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Ferroptosis contributes to the pathogenesis of atrial fibrillation (AF), although the mechanisms are still largely uncovered. The current study was designed to explore the pharmacological effects of icariin against ethanol-induced atrial remodeling, if any, and the mechanisms involved with a focus on SIRT1 signaling. Excessive ethanol-treated animals were administered with Ferrostatin-1, Erastin or icariin to evaluate the potential effects of icariin or ferroptosis. Then, the underling mechanisms was further explored in the in vitro experiments using HL-1 atrial myocytes. Excessive ethanol administration caused significant atrial damage as evidenced by increased susceptibility to AF, altered atrial conduction pattern, atrial enlargement, and enhanced fibrotic markers. These detrimental effects were reversed by Ferrostatin-1 or icariin treatment, while Erastin co-administration markedly abolished the beneficial actions conferred by icariin. Mechanistically, ethanol-treated atria exhibited markedly up-regulated pro-ferroptotic protein (PTGS2, ACSL4, P53) and suppressed anti-ferroptotic molecules (GPX4, FTH1). Icariin treatment inhibited ethanol-induced atrial ferroptosis by reducing atrial mitochondrial damage, ROS accumulation and iron overload. Interestingly, the in vivo and in vitro data showed that icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to AF. Icariin protects against atrial damage by inhibiting ferroptosis via SIRT1 signaling. Its role as a prophylactic/therapeutic drug deserves further clinical study.
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Fibrilação Atrial , Remodelamento Atrial , Ferroptose , Animais , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/tratamento farmacológico , Apoptose , Sirtuína 1/genética , Proteína Supressora de Tumor p53 , Etanol/toxicidadeRESUMO
Sporisorium scitamineum and Ustilago maydis are two fungal pathogens causing severe sugarcane and maize diseases, respectively. Sexual mating of compatible sporidia is essential for these pathogens to form infections dikaryotic mycelia and cause smut diseases. We showed recently that in the presence of exogenous glucose, the Pseudomonas sp. strain ST4 could block the fungal mating and display a strong disease suppression potency on S. scitamineum. With the aim of conferring strain ST4 the ability to metabolize sucrose in plants for glucose production, we identified a strong native promoter pSsrA in strain ST4 and additional promoter elements to facilitate translation and peptide translocation for the construction of a fusion gene encoding sucrose metabolism. The cscA gene encoding sucrose hydrolase from Pseudomonas protegens Pf-5 was fused to the promoter pSsrA, a translational coupler bicistronic design and a Tat signal peptide, which was then cloned into mini-Tn7 transposon. This synthetic gene cassette was integrated into the chromosome of strain ST4, and the resultant engineered strain ST4E was able to hydrolyze sucrose with high efficiency and displayed elevated inhibitory activity on the mating and virulence of S. scitamineum and U. maydis. The findings from this study provide a valuable device and useful clues for the engineering of sucrose metabolism in non- or weak-sucrose-utilizing bacterial strains and present an improved biocontrol agent against plant smut pathogens. IMPORTANCE Sporisorium scitamineum and Ustilago maydis are typical dimorphic fungi causing severe sugarcane and maize smut diseases, respectively. Sexual mating of compatible sporidia is essential for these pathogens to form infections dikaryotic mycelia and cause smut diseases. We previously demonstrated that the biocontrol strain Pseudomonas sp. ST4 could block the fungal mating and displays a strong suppression potency on smut diseases, while it was unable to utilize the host-sourced sucrose for glucose production critical for antifungus efficiency. In this study, we constructed a high-expression gene cassette for minitransposon-mediated genome integration and sucrose hydrolysis in the bacterial periplasmic space. The resultant engineered strain ST4E was able to hydrolyze sucrose and inhibit the mating and hyphal growth of S. scitamineum and U. maydis. These findings provide a valuable tool and useful clues for the engineering of sucrose metabolism in non- or weak-sucrose-utilizing bacterial strains and present an improved biocontrol agent against plant smut pathogens.
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Basidiomycota , Saccharum , Ustilaginales , Ustilago , Ustilaginales/genética , Virulência , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia , Saccharum/genética , Saccharum/metabolismo , Saccharum/microbiologia , Ustilago/genéticaRESUMO
INTRODUCTION: Some studies have found that probiotics can improve cognitive impairment in Alzheimer's disease, although the specific molecular mechanism by which this occurs has not been reported. Our previous research found that probiotics inhibited bacteria-related Toll-like receptor 4- and retinoic-acid-inducible gene-I-mediated nuclear factor-κB signaling pathways to improve cognitive impairment. However, it is unclear whether probiotics have similar effects on other pattern recognition receptors that respond to bacteria. METHODS: Nine-month-old senescence-accelerated mouse prone 8 (SAMP8) mice received ProBiotic-4 (a mixture of Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus casei, and Bifidobacterium lactis) orally for 12 weeks. The effects on other bacteria-related pattern recognition receptors were then investigated. RESULTS: ProBiotic-4-treated SAMP8 mice showed improvement in memory deficits, synaptic and cerebral neuronal injuries, and microglial activation. ProBiotic-4 also markedly increased the expression of intestinal tight junction proteins (i.e., claudin-1, occludin, and zonula occluden-1), decreased the expression of interleukin-1ß at both the mRNA and protein levels, and reduced the expression of caspase-11, cleaved caspase-1, and α-kinase 1 (ALPK1) in the intestine and brain. CONCLUSIONS: These findings suggest that probiotics may have therapeutic potential for the treatment of inflammation in the gut-brain axis and for cognitive impairment. The mechanism of action of probiotics appears to be related to inhibition of the caspase-11/caspase-1 pathway and reduction of ALPK1 expression.
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The integrated in-plane growth of graphene nanoribbons (GNRs) and hexagonal boron nitride (h-BN) could provide a promising route to achieve integrated circuitry of atomic thickness. However, fabrication of edge-specific GNRs in the lattice of h-BN still remains a significant challenge. Here we developed a two-step growth method and successfully achieved sub-5-nm-wide zigzag and armchair GNRs embedded in h-BN. Further transport measurements reveal that the sub-7-nm-wide zigzag GNRs exhibit openings of the bandgap inversely proportional to their width, while narrow armchair GNRs exhibit some fluctuation in the bandgap-width relationship. An obvious conductance peak is observed in the transfer curves of 8- to 10-nm-wide zigzag GNRs, while it is absent in most armchair GNRs. Zigzag GNRs exhibit a small magnetic conductance, while armchair GNRs have much higher magnetic conductance values. This integrated lateral growth of edge-specific GNRs in h-BN provides a promising route to achieve intricate nanoscale circuits.
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Targeting mitochondrial quality control with melatonin has been found promising for attenuating diabetic cardiomyopathy (DCM), although the underlying mechanisms remain largely undefined. Activation of SIRT6 and melatonin membrane receptors exerts cardioprotective effects while little is known about their roles during DCM. Using high-fat diet-streptozotocin-induced diabetic rat model, we found that prolonged diabetes significantly decreased nocturnal circulatory melatonin and heart melatonin levels, reduced the expressions of cardiac melatonin membrane receptors, and decreased myocardial SIRT6 and AMPK-PGC-1α-AKT signaling. 16 weeks of melatonin treatment inhibited the progression of DCM and the following myocardial ischemia-reperfusion (MI/R) injury by reducing mitochondrial fission, enhancing mitochondrial biogenesis and mitophagy via re-activating SIRT6 and AMPK-PGC-1α-AKT signaling. After the induction of diabetes, adeno-associated virus carrying SIRT6-specific small hairpin RNA or luzindole was delivered to the animals. We showed that SIRT6 knockdown or antagonizing melatonin receptors abolished the protective effects of melatonin against mitochondrial dysfunction as evidenced by aggravated mitochondrial fission and reduced mitochondrial biogenesis and mitophagy. Additionally, SIRT6 shRNA or luzindole inhibited melatonin-induced AMPK-PGC-1α-AKT activation as well as its cardioprotective actions. Collectively, we demonstrated that long-term melatonin treatment attenuated the progression of DCM and reduced myocardial vulnerability to MI/R injury through preserving mitochondrial quality control. Melatonin membrane receptor-mediated SIRT6-AMPK-PGC-1α-AKT axis played a key role in this process. Targeting SIRT6 with melatonin treatment may be a promising strategy for attenuating DCM and reducing myocardial vulnerability to ischemia-reperfusion injury in diabetic patients.
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Cardiomiopatias Diabéticas/prevenção & controle , Melatonina/farmacologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Biogênese de Organelas , Sirtuínas/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/enzimologia , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/patologia , Proteína Forkhead Box O3/metabolismo , Masculino , Mitocôndrias Cardíacas/enzimologia , Mitocôndrias Cardíacas/ultraestrutura , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/ultraestrutura , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Sirtuínas/genética , Fatores de TempoRESUMO
Increased expression of the small nucleolar RNA host gene 6 (SNHG6) has been reported in different cancers, such as hepatocellular carcinoma, colorectal cancer, and lung cancer. The high expression level of SNHG6 is associated with tumor progression and poor prognosis. This paper provides an overview of recent studies on the oncogenic role and potential clinical utilities of SNHG6. Upregulated SNHG6 arrests tumor cell cycle and reduces apoptosis but promotes migration, invasion, metastasis, epithelial-mesenchymal transition (EMT), and chemoresistance in tumors. Mechanically, SNHG6 primarily sponges tumor suppressor microRNA (miRNA), functioning as a competing endogenous RNA. Once sponged, miRNA is unable to degrade, silence, or hamper the translation of its downstream, mostly oncogenic genes, ultimately driving cancer-related processes. Thus, SNHG6 might serve as a biomarker for cancer diagnosis and prognosis.
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Aberrant substance P/neurokinin-1 receptor (SP/NK-1R) system activation plays a critical role in various disorders, however, little is known about the expression and the detailed molecular mechanism of the SP and NK-1R in gallbladder cancer (GBC). In this study, we firstly analyzed the expression and clinical significance of them in patients with GBC. Then, cellular assays were performed to clarify their biological role in GBC cells. Moreover, we investigated the molecular mechanisms regulated by SP/NK-1R. Meanwhile, mice xenografted with human GBC cells were analyzed regarding the effects of SP/NK1R complex in vivo. Finally, patient samples were utilized to investigate the effect of SP/NK-1R. The results showed that SP and NK-1R were highly expressed in GBC. We found that SP strongly induced GBC cell proliferation, clone formation, migration and invasion, whereas antagonizing NK-1R resulted in the opposite effects. Moreover, SP significantly enhanced the expression of NF-κB p65 and the tumor-associated cytokines, while, Akt inhibitor could reverse these effects. Further studies indicated that decreasing activation of NF-κB or Akt diminished GBC cell proliferation and migration. In consistent with results, immunohistochemical staining showed high levels of Akt, NF-κB and cytokines in tumor tissues. Most importantly, the similar conclusion was obtained in xenograft mouse model. Our findings demonstrate that NK-1R, after binding with the endogenous agonist SP, could induce GBC cell migration and spreading via modulation of Akt/NF-κB pathway.
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Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias da Vesícula Biliar/metabolismo , Receptores da Neurocinina-1/metabolismo , Substância P/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias da Vesícula Biliar/genética , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno , Receptores da Neurocinina-1/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fator de Transcrição RelA/metabolismo , Transplante Heterólogo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
It has been demonstrated that the anti-oxidative and cardioprotective effects of melatonin are, at least in part, mediated by its membrane receptors. However, the direct downstream signaling remains unknown. We previously found that melatonin ameliorated myocardial ischemia-reperfusion (MI/R) injury in diabetic animals, although the underlying mechanisms are also incompletely understood. This study was designed to determine the role of melatonin membrane receptors in melatonin's cardioprotective actions against diabetic MI/R injury with a focus on cGMP and its downstream effector PKG. Streptozotocin-induced diabetic Sprague-Dawley rats and high-glucose medium-incubated H9c2 cardiomyoblasts were utilized to determine the effects of melatonin against MI/R injury. Melatonin treatment preserved cardiac function and reduced oxidative damage and apoptosis. Additionally, melatonin increased intracellular cGMP level, PKGIα expression, p-VASP/VASP ratio and further modulated myocardial Nrf-2-HO-1 and MAPK signaling. However, these effects were blunted by KT5823 (a selective inhibitor of PKG) or PKGIα siRNA except that intracellular cGMP level did not changed significantly. Additionally, our in vitro study showed that luzindole (a nonselective melatonin membrane receptor antagonist) or 4P-PDOT (a selective MT2 receptor antagonist) not only blocked the cytoprotective effect of melatonin, but also attenuated the stimulatory effect of melatonin on cGMP-PKGIα signaling and its modulatory effect on Nrf-2-HO-1 and MAPK signaling. This study showed that melatonin ameliorated diabetic MI/R injury by modulating Nrf-2-HO-1 and MAPK signaling, thus reducing myocardial apoptosis and oxidative stress and preserving cardiac function. Importantly, melatonin membrane receptors (especially MT2 receptor)-dependent cGMP-PKGIα signaling played a critical role in this process.
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Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Coração/efeitos dos fármacos , Melatonina/farmacologia , Traumatismo por Reperfusão/metabolismo , Acetilcisteína/metabolismo , Animais , Apoptose , Membrana Celular/metabolismo , Sobrevivência Celular , Diabetes Mellitus Experimental , Ativação Enzimática , Regulação da Expressão Gênica , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Transdução de Sinais , Triptaminas/farmacologiaRESUMO
This study was conducted to explore the hypothesis that the endogenous superoxide anions (O2-) and nitric oxide (NO) system of the paraventricular nucleus (PVN) regulates the cardiac sympathetic afferent reflex (CSAR) contributing to sympathoexcitation in obese rats induced by a high-fat diet (42% kcal as fat) for 12 weeks. CSAR was evaluated by monitoring the changes of renal sympathetic nerve activity (RSNA) and the mean arterial pressure (MAP) responses to the epicardial application of capsaicin (CAP) in anaesthetized rats. In obese rats with hypertension (OH group) or without hypertension (OB group), the levels of PVN O2-, angiotensinII (Ang II), Ang II type 1 receptor (AT1R), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were elevated, whereas neural NO synthase (nNOS) and NO were significantly reduced. Moreover, CSAR was markedly enhanced, which promoted the elevation of plasma norepinephrine levels. The enhanced CSAR was attenuated by PVN application of the superoxide scavenger polyethylene glycol-superoxide dismutase (PEG-SOD) and the NO donor sodium nitroprusside (SNP), and was strengthened by the superoxide dismutase inhibitor diethyldithiocarbamic acid (DETC) and the nNOS inhibitor N(ω)-propyl-l-arginine hydrochloride (PLA); conversely, there was a smaller CSAR response to PLA or SNP in rats that received a low-fat (12% kcal) diet. Furthermore, PVN pretreatment with the AT1R antagonist losartan or with PEG-SOD, but not SNP, abolished Ang II-induced CSAR enhancement. These findings suggest that obesity alters the PVN O2- and NO system that modulates CSAR and promotes sympathoexcitation.
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Coração/fisiopatologia , Óxido Nítrico/metabolismo , Obesidade/fisiopatologia , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Reflexo , Superóxidos/metabolismo , Animais , Pressão Sanguínea , Coração/inervação , Frequência Cardíaca , Masculino , Óxido Nítrico/análise , Obesidade/complicações , Obesidade/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxidos/análise , Sistema Nervoso Simpático/fisiopatologiaRESUMO
BACKGROUND: Atrial fibrillation (AF) is often associated with atrial fibrosis and oxidative stress. Neferine, a bisbenzylisoquinoline alkaloid, has been reported to exert an antiarrhythmic effect. However, its impact on Angiotensin II (Ang II) infusion-induced AF and the underlying mechanism remains unclear. This study aimed to investigate whether neferine alleviates Ang II-induced AF and explore the underlying mechanisms. METHODS: Mice subjected to Ang II infusion to induce AF were concurrently treated with neferine or saline. AF incidence, myocardial cell size, fibrosis, and oxidative stress were then examined. RESULTS: Neferine treatment inhibited Ang II-induced AF, atrial size augmentation, and atrial fibrosis. Additionally, we observed that Ang II increased reactive oxygen species (ROS) generation, induced mitochondrial membrane potential depolarization, and reduced glutathione (GSH) and superoxide dismutase (SOD) levels, which were reversed to some extent by neferine. Mechanistically, neferine activated the Nrf2/HO-1 signaling pathway and inhibited TGF-ß/p-Smad2/3 in Ang II-infused atria. Zinc Protoporphyrin (ZnPP), an HO-1 inhibitor, reduced the anti-oxidative effect of neferine to some extent and subsequently abolished the beneficial effect of neferine on Ang II-induced AF. CONCLUSIONS: These findings provide hitherto undocumented evidence that the protective role of neferine in Ang II-induced AF is dependent on HO-1.
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Angiotensina II , Fibrilação Atrial , Benzilisoquinolinas , Fibrose , Fator 2 Relacionado a NF-E2 , Transdução de Sinais , Proteína Smad3 , Fator de Crescimento Transformador beta , Animais , Angiotensina II/farmacologia , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/metabolismo , Fibrilação Atrial/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , Camundongos , Benzilisoquinolinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/metabolismo , Masculino , Fator de Crescimento Transformador beta/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteína Smad2/metabolismo , Regulação para Cima/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Heme Oxigenase (Desciclizante)/metabolismo , Proteínas de Membrana , Heme Oxigenase-1RESUMO
BACKGROUND: A symptomatic reduction in left ventricular ejection fraction (LVEF) is the main reason for postoperative heart failure after valve replacement surgery. However, postoperative heart failure occurs in patients with normal preoperative LVEF. Therefore, we examined clinical and echocardiographic data of patients with rheumatic heart disease to determine additional risk factors for low LVEF in the postoperative period. METHODS AND RESULTS: Ninety-seven patients with rheumatic heart disease (RHD) who underwent mitral valve replacement for severe mitral valve stenosis were included retrospectively in this study. All patients had normal LVEF before surgery. Patients were divided into 2 groups based on postoperative LVEF 6 months after surgery. Groups A had normal postoperative LVEF (82 cases, 84.5%), and group B had low postoperative LVEF (15 cases, 15.5%). Clinical and electrocardiographic data were collected to determine risk factors for deterioration in cardiac function. Multivariate analysis revealed that preoperative low systolic peak velocities at the lateral tricuspid annulus (St) and no or mild aortic stenosis were independent risk factors for cardiac deterioration in patients with normal preoperative LVEF. Individuals with preoperative St ≤ 4.8 cm/s were more likely to develop lower LVEF at follow-up (χ(2) = 7.54; P = .006; odds ratio 5.03, 95% confidence interval 1.31-20.82). All 15 patients who had normal preoperative LVEF but abnormal postoperative LVEF had no or only mild aortic valve stenosis. CONCLUSIONS: Decreased right ventricular function and no or mild aortic stenosis were independent risk factors for low LVEF at follow-up in patients with RHD who had normal preoperative LVEF. The velocity of the tricuspid valve ring should be included in preoperative evaluations to improve the accuracy of postsurgical prognosis and clinical decision making.
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Implante de Prótese de Valva Cardíaca/efeitos adversos , Estenose da Valva Mitral/epidemiologia , Estenose da Valva Mitral/cirurgia , Complicações Pós-Operatórias/epidemiologia , Cardiopatia Reumática/epidemiologia , Cardiopatia Reumática/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Implante de Prótese de Valva Cardíaca/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Estenose da Valva Mitral/fisiopatologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Cardiopatia Reumática/fisiopatologia , Fatores de Risco , Volume Sistólico/fisiologia , Disfunção Ventricular Direita/diagnóstico , Disfunção Ventricular Direita/fisiopatologiaRESUMO
OBJECTIVE: To summarize the early and midterm outcomes of artificial chordae transplant in mitral valve repair. METHODS: A total of 50 patients underwent mitral valve repair with artificial chordae transplant from January 2009 to January 2010 in General Hospital of Shenyang Military Command. Follow-up was conducted on 48 cases (96%) for 3-4 years. RESULTS: No early postoperative mortality occurred. All cases had cardiac function New York Heart Association (NYHA) grade I/II at discharge. Among 48 cases, one died of cerebral infarction after 13 months and the reminder survived and no one underwent reoperation. Among survivors, 45 cases were in cardiac function NYHA grade I and another 2 in grade II. Echocardiography showed that postoperative 3 years left atrial diameter, left ventricular end-diastolic dimension, left ventricular end-systolic dimension and the ratio of regurgitation beam area and left atrial area were significantly smaller than those preoperative ones (39.5% ± 9.7% vs 5.6% ± 0.1%, P < 0.01) and left ventricular ejection fraction increased markedly (0.55 ± 0.06 vs 0.67 ± 0.07, P < 0.01). There was no instance of artificial chordae rupture. CONCLUSION: Gore-Tex artificial chordae transplant is a safe and effective technique in mitral valve repair with excellent early and midterm operative outcomes.
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Cordas Tendinosas/transplante , Implante de Prótese de Valva Cardíaca/métodos , Próteses Valvulares Cardíacas , Insuficiência da Valva Mitral/cirurgia , Idoso , Feminino , Implante de Prótese de Valva Cardíaca/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral , Resultado do TratamentoRESUMO
One-third of patients with end-stage chronic kidney disease (CKD) experience diabetic nephropathy (DN), which worsens the progression of renal dysfunction. However, preventive measures for DN are lacking. Lactobacillus acidophilus TYCA06, Bifidobacterium longum subsp. infantis BLI-02, and Bifidobacterium bifidum VDD088 probiotic strains have been demonstrated to delay CKD progression. This study evaluated their biological functions to stabilize blood-glucose fluctuations and delay the deterioration of renal function. The db/db mice were used to establish a DN animal model. This was supplemented with 5.125 × 109 CFU/kg/day (high dose) or 1.025 × 109 CFU/kg/day (low dose) mixed with probiotics containing TYCA06, BLI-02, and VDD088 for 8 weeks. Blood urea nitrogen (BUN), serum creatinine, blood glucose, and urine protein were analyzed. Possible mechanisms underlying the alleviation of DN symptoms by probiotic strains were evaluated through in vitro tests. Animal experiments revealed that BUN, serum creatinine, and blood glucose upon probiotic administration were significantly lower than in the control group. The rate of change of urine protein decreased significantly, and blood pressure, glucose tolerance, and renal fibrosis were improved. In vitro testing indicated that TYCA06 and BLI-02 significantly increased acetic acid concentration. TYCA06, BLI-02, and VDD088 were associated with better antioxidation, anti-inflammation, and glucose consumption activities relative to the control. A combination of the probiotics TYCA06, BLI-02, and VDD088 attenuated renal function deterioration and improved blood-glucose fluctuation in a diabetes-induced CKD mouse model.
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Diabetes Mellitus , Nefropatias Diabéticas , Probióticos , Insuficiência Renal Crônica , Camundongos , Animais , Glicemia/metabolismo , Pressão Sanguínea , Creatinina , Glucose , Probióticos/uso terapêutico , Modelos Animais de DoençasRESUMO
Different from hexagonal boron nitride (hBN) sheets, the bandgap of hBN nanoribbons (BNNRs) can be changed by spatial/electrostatic confinement. It is predicted that a transverse electric field can narrow the bandgap and even cause an insulator-metal transition in BNNRs. However, experimentally introducing an overhigh electric field across the BNNR remains challenging. Here, it is theoretically and experimentally demonstrated that water adsorption greatly reduces the bandgap of zigzag-oriented BNNRs (zBNNRs). Ab initio calculations show that water molecules can be favorably assembled within the trench between two adjacent BNNRs to form a polar ice layer, which induces a transverse equivalent electric field of over 2 V nm-1 accounting for the bandgap reduction. Field-effect transistors are successfully fabricated from zBNNRs with different widths. The conductance of water-adsorbed zBNNRs can be tuned over 3 orders in magnitude via modulation of the equivalent electrical field at room temperature. Furthermore, photocurrent response measurements are taken to determine the optical bandgaps of zBNNRs with water adsorption. The zBNNR with increased width can exhibit a bandgap down to 1.17 eV. This study offers fundamental insights into new routes toward realizing electronic/optoelectronic devices and circuits based on hexagonal boron nitride.
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OBJECTIVE: To develop the national neglect norms for rural children aged 3 to 6 years, which are suitable for Chinese situations. METHODS: According to the multi-stage stratified cluster sampling principle, 84 towns of 10 provinces or municipalities were selected in China. Children aged 3 to 6 years were surveyed in November 2010, the sample of analysis were 3240 (of whom males were 49.6% (1608/3240) and the Han nationality were 93.3% (3023/3240)). Questionnaire was designed by authors and deleted items that did not meet the requirements through several statistical analysis methods, such as item analysis method, factor analysis method, reliability analysis method. The reliability analysis and validity analysis were used to test the stability and reliability of the norm. The evaluation criteria of the scale was determined by the percentile method, then the initial development of the norm completed. RESULTS: After deleting inappropriate items by statistical processing, finally, the scale consisted of 57 items, and included 6 neglected dimensions (physical neglect, emotional neglect, educational neglect, safe neglect, medical neglect and social neglect). Its item loadings ranged from 0.359 to 0.789, which met the statistical requirements. The scale's total Cronbach α coefficients 0.904, the total split-half reliability coefficients were 0.820, the 6 neglect dimensions' Cronbach α coefficients ranged from 0.620 to 0.815, the 6 neglect dimensions' split-half reliability coefficients ranged from -0.034 to 0.789, the scale's parallel reliability were 0.785 and it's re-test reliability were 0.613. After construct validity, external validity and content validity testing, the result showed that this scale could effectively reflect the real neglected status of children investigated. The total neglect cut-off score of this scale were 121. CONCLUSION: The scale has good stability and reliability. And it adapts Chinese conditions and it's convenient to operate.
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Maus-Tratos Infantis/diagnóstico , Testes Psicológicos , Inquéritos e Questionários , Maus-Tratos Infantis/prevenção & controle , Pré-Escolar , China , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , População Rural , Estudos de Amostragem , Inquéritos e Questionários/normasRESUMO
OBJECTIVE: To explore the status of child neglect among rural areas children aged 0 - 6 years in China. METHODS: A total of 7411 rural children aged 0 - 6 years old who were composed of two age groups (3315 children aged 0 - 2 years old and 4096 children aged 3 - 6 years old) were multistage stratified randomly sampled from 84 villages which were representative of 10 provinces of China, in accordance with sex and age in November 2010. To identify the child neglect based on the Neglect Norms for Children Aged 0 to 2 and 3 to 6 Years Old in Rural Areas of China, SPSS 13.0 was employed for analyzing neglect frequency and degree for every group of different age, sex and neglect type (including physical, emotional, educational, medical, safety and social neglects). χ(2) test and analysis of variance were also used. RESULTS: The degree of child neglect for the children aged 0 - 2 years old was 45.01 ± 7.56, the neglect frequency was 54.9% (1819/3315); the degree of child neglect for the children aged 3 - 6 years old was 44.42 ± 7.57, the neglect frequency was 53.8% (2203/4096). The neglect frequency of children aged 0, 1, 2 years old were 58.5% (654/1117), 52.2% (597/1144), 53.9% (568/1054) (P < 0.05). For children aged 3 - 6 years old, the degrees of emotional and safety neglect for males (44.60 ± 7.86, 36.82 ± 9.03) were higher than females (44.03 ± 7.72, 36.25 ± 9.05) (P < 0.05); and the frequencies of emotional and social neglect for males (16.8% (349/2072), 28.3% (586/2072)) were also higher than females (14.1% (286/2024), 24.8% (503/2024)) (P < 0.05). All children of two age groups suffered neglect mainly on one of the six neglect types (incidences were 20.6% (683/3315) and 22.7% (931/4096)). For 0-2 age groups, the higher neglect frequencies happened in the single-parent family and the remarried family (62.5% (15/24) and 63.2% (12/19)), but for children aged 3 - 6 years old groups, it happened in the single-parent family (60.0%, 27/45). CONCLUSION: Degree and frequency of child neglect among children aged 0 to 6 years old in the rural areas of China are high, and we should find out risk factors and provide efficient prevention measures.
Assuntos
Maus-Tratos Infantis/prevenção & controle , Maus-Tratos Infantis/estatística & dados numéricos , Pré-Escolar , China , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , População Rural , Inquéritos e QuestionáriosRESUMO
Objective: This study aimed to examine the sleep arrangements and soothing methods and to assess their associations with sleep problems among children aged < 3 years in China. Methods: A cross-sectional survey was conducted in 2019 from six provinces in China. A total of 1,195 caregivers of children aged 0-35 months were included in the study. Data on sleep arrangements, soothing methods, and sleep problems (i.e., frequent night awakenings and difficulty falling asleep) were assessed using the Brief Infant Sleep Questionnaire. The reasons for bed-sharing in sleep arrangements were recorded using a self-designed questionnaire. Results: The bed-sharing practice was very prevalent at any age, which ranged from 69.9% to 78.3%. Most infants fell asleep while feeding or being rocked/held before age 12 months. By age 35 months, 62.4% of the children fell asleep in bed near parents. The most common reasons for bed-sharing were breastfeeding/feeding and convenience. Parental involvement when falling asleep was significantly related with frequent night awakenings and difficulty falling asleep. No association was found between bed-sharing and sleep. Conclusion: Bed-sharing and parental involvement were very common among Chinese children aged < 3 years. Children who fall asleep with parental involvement were more likely to have sleep problems.
Assuntos
Povo Asiático , Comportamento do Lactente , Transtornos do Sono-Vigília , Sono/fisiologia , Leitos , Pré-Escolar , China , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Higiene do Sono , Inquéritos e QuestionáriosRESUMO
Mitochondrial reactive oxygen species (ROS) damage and atrial remodeling serve as the crucial substrates for the genesis of atrial fibrillation (AF). Branched-chain amino acids (BCAAs) catabolic defect plays critical roles in multiple cardiovascular diseases. However, the alteration of atrial BCAA catabolism and its role in AF remain largely unknown. This study aimed to explore the role of BCAA catabolism in the pathogenesis of AF and to further evaluate the therapeutic effect of melatonin with a focus on protein kinase G (PKG)-cAMP response element binding protein (CREB)-Krüppel-like factor 15 (KLF15) signaling. We found that angiotensin II-treated atria exhibited significantly elevated BCAA level, reduced BCAA catabolic enzyme activity, increased AF vulnerability, aggravated atrial electrical and structural remodeling, and enhanced mitochondrial ROS damage. These deleterious effects were attenuated by melatonin co-administration while exacerbated by BCAA oral supplementation. Melatonin treatment ameliorated BCAA-induced atrial damage and reversed BCAA-induced down-regulation of atrial PKGIα expression, CREB phosphorylation as well as KLF15 expression. However, inhibition of PKG partly abolished melatonin-induced beneficial actions. In summary, these data demonstrated that atrial BCAA catabolic defect contributed to the pathogenesis of AF by aggravating tissue fibrosis and mitochondrial ROS damage. Melatonin treatment ameliorated Ang II-induced atrial structural as well as electrical remodeling by activating PKG-CREB-KLF15. The present study reveals additional mechanisms contributing to AF genesis and highlights the opportunity of a novel therapy for AF by targeting BCAA catabolism. Melatonin may serve as a potential therapeutic agent for AF intervention.
Assuntos
Fibrilação Atrial , Melatonina , Aminoácidos de Cadeia Ramificada , Angiotensina II , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteínas Quinases Dependentes de GMP Cíclico/genética , Humanos , Fatores de Transcrição Kruppel-Like , Melatonina/farmacologiaRESUMO
BACKGROUND: Probiotics had been used to decreased bilirubin level in neonatal jaundice (NJ) without being further studied mechanism and stratification. The intestinal pathogen Escherichia coli produced ß-glucuronidase would increase enterohepatic circulation and elevate serum bilirubin levels (SBLs) which might worsen the disease process of NJ. STUDY OBJECTIVE: We hypothesized that some probiotics could decrease bilirubin level through inhibiting the growth of E. coli. It's assumed that adjuvant probiotic intervention might accelerate the phototherapy for NJ and alleviate the severity of the NJ. Besides, it's further study the efficacy of the probiotic intervention in NJ among the full-term and preterm newborns. MATERIALS AND METHODS: Firstly, the Bifidobacterium animalis subsp. lactis CP-9 was screened for its anti-E. coli activity. Then, it was orally administered to newborns with NJ in combination with conventional phototherapy (wavelength 425-457 nm) to determine its efficacy. 83 neonatal patients whose serum bilirubinemia was at a concentration ofâ ≥â 15 mg/dL were participated the double-blind randomized trial and conducted in the neonatal ward of China Medical University Children's Hospital (CMUCH, Taichung, Taiwan). The test was conducted in 2 groups: experimental group: phototherapyâ +â B. animalis subsp. lactis CP-9 (nâ =â 43; 5â ×â 109 CFU/capsule) and control group: phototherapyâ +â placebo (nâ =â 40). The SBL and total phototherapy duration were measured. RESULTS: The experimental group showed improved serum bilirubin decline rate (-0.16â ±â 0.02 mg/dL/h; Pâ =â .009, 95% CI -0.12 to -0.2), particularly in the first 24 hour of in-hospital care, and reduced total phototherapy duration (44.82â ±â 3.23 h; Pâ =â .011, 95% CI: 51.3-38.2) compared with the control group. Especially, probiotics had a significant therapeutic effect (serum bilirubin decline rate: -0.18â ±â 0.02 mg/dL/h, 95% CI -0.12 to -0.23, Pâ =â .014; phototherapy duration: 43.17â ±â 22.72 h, 95% CI 51.9-34.3, Pâ =â .019) in the low-risk subgroup (full-term newborns). CONCLUSIONS: In conclusion, B. animalis subsp. lactis CP-9 synergistically improves treatment outcomes of NJ during in-hospital phototherapy including reduced total phototherapy duration and improved serum bilirubin decline rate, particularly in full-term newborns.
Assuntos
Bifidobacterium animalis , Icterícia Neonatal , Probióticos , Criança , Humanos , Recém-Nascido , Icterícia Neonatal/terapia , Probióticos/uso terapêutico , Resultado do Tratamento , BilirrubinaRESUMO
Excessive alcohol consumption has long been identified as a risk factor for adverse atrial remodeling and atrial fibrillation (AF). Icariin is a principal active component from traditional Chinese medicine Herba Epimedii and has been demonstrated to exert potential antiarrhythmic effect. The present study was designed to evaluate the effect of icariin against alcohol-induced atrial remodeling and disruption of mitochondrial dynamics and furthermore, to elucidate the underlying mechanisms. Excessive alcohol-treated C57BL/6 J mice were infected with serotype 9 adeno-associated virus (AAV9) carrying mouse SIRT3 gene or negative control virus. Meanwhile, icariin (50 mg/kg/d) was administered to the animals in the presence or absence of AAV9 carrying SIRT3 shRNA. We noted that 8 weeks of icariin treatment effectively attenuated alcohol consumption-induced atrial structural and electrical remodeling as evidenced by reduced AF inducibility and reversed atrial electrical conduction pattern as well as atrial enlargement. Furthermore, icariin-treated group exhibited significantly enhanced atrial SIRT3-AMPK signaling, decreased atrial mitoSOX fluorescence and mitochondrial fission markers, elevated mitochondrial fusion markers (MFN1, MFN2) as well as NRF-1-Tfam-mediated mitochondrial biogenesis. Importantly, these beneficial effects were mimicked by SIRT3 overexpression while abolished by SIRT3 knockdown. These data revealed that targeting atrial SIRT3-AMPK signaling and preserving mitochondrial dynamics might serve as the novel therapeutic strategy against alcohol-induced AF genesis. Additionally, icariin ameliorated atrial remodeling and mitochondrial dysfunction by activating SIRT3-AMPK signaling, highlighting the use of icariin as a promising antiarrhythmic agent in this circumstance.