrophobic/superoleophilic membrane was prepared for oil-/water separation. The modified membrane surface displayed a petal-like micro-structure and a water contact angle (WCA) of 162.3°, while the oil contact angle was decreased to 0°. What's more, the membrane exhibited excellent oil-/water separation under gravity, recyclability, and a separation efficiency (>95 %), and it was both pH and salt resistant. The membrane also remained durably hydrophobic after 10 separation cycles. And the separation methodology is expected to be highly energy-efficient.
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Celulosa/química , Gluconacetobacter xylinus/metabolismo , Gravitación , Tecnología Química Verde/métodos , Interacciones Hidrofóbicas e Hidrofílicas , Membranas Artificiales , Aceites/química , Polisacáridos Bacterianos/química , Agua/química , Concentración de Iones de Hidrógeno , Lignina/química , Hojas de la Planta/química , Polisacáridos/química , Porosidad , Resistencia a la TracciónRESUMEN
Bacterial infections are currently a major concern to human health. Amino acid-based supramolecular polymer hydrogels, which boast intrinsic antibacterial activity, are an important solution due to their good biocompatibility, cost effectiveness, and tunable structural properties. Herein, we reported three types of transparent supramolecular hydrogel with intrinsic antibacterial activity from self-assembly of commercially available Fmoc-tryptophan (Fmoc-W), Fmoc-methionine (Fmoc-M), and Fmoc-tyrosine (Fmoc-Y). The resulting hydrogels selectively inhibited the growth of Gram-positive bacteria. Moreover, the order of antibacterial activity was Fmoc-W hydrogel > Fmoc-M hydrogel > Fmoc-Y hydrogel. The critical aggregation concentration (CAC) values were found at concentrations of approximately 0.0293, 0.1172, and 0.4688 mM for Fmoc-W, Fmoc-M, and Fmoc-Y, respectively. Transmission electron microscope (TEM) images revealed rigid and aligned nanofibers for Fmoc-W hydrogel, while flexible nanofibers for Fmoc-M hydrogel and Fmoc-Y hydrogel. The results indicated that stronger aggregation capability of the gelator and the synergistic nanostructural morphology with more rigid and aligned nanofibers can lead to higher antibacterial activity of its corresponding hydrogel. In addition, the molecular arrangements of Fmoc-amino acids in the hydrogels may also contribute to their antibacterial activity. These results can guide the rational design, fabrication, and future application of other self-assembled amino acid-based hydrogels with excellent antibacterial activity.
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Aminoácidos/farmacología , Antibacterianos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Hidrogeles/farmacología , Aminoácidos/química , Antibacterianos/química , Hidrogeles/química , Sustancias Macromoleculares/química , Sustancias Macromoleculares/farmacología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Surface oxidation of bacterial cellulose (BC) was done with the TEMPO-mediated oxidation mechanism system. After that, TEMPO-oxidized bacterial cellulose (TOBC) was impregnated with silver sulfadiazine (AgSD) to prepare nanocomposite membranes. Fourier transform infrared spectroscopy (FTIR) was carried out to determine the existence of aldehyde groups on BC nanofibers and X-ray diffraction (XRD) demonstrated the degree of crystallinity. FESEM analysis revealed the impregnation of AgSD nanoparticles at TOBC nanocomposites with the average diameter size ranging from 11 nm to 17.5 nm. The sample OBCS3 showed higher antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli by the disc diffusion method. The results showed AgSD content, dependent antibacterial activity against all tested bacteria, and degree of crystallinity increases with TOBC and AgSD. The main advantage of the applications of TEMPO-mediated oxidation to BC nanofibers is that the crystallinity of BC nanofibers is unchanged and increased after the oxidation. Also enhanced the reactivity of BC as it is one of the most promising method for cellulose fabrication and functionalization. We believe that the novel composite membrane could be a potential candidate for biomedical applications like wound dressing, BC scaffold, and tissue engineering.
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Physcion (1,8-dihydroxy-3-methoxy-6-methyl-9,10-anthracenedione) is a bioactive component found in Polygoni Multiflori Radix (PMR), which has been widely used as traditional Chinese medicine. Unfortunately, studies showed hepatotoxicity of PMR during its clinical use. The mechanisms of its toxic action remain unknown. The major objectives of this study were to characterize oxidative metabolites of physcion in vitro and in vivo and to determine the electrophilicity of the parent compound and its oxidative metabolites. Five oxidative metabolites (M1-M5) were detected in rat liver microsomal incubations after exposure to physcion, and the formation of the metabolites was NADPH dependent. M1-M4 were monohydroxylation metabolites, and M5 was O-demethylation metabolite. A total of three N-acetylcysteine (NAC) conjugates (M6-M8) were observed in rat liver microsomes fortified with NAC as a trapping agent. M6 was derived from M4 conjugated with a molecule of NAC; M7 and M8 originated from parent compound physcion adducted with a molecule of NAC, respectively. M1-M8 were also observed in urine of rats given physcion. HLM incubations produced four oxidative metabolites and two NAC conjugates. The structures of M3, M7, and M8 were characterized by LC-Q-TOF MS and NMR. Recombinant P450 enzyme incubations demonstrated that CYPs2C19, 1A2, 2B6, and 3A4 were mainly involved in hydroxylation of physcion. The metabolism study assisted us to better understand the mechanisms of physcion-induced hepatotoxicity.
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Emodina/análogos & derivados , Animales , Sistema Enzimático del Citocromo P-450/química , Sistema Enzimático del Citocromo P-450/metabolismo , Emodina/síntesis química , Emodina/química , Emodina/metabolismo , Humanos , Hidroxilación , Masculino , Estructura Molecular , Oxidación-Reducción , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismoRESUMEN
PURPOSE: This study aimed to compare the difference in mechanical behavior between two types of female-part clips of the Stress-Free Implant Bar (SFI-Bar) system during simulation of insertion-removal cycles. MATERIALS AND METHODS: A total of 10 samples simulating SFI-Bar-attachment-retained implant overdentures were fabricated and randomly divided into two groups (n = 5). One group used E-clips (Elitor alloy) as the female part of the SFI-Bar, and the other used T-clips (all titanium grade IV with red nylon inserts). A total of 14,000 insertion-removal cycles were carried out on each sample. Retentive forces from each cycle were recorded for analysis. RESULTS: Significant differences were found between the two groups (P < .05). CONCLUSION: The retentive force of E-clips increased as the number of dislodging cycles increased, suggesting that some adjustment may be needed to lower this part's retentive force. T-clips with changeable nylon inserts were deformed after about 4,200 insertion-removal cycles, which interfered with insertion. This indicated that T-clips may need replacement after 2 to 3 years of clinical use.
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Prótesis Dental de Soporte Implantado/instrumentación , Retención de Dentadura/instrumentación , Prótesis de Recubrimiento , Aleaciones Dentales/química , Materiales Dentales/química , Diseño de Dentadura , Humanos , Ensayo de Materiales , Nylons/química , Distribución Aleatoria , Estrés Mecánico , Factores de Tiempo , Titanio/químicaRESUMEN
OBJECTIVES: It is known that the expression, activity and alternative splicing of Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) are dysregulated in the cardiac remodeling process. Recently, we found a further signaling pathway, by which dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) regulates the alternative splicing of CaMKIIδ via the alternative splicing factor (ASF), i.e., Dyrk1A-ASF-CaMKIIδ. In this study, we aimed to investigate whether Dyrk1A-ASF-CaMKIIδ signaling was involved in valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats. METHODS: Rats were subjected to two kidney-one clip (2K1C) surgery and then treated with valsartan (30 mg/kg/day) for 8 weeks. Hypertrophic parameter analysis was then performed. Western blot analysis was used to determine the protein expression of Dyrk1A and ASF and RT-PCR was used to analyze the alternative splicing of CaMKIIδ in the left ventricular (LV) sample. RESULTS: Valsartan attenuated cardiac hypertrophy in 2K1C rats but without impairment of cardiac systolic function. Increased protein expression of Dyrk1A and decreased protein expression of ASF were observed in the LV sample of 2K1C rats. Treatment of 2K1C rats with valsartan reversed the changes in Dyrk1A and ASF expression in the LV sample. Valsartan adjusted the 2K1C-induced imbalance in alternative splicing of CaMKIIδ by upregulating the mRNA expression of CaMKIIδC and downregulating the mRNA expression of CaMKIIδA and CaMKIIδB. CONCLUSIONS: Valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats was mediated, at least partly, by Dyrk1A-ASF-CaMKIIδ signaling.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Cardiomegalia/tratamiento farmacológico , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Valsartán/farmacología , Empalme Alternativo , Análisis de Varianza , Animales , Western Blotting , Ecocardiografía , Hipertensión , Masculino , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Quinasas DyrKRESUMEN
In vitro experiments have shown that the upregulation of small-conductance Ca(2+)-activated K(+) (SK) channels in ventricular epicardial myocytes is responsible for spontaneous ventricular fibrillation (VF) in failing ventricles. However, the role of SK channels in regulating VF has not yet been described in in vivo acute myocardial infarction (AMI) animals. The present study determined the role of SK channels in regulating spontaneous sustained ventricular tachycardia (SVT) and VF, the inducibility of ventricular tachyarrhythmias, and the effect of inhibition of SK channels on spontaneous SVT/VF and electrical ventricular instability in AMI rats. AMI was induced by ligation of the left anterior descending coronary artery in anesthetized rats. Spontaneous SVT/VF was analyzed, and programmed electrical stimulation was performed to evaluate the inducibility of ventricular tachyarrhythmias, ventricular effective refractory period (VERP), and VF threshold (VFT). In AMI, the duration and episodes of spontaneous SVT/VF were increased, and the inducibility of ventricular tachyarrhythmias was elevated. Pretreatment in the AMI group with the SK channel blocker apamin or UCL-1684 significantly reduced SVT/VF and inducibility of ventricular tachyarrhythmias (P < 0.05). Various doses of apamin (7.5, 22.5, 37.5, and 75.0 µg/kg iv) inhibited SVT/VF and the inducibility of ventricular tachyarrhythmias in a dose-dependent manner. Notably, no effects were observed in sham-operated controls. Additionally, VERP was shortened in AMI animals. Pretreatment in AMI animals with the SK channel blocker significantly prolonged VERP (P < 0.05). No effects were observed in sham-operated controls. Furthermore, VFT was reduced in AMI animals, and block of SK channels increased VFT in AMI animals, but, again, this was without effect in sham-operated controls. Finally, the monophasic action potential duration at 90% repolarization (MAPD(90)) was examined in the myocardial infarcted (MI) and nonmyocardial infarcted areas (NMI) of the left ventricular epicardium. Electrophysiology recordings showed that MAPD(90) in the MI area was shortened in AMI animals, and pretreatment with SK channel blocker apamin or UCL-1684 significantly prolonged MAPD(90) (P < 0.05) in the MI area but was without effect in the NMI area or in sham-operated controls. We conclude that the activation of SK channels may underlie the mechanisms of spontaneous SVT/VF and susceptibility to ventricular tachyarrhythmias in AMI. Inhibition of SK channels normalized the shortening of MAPD(90) in the MI area, which may contribute to the inhibitory effect on spontaneous SVT/VF and inducibility of ventricular tachyarrhythmias in AMI.
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Infarto del Miocardio/complicaciones , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/metabolismo , Taquicardia Ventricular/etiología , Fibrilación Ventricular/etiología , Potenciales de Acción , Alcanos/farmacología , Animales , Antiarrítmicos/farmacología , Apamina/farmacología , Estimulación Cardíaca Artificial , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Electrocardiografía , Frecuencia Cardíaca , Masculino , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Infarto del Miocardio/fisiopatología , Bloqueadores de los Canales de Potasio/farmacología , Compuestos de Quinolinio/farmacología , Ratas , Ratas Sprague-Dawley , Periodo Refractario Electrofisiológico , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/efectos de los fármacos , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/genética , Taquicardia Ventricular/genética , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/prevención & control , Factores de Tiempo , Fibrilación Ventricular/genética , Fibrilación Ventricular/metabolismo , Fibrilación Ventricular/fisiopatología , Fibrilación Ventricular/prevención & controlRESUMEN
OBJECTIVE: To determine the protein expression of Calpain I, mRNA and protein expressions and activity of calcineurin, and the alternative splicing of Ca/calmodulin-dependent protein kinase II (CaMKII) δ in the hypertrophic heart, and to investigate the effect of angiotensin II type 1 receptor blocker valsartan (Val) on cardiac hypertrophy and the level of Calpain I, calcineurin and CaMKIIδ in renovascular hypertensive rats model. METHODS: Rats were randomly divided into sham-operated control (n=8), hypertension (n=8) and hypertension plus Val (n=8, 30 mg×kg(-1)×(-1)). The renovascular hypertension was induced by two kidney-one clip methods in rats. The ratio of left ventricular weight to body weight was measured, the mRNA expression of calcineurin and alternative splicing of CaMKIIδ were determined by RT-PCR, the protein expression of Calpain I and calcineurin were measured by Western blot and the activity of calcineurin activity was assayed by a specialized kit. RESULTS: Eight weeks after procedure, hypertension rats developed significantly cardiac hypertrophy, and the protein expression of Calpain I, mRNA and protein expression and the activity of calcineurin were significantly increased compared sham-operated control rats (all P<0.01), the mRNA expression of CaMKIIδA and B increased, CaMKIIδC mRNA decreased (P<0.01). Treatment with valsartan effectively attenuated cardiac hypertrophy and reversed hypertension induced changes on myocardial Calpain I, calcineurin and CaMKIIδ. CONCLUSION: Valsartan attenuates cardiac hypertrophy in renovascular hypertensive rats, possibly through inhibiting Calpain I, calcineurin and CaMKIIδ signaling pathways.
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Hipertensión Renovascular/metabolismo , Miocardio/metabolismo , Transducción de Señal , Tetrazoles/farmacología , Valina/análogos & derivados , Animales , Calcineurina/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Calpaína/metabolismo , Hipertensión Renovascular/tratamiento farmacológico , Hipertensión Renovascular/patología , Masculino , Miocardio/patología , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Tetrazoles/uso terapéutico , Valina/farmacología , Valina/uso terapéutico , ValsartánRESUMEN
Apolipoprotein E (ApoE) genotypes were studied in order to determine the prevalence and effect on lipid parameters in normal Han Chinese population. Fragments of ApoE gene forth exon containing codon 112 and 158 polymorphic locus were amplified by PCR, and then digested with Cfo I endonuclease. Genotypes and alleles frequencies of 168 healthy Han Chinese were calculated. The frequency of genotypes epsilon3/3, epsilon3/4, and epsilon2/3 was found to be 75.00, 10.70, and 11.90%, respectively, and 0.60, 1.20, and 0.60% for epsilon2/2, epsilon2/4, and epsilon4/4. The effects of ApoE genotypes and alleles on lipid parameters were analyzed. The effects of ApoE alleles on TC, LDL-C, ApoB was: along a decreasing gradient epsilon4 > epsilon3 > epsilon2. The effect of epsilon4 allele was to increase serum levels of TC, LDL-C and ApoB, and epsilon2 allele had an effect opposite to that of epsilon4 allele. Results obtained in this study indicate that ApoE polymorphism is an independent genetic factor on individual serum levels of lipids and apolipoproteins.
Asunto(s)
Apolipoproteínas E/genética , Lípidos/sangre , Polimorfismo Genético/genética , Apolipoproteínas/sangre , Apolipoproteínas B/sangre , China/epidemiología , Colesterol/sangre , LDL-Colesterol/sangre , Exones , Frecuencia de los Genes , Genotipo , HumanosRESUMEN
OBJECTIVE: To investigate the effect of atorvastatin on the expression of angiotensin converting enzyme 2 (ACE2) mRNA and its protein in hypertrophic myocardium in rats. METHODS: Suprarenal abdominal aortic coarctation was performed to create the pressure overload induced left ventricular hypertrophy model in rats. RESULTS: Rats were randomly divided into 5 groups: (1) normal control group (Group A); (2) normal control group treated with atorvastatin [(5 mg/(kg.dd), Group B]; (3) sham group (Group C); (4) atorvastatin given orally by gastric gavage for 4 weeks [5 mg/(kg.dd),Group D]; (5) vehicle group (Group E). Stained pathological section was observed under light microscope to measure cardiomyocyte diameter transversa and collagen volume fraction. ACE2 mRNA and its protein expression were detected by real-time RT-PCR and Western blot. Compared with Group A,B, and C, the left ventricular mass index, cardiomyocyte diameter transversa and collagen volume fraction in Group E increased statistically (P< 0.01), ACE2 mRNA and its protein expression also elevated remarkably (P< 0.01). Compared with Group E, the above mentioned indexes in Group D reduced significantly (P< 0.01). CONCLUSION: ACE2 mRNA and its protein expression increase significantly in hypertrophic myocardium in rats; atorvastatin can attenuate cardiac hypertrophy due to pressure overload in rats effectively, and part of this anti-hypertrophy effect may be attributed to decrease ACE2 mRNA and protein expression.